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Adhesive strength of autologous fibrin glue.
Yoshida, H; Hirozane, K; Kamiya, A
To establish an easy and rapid method for measuring the adhesive strength of fibrin glue and to clarify the factor(s) most affecting the strength, a study was made on the effect of the concentration of plasma components on the strength of cryoprecipitate (Cryo) prepared from a subject's own autologous plasma to be used as fibrin glue. The adhesive strength of the Cryo was measured with various supporting materials instead of animal skin using a tester of tension and compression. The results were as follows: (1) the strength of Cryo applied to ground flat glass (4 cm2) was significantly greater than that applied to clear glass, clear plastic, or smooth and flat wood chips; (2) the adhesive strength of Cryo depended on the concentration of thrombin with the optimal concentration being 50 units/ml; (3) the concentration of CaCl2 did not affect the adhesive strength of Cryo; (4) the adhesive reaction was dependent on the temperature and the adhesive strength more quickly reached a steady state at 37 degrees C than at lower temperature; (5) the adhesive strength was correlated well with the total concentration of fibrinogen and fibronectin. These results indicate that the adhesive strength of Cryo can be easily and quickly evaluated using a tester and ground glass with thrombin at 50 units/ml, and that the adhesive strength of Cryo can be predicted from the total concentration of fibrinogen and fibronectin. PMID:10726885
Use of autologous fibrin glue for endoscopic treatment of esophageal lesions
Lucas, Matthias; Seeber, Petra
Background and study aims: Esophageal leaks are a potentially life-threatening condition. One treatment option is injection therapy with commercially available fibrin glue. We describe herein a method to close esophageal leaks by injecting autologous fibrin glue prepared exclusively with the patient's own blood. PMID:26528493
Clinical evaluations of autologous fibrin glue and polyglycolic acid sheets as oral surgical wound coverings after partial glossectomy.
Kouketsu, Atsumu; Nogami, Shinnosuke; Fujiwara, Minami; Mori, Shiro; Yamauchi, Kensuke; Hashimoto, Wataru; Miyashita, Hitoshi; Kurihara, Jun; Kawai, Tadashi; Higuchi, Keisuke; Takahashi, Tetsu
Polyglycolic acid (PGA) sheets and commercial fibrin glue are commonly used to cover open wound surfaces in oral surgery. Compared to commercial fibrin glue composed of pooled allogeneic blood, autologous fibrin glue is less expensive and poses lower risks of viral infection and allergic reaction. Here, we evaluated postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding in 24 patients who underwent partial glossectomy plus the application of a PGA sheet and an autologous fibrin glue covering (autologous group) versus 11 patients in whom a PGA sheet and commercial fibrin glue were used (allogeneic group). The evaluated clinical measures were nearly identical in both groups. Remarkable wound surface granulation was recognized in two cases in the autologous group. No complications were observed in either group, including viral infection or allergic reaction. Abnormal postoperative bleeding in the wound region was observed in one case in the allogeneic group. Coagulation and adhesion of the autologous fibrin glue were equivalent to those of conventional therapy with a PGA sheet and commercial fibrin glue. Thus, our results show that covering wounds with autologous fibrin glue and PGA sheets may help avoid the risks of viral infection and allergic reaction in partial glossectomy cases. PMID:27341770
Autologous Fibrin Glue as an Encapsulating Scaffold for Delivery of Retinal Progenitor Cells
Ahmed, Tamer A. E.; Ringuette, Randy; Wallace, Valerie A.; Griffith, May
The retina is a highly sophisticated piece of the neural machinery that begins the translation of incoming light signals into meaningful visual information. Several degenerative diseases of the retina are characterized by photoreceptor loss and eventually lead to irreversible blindness. Regenerative medicine, using tissue engineering-based constructs to deliver progenitor cells or photoreceptors along with supporting carrier matrix is a promising approach for restoration of structure and function. Fresh fibrin glue (FG) produced by the CryoSeal®FS system in combination with mouse retinal progenitor cells (RPCs) were evaluated in this study. In vitro expanded RPCs isolated from postnatal mouse retina were encapsulated into FG and cultured in the presence of the protease inhibitor, tranexamic acid. Encapsulation of RPCs into FG did not show adverse effects on cell proliferation or cell survival. RPCs exhibited fibroblast-like morphology concomitantly with attachment to the encapsulating FG surface. They expressed α7 and β3 integrin subunits that could mediate attachment to fibrin matrix via an RGD-independent mechanism. The three-dimensional environment and the attachment surface provided by FG was associated with a rapid down-regulation of the progenitor marker SOX2 and enhanced the expression of the differentiation markers cone-rod homeobox and recoverin. However, the in vitro culture conditions did not promote full differentiation into mature photoreceptors. Nevertheless, we have shown that autologous fibrin, when fabricated into a scaffold for RPCs for delivery to the retina, provides the cells with external cues that could potentially improve the differentiation events. Hence, transient encapsulation of RPCs into FG could be a valid and potential treatment strategy to promote retinal regeneration following degenerative diseases. However, further optimization is necessary to maximize the outcomes in terms of mature photoreceptors. PMID:25692127
Panda, Anita; Kumar, Sandeep; Kumar, Abhiyan; Bansal, Raseena; Bhartiya, Shibal
Suturing is a time consuming task in ophthalmology and suture induced irritation and redness are frequent problems. Postoperative wound infection and corneal graft rejection are examples of possible suture related complications. To prevent these complications, ophthalmic surgeons are switching to sutureless surgery. A number of recent developments have established tissue adhesives like cyanoacrylate glue and fibrin glue as attractive alternatives to sutures. A possible and promising new application for tissue adhesives is to provide a platform for tissue engineering. Currently, tissue glue is being used for conjunctival closure following pterygium and strabismus surgery, forniceal reconstruction surgery, amniotic membrane transplantation, lamellar corneal grafting, closure of corneal perforations and descematoceles, management of conjunctival wound leaks after trabeculectomy, lid surgery, adnexal surgery and as a hemostat to minimise bleeding. The purpose of this review is to discuss the currently available information on fibrin glue. PMID:19700876
Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue
Cocero, Nadia; Pucci, Fabrizio; Messina, Maria; Pollio, Berardino; Mozzati, Marco; Bergamasco, Laura
Background Dental extractions in haemophiliacs may cause secondary bleeding, requiring repeated surgical and haematological interventions. As a local haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived product, it carries the risk of viral infections. We, therefore, compared fibrin glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a controlled trial. Material and methods One hundred and twenty patients with different blood disorders were randomised into two cohorts to undergo dental extraction procedures without hospitalisation. Prior to the extractions, patients underwent systemic haematological treatment. Complications were defined as secondary bleeding after the 7-day follow-up period or protracting after the repair procedure. Results There were 106 extractions (7 retained 3rd molars) in the group managed with fibrin glue: secondary bleeding affected 3/60 patients (5%) on the third day after extraction and necessitated additional surgery and systemic treatment (in one case the procedure had to be repeated on the 7th day). In the PRGF arm there were 98 extractions (23 retained 3rd molars): secondary bleeding affected two patients (3.3%) on the first day after extraction and was arrested with surgery without systemic treatment. Four out of the five secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or liver disease significantly increased the bleeding risk. Discussion The bleeding rates in the study and control arm prove that PRGF works as well as fibrin glue as a local haemostatic. Further assets are that PRGF has autologous origin, does not require additional systemic treatment in post-extraction repair surgery, is associated with an earlier onset of neo-angiogenesis and, overall, can reduce patients' distress and costs to the health system. PMID:25369587
[Fibrin glue and bone regeneration].
Zilch, H; Wolff, R
The osteoinductive property of fibrin glue with and without admixture of aprotinin was proven in animal model. Aprotinin as an inhibitor of the fibrinolysis is supposed to be an inhibitor of the osteogenesis, too. Three holes of 4 mm diameter and 2 mm depth were placed into the diaphysis of both femura in 12 adults dogs. The defects were filled with either pure fibrin glue or with glue containing aprotinin (3000 KIE), or with nothing (vacant). After 8 weeks the quantity of the new built woven-bone was examined by plane geometry and the "Bone Metabolising Unit (BMU)" (Frost) which are crossing the border of lamellar bone and new woven bone were counted out. There was seen no statistical significantly between the three groups neither in the quantity of new bone nor in the BMU. Therefore the fibrin glue has no osteoinductive property. PMID:2441537
Fibrin Glue as a Drug Delivery System
Spicer, Patrick P.; Mikos, Antonios G.
Fibrin glue has been used surgically for decades for hemostasis as well as a sealant. It has also been researched as both a gel for cell delivery and a vehicle for drug delivery. The drug delivery applications for fibrin glue span tissue engineering to chemotherapy and involve several mechanisms for drug matrix interactions and control of release kinetics. Additionally, drugs or factors can be loaded in the gel via impregnation and tethering to the gel through covalent linkages or affinity based systems. This review highlights recent research of fibrin glue as a drug delivery vehicle. PMID:20637815
Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocytes during 36 weeks in rabbit model.
Kazemnejad, Somaieh; Khanmohammadi, Manijeh; Mobini, Sahba; Taghizadeh-Jahed, Masoud; Khanjani, Sayeh; Arasteh, Shaghayegh; Golshahi, Hannaneh; Torkaman, Giti; Ravanbod, Roya; Heidari-Vala, Hamed; Moshiri, Ali; Tahmasebi, Mohammad-Naghi; Akhondi, Mohammad-Mehdi
The reconstruction capability of osteochondral (OCD) defects using silk-based scaffolds has been demonstrated in a few studies. However, improvement in the mechanical properties of natural scaffolds is still challengeable. Here, we investigate the in vivo repair capacity of OCD defects using a novel Bombyx mori silk-based composite scaffold with great mechanical properties and porosity during 36 weeks. After evaluation of the in vivo biocompatibility and degradation rate of these scaffolds, we examined the effectiveness of these fabricated scaffolds accompanied with/without autologous chondrocytes in the repair of OCD lesions of rabbit knees after 12 and 36 weeks. Moreover, the efficiency of these scaffolds was compared with fibrin glue (FG) as a natural carrier of chondrocytes using parallel clinical, histopathological and mechanical examinations. The data on subcutaneous implantation in mice showed that the designed scaffolds have a suitable in vivo degradation rate and regenerative capacity. The repair ability of chondrocyte-seeded scaffolds was typically higher than the scaffolds alone. After 36 weeks of implantation, most parts of the defects reconstructed by chondrocytes-seeded silk scaffolds (SFC) were hyaline-like cartilage. However, spontaneous healing and filling with a scaffold alone did not eventuate in typical repair. We could not find significant differences between quantitative histopathological and mechanical data of SFC and FGC. The fabricated constructs consisting of regenerated silk fiber scaffolds and chondrocytes are safe and suitable for in vivo repair of OCD defects and promising for future clinical trial studies. PMID:26822846
[Treatment of pseudoarthrosis of the carpal scaphoid with fibrin glue].
Carozzi, S
The author think that "Fibrin Seal Glue" and mechanical syntesis is an opimal method for osteosintesis of the Carpal scaphoid. He speaks about 5 patients treated with optimal results in 50 days mean. PMID:6395974
Autologous fibrin sealant (Vivostat®) in the neurosurgical practice: Part I: Intracranial surgical procedure
Graziano, Francesca; Certo, Francesco; Basile, Luigi; Maugeri, Rosario; Grasso, Giovanni; Meccio, Flavia; Ganau, Mario; Iacopino, Domenico G.
Background: Hemorrhages, cerebrospinal fluid (CSF) fistula and infections are the most challenging postoperative complications in Neurosurgery. In this study, we report our preliminary results using a fully autologous fibrin sealant agent, the Vivostat® system, in achieving hemostasis and CSF leakage repair during cranio-cerebral procedures. Methods: From January 2012 to March 2014, 77 patients were studied prospectively and data were collected and analyzed. Autologous fibrin sealant, taken from patient's blood, was prepared with the Vivostat® system and applied on the resection bed or above the dura mater to achieve hemostasis and dural sealing. The surgical technique, time to bleeding control and associated complications were recorded. Results: A total of 79 neurosurgical procedures have been performed on 77 patients. In the majority of cases (98%) the same autologous fibrin glue provided rapid hemostasis and dural sealing. No patient developed allergic reactions or systemic complications in association with its application. There were no cases of cerebral hematoma, swelling, infection, or epileptic seizures after surgery whether in the immediate or in late period follow-up. Conclusions: In this preliminary study, the easy and direct application of autologous fibrin sealant agent helped in controlling cerebral bleeding and in providing prompt and efficient dural sealing with resolution of CSF leaks. Although the use of autologous fibrin glue seems to be safe, easy, and effective, further investigations are strongly recommended to quantify real advantages and potential limitations. PMID:25984391
Effect of collagen sponge and fibrin glue on bone repair
SANTOS, Thiago de Santana; ABUNA, Rodrigo Paolo Flores; de ALMEIDA, Adriana Luisa Gonçalves; BELOTI, Marcio Mateus; ROSA, Adalberto Luiz
ABSTRACT The ability of hemostatic agents to promote bone repair has been investigated using in vitro and in vivo models but, up to now, the results are inconclusive. Objective In this context, the aim of this study was to compare the potential of bone repair of collagen sponge with fibrin glue in a rat calvarial defect model. Material and Methods Defects of 5 mm in diameter were created in rat calvariae and treated with either collagen sponge or fibrin glue; untreated defects were used as control. At 4 and 8 weeks, histological analysis and micro-CT-based histomorphometry were carried out and data were compared by two-way ANOVA followed by Student-Newman-Keuls test when appropriated (p≤0.05). Results Three-dimensional reconstructions showed increased bone formation in defects treated with either collagen sponge or fibrin glue compared with untreated defects, which was confirmed by the histological analysis. Morphometric parameters indicated the progression of bone formation from 4 to 8 weeks. Additionally, fibrin glue displayed slightly higher bone formation rate when compared with collagen sponge. Conclusion Our results have shown the benefits of using collagen sponge and fibrin glue to promote new bone formation in rat calvarial bone defects, the latter being discreetly more advantageous. PMID:26814464
Successful management of congenital chyloperitoneum with fibrin glue.
Antao, Brice; Croaker, David; Squire, Roly
Chylous ascites in children has been treated in a variety of ways, including a low-fat diet, medium chain triglycerides, diuretics, total parental nutrition, surgical exploration, and internal peritoneo-venous shunting. The authors describe a child with persistent congenital chyloperitoneum treated successfully with the application of fibrin glue and recommend this as an effective alternative to traditional approaches. PMID:14614734
Warning: fatal reaction to the use of fibrin glue in deep hepatic wounds. Case reports.
Berguer, R; Staerkel, R L; Moore, E E; Moore, F A; Galloway, W B; Mockus, M B
Two cases of severe hypotension following the use of fibrin glue for hemostasis in hepatic injuries are reported. A systemic reaction to bovine thrombin via large venous lacerations is suspected. A preliminary animal study supports this hypothesis. Caution is advised in the use of fibrin glue for hemostasis in deep hepatic wounds. PMID:2002531
Evaluation of an in vivo heterotopic model of osteogenic differentiation of equine bone marrow and muscle mesenchymal stem cells in fibrin glue scaffold.
McDuffee, Laurie A; Esparza Gonzalez, Blanca P; Nino-Fong, Rodolfo; Aburto, Enrique
Autologous mesenchymal stem cells (MSCs) have been used as a potential cell-based therapy in various animal and human diseases. Their differentiation capacity makes them useful as a novel strategy in the treatment of tissue injury in which the healing process is compromised or delayed. In horses, bone healing is slow, taking a minimum of 6-12 months. The osteogenic capacity of equine bone marrow and muscle MSCs mixed with fibrin glue or phosphate-buffered saline (PBS) as a scaffold is assessed. Bone production by the following groups was compared: Group 1, bone marrow (BM) MSCs in fibrin glue; Group 2, muscle (M) MSCs in fibrin glue; Group 3, BM MSCs in PBS; Group 4, M MSCs in PBS and as a control; Group 5, fibrin glue without cells. BM and M MSCs underwent osteogenic stimulation for 48 h prior to being injected intramuscularly into nude mice. After 4 weeks, the mice were killed and muscle samples were collected and evaluated for bone formation and mineralization by using radiology, histochemistry and immunohistochemistry. Positive bone formation and mineralization were confirmed in Group 1 in nude mice based on calcium deposition and the presence of osteocalcin and collagen type I; in addition, a radiopaque area was observed on radiographs. However, no evidence of mineralization or bone formation was observed in Groups 2-5. In this animal model, equine BM MSCs mixed with fibrin glue showed better osteogenic differentiation capacity compared with BM MSCs in PBS and M MSCs in either carrier. PMID:24258028
Sutureless colon anastomosis with fibrin glue in the rat.
Haukipuro, K A; Hulkko, O A; Alavaikko, M J; Laitinen, S T
The only technique available for creating an intestinal anastomosis without tissue strangulation is gluing. Theoretically, this could lead to a higher hydroxyproline content and greater mechanical strength than in a sutured anastomosis. To test the hypothesis, 83 rats underwent left colon resection and inverted primary anastomosis with either one layer of sutures (NG group) or fibrin glue (FG group). Seven-day FG anastomoses showed less adhesions (P = .02) but one subclinical leakage and a further radiologic one, compared with a greater amount of adhesions but no leakages in the NG group. The mean bursting pressures (mmHg) in the FG and NG groups, respectively, were 25 +/- 20 (SD) and 63 +/- 23 (N.S.) 30 minutes after surgery, 107 +/- 33 and 115 +/- 30 after one day, 81 +/- 31 and 133 +/- 26 (P less than .001) after four days, and 161 +/- 36 and 175 +/- 24 after seven days. The somewhat earlier rise in hydroxyproline content in the glued anastomoses did not lead to significant intergroup differences. The glued anastomoses were thus weak during the critical lag period of healing. Also, by preventing adhesion formation, the glue may reduce the extra blood supply from perianastomotic vessels. The outcomes might have differed more under demanding experimental or clinical situations. PMID:2456902
Fibrin glue as a protective tool for microanastomoses in limb reconstructive surgery
Langer, Stefan; Schildhauer, Thomas A.; Dudda, Marcel; Sauber, Jeannine; Spindler, Nick
Aim: Fibrin glue becomes a more and more routinely used tool for stabilization of microanastomoses and nerve repair. This paper summarizes the technical properties and advantages of its use in a wide variety of microsurgical contexts, and includes an exemplary limb reconstructive case. Patients and methods: A total of 131 patients who had undergone elective and emergency microsurgery mainly of the limbs were retrospectively analyzed, as was the use of free flaps. Results: The use of fibrin glue allows for proper positioning of anastomoses and repaired nerves. No torsion of the pedicle could be seen. The flap survival rated >94%. The fibrin glue could stay in place in >99%. In the rare case of revision, the fibrin glue could easily be removed without damaging the region of the microanastomosis. Conclusion: Fibrin glue should not be used to repair insufficient, i.e., leaking anastomoses, but it does protect the site of anastomosis from tissue and fluid pressure. It prevents the pedickle from torsion and its use facilitates relocation of the microanastomoses in cases of revision surgery. PMID:26759762
Hybrid composites of calcium phosphate granules, fibrin glue, and bone marrow for skeletal repair.
Le Nihouannen, Damien; Goyenvalle, Eric; Aguado, Eric; Pilet, Paul; Bilban, Melitta; Daculsi, Guy; Layrolle, Pierre
Synthetic bone substitutes, such as calcium phosphate ceramics, give good results in clinical applications. In order to adapt to surgical sites, bioceramics come in the form of blocks or granules, and are either dense or porous. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial with the biochemical properties of each component. Critical-sized defects in the femoral condyle of rabbits were filled with TricOs/fibrin glue/bone marrow hybrid/composite material. The TricOs granules (1-2 mm) were composed of hydroxyapatite and beta tricalcium phosphate (60/40 in weight). The fibrin glue was composed of fibrinogen, thrombin and other biological factors and mixed with MBCP granules either simultaneously or sequentially. Bone marrow was also added to the MBCP/fibrin composite prior to filling the defects. After 3, 6, 12, and 24 weeks of implantation, the newly-formed bone was analysed with histology, histomorphometry and mechanical tests. The newly-formed bone had grown centripetally. Simultaneous application of fibrin glue showed better results for mechanical properties than sequential application after 6 weeks. Around 40% of bone had formed after 24 weeks in the three groups. Although the addition of bone marrow did not improve bone formation, the MBCP/fibrin material could be used in clinical bone filling applications. PMID:17117470
A new technique using fibrin glue in the management of auricular hematoma.
Mohamad, Shwan H; Barnes, Martyn; Jones, Stephen; Mahendran, Suresh
: This study aims to describe a new technique for the management of auricular hematoma using fibrin glue. Five difficult cases of auricular hematoma were managed using this technique, including 2 recurrent and 3 delayed presentations. After skin preparation and local anesthetic, an incision was made, the hematoma was evacuated, and the cavity was washed out with saline. Fibrin glue was applied liberally; a dental roll pressure dressing was applied and secured with a prolene bead suture. The patients were given a course of oral antibiotic and reviewed after 5 days for removal of the external dressing. They were later assessed to exclude re-accumulation of the hematoma. All patients had complete resolution of the hematoma without re-accumulation; they were satisfied with the cosmetic results and experienced no complications. This case series provides evidence that fibrin glue is effective in the management of auricular hematoma. Larger studies may provide further evidence of the effectiveness of this new technique. PMID:24699189
Characterization of a fibrin glue-GDNF slow-release preparation.
Cheng, H; Fraidakis, M; Blombäck, B; Lapchak, P; Hoffer, B; Olson, L
One novel method to deliver trophic factor locally in the CNS is to mix it into fibrin glue. In the present studies, [125I]-labeled GDNF-containing fibrin glue balls were used to determine binding and spread of the trophic factor. First, the binding of different concentrations of [125I]-labeled GDNF in fibrin glue was determined in vitro. Within the six concentrations used (from 200 nM to 0.004 nM, 0 M as control), there was a strong linear correlation between the [125I]-GDNF concentration and the recovered radioactivity (r = 0.992). The mean bound radioactivity in 16 samples with 4 nM [125I]-GDNF was 71262 +/- 2710 CPM, and accounted for 89.8% of the mean initial count of free [125I]-GDNF (79369 +/- 3499 CPM). Second, [125I]-GDNF-containing glue balls were implanted into the anterior chamber of adult rats. The implanted fibrin glue balls decreased in size with time, but could still be identified on the irises 2 wk after implantation. Radioactivity was concentrated at the implantation sites in the early stages with a distribution in the surrounding iris tissue, which became separated into focal radioactive spots at the third week. Counts of radioactivity were significantly higher in the [125I]-GDNF glue ball-implanted irises than controls until 14 days after implantation. A study of the [125I] decay over time using least-squares linear regression demonstrated first-order kinetics (r = -0.98, p <0.02) with k = 0.0091 and T 1/2 = 76 h. Finally, [125I]-GDNF-containing glue balls were implanted in the spinal cord of adult rats. Radioactivity was concentrated at the implantation sites in the early stages and was later distributed more widely in the surrounding thoracic cord. The [125I]-GDNF-containing glue degraded over time and became a porous meshwork with decreasing radioactivity at the later time points. Radioactivity in the spinal cords subjected to implantation of [125I]-GDNF-containing glue balls was higher than in controls for 14 days. Study of the [125I] decay
Hemostasis of solid viscus trauma by intraparenchymal injection of fibrin glue.
Hauser, C J
Fibrin glue (FG) is an effective hemostatic agent applied topically to the spleen. In this study, FG was found to be an effective hemostatic agent when applied topically in standardized wounds of the canine liver, spleen, and pancreas. It was markedly more effective, however, when injected intraparenchymally. In a case of severe blunt trauma in a patient with acute alcoholic hepatitis, intraparenchymal FG was lifesaving. Fibrin glue is a useful adjunct in the management of trauma to all the abdominal solid viscera. Intraparenchymal injection is the preferred mode of FG application. PMID:2465750
Fibrin glue repair leads to enhanced axonal elongation during early peripheral nerve regeneration in an in vivo mouse model
Koulaxouzidis, Georgios; Reim, Gernot; Witzel, Christian
Microsurgical suturing is the gold standard of nerve coaptation. Although literature on the usefulness of fibrin glue as an alternative is becoming increasingly available, it remains contradictory. Furthermore, no data exist on how both repair methods might influence the morphological aspects (arborization; branching) of early peripheral nerve regeneration. We used the sciatic nerve transplantation model in thy-1 yellow fluorescent protein mice (YFP; n = 10). Pieces of nerve (1cm) were grafted from YFP-negative mice (n = 10) into those expressing YFP. We performed microsuture coaptations on one side and used fibrin glue for repair on the contralateral side. Seven days after grafting, the regeneration distance, the percentage of regenerating and arborizing axons, the number of branches per axon, the coaptation failure rate, the gap size at the repair site and the time needed for surgical repair were all investigated. Fibrin glue repair resulted in regenerating axons travelling further into the distal nerve. It also increased the percentage of arborizing axons. No coaptation failure was detected. Gap sizes were comparable in both groups. Fibrin glue significantly reduced surgical repair time. The increase in regeneration distance, even after the short period of time, is in line with the results of others that showed faster axonal regeneration after fibrin glue repair. The increase in arborizing axons could be another explanation for better functional and electrophysiological results after fibrin glue repair. Fibrin glue nerve coaptation seems to be a promising alternative to microsuture repair. PMID:26330844
Comparison of fibrin glue and suture in the healing of teat incisions in lactating goats.
Alan, M; Yener, Z; Tasal, I; Bakir, B
The aims of this study were to investigate whether fibrin glue can be used to close experimentally induced incisions of the teat (mammary papillae) in lactating goats and to compare the healing of the glued with the sutured incisions. Four clinically healthy lactating dairy goats, namely 8 mammary papillae were used. After surgical preparation of the papillae, a 3.5 cm long incision of each papilla was made through skin, muscular layer and mucosa into the papillary sinus. The wounds in the right papillae in all goats were closed with U-shaped uninterrupted 00 chromic catgut sutures. The wounds in the left papillae in all goats were closed, using fibrin glue. One incision was seen to be dehisced and fistulous one day after in fibrin glued teats. The animals were slaughtered 8 days after surgical manipulation. The mammary papillae were removed and examined in the viewpoint on gross and microscopic findings. The healing of wounds was slower and feeble in glued mammary papillary incisions, however faster and stronger in sutured incisions on day 8 after operations. But, available outcomes like less tissue thickness and positive cosmetic results could be obtained byfibrin glue used on mammary papillary incisions, which are very important for teats to be milked by hand and milking machine. Results suggest that it is advisable to use only one or two simple interrupted sutures in teat incisions glued with fibrin to prevent the dehiscence but with a more reliable healing than the sutured incisions. PMID:18547021
Fibrin glue from stored human plasma. An inexpensive and efficient method for local blood bank preparation.
Spotnitz, W D; Mintz, P D; Avery, N; Bithell, T C; Kaul, S; Nolan, S P
European surgeons have used fibrin glue extensively during thoracic, cardiovascular, and general surgical operations. Until now, however, it has been available only as a commercial preparation made from pooled human plasma, and it has not been approved by the U.S. Food and Drug Administration for use in the United States because of a high associated risk of hepatitis and acquired immune deficiency syndrome. Methods of obtaining fibrinogen, an essential component of fibrin glue, from cryoprecipitate or fresh frozen plasma have been published recently. However, the cryoprecipitate method results in relatively low concentrations of fibrinogen, which can reduce glue effectiveness. The fresh frozen plasma method is more expensive and does not meet the standards of the American Association of Blood Banks for the "closed" system required for safe handling and management of blood component products. Both the cryoprecipitate and the fresh frozen plasma methods result in waste of unstable clotting factors. These factors are necessary to replace human plasma clotting deficiencies but are not necessary for the production of fibrin glue. The authors have developed an efficient, high-concentration blood bank method for producing and maintaining a local supply of a safer and less expensive but equally effective material derived from stored human plasma. This material is produced using approved blood bank techniques for a "closed" system in blood component production, thus reducing the risks of contamination and infection, and its fibrinogen concentration is higher than that of standard cryoprecipitate. The cost of 1 unit of this fibrin glue is comparable to that for 1 unit of cryoprecipitate and less than that for 1 unit of fresh frozen plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2440358
Evaluation of bone matrix gelatin/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering.
Wang, Z H; Zhang, J; Zhang, Q; Gao, Y; Yan, J; Zhao, X Y; Yang, Y Y; Kong, D M; Zhao, J; Shi, Y X; Li, X L
This study was designed to evaluate bone matrix gelatin (BMG)/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering. Chondrocytes were isolated from costal cartilage of Sprague-Dawley rats and seeded on BMG/fibrin glue or chitosan/gelatin composite scaffolds. After different in vitro culture durations, the scaffolds were subjected to hematoxylin and eosin, Masson's trichrome, and toluidine blue staining, anti-collagen II and anti-aggrecan immunohistochemistry, and scanning electronic microscopy (SEM) analysis. After 2 weeks of culture, chondrocytes were distributed evenly on the surfaces of both scaffolds. Cell numbers and the presence of extracellular matrix components were markedly increased after 8 weeks of culture, and to a greater extent on the chitosan/gelatin scaffold. The BMG/fibrin glue scaffold showed signs of degradation after 8 weeks. Immunofluorescence analysis confirmed higher levels of collagen II and aggrecan using the chitosan/gelatin scaffold. SEM revealed that the majority of cells on the surface of the BMG/fibrin glue scaffold demonstrated a round morphology, while those in the chitosan/gelatin group had a spindle-like shape, with pseudopodia. Chitosan/gelatin scaffolds appear to be superior to BMG/ fibrin glue constructs in supporting chondrocyte attachment, proliferation, and biosynthesis of cartilaginous matrix components. PMID:27525846
Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses
Buen, Eliseo Portilla-de; Orozco-Mosqueda, Abel; Leal-Cortés, Caridad; Vázquez-Camacho, Gonzalo; Fuentes-Orozco, Clotilde; Alvarez-Villaseñor, Andrea Socorro; Macías-Amezcua, Michel Dassaejv; González-Ojeda, Alejandro
OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g) treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal) or high-risk (ischemic) end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL) or low (40 mg/mL) concentrations and thrombin at high (1000 IU/mL) or low (500 IU/mL) concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery. PMID:24714834
Fibrin glue-assisted for the treatment of corneal perforations using glycerin-cryopreserved corneal tissue
Dong, Nuo; Li, Cheng; Chen, Wen-Sheng; Qin, Wen-Juan; Xue, Yu-Hua; Wu, Hu-Ping
AIM To evaluate the outcomes and safety of lamellar keratoplasty (LK) assisted by fibrin glue in corneal perforations. METHODS Six eyes of 6 patients affected by different corneal pathologies (2 posttraumatic corneal scar and 3 bacterial keratitis) underwent LK procedures by using fibrin glue. The mean corneal perforation diameter was 1.35±0.64mm (range, 0.7-2.5mm), and the greatest diameter of the ulcerative stromal defect was 2.47±0.77mm in average (range, 1.5-3.5mm). The donor corneal lamella diameters were 0.20-mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape: mean donor diameter was 8.34±0.28mm (range, 8.2-8.7mm) and mean thickness was 352±40.27mm (range, 220-400mm). Mean follow-up was 7.33±1.97 months (range, 6-11 months). Postoperatively, the graft status, graft clarity, anterior chamber response, the visual prognosis, intraocular pressures, and postoperative complications were recorded. RESULTS All the corneal perforations were successfully healed after the procedure. The best-corrected visual acuity (BCVA) ranged from 20/1 000 to 20/50 in their initial presentation, and from 20/100 to 20/20 in their last visit, showed increase in all the patients. No major complications such as graft dislocation and graft failure were noted. Neovascularization developed in the superficial stroma of donor graft in 1 case. High intraocular pressure developed on day 2 after surgery, while was remained in normal range after application of anti-glaucomatous eyedrops for 1 week in 1 case. CONCLUSION Fibrin glue-assisted sutureless LK is valuable for maintaining the ocular integrity in the treatment of corneal perforations. PMID:24634865
Endoluminal embolization of bilateral atherosclerotic common iliac aneurysms with fibrin tissue glue (Beriplast)
Beese, Richard C.; Tomlinson, Mark A.; Buckenham, Timothy M.
The standard surgical approach to nonleaking iliac aneurysms found at repair of a leaking abdominal aortic aneurysm is to minimize the operative risk by repairing the abdominal aorta only. This means that the bypassed iliac aneurysms may have to be repaired later. As this population of patients are usually elderly with coexisting medical problems, interventional radiology is being used to embolize these aneurysms, thus avoiding the morbidity and mortality associated with further general anesthesia and surgery. Various materials and stents have been reported to be effective in the treatment of iliac aneurysms. We report the successful use of endoluminal fibrin tissue glue (Beriplast) to treat two large iliac aneurysms in a patient who had had a previous abdominal aortic aneurysm repair. We discuss the technique involved and the reasons why we used tissue glue in this patient.
Fixation of fractured inferior orbital wall using fibrin glue in inferior blowout fracture surgery.
Jo, Eun Jun; Yang, Ho Jik; Kim, Jong Hwan
The objectives of surgical treatment for orbital fracture are to return soft tissue to its original position as well as reduce and fix the bone fragments properly. Reduction of the orbital bone through a subciliary or conjunctival incision and reduction using a urinary balloon catheter were simultaneously performed on 53 patients between 2010 and 2013. Fibrin glue was used to attach the reduced bone fragments. These patients had less than 2 cm(2) of bone defect and showed diplopia, eye movement limitation, and enophthalmos. Diplopia, eye movement limitation, and enophthalmos were each reduced to 3/32, 2/25, and 2/48, respectively. There were no adverse effects, such as infection or hematoma, and because implants were not used, there was no possibility of its extrusion or foreign body reaction. The operation time decreased compared with when using an implant, and the bone fragments remained in a fixed position even after removing the urinary balloon catheter. Therefore, the use of fibrin glue proved to be effective in orbital floor fractures. PMID:25565237
Free-electron laser effects on fibrin tissue glue: a preliminary study
NASA Astrophysics Data System (ADS)
Joos, Karen M.; Topadze, Katie; Shieh, Charles; Shen, Jin-Hui; Casagrande, Vivien A.
One glaucoma challenge is the treatment of leaking trabeculectomy blebs. Simple methods such as patching, autologous blood injection, compression sutures or cyanoacrylate glue application often fail. Because the conjunctiva is thin and ischemic, it often can't be sutured together so major surgery is required to excise the thin tissue and advance healthy conjunctiva. We report the preliminary results of Tisseel and Tisseel treated with two wavelengths from Vanderbilt's free electron laser placed on leaking trabeculectomy bleb holes in Dutch belted rabbits. The holes were healed at one week in the sutured group and in the 7.7 micrometer FEL-treated Tisseel group. One hole was healed in the cyanoacrylate glue-treated group. Holes remained in the other treatment groups. Tisseel irradiated with 7.7 micrometer energy from the free electron laser may promote healing of trabeculectomy bleb holes.
Scalded Skin of Rat Treated by Using Fibrin Glue Combined with Allogeneic Bone Marrow Mesenchymal Stem Cells
Yang, Yadong; Li, Ying; Fang, Guojian; Zhang, Keji
Background It is difficult to achieve satisfactory results with the traditional treatment of large-area skin defects and deep burns. Objective To test the treatment effect of an active dressing film made of a mixture of fibrin glue and bone marrow mesenchymal stem cells (BMSCs) for repairing burn wounds on the skin of rats. Methods Two scald wounds were made on the back of each rat. A total of 30 scald wounds were randomly divided into 3 groups, with 10 wounds in each group. In the experimental treatment group, the scald wounds were covered with the fibrin glue and BMSC mixture. The wounds of the experimental control group were covered with fibrin glue only. No intervention was administered to the blank control group. Thirty days after treatment, pathological sections were cut from the scalded local tissues of all rats from the 3 groups and observed with a microscope. Results The speed of scald wound healing in the experimental treatment group was faster than the other 2 groups. In the experimental treatment group, histopathological analysis revealed that the sebaceous glands showed obviously proliferous at the edge of the new tissue and gradually extended to the deep dermal layer of the new tissue. Conclusion BMSCs may have an active role in promoting skin tissue repair and generating skin appendages. Allogeneic BMSCs mixed with fibrin glue can contribute to the quick formation of a film-like gel over the scald wounds, which might be of significance for emergency treatment and skin-grafting operations. PMID:24966626
Successful Treatment of Congenital Chyloperitoneum with Platelet-Rich Fibrin Glue
Joudi, Marjan; Alamdari, Daryoush Hamidi; Rahimi, Hamid-Reza
Background Congenital chyloperitoneum is an uncommon clinical condition. A few cases of congenital chyloperitoneum in children have been described who were treated in a variety of methods. Case Presentation Congenital chyloperito was diagnosed in a 5-day-old baby boy with a significant abdominal distension. Due to the failed conservative managements by medium-chain triglycerides (MCT) enriched milk and partial parenteral nutrition (PPN), the authors tried platelet rich fibrin glue (PRFG) as an alternative choice which was applied through an already inserted intra-abdominal catheter. PRFG successfully stopped the lymph leakage from all over the small intestinal mesentery; thereby PRFG may be considered as an effective alternative treatment before surgical intervention. Conclusion Applying PRFG is an easy, safe, and effective alternative option that may be used to close the chylous ascites lymph leakage in children if conservative management with PPN fails. PMID:23795263
Fibrin glue protection of primary anastomosis in the obstructed left colon. An experimental study on the rat.
Hulkko, O A; Haukipuro, K A; Laitinen, S T
A left-sided colon obstruction was produced with a polypropylene sling in 65 rats. Colon resection and primary anastomosis were performed three days later. The animals were then randomly allocated to the FG (fibrin glue) group receiving sealing of the anastomosis with 0.4 ml of fibrin glue (Beriplast R), or to the NG (non-glue) group. The anastomoses were assessed 30 min, two days and four days later. Adhesion formation was similar in both groups. The number of macroscopic or radiological leakages did not differ either. At 30 min the mean bursting pressure was 74.6 +/- 8.6 (SD) mmHg in the FG group and 58.3 +/- 21.6 mmHg in NG (non-glue) group (p less than 0.05, Mann-Whitney test). Later on the strength of the anastomoses was equal in both groups. We conclude that the initial sealing of weak points in the anastomoses was beneficial but the inherent strength per se could not be enhanced. PMID:2451367
Medpor Implant Fixation Using Fibrin Glue in the Treatment of Medial Orbital Wall Fracture.
Kang, Nakheon; Song, Seung Han; Kyung, Hyunwoo; Oh, Sang-Ha
The optimal treatment modalities are determined based on the symptoms and degree of the bone defects in patients with medial orbital wall blowout fracture. Most of the patients in this series underwent implant surgery. However, there are many patients whose implants were not fixed during surgery. Therefore, some patients who had implant migration occurred had been reported. We have therefore used methods for applying fibrin glue (Tisseel, Baxter Healthcare, Norfolk, United Kingdom) for the fixation of implant. Between 2007 and 2013, a total of 168 patients underwent porous polyethylene orbital implant (Medpor) surgery with the application of Tisseel. All the patients underwent surgical treatments via a transcaruncular approach, for which the Medpor was used. Postoperative complications include 6 cases of the limitation of extraoccular movement, 10 cases of diplopia, and 7 cases of enophthalmos. However, there were no specific complications caused by Tisseel. All the patients were satisfied with the treatment outcomes. In this study, we report the usefulness of Tisseel in the fixation of the medial orbital wall fracture using the Medpor implant with a review of literatures. PMID:26080196
Fibrin glue eliminates the need for packing after complex liver injuries.
Feinstein, A. J.; Varela, J. E.; Cohn, S. M.; Compton, R. P.; McKenney, M. G.
Hemostasis after traumatic liver injury can be extremely difficult to obtain, particularly in coagulopathic patients who have suffered extensive liver damage. We determined the ability of a fibrin glue preparation (FG) to terminate ongoing bleeding using a new, clinically relevant porcine model of complex hepatic injury. Anesthetized swine (n = 6, 18 to 19 kg) received an external blast to the right upper abdomen and were immediately anticoagulated with intravenous heparin (200 u/kg). Uncontrolled hemorrhage from blast continued from time of injury (t = 0 minutes) to t = 15 minutes. Lactated Ringer's solution was infused to keep mean arterial pressure (MAP) > 80 mm Hg until the end of experiment (t = 90 minutes). Animals underwent routine surgical techniques to control bleeding, and FG was employed in the event these measures failed. Estimated blood loss and fluid resuscitation volume were measured. Serial MAP, arterial base excess, and temperature were recorded. Animals were severely injured with significant blood loss prior to laparotomy (26 +/- 6 cc/kg) and during routine surgical efforts to arrest hemorrhage (11 +/- 2 cc/kg). Bleeding could not be controlled with standard techniques in any animal. FG rapidly controlled hemorrhage and eliminated the need for packing. Re-bleeding was noted in only one animal (portal vein injury). FG can control severe hepatic hemorrhage when surgical techniques fail. Further work in the clinical arena is warranted to determine the potential benefits of FG in arresting hemorrhage in hemodynamically unstable coagulopathic patients with complex hepatic injuries. PMID:11769337
Reckers, Leandro José; Fagundes, Djalma José; Pozo Raymundo, José Luiz; Granata Júnior, Geraldo Sérgio de Mello; Moreira, Márcia Bento; Paiva, Vanessa Carla; Negrini Fagundes, Anna Luiza; Cohen, Moises
Objective: To evaluate the ability of fibrin adhesive in promoting the meniscus fixation within two, four and eight weeks compared to the conventional soft-tissue suture technique. Materials and Methods: 36 right medial menisci of rabbits preserved at negative 73° Celsius for 30 days were transplanted to animals of the same sample and fixed with soft-tissue suture or fibrin glue. After 2, 4 or 8 weeks, the appearance of the menisci and the quality of fixation were macroscopically checked and evaluated by a scoring system. The findings were subjected to the statistical study of variance analysis (p ≤ 0.05%). Results: The deep-frozen meniscus preservation maintained the integrity of the meniscus transplant, and, macroscopically, there was no significant reduction of the length of the meniscus in all post-transplant periods (p = 0.015). The menisci fixed with fibrin showed slight changes in color and surface roughness. There were no signs of rejection or infection in both groups. Suture fixation scoring was superior (p = 0.015) in all periods (80% of total fixation) as compared to the setting promoted by fibrin (20% of total fixation). Conclusion: The homologous transplantation of the meniscus of rabbits experienced various degrees of integration to the knee according to the fixation method; the surgical soft tissues suturing technique was shown to be superior in the evaluation of scores compared to the fixation with fibrin adhesive. PMID:27004186
Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype
Puente, Pilar de la
Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.
Filling and shielding for postoperative gastric perforations of endoscopic submucosal dissection using polyglycolic acid sheets and fibrin glue
Takimoto, Kengo; Hagiwara, Akeo
Background and study aims: Many medical institutions in Japan perform endoscopic mucosal dissection (ESD) to treat early gastric cancer. Perforations can occur during ESD, and clipping has been reported as useful for treating small pinhole perforations. However, it is often difficult to close postoperative perforations because they usually have large diameters, and the muscle layer around the perforated region is often fragile, so additional open surgery is the only currently used method to treat large perforations and delayed perforations. Another method for large perforation is needed to treat perforations endoscopically. Ono et al. reported a case in which a postoperative perforation was closed using a polyglycolic acid (PGA) sheet and fibrin glue. In addition, it has been used by the authors' group to repair duodenal injuries that occur during ESD. We report 3 cases in which PGA sheets and fibrin glue were successfully used to repair postoperative gastric perforations endoscopically. This method is simple, safe, and effective, and is a new way to treat large perforations and delayed perforations that occur following ESD. PMID:27556075
Optimization and Use of 3D sintered porous material in medical field for mixing fibrin glue.
NASA Astrophysics Data System (ADS)
Delmotte, Y.; Laroumanie, H.; Brossard, G.
In medical field, Mixing of two or more chemical components (liquids and/or gases) is extremely important as improper mixing can affect the physico-chemical properties of the final product. At Baxter Healthcare Corporation, we are using a sintered porous material (PM) as a micro-mixer in medical device for mixing Fibrinogen and Thrombin in order to obtain a homogeneous polymerized Fibrin glue clot used in surgery. First trials were carried out with an interconnected PM from Porvair® (made of PE - porosity: 40% - permeability: 18Darcy). The injection rate is very low, usually about 10mL/min (Re number about 50) which keeps fluids in a laminar flow. Such a low flow rate does not favour mixing of fluids having gradient of viscosity if a mixer is not used. Promising results that were obtained lead the team to understand this ability to mix fluids which will be presented in the poster. Topology of porous media (PM) which associates a solid phase with interconnected (or not) porous structure is known and used in many commodity products. Researches on PM usually focus on flows inside this structure. By opposition to transport and filtration capacity, as well as mechanic and thermic properties, mixing is rarely associated with PM. However over the past few years, we shown that some type of PM have a real capacity to mix certain fluids. Poster will also describe the problematic of mixing complex biological fluids as fibrinogen and Thrombin. They indeed present a large viscosity difference (ratio about 120) limiting the diffusion and the interaction between the two solutions. As those products are expensive, we used Water (1cPo) and Glycerol 87% (120cPo) which are matching the viscosities of Thrombin and Fibrinogen. A parametric investigation of the "porous micro-mixer" as well as a scale up investigation was carried out to examine the influence of both diffusion and advection to successful mix fluids of different viscosity. Experiments were implemented with Planar Laser
Haemostasis with fibrin glue injection into the pericardial space for right ventricular perforation caused by an iatrogenic procedural complication.
Arai, Hirofumi; Miyamoto, Takamichi; Hara, Nobuhiro; Obayashi, Tohru
An 89-year-old woman with severe aortic valve stenosis and bradycardia presented with circulatory shock due to cardiac tamponade. We performed pericardiocentesis, and then diagnosed right ventricular perforation by echocardiography with microcavitation contrast medium just before inserting a drainage tube. We then inserted the drainage tube in the appropriate position and withdrew blood-filled fluid. The patient was haemodynamically stabilised, but haemorrhage from the perforation site continued for a few days. We injected fibrin glue into the pericardial space through the drainage tube and achieved haemostasis. Thus, we avoided surgery to close the perforation in this high-risk patient. There was no recurrence of haemorrhage. She subsequently had elective aortic valve replacement at another hospital. No adhesions in the pericardial space were seen during surgery. PMID:27190133
Fibrin glue is a candidate scaffold for long-term therapeutic protein expression in spontaneously differentiated adipocytes in vitro
Aoyagi, Yasuyuki; Kuroda, Masayuki; Asada, Sakiyo; Tanaka, Shigeaki; Konno, Shunichi; Tanio, Masami; Aso, Masayuki; Okamoto, Yoshitaka; Nakayama, Toshinori; Saito, Yasushi; Bujo, Hideaki
Adipose tissue is expected to provide a source of cells for protein replacement therapies via auto-transplantation. However, the conditioning of the environment surrounding the transplanted adipocytes for their long-term survival and protein secretion properties has not been established. We have recently developed a preparation procedure for preadipocytes, ceiling culture-derived proliferative adipocytes (ccdPAs), as a therapeutic gene vehicle suitable for stable gene product secretion. We herein report the results of our evaluation of using fibrin glue as a scaffold for the transplanted ccdPAs for the expression of a transduced gene in a three-dimensional culture system. The ccdPAs secreted the functional protein translated from an exogenously transduced gene, as well as physiological adipocyte proteins, and the long viability of ccdPAs (up to 84 days) was dependent on the fibrinogen concentrations. The ccdPAs spontaneously accumulated lipid droplets, and their expression levels of the transduced exogenous gene with its product were maintained for at least 56 days. The fibrinogen concentration modified the adipogenic differentiation of ccdPAs and their exogenous gene expression levels, and the levels of exogenously transduced gene expression at the different fibrinogen concentrations were dependent on the extent of adipogenic differentiation in the gel. These results indicate that fibrin glue helps to maintain the high adipogenic potential of cultured adipocytes after passaging in a 3D culture system, and suggests that once they are successfully implanted at the transplantation site, the cells exhibit increased expression of the transduced gene with adipogenic differentiation.
Effect of fibrin glue and endothelial cell growth factor on the early healing response of the transplanted allogenic meniscus: a pilot study.
Nabeshima, Y; Kurosaka, M; Yoshiya, S; Mizuno, K
Twentyfour meniscal allotransplantations were conducted in 12 adult mongrel dogs. The medial meniscus was replaced using a deep-frozen meniscal allograft. The junction between the meniscus and capsule was treated in one of the three ways. In the control group, the meniscus was sutured only to the adjacent capsular tissue (group C). In the second group, fibrin glue was injected at the junction (group F), and in the third group, fibrin glue and endothelial cell growth factor (ECGF) were injected at the juncture between the transplanted meniscus and the adjacent capsule before the meniscus was sutured (group FE). Histological observation was performed to investigate the effect of fibrin glue and ECGF on the healing process of transplants at various intervals of 1, 4, 8 and 12 weeks. No immunological response was noted in any of the knees. The healing of the transplanted meniscus was first observed at the peripheral attachment. Also, the pannus-like tissue extended from the synovium to the surface of the meniscus. The healing rate in each group at 1 week and 12 weeks was 22% and 77% in group C, 52% and 80% in group F, and 64% and 80% in group FE, respectively. At 4 and 8 weeks, early cellular repopulation was found in group FE and the area which contained new cells was larger than the acellular central core at 8 weeks. However, there was no difference among the three groups at 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7773819
Staple Line Coverage with a Polyglycolic Acid Patch and Fibrin Glue without Pleural Abrasion after Thoracoscopic Bullectomy for Primary Spontaneous Pneumothorax
Hong, Ki Pyo; Kim, Do Kyun; Kang, Kyung Hoon
Background This study was conducted to determine the efficacy of staple line coverage using a polyglycolic acid patch and fibrin glue without pleural abrasion to prevent recurrent postoperative pneumothorax. Methods A retrospective analysis was carried out of 116 operations performed between January 2011 and April 2013. During this period, staple lines were covered with a polyglycolic acid patch and fibrin glue in 58 cases (group A), while 58 cases underwent thoracoscopic bullectomy only (group B). Results The median follow-up period was 33 months (range, 22 to 55 months). The duration of chest tube drainage was shorter in group A (group A 2.7±1.2 day vs. group B 3.9±2.3 day, p=0.001). Prolonged postoperative air leakage occurred more frequently in group B than in group A (43% vs. 19%, p=0.005). The postoperative recurrence rate of pneumothorax was significantly lower in group A (8.6%) than in group B (24.1%) (p=0.043). The total cost of treatment during the follow-up period, including the cost for the treatment of postoperative recurrent pneumothorax, was not significantly different between the two groups (p=0.43). Conclusion Without pleural abrasion, staple line coverage with a medium-sized polyglycolic acid patch and fibrin glue after thoracoscopic bullectomy for primary spontaneous pneumothorax is a useful technique that can reduce the duration of postoperative pleural drainage and the postoperative recurrence rate of pneumothorax. PMID:27066431
The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats.
Mehanna, Radwa A; Nabil, Iman; Attia, Noha; Bary, Amany A; Razek, Khalid A; Ahmed, Tamer A E; Elsayed, Fatma
Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although--later--none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM-via fibrin vehicle--could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740
The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats
Mehanna, Radwa A.; Nabil, Iman; Attia, Noha; Bary, Amany A.; Razek, Khalid A.; Ahmed, Tamer A. E.; Elsayed, Fatma
Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure. PMID:26236740
Mini-open transthoracic approach for resection of a calcified herniated thoracic disc and repair of the dural surface with fibrin glue: a case report.
Yoshioka, Katsuhito; Murakami, Hideki; Demura, Satoru; Kato, Satoshi; Tsuchiya, Hiroyuki
This study reports a case of severe anterior compression of the spinal cord by a calcified herniated thoracic disc at the T9/10 level in a 46-year-old woman. She underwent resection of the calcified herniated thoracic disc and the integrated dura, using a microscopically assisted mini-open transthoracic approach. The remaining dura mater was shaped and repaired by alternate overlapping without suture. The dural surface was reinforced with a combination of fibrin glue and a polyglycolic acid sheet. This novel procedure prevented postoperative cerebrospinal fluid leakage. The patient made an excellent recovery, without any complications. PMID:26321561
Cascade® Autologous System Platelet-Rich Fibrin Matrix in the Treatment of Chronic Leg Ulcers
O'Connell, Sean M.; Hessler, Karen; Dardik, Herbert
Problem Lower extremity ulcers (venous, diabetic) are often unresponsive to standard treatment. Various systemic and local cellular, vascular, and anatomical factors can result in nonhealing wounds that are refractory to normal healing processes and standard care. Solution Several published wound care guidelines strongly suggest that if an ulcer does not respond to standard good wound care within 4 weeks, then advanced wound therapies should be considered. These advanced therapies include wound bed preparation agents (negative wound pressure therapy, hyperbaric oxygen), recombinant growth factors, or bioengineered cell therapies. New Technology The Cascade® system produces platelet-rich fibrin matrix (PRFM), a novel autologous sterile biologic, produced at the bedside from a small volume (18 mL) of the patient's own blood by using Vacutainer® separation technology optimized for fibrin and platelet isolation. Prepared as an easy to apply, suturable membrane, without the use of exogenous thrombin, PRFM consists of a dense cross-linked fibrin lattice containing intact, viable platelets with their full complement of platelet-derived growth factors. Indications for Use From the FDA 510(k) clearance: The Cascade system "is designed to be used for the safe and rapid preparation of autologous platelet-rich plasma from a small sample of blood at the patient point of care." PRFM has been used to successfully treat severe venous leg ulcer (VLU), neuropathic diabetic foot ulcer (DFU), mixed arterial and Charcot-deformity associated foot ulcers. Cautions When treating venous or DFUs, the Cascade system should be used together with standard wound care practice (therapeutic compression for VLU and weight off-loading, debridement, and infection control for DFU) in patients with an adequate blood supply to the lower limb. PMID:24527280
Treatment of life-threatening wounds with a combination of allogenic platelet-rich plasma, fibrin glue and collagen matrix, and a literature review
Currently there is no ideal procedure for the treatment of recalcitrant ulcers that are unresponsive to the majority of common treatments. However, several novel approaches have been proposed, including bone marrow stem cells, platelets, fibrin glue and collagen matrix. For the first approach treatment of a chronic wound, a non-invasive method is highly desirable. The present study was undertaken with the aim of evaluating the effect of a combination of platelets, fibrin glue and collagen matrix (PFC) in one treatment. A total of ten patients with aggressive, refractory, life-threatening wounds were recruited for the study and their treatment effects were evaluated. Initially, the ulcers were extensively debrided, measured and photographed at weekly intervals. The PFC combination was applied topically to the wound every two days. Following treatment, the wound was completely closed in nine patients and was markedly reduced in the other patient. The mean 100% healing time for the nine patients was 11.3±5.22 weeks. There was no evidence of local or systemic complications or any abnormal tissue formation, keloid or hypertrophic scarring. Therefore, the results of the present study indicate that in the first approach, the combination of PFC components may be used safely in order to synergize the effect of chronic wound healing. PMID:25009595
Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits
Li, Yunfeng; Li, Rui; Hu, Jing; Song, Donghui; Jiang, Xiaowen
Introduction Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. Material and methods The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. Results It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. Conclusions The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID:27279839
Aulogous fibrin sealant (Vivostat®) in the neurosurgical practice: Part II: Vertebro-spinal procedures
Graziano, Francesca; Maugeri, Rosario; Basile, Luigi; Meccio, Favia; Iacopino, Domenico Gerardo
Background: Epidural hematomas, cerebrospinal fluid fistula, and spinal infections are challenging postoperative complications following vertebro-spinal procedures. We report our preliminary results using autologous fibrin sealant as both fibrin glue and a hemostatic during these operations. Methods: Prospectively, between January 2013 and March 2015, 68 patients received an autologous fibrin sealant prepared with the Vivostat® system applied epidurally to provide hemostasis and to seal the dura. The surgical technique, time to bleeding control, and associated complications were recorded. Results: Spinal procedures were performed in 68 patients utilizing autologous fibrin glue/Vivostat® to provide rapid hemostasis and/or to seal the dura. Only 2 patients developed postoperative dural fistulas while none exhibited hemorrhages, allergic reactions, systemic complications, or infections. Conclusions: In this preliminary study, the application of autologous fibrin sealant with Vivostat® resulted in rapid hemostasis and/or acted as an effective dural sealant. Although this product appears to be safe and effective, further investigations are warranted. PMID:26904371
Fibrin sealant augmentation with autologous pericranium for duraplasty after suboccipital decompression in Chiari 1 patients: A case series
Lam, Fred C.; Penumaka, Anirudh; Chen, Clark C.; Fischer, Edwin G.; Kasper, Ekkehard M.
Background: The Chiari 1 malformation (CM1) involves decent of the tonsils of the cerebellum through the foramen magnum. Symptomatic disease requires a posterior fossa decompression with or without an expansile duraplasty. To date, the optimal surgical treatment for CM1 has not been delineated. The extent of bony removal, size of the dural opening, necessity for expansion of the dural space, choice of materials for the duraplasty, and possible need for augmentation with dural sealant are all factors that continue to be debated amongst neurological surgeons worldwide. We herein evaluate the use of fibrin sealant augmentation in combination with locally harvested autologous pericranium for duraplasty in adult CM1 decompression. Methods: Retrospective data collected from January 2006 to December 2011. Data were reviewed for surgical site infection or meningitis, cerebrospinal fluid leak, symptomatic pseudomeningocele, radiographic improvement of hindbrain compression, and postoperative recurrence of symptoms at a minimum of 1 year of follow-up. Outcomes were studied clinically, radiographically, as well as by using a patient-specific questionnaire. Results: Twenty-two consecutive patients were included. One patient required a revision for a delayed graft dehiscence in the setting of a rare form of aseptic meningitis with cerebrospinal fluid (CSF) pleocytosis due to a nonsteroidal anti-inflammatory drug (NSAID) allergy. All remaining patients had successful decompressions with full resolution of their symptoms except for one patient who had persistent headaches. Conclusion: Autologous pericranium with dural sealant augmentation is an effective technique for expansile duraplasty in CM1 decompressions. PMID:23493237
Biochemical, mechanical, and morphological properties of a completely autologous platelet-rich wound sealant.
Wu, Xiuwen; Ren, Jianan; Luan, Jianfeng; Yao, Gengong; Li, Jieshou
The optimal composition of fibrin sealant preparations is not known. We, therefore, sought to construct a series of sealants from autologous components and compare their functioning to Bioseal a commonly used sealant. Characteristics of the platelet-rich plasma, cryoprecipitate, and thrombin were determined and compared to commercial glue from composition, function, and microscopy aspects. The concentrations of platelets as well as fibronectin in autologous fibrin glues were significantly higher than those in commercial ones (P < 0.001). Mechanical values (maximum amplitude and clot strength) obtained from thrombelastograph assays in two groups were not significantly different (P > 0.05). A dense platelet surface and fibrin net structures could be observed in the autologous samples, whereas there were only sparse fibrin nets without cellular components in Bioseal. Characterization of autologous and Bioseal fibrin sealants and their performance do not have significant difference in biochemical and mechanical properties. The entirely autologous platelet-rich gel in the present study may get wide application in future practice after confirmation of its safety, efficiency, and economic benefits. PMID:22395185
Articular cartilage restoration in load-bearing osteochondral defects by implantation of autologous chondrocyte-fibrin constructs: an experimental study in sheep.
Munirah, S; Samsudin, O C; Chen, H C; Salmah, S H Sharifah; Aminuddin, B S; Ruszymah, B H I
Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous 'chondrocyte-fibrin' construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O'Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI. PMID:17785753
Full-thickness skin wound healing using autologous keratinocytes and dermal fibroblasts with fibrin: bilayered versus single-layered substitute.
Idrus, Ruszymah Bt Hj; Rameli, Mohd Adha bin P; Low, Kiat Cheong; Law, Jia Xian; Chua, Kien Hui; Latiff, Mazlyzam Bin Abdul; Saim, Aminuddin Bin
Split-skin grafting (SSG) is the gold standard treatment for full-thickness skin defects. For certain patients, however, an extensive skin lesion resulted in inadequacies of the donor site. Tissue engineering offers an alternative approach by using a very small portion of an individual's skin to harvest cells for propagation and biomaterials to support the cells for implantation. The objective of this study was to determine the effectiveness of autologous bilayered tissue-engineered skin (BTES) and single-layer tissue-engineered skin composed of only keratinocytes (SLTES-K) or fibroblasts (SLTES-F) as alternatives for full-thickness wound healing in a sheep model. Full-thickness skin biopsies were harvested from adult sheep. Isolated fibroblasts were cultured using medium Ham's F12: Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum, whereas the keratinocytes were cultured using Define Keratinocytes Serum Free Medium. The BTES, SLTES-K, and SLTES-F were constructed using autologous fibrin as a biomaterial. Eight full-thickness wounds were created on the dorsum of the body of the sheep. On 4 wounds, polyvinyl chloride rings were used as chambers to prevent cell migration at the edge. The wounds were observed at days 7, 14, and 21. After 3 weeks of implantation, the sheep were euthanized and the skins were harvested. The excised tissues were fixed in formalin for histological examination via hematoxylin-eosin, Masson trichrome, and elastin van Gieson staining. The results showed that BTES, SLTES-K, and SLTES-F promote wound healing in nonchambered and chambered wounds, and BTES demonstrated the best healing potential. In conclusion, BTES proved to be an effective tissue-engineered construct that can promote the healing of full-thickness skin lesions. With the support of further clinical trials, this procedure could be an alternative to SSG for patients with partial- and full-thickness burns. PMID:24637651
Use of fibrin glue in preventing pseudorecurrence after laparoscopic total extraperitoneal repair of large indirect inguinal hernia
Sürgit, Önder; Çavuşoğlu, Nadir Turgut; Ünal, Yılmaz; Koşar, Pınar Nergis; İçen, Duygu
Purpose Seroma is among the most common complications of laparoscopic total extraperitoneal (TEP) for especially large indirect inguinal hernia, and may be regarded as a recurrence by some patients. A potential area localized behind the mesh and extending from the inguinal cord into the scrotum may be one of the major etiological factors of this complication. Our aim is to describe a novel technique in preventing pseudorecurrence by using fibrin sealant to close that potential dead space. Methods Forty male patients who underwent laparoscopic TEP for indirect inguinal hernia with at least 100-mL volume were included in this prospective clinical study. While fibrin sealant was used to close the potential dead space in the study group, nothing was used in the control group. The volume of postoperative fluid collection on ultrasound was compared between the groups. Results Patient characteristics and the volumes of hernia sac were similar between the 2 groups. The mean volume of postoperative fluid collection was found as 120.2 mL in the control group and 53.7 mL in the study group, indicating a statistical significance (P < 0.001). Conclusion Minimizing the potential dead space with a fibrin sealant can reduce the amount of postoperative fluid collection, namely the incidence of pseudorecurrence. PMID:27617253
Use of Autologous Human mesenchymal Stromal Cell/Fibrin Clot Constructs in Upper Limb Non-Unions: Long-Term Assessment
Bottai, Vanna; Ghilardi, Marco; D'Alessandro, Delfo; Danti, Serena; Dell'Osso, Giacomo; Guido, Giulio; Petrini, Mario
Background Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. Aims We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. Methods and Findings Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation. Conclusions Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients. PMID:24023694
Treatment of non-healing sternum wound after open-heart surgery with allogenic platelet-rich plasma and fibrin glue-preliminary outcomes
Tashnizi, Mohammad Abbasi; Alamdari, Daryoush Hamidi; Khayami, Mohammad Esmail; Rahimi, Hamid Reza; Moeinipour, Aliasghar; Amouzeshi, Ahmad; Seifalian, Alexander M.
Introduction: Non-healing wound in the sternal region after coronary arteries bypass graft surgery is a serious complication. For healing a chronic wound, several novel approaches have been proposed recently such as using bone marrow stem cells, platelets and fibrin glue (PFG); but a non-invasive method is highly desirable in the first approach for treatment. The current study was undertaken to evaluate the effect of the combination of PFG in one treatment. Materials and Methods: We report on the treatment of six patients with life-threatening chronic sternum wounds, which caused septicemia with multi-drug resistant pathogens. The ulcers were extensively debrided initially and were measured and photographed at weekly intervals. The combination of PFG was applied topically on the wound after every 2 days. Results: The wounds were completely closed in five patients and significantly reduced in size in one. There was no evidence of local or systemic complications and any abnormal tissue formation, keloid or hypertrophic scarring. Conclusions: Our study suggests, in the first approach, PFG can be used safely in order to heal a non healing sternum wound following coronary artery bypass surgery. PMID:24459346
Combined left hepatectomy with fenestration and using a harmonic scalpel, fibrin glue and closed suction drainage to prevent bile leakage and ascites in the management of symptomatic polycystic liver disease: a case report
Introduction Surgical treatment is the usual therapy for patients with polycystic liver disease and with severe symptoms, yet the results of surgery are often disappointing and the optimal surgical approach is uncertain. Case presentation We present the case of a 41-year-old Greek woman who underwent combined left hepatectomy with fenestration for symptomatic polycystic liver disease using ultrasound scalpel, fibrin glue and closed suction drain to prevent bile leakage, haemorrhage and ascites. Liver resection using the ultrasound scissors allowed quick parenchyma dissection under haemostatic conditions with safe coagulation of small vessels and bile ducts. Moreover, the ultrasound scalpel was applied to the cyst cavities exposed on the peritoneum to ablate the fluid-producing epithelial cyst lining. We also covered the cut cystic cavities exposed to the peritoneum surface of the liver with fibrin glue. Instead of allowing the opened cysts to drain into the abdominal cavity, we used two wide bore closed suction fluted drains. We did not observe excessive fluid loss through the drainage after the second postoperative day. The drain tubes were removed on the third postoperative day. Conclusion In our patient, effective treatment of ascites and prevention of bile leakage and bleeding indicate that this new approach is promising and may become a useful surgical technique for polycystic liver disease.
A Novel Approach for Treatment of an Unusual Presentation of Radicular Cysts Using Autologous Periosteum and Platelet-Rich Fibrin in Combination with Demineralized Freeze-Dried Bone Allograft
Patil, Veena A.; Desai, Manthan H.; Patil, Veerendra S.; Reddy Kaveti, Hanisha; Ganji, Kiran Kumar; Danappanavar, Prasanna M.
Radicular cysts are the most common cystic lesions affecting the jaws. They are most commonly found at the apices of the involved teeth. This condition is usually asymptomatic but can result in a slow-growth tumefaction in the affected region. The following case report presents the successful treatment of radicular cysts using autologous periosteum and platelet-rich fibrin with demineralized freeze-dried bone allograft. PMID:23984115
ERIC Educational Resources Information Center
Guhin, Paula
There's something irresistible about squeezing out lines and shapes with a bottle of glue. It's fun, yes. But, even better: it's tactile. The glue dries slightly raised on the surface, lending itself to several exciting treatments. In this article, the author describes some activities that confirm how a simple art material like glue can be…
NASA Technical Reports Server (NTRS)
A mytilus edilus, a common blue ocean mussel is attaching itself to the underside of a wet glass in a laboratory. It secretes a glue like substance in the form of multiple threads which attach to surfaces such as shells, rocks, piers and ships. This natural super glue hardens within minutes and tightly affixes to its selected platform even in the roughest seas. Its superior adhesive properties suggest many practical applications. One company, Bio-Polymers, Inc., has developed a synthetic mussel glue for the commercial market.
Dural repair using autologous fat: Our experience and review of the literature
Di Vitantonio, Hambra; De Paulis, Danilo; Del Maestro, Mattia; Ricci, Alessandro; Dechordi, Soheila Raysi; Marzi, Sara; Millimaggi, Daniele F.; Galzio, Renato J.
Background: Various materials have been proposed to obliterate dead spaces and to reconstruct dural defects during a neurosurgical approach. This study describes our technique of using the abdominal autologous fat graft and evaluates the complications and characteristics related to the use of this tissue during cranial procedures. Methods: Autologous fat grafts were used in 296 patients with basicranial and convexity extraaxial tumors from April 2005 to January 2015. The adipose tissue was removed from the paraumbilical abdominal region and was transformed into a thin foil. When possible, a watertight suture was made between the dural or bone edge with a fat graft. We always used fibrin glue to reinforce the dural closure. Results: Complications occurred between 2 days and 1 year following procedure. Cerebrospinal fluid leaks were found in 11 cases. No case of mortality, pseudomeningoceles, fistula, infections, bacterial meningitides, or lipoid meningitides was reported. No patient required removal of the graft. No adhesion was observed between the brain and the autologous fat. Other fat-related complications observed were 2 cases of fat necrosis in the abdomen and 2 cases of abdominal hemorrhage. Conclusion: The technique of harvesting and applying fat grafts is fairly simple, although it must be performed meticulously to be effective. Our experience has led us to believe that the use of fat grafts presents low morbidity and mortality. However, a neurosurgeon should never forget the possible late or early complications related to the use of fat grafts. PMID:27500007
Closing microvascular lesions with fibrin sealant-attached muscle pads.
Fehm, Nando Percy; Vatankhah, Bijan; Dittmar, Michael S; Tevetoglu, Yesim; Retzl, Gerald; Horn, Markus
Fibrin sealants are used in a variety of surgical procedures, mainly for purposes of hemostasis and assisted wound healing. The combined use of fibrin sealant and autologous muscle pads for hemostasis was not reported previously. Arterial incisions in the common carotid artery in rats were closed by the combined application of fibrin sealant and an autologous muscle pad. Postsurgical vessel patency and degree of stenosis were evaluated by color duplex sonography, computed tomography angiography, and postmortem histology. The combined application of muscle pad and fibrin sealant and achievement of hemostasis was feasible in all animals. Seventy-eight percent of animals showed no or only slight postsurgical vessel stenosis. Our method is simple and quick to perform, showing a high potential for hemostasis in microvascular lesions. Therefore, it might be used in future experimental studies for conservation of vessel patency after arterial catheterization and in experimental or clinical vascular surgery. PMID:16184526
The effects of fibrin tissue adhesive on the middle ear.
Katzke, D; Pusalkar, A; Steinbach, E
This study investigated the effects of fibrin glue ('Tissucol', Immuno Pty. Ltd.) in the middle and inner ear. Small amounts of the adhesive were used in 36 operations performed on 18 rabbits. The light microscopic examination of these ears four, eight and 12 weeks after surgery showed that the adhesive was well tolerated and that it did not have any toxic effect on the middle ear or membranous labyrinth. The fibrin tissue adhesive can therefore safely be used to facilitate reconstructive middle-ear surgery and, with the aid of fascia, also for the closure of labyrinthine fistulae; or to achieve a definite seal of oval window niche after stapes surgery. PMID:6600776
[Animal experiments on cementing small osteochondral fragments with fibrin glue].
Zilch, H
An experiment on revascularization of glued osteochondral fragments was carried out. A chiseled part of the medial femoral condyle of the knee joint of the rabbit was fixed on the right side with an acryl adhesive and on the left side with a new fibrinogen adhesive system (FAS), consisting of highly concentrated fibrinogen, thrombin, and factor XIII. The animals were sacrificed after three, six, ten, and twenty eight days. The FAS is changed into granulation tissue rich in vessels and, therefore, there is a quick revascularization of the fragments soon after three days. On the contrary the acryl adhesive is a foreign body and prevents ingrowth of capillaries during the time of investigation. Immobilization with plaster is necessary to prevent the fragment from gliding off. PMID:6972890
TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application.
Kim, Keumyeon; Lee, Haeshin; Hong, Seonki
This video describes the simplest protocol for preparing biodegradable surgical glue that has an effective hemostatic ability and greater water-resistant adhesion strength than commercial tissue adhesives. Medical adhesives have attracted great attention as potential alternative tools to sutures and staples due to their convenience in usage with minimal invasiveness. Although there are several protocols for developing tissue adhesives including those commercially available such as fibrin glues and cyanoacrylate-based materials, mostly they require a series of chemical syntheses of organic molecules, or complicated protein-purification methods, in the case of bio-driven materials (i.e., fibrin glue). Also, the development of surgical glues exhibiting high adhesive properties while maintaining biodegradability is still a challenge due to difficulties in achieving good performance in the wet environment of the body. We illustrate a new method to prepare a medical glue, known as TAPE, by the weight-based separation of a water-immiscible supramolecular aggregate formed after a physical mixing of a plant-derived, wet-resistant adhesive molecule, Tannic Acid (TA), and a well-known biopolymer, Poly(Ethylene) glycol (PEG). With our approach, TAPE shows high adhesion strength, which is 2.5-fold more than commercial fibrin glue in the presence of water. Furthermore, TAPE is biodegradable in physiological conditions and can be used as a potent hemostatic glue against tissue bleeding. We expect the widespread use of TAPE in a variety of medical settings and drug delivery applications, such as polymers for muco-adhesion, drug depots, and others. PMID:27341544
ERIC Educational Resources Information Center
Roy, Ken
While glue guns are very useful, there are safety issues. Regardless of the temperature setting, glue guns can burn skin. The teacher should demonstrate and supervise the use of glue guns and have a plan should a student get burned. There should be an initial first aid protocol in place, followed by a visit to the school nurse. An accident report…
What Is the Biological and Clinical Relevance of Fibrin?
Litvinov, Rustem I; Weisel, John W
As our knowledge of the structure and functions of fibrinogen and fibrin has increased tremendously, several key findings have given some people a superficial impression that the biological and clinical significance of these clotting proteins may be less than earlier thought. Most strikingly, studies of fibrinogen knockout mice demonstrated that many of these mice survive to weaning and beyond, suggesting that fibrin(ogen) may not be entirely necessary. Humans with afibrinogenemia also survive. Furthermore, in recent years, the major emphasis in the treatment of arterial thrombosis has been on inhibition of platelets, rather than fibrin. In contrast to the initially apparent conclusions from these results, it has become increasingly clear that fibrin is essential for hemostasis; is a key factor in thrombosis; and plays an important biological role in infection, inflammation, immunology, and wound healing. In addition, fibrinogen replacement therapy has become a preferred, major treatment for severe bleeding in trauma and surgery. Finally, fibrin is a unique biomaterial and is used as a sealant or glue, a matrix for cells, a scaffold for tissue engineering, and a carrier and/or a vector for targeted drug delivery. PMID:27056152
Influence of Delivery Method on Neuroprotection by Bone Marrow Mononuclear Cell Therapy following Ventral Root Reimplantation with Fibrin Sealant
Barbizan, Roberta; Castro, Mateus V.; Barraviera, Benedito; Ferreira, Rui S.; Oliveira, Alexandre L. R.
The present work compared the local injection of mononuclear cells to the spinal cord lateral funiculus with the alternative approach of local delivery with fibrin sealant after ventral root avulsion (VRA) and reimplantation. For that, female adult Lewis rats were divided into the following groups: avulsion only, reimplantation with fibrin sealant; root repair with fibrin sealant associated with mononuclear cells; and repair with fibrin sealant and injected mononuclear cells. Cell therapy resulted in greater survival of spinal motoneurons up to four weeks post-surgery, especially when mononuclear cells were added to the fibrin glue. Injection of mononuclear cells to the lateral funiculus yield similar results to the reimplantation alone. Additionally, mononuclear cells added to the fibrin glue increased neurotrophic factor gene transcript levels in the spinal cord ventral horn. Regarding the motor recovery, evaluated by the functional peroneal index, as well as the paw print pressure, cell treated rats performed equally well as compared to reimplanted only animals, and significantly better than the avulsion only subjects. The results herein demonstrate that mononuclear cells therapy is neuroprotective by increasing levels of brain derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF). Moreover, the use of fibrin sealant mononuclear cells delivery approach gave the best and more long lasting results. PMID:25157845
Fibrin gel as alternative scaffold for respiratory tissue engineering.
Cornelissen, Christian G; Dietrich, Maren; Krüger, Stefan; Spillner, Jan; Schmitz-Rode, Thomas; Jockenhoevel, Stefan
Fibrin gel has proven a valuable scaffold for tissue engineering. Complex geometries can be produced by injection molding; it offers effective cell seeding and can be produced autologous. In order to evaluate its suitability for respiratory tissue engineering, we examined proliferation, functionality, and differentiation of respiratory epithelial cells on fibrin gel in comparison to culture on collagen-coated, microporous membranes. Respiratory epithelial cells formed a confluent layer by day 4, and proliferation showed no significant difference with respect to surface. Measurement of the transepithelial electrical resistance reflected the development of a confluent epithelial cell layer and the subsequent initiation of adequate ion-transfer processes. Appearance of ciliae could be detected at similar time points, and ciliary beating could be observed for cells on both surfaces. Histology and immunohistochemistry of cells grown on fibrin gel revealed the onset of adequate differentiation. As no significant differences in respiratory epithelial cells' proliferation, function, and differentiation could be observed between cells grown on fibrin gel compared to cells on a collagen-coated, microporous surface, we concluded that fibrin gel might prove a suitable scaffold for respiratory tissue engineering and merits further investigation to overcome the limitations associated with scaffolds currently in use. PMID:22009317
A prospective, randomized, double-blind trial of the use of fibrin sealant for face lifts.
Oliver, D W; Hamilton, S A; Figle, A A; Wood, S H; Lamberty, B G
Fibrin sealant imitates the final phase of the blood coagulation process. Fibrinogen is converted into fibrin on a tissue surface by the action of thrombin, which is then cross-linked by factor XIIIa, creating a mechanically stable fibrin network. This fibrin network is thought to reduce the amount of postoperative bleeding by sealing capillary vessels and allowing raw operative surfaces to adhere. The authors conducted a prospective, double-blind, randomized, controlled trial on the use of fibrin sealant in 20 consecutive patients undergoing bilateral face lifts by the same surgeon. Each patient was randomized for the use of fibrin sealant on either the right or the left side with the contralateral side acting as the control. Total drainage was recorded on each side for 24 hours before drains were removed. The age range of the patients in the trial (all of whom were women) was 44 to 70 years (mean, 55). The side treated with fibrin glue had a median drainage of 10 ml and the control side 30 ml. The Wilcoxon signed rank test shows a significant difference in drainage between sides (p = 0.002). The reduction in postoperative drainage could also reduce pain and bruising, increasing patient satisfaction with this procedure. The need for drains may also be obviated. PMID:11743409
Glue Sniffers with Special Needs.
ERIC Educational Resources Information Center
O'Connor, Denis
Glue sniffing and solvent misuse have seriously affected children and teenagers throughout the United Kingdom. This article discusses glue sniffing in terms of prevalence, association with disability, physical and psychological effects, signs and symptoms, counseling for sniffers, and successful interventions including an approach using videotape…
Rapidly light-activated surgical protein glue inspired by mussel adhesion and insect structural crosslinking.
Jeon, Eun Young; Hwang, Byeong Hee; Yang, Yun Jung; Kim, Bum Jin; Choi, Bong-Hyuk; Jung, Gyu Yong; Cha, Hyung Joon
Currently approved surgical tissue glues do not satisfy the requirements for ideal bioadhesives due to limited adhesion in wet conditions and severe cytotoxicity. Herein, we report a new light-activated, mussel protein-based bioadhesive (LAMBA) inspired by mussel adhesion and insect dityrosine crosslinking chemistry. LAMBA exhibited substantially stronger bulk wet tissue adhesion than commercially available fibrin glue and good biocompatibility in both in vitro and in vivo studies. Besides, the easily tunable, light-activated crosslinking enabled an effective on-demand wound closure and facilitated wound healing. Based on these outstanding properties, LAMBA holds great potential as an ideal surgical tissue glue for diverse medical applications, including sutureless wound closures of skin and internal organs. PMID:26197411
Treatment of osteochondral defects in the rabbit's knee joint by implantation of allogeneic mesenchymal stem cells in fibrin clots.
Berninger, Markus T; Wexel, Gabriele; Rummeny, Ernst J; Imhoff, Andreas B; Anton, Martina; Henning, Tobias D; Vogt, Stephan
bone (11). The sandwich-technique combines bone grafting with current approaches in Tissue Engineering (5,6). This combination seems to be able to overcome the limitations seen in osteochondral grafts alone. After autologous bone grafting to the subchondral defect area, a membrane seeded with autologous chondrocytes is sutured above and facilitates to match the topology of the graft with the injured site. Of course, the previous bone reconstruction needs additional surgical time and often even an additional surgery. Moreover, to date, long-term data is missing (12). Tissue Engineering without additional bone grafting aims to restore the complex structure and properties of native articular cartilage by chondrogenic and osteogenic potential of the transplanted cells. However, again, it is usually only the cartilage tissue that is more or less regenerated. Additional osteochondral damage needs a specific further treatment. In order to achieve a regeneration of the multilayered structure of osteochondral defects, three-dimensional tissue engineered products seeded with autologous/allogeneic cells might provide a good regeneration capacity (11). Beside autologous chondrocytes, mesenchymal stem cells (MSC) seem to be an attractive alternative for the development of a full-thickness cartilage tissue. In numerous preclinical in vitro and in vivo studies, mesenchymal stem cells have displayed excellent tissue regeneration potential (13,14). The important advantage of mesenchymal stem cells especially for the treatment of osteochondral defects is that they have the capacity to differentiate in osteocytes as well as chondrocytes. Therefore, they potentially allow a multilayered regeneration of the defect. In recent years, several scaffolds with osteochondral regenerative potential have therefore been developed and evaluated with promising preliminary results (1,15-18). Furthermore, fibrin glue as a cell carrier became one of the preferred techniques in experimental cartilage
Platelet Rich Fibrin in Periodontal Regeneration
Arunachalam, Muthukumaraswamy; Pulikkotil, Shaju J.; Sonia, Nath
Periodontitis is a chronic bacterial infection resulting in destruction of the supporting structures of the teeth. Regeneration of the lost tissues has faced difficulties primarily due to the lack of support during the intricate healing processes. A surgical additive which can 'jump start' the healing process to a more predictable regenerative process is always on the wish list of any periodontist. Platelet-rich fibrin (PRF) is a second generation platelet concentrate that has been considered to be an important, easy to obtain, predictable surgical additive for periodontal regeneration. This autologous scaffold provides the much needed bio-chemical mediators which has the potential for enhancing reconstruction of the periodontium. This review article tries to understand as to why PRF would be an important link to reach predictable periodontal regeneration. PMID:27386002
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2010 CFR
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2012 CFR
... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2014 CFR
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... Animal glue. Animal glue may be safely used as a component of articles intended for use in producing... the provisions of this section. (a) Animal glue consists of the proteinaceous extractives...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2013 CFR
... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of...
21 CFR 178.3120 - Animal glue.
Code of Federal Regulations, 2011 CFR
... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Animal glue. 178.3120 Section 178.3120 Food and... and Production Aids § 178.3120 Animal glue. Animal glue may be safely used as a component of articles..., transporting, or holding food, subject to the provisions of this section. (a) Animal glue consists of...
Human Adipose Stromal Vascular Cell Delivery in a Fibrin Spray
Zimmerlin, Ludovic; Rubin, J. Peter; Pfeifer, Melanie E.; Moore, L.R.; Donnenberg, Vera S.; Donnenberg, Albert D.
Background Adipose tissue represents a practical source of autologous mesenchymal stromal cells (MSC) and vascular-endothelial progenitor cells, available for regenerative therapy without in vitro expansion. One of the problems confronting the therapeutic application of such cells is how to immobilize them at the wound site. Here, we evaluated in vitro the growth and differentiation of human adipose stromal vascular fraction (SVF) cells after delivery using a fibrin spray system. Methods SVF cells were harvested from four human adult patients undergoing elective abdominoplasty using the LipiVage™ system. After collagenase digestion, mesenchymal and endothelial progenitor cells (pericytes, supra-adventitial stromal cells, endothelial progenitors) were quantified by flow cytometry before culture. SVF cells were applied to culture vessels using the Tisseel™ fibrin spray system. SVF cell growth and differentiation was documented by immunofluorescence staining and photomicrography. Results SVF cells remained viable following application and were expanded up to three weeks, when they reached confluence and adipogenic differentiation. Under angiogenic conditions, SVF cells formed endothelial (vWF+, CD31+ and CD34+) tubules surrounded by CD146+ and α-SMA+ perivascular/stromal cells. Discussion Human adipose tissue is a rich source of autologous stem cells, which are readily available for regenerative applications such as wound healing, without in vitro expansion. Our results indicate that mesenchymal and endothelial progenitor cells, prepared in a closed system from unpassaged lipoaspirate samples, retain their growth and differentiation capacity when applied and immobilized on a substrate using a clinically approved fibrin sealant spray system. PMID:23260090
David Lawrence
The GlueX detector is being built along with the new experimental Hall D at Jefferson lab as part of the 12~GeV upgrade project which received CD-3 approval in fall 2008. GlueX is a fixed target experiment built around a 2~Tesla superconducting solenoid having charged particle tracking and calorimetry with large acceptance. A high rate DAQ system consisting of pipeline electronics will allow the detector to operate at high luminosity ($10^{8}$ tagged $\\gamma$/sec on target). Details on the photon beam and GlueX detector are given including capabilities in resolutions and rates.
Preservation of the cardiac function in infarcted rat hearts by the transplantation of adipose-derived stem cells with injectable fibrin scaffolds.
Zhang, Xuelian; Wang, Haibin; Ma, Xiang; Adila, Azhati; Wang, Baozhu; Liu, Fen; Chen, Bangdang; Wang, Changyong; Ma, Yitong
Cell-based therapy can improve cardiac function but is limited by the low cell retention and survival within ischemic tissues. Injectable cardiac tissue engineering aims to support cell-based therapies and enhance their efficacy for cardiac diseases. So far, no research has been devoted to studying the usefulness of the combination of fibrin glue (as scaffold) and adipose-derived stem cells (ADSCs) to treat myocardial infarction. In our study, the rat ADSCs were isolated from subcutaneous adipose tissues. The surface phenotype of these cells was analyzed by flow cytometry. The fibrin glue was then co-injected with ADSCs into the left ventricular wall of rat infarction models. The structure and functional consequences of transplantation were determined by detailed histological analysis and echocardiography. Most cultured ADSCs expressed CD105 and CD90, and were negative for CD34 and CD45. After injection, both the 24-h cell retention and four-week graft size were significantly higher and larger in the Fibrin + ADSCs group than those of the ADSCs group alone (P < 0.01). The heart function improved significantly in the Fibrin + ADSCs group compared with that of the ADSCs group four weeks after transplantation (P < 0.01). In addition, the arteriole densities within the infarcted area improved significantly in the Fibrin + ADSCs group compared with those in the ADSCs group four weeks after transplantation (P < 0.01). In conclusion, the ADSCs with the fibrin glue has the therapeutic potential to improve the function of infarcted hearts. The method of in situ injectable tissue engineering combining fibrin glue with ADSCs is promising clinically. PMID:21127347
Traumatic dislocation of the incudostapedial joint repaired with fibrin tissue adhesive.
Nikolaidis, Vasilios
We present a case of traumatic dislocation of the incudostapedial joint (ISJ) and a simple method for controlled application of the glue using commercial fibrin tissue adhesive. A 26-year-old female presented to our ENT clinic for hearing impairment to her left ear 2 months after a head trauma due to a motorcycle accident. The audiogram revealed a 40- to 50-dB HL conductive hearing loss with a notch configuration in bone conduction curve on the left ear. Computed tomography of the left temporal bone revealed a longitudinal fracture line. An exploratory tympanotomy was performed under general anesthesia. The ISJ was found dislocated while the incus was trapped by the edges of the bony lateral attic wall fracture. A small bony edge that impeded incus movement was removed and a small amount of the glue was precisely applied to the lenticular process of the incus with an angled incision knife. The long process of the incus was firmly pressed over the stapes for 30 seconds with a 90° hook and 60 seconds after the application of the glue the ISJ was repaired. One year after our patient achieved full airbone gap (ABG) closure (ABG, ≤10 dB HL), while she demonstrated overclosure in frequencies 2 and 4 kHz. Fibrin tissue glue allowed safe, rapid, and accurate repair of the ISJ and resulted in an anatomically normal articulation as the mass and shape of the ossicles was preserved. Moreover, our patient achieved full ABG closure. PMID:21344438
Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).
Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung
Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409
Transglutaminases: nature's biological glues.
Griffin, Martin; Casadio, Rita; Bergamini, Carlo M
Transglutaminases (Tgases) are a widely distributed group of enzymes that catalyse the post-translational modification of proteins by the formation of isopeptide bonds. This occurs either through protein cross-linking via epsilon-(gamma-glutamyl)lysine bonds or through incorporation of primary amines at selected peptide-bound glutamine residues. The cross-linked products, often of high molecular mass, are highly resistant to mechanical challenge and proteolytic degradation, and their accumulation is found in a number of tissues and processes where such properties are important, including skin, hair, blood clotting and wound healing. However, deregulation of enzyme activity generally associated with major disruptions in cellular homoeostatic mechanisms has resulted in these enzymes contributing to a number of human diseases, including chronic neurodegeneration, neoplastic diseases, autoimmune diseases, diseases involving progressive tissue fibrosis and diseases related to the epidermis of the skin. In the present review we detail the structural and regulatory features important in mammalian Tgases, with particular focus on the ubiquitous type 2 tissue enzyme. Physiological roles and substrates are discussed with a view to increasing and understanding the pathogenesis of the diseases associated with transglutaminases. Moreover the ability of these enzymes to modify proteins and act as biological glues has not gone unnoticed by the commercial sector. As a consequence, we have included some of the present and future biotechnological applications of this increasingly important group of enzymes. PMID:12366374
Curtis A. Meyer
The GlueX experiment at Jefferson Lab is part of the planned CEBAF 12GeV upgrade. The project received its Critical Decision 1 (CD1) in February of 2006, and CD2 is anticipated in 2007. The GlueX experiment will search for and study the spectrum of gluonic excitations of mesons in the 1.5 to 2.5GeV/c^2 mass region using an 8.5 to 9GeV beam of linearly polarized photons.
NASA Technical Reports Server (NTRS)
Allen, S W; Truax, T R
This report was prepared for the National Advisory Committee for Aeronautics and presents the results of investigations conducted by the Forest Products Laboratory of the United States Forest Service on the manufacture, preparation, application, testing and physical properties of the different types of glues used in wood airplane parts.
Fabrication and physical and biological properties of fibrin gel derived from human plasma
NASA Astrophysics Data System (ADS)
Zhao, Haiguang; Ma, Lie; Zhou, Jie; Mao, Zhengwei; Gao, Changyou; Shen, Jiacong
The fast development of tissue engineering and regenerative medicine drives the old biomaterials, for example, fibrin glue, to find new applications in these areas. Aiming at developing a commercially available hydrogel for cell entrapment and delivery, in this study we optimized the fabrication and gelation conditions of fibrin gel. Fibrinogen was isolated from human plasma by a freeze-thaw circle. Gelation of the fibrinogen was accomplished by mixing with thrombin. Absorbance of the fibrinogen/thrombin mixture at 550 nm as a function of reaction time was monitored by UV-VIS spectroscopy. It was found that the clotting time is significantly influenced by the thrombin concentration and the temperature, while less influenced by the fibrinogen concentration. After freeze-drying, the fibrin gel was characterized by scanning electron microscopy (SEM), revealing fibrous microstructure. Thermal gravimetric analysis found that the degradation temperature of the crosslinked fibrin gel starts from 288 °C, which is about 30 °C higher than that of the fibrinogen. The hydrogel has an initial water-uptake ratio of ~50, decreased to 30-40 after incubation in water for 11 h depending on the thrombin concentration. The fibrin gels lost their weights in PBS very rapidly, while slowly in DMEM/fetal bovine serum and DMEM. In vitro cell culture found that human fibroblasts could normally proliferate in the fibrin gel with spreading morphology. In conclusion, the fibrin gel containing higher concentration of fibrinogen (20 mg ml-1) and thrombin (5 U ml-1) has suitable gelation time and handling properties, and thus is applicable as a delivery vehicle for cells such as fibroblasts.
Novel Technique Using Polyester Fabric and Fibrin Sealant Patch for Acute Aortic Dissection.
Ohira, Suguru; Fukumoto, Atsushi; Matsushiro, Takuya; Yaku, Hitoshi
We describe a simple and effective technique for acute aortic dissection using a combination of polyester fabric and a fibrin sealant patch (FSP) to achieve effective reinforcement and haemostasis of the aortic stump. Firstly, the 0.61mm thick knitted polyester fabric sheet was cut to half of the size of the FSP. Next, fibrin glue was sprayed onto the collagen layer of the FSP. Subsequently, a fabric sheet was placed upon it, and the FSP was put together with the irrigated collagen layer, and then completely dried to bind the patch. As a result, the dry fibrinogen/thrombin layers, as an adhesive surface, faced outward. This patch was trimmed to a 10-15-mm-wide strip. The composite patch was inserted into the false lumen. The stump was gently pressed to fix the aortic intima and adventitia. There are several advantages: the combined patch can be prepared during systemic cooling, and therefore can minimise the circulatory arrest time; secondly, the false lumen is not directly exposed to fibrin glue and so the risk of embolism is extremely low; thirdly, the expected haemostatic effect is greater as FSP lines the exterior of the intima, achieving haemostasis for suture holes. PMID:27011040
Hyaluronan and Fibrin Biomaterial as Scaffolds for Neuronal Differentiation of Adult Stem Cells Derived from Adipose Tissue and Skin
Gardin, Chiara; Vindigni, Vincenzo; Bressan, Eriberto; Ferroni, Letizia; Nalesso, Elisa; Puppa, Alessandro Della; D'Avella, Domenico; Lops, Diego; Pinton, Paolo; Zavan, Barbara
Recently, we have described a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. Due to their possible application in neuronal tissue regeneration, here we tested two kinds of scaffold well known in tissue engineering application: hyaluronan based membranes and fibrin-glue meshes. Neurospheres from skin and adipose tissue were seeded onto two scaffold types: hyaluronan based membrane and fibrin-glue meshes. Neurospheres were then induced to acquire a glial and neuronal-like phenotype. Gene expression, morphological feature and chromosomal imbalance (kariotype) were analyzed and compared. Adipose and skin derived neurospheres are able to grow well and to differentiate into glial/neuron cells without any chromosomal imbalance in both scaffolds. Adult cells are able to express typical cell surface markers such as S100; GFAP; nestin; βIII tubulin; CNPase. In summary, we have demonstrated that neurospheres isolated from skin and adipose tissues are able to differentiate in glial/neuron-like cells, without any chromosomal imbalance in two scaffold types, useful for tissue engineering application: hyaluronan based membrane and fibrin-glue meshes. PMID:22072917
Polyphosphate enhances fibrin clot structure
Smith, Stephanie A.
Polyphosphate, a linear polymer of inorganic phosphate, is present in platelet dense granules and is secreted on platelet activation. We recently reported that polyphosphate is a potent hemostatic regulator, serving to activate the contact pathway of blood clotting and accelerate factor V activation. Because polyphosphate did not alter thrombin clotting times, it appeared to exert all its procoagulant actions upstream of thrombin. We now report that polyphosphate enhances fibrin clot structure in a calcium-dependent manner. Fibrin clots formed in the presence of polyphosphate had up to 3-fold higher turbidity, had higher mass-length ratios, and exhibited thicker fibers in scanning electron micrographs. The ability of polyphosphate to enhance fibrin clot turbidity was independent of factor XIIIa activity. When plasmin or a combination of plasminogen and tissue plasminogen activators were included in clotting reactions, fibrin clots formed in the presence of polyphosphate exhibited prolonged clot lysis times. Release of polyphosphate from activated platelets or infectious microorganisms may play an important role in modulating fibrin clot structure and increasing its resistance to fibrinolysis. Polyphosphate may also be useful in enhancing the structure of surgical fibrin sealants. PMID:18544683
Platelet rich fibrin in jaw defects
NASA Astrophysics Data System (ADS)
Nica, Diana; Ianes, Emilia; Pricop, Marius
Platelet rich fibrin (PRF) is a tissue product of autologous origin abundant in growth factors, widely used in regenerative procedures. Aim of the study: Evaluation of the regenerative effect of PRF added in the bony defects (after tooth removal or after cystectomy) Material and methods: The comparative nonrandomized study included 22 patients divided into 2 groups. The first group (the test group) included 10 patients where the bony defects were treated without any harvesting material. The second group included 12 patients where the bony defects were filled with PRF. The bony defect design was not critical, with one to two walls missing. After the surgeries, a close clinically monitoring was carried out. The selected cases were investigated using both cone beam computer tomography (CBCT) and radiographic techniques after 10 weeks postoperatively. Results: Faster bone regeneration was observed in the bony defects filled with PRF comparing with the not grafted bony defects. Conclusions: PRF added in the bony defects accelerates the bone regeneration. This simplifies the surgical procedures and decreases the economic costs.
The Use Fibrin Sealant after Spinal Intradural Tumor Surgery: Is It Necessary?
Won, Young Il; Chung, Chun Kee; Jahng, Tae-Ahn; Park, Sung Bae
Objective A fibrin sealant is commonly applied after closure of an incidental or intended durotomy to reduce the complications associated with the leakage of cerebrospinal fluid. Routine usage might not be essential after closure of an intended durotomy, which has clear cut-margins. We investigated the efficacy of fibrin sealants for primary intradural spinal cord tumor surgery. Methods A retrospective review was performed for 231 consecutive surgically treated patients with primary intradural spinal cord tumors without extradural extension. Fibrin sealants were not used for 47 patients (group I: age, 51.57±16.75 years) and were applied to 184 patients (group II: age, 48.8±14.7 years). The surgical procedures were identical except for the use of a fibrin sealant after closure of the durotomy. The primary outcome was the occurrence of complications (wound problems, hematoma collection, infection, and neurological deterioration). The covariates were age, sex, body mass index, operation time, pre-/postoperative ambulation, number of laminectomies, and type of tumor. Results Schwannoma was the most common pathology (n=134), followed by meningioma (n=35) and ependymoma (n=31). Complications occurred in 13 patients (3 in group I and 10 in group II, p=0.73). The postoperative ambulation status (p<0.01; odds ratio, 28.8; 95% confidence interval, 6.9-120.0) and operation time (p=0.04; cutoff, 229 minutes; sensitivity, 62%; specificity, 72%) were significant factors, whereas the use of a fibrin glue was not (p=0.47). Conclusion The use of a fibrin sealant might not be essential to reduce complications after surgery for primary spinal intradural tumor. PMID:27123027
A new heterologous fibrin sealant as a scaffold to cartilage repair-Experimental study and preliminary results.
de Barros, Caio Nunes; Miluzzi Yamada, Ana Lúcia; Junior, Rui Seabra F; Barraviera, Benedito; Hussni, Carlos Alberto; de Souza, Jaqueline Brandão; Watanabe, Marcos Jun; Rodrigues, Celso Antônio; Garcia Alves, Ana Liz
Autologous fibrin gel is commonly used as a scaffold for filling defects in articular cartilage. This biomaterial can also be used as a sealant to control small hemorrhages and is especially helpful in situations where tissue reparation capacity is limited. In particular, fibrin can act as a scaffold for various cell types because it can accommodate cell migration, differentiation, and proliferation. Despite knowledge of the advantages of this biomaterial and mastery of the techniques required for its application, the durability of several types of sealant at the site of injury remains questionable. Due to the importance of such data for evaluating the quality and efficiency of fibrin gel formulations on its use as a scaffold, this study sought to analyze the heterologous fibrin sealant developed from the venom of Crotalus durissus terrificus using studies in ovine experimental models. The fibrin gel developed from the venom of this snake was shown to act as a safe, stable, and durable scaffold for up to seven days, without causing adverse side effects. Fibrin gel produced from the venom of the Crotalus durissus terrificus snake possesses many clinical and surgical uses. It presents the potential to be used as a biomaterial to help repair skin lesions or control bleeding, and it may also be used as a scaffold when applied together with various cell types. The intralesional use of the fibrin gel from the venom of this snake may improve surgical and clinical treatments in addition to being inexpensive and adequately consistent, durable, and stable. The new heterologous fibrin sealant is a scaffold candidate to cartilage repair in this study. PMID:26264444
Glue Film Thickness Measurements by Spectral Reflectance
B. R. Marshall
Spectral reflectance was used to determine the thickness of thin glue layers in a study of the effect of the glue on radiance and reflectance measurements of shocked-tin substrates attached to lithium fluoride windows. Measurements based on profilometry of the components were found to be inaccurate due to flatness variations and deformation of the tin substrate under pressure during the gluing process. The accuracy of the spectral reflectance measurements were estimated to be ±0.5 μm, which was sufficient to demonstrate a convincing correlation between glue thickness and shock-generated light.
Esthetics and super glue: a case report.
Winkler, Sheldon; Wood, Robert; Facchiano, Anne M; Bergloff, Jonathan F
This article describes how a man attempted to repair damage to his maxillary teeth with super glue. Such action is discouraged, however, because of possible adverse reactions in the hard and soft tissues. PMID:14719578
Spiders Tune Glue Viscosity to Maximize Adhesion.
Amarpuri, Gaurav; Zhang, Ci; Diaz, Candido; Opell, Brent D; Blackledge, Todd A; Dhinojwala, Ali
Adhesion in humid conditions is a fundamental challenge to both natural and synthetic adhesives. Yet, glue from most spider species becomes stickier as humidity increases. We find the adhesion of spider glue, from five diverse spider species, maximizes at very different humidities that matches their foraging habitats. By using high-speed imaging and spreading power law, we find that the glue viscosity varies over 5 orders of magnitude with humidity for each species, yet the viscosity at maximal adhesion for each species is nearly identical, 10(5)-10(6) cP. Many natural systems take advantage of viscosity to improve functional response, but spider glue's humidity responsiveness is a novel adaptation that makes the glue stickiest in each species' preferred habitat. This tuning is achieved by a combination of proteins and hygroscopic organic salts that determines water uptake in the glue. We therefore anticipate that manipulation of polymer-salts interaction to control viscosity can provide a simple mechanism to design humidity responsive smart adhesives. PMID:26513350
[Cementing of small osteochondral fragments in hand surgery using a fibrin glue--clinical experiences].
Zilch, H; Talke, M
A short historical review of the development of a new fibrinogen adhesive system, consisting of highly concentrated fibrinogen, thrombin, and factor XIII, is given. Small osteochondral fragments are well fixed with this system. This was demonstrated in five cases with good success, the fragments being early revascularized. Some of these patients have had severe damage to the finger joint surface. The problems of a prematured fibrinolysis were discussed. PMID:6972891
Animal experiments on hemostasis with a collagen-fibrin tissue-adhesive sealant in the nephrostomy tract.
Pfab, R; Ascherl, R; Erhardt, W; Geissdörfer, K; Stemberger, A; Blümel, G; Hartung, R
After a median laparatomy, nephrostomy was performed on 22 porcine kidneys: puncture, dilatation and introduction of a 26-French operating sheath through the parenchyma into the renal pelvis. At the end of the operation, an 8-French nephrostomy catheter prepared with a collagen-fibrin tissue-adhesive sealant was introduced through the operating sheath and the sheath was afterwards extracted. The hemostasis in the nephrostomy tract was very good in all 22 cases. There were no complications such as wound infection or stone formation during a post-operative period of between one and 95 days. Experimental investigations showed severe bleeding in nontamponade of the nephrostomy tract, in tamponade with an 8-French nephrostomy catheter and in tamponade of the nephrostomy tract with the collagen fleece wrapped around an 8-French nephrostomy catheter but not coated with the fibrin glue. PMID:2441506
Astrocytes: Everything but the glue
Gonzalez-Perez, Oscar; Lopez-Virgen, Veronica; Quiñones-Hinojosa, Alfredo
The current knowledge in neuroscience indicates that neural tissue has two major cell populations: neurons and glia (term derived from the Greek word for glue). Neuronal population is characterized by the capacity to produce action potentials, whereas glial cells are typically identified as the subordinate cell population of neurons. To date, this point of view has changed dramatically and growing evidence indicates that glial cells play a crucial role in normal mental functions and the pathogenesis of neurological diseases. Classically, glial cells include four major populations clearly discernible in the adult brain: astrocytes, oligodendrocytes, microglia cells and NG2 glia. Astrocytes, also referred as to astroglia, are by far the most abundant cell lineage in the adult brain. These cells are in close contact with several tissue components of the brain parenchyma including neurons, vasculature, extracellular matrix and other glial populations. Hence, the number and strategic position of astrocytes provide them with exceptional capacity for modulating multiple functions in the neural tissue. PMID:25938129
Autologous Microvascular Breast Reconstruction
Ramakrishnan, Venkat
Autologous microvascular breast reconstruction is widely accepted as a key component of breast cancer treatment. There are two basic donor sites; the anterior abdominal wall and the thigh/buttock region. Each of these regions provides for a number of flaps that are successfully utilised in breast reconstruction. Refinement of surgical technique and the drive towards minimising donor site morbidity whilst maximising flap vascularity in breast reconstruction has seen an evolution towards perforator based flap reconstructions, however myocutaneous flaps are still commonly practiced. We review herein the current methods of autologous microvascular breast reconstruction. PMID:23362474
Autologous Therapies in Dermatology
Kumar, Sumir; Mahajan, Bharat Bhushan; Singh, Amarbir
Autologous therapy is a therapeutic intervention that uses an individual's cells or tissues, which are processed outside the body, and reintroduced into the donor. This emerging field presently represents a mere tip of the iceberg with much knowledge and applications yet to be discovered. It, being free from risks of hypersensitivity reactions and transmission of infectious agents, has been explored in various fields, such as plastic surgery, orthopedics, and dermatology. This review article focuses on various forms of autologous therapies used in dermatology along with their applications and mechanisms of action. PMID:25584137
Imaging Thromboembolism with Fibrin-Avid 99mTc-Peptide: Evaluation in Swine
Aruva, Mohan R.; Daviau, Judy; Sharma, Shubh S.; Thakur, Mathew L.
A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for α-chain-fibrin was labeled with 99mTc (99mTc-TP850) and evaluated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). Methods Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVT was induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. 99mTc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, including blood and normal lungs, were harvested and, concomitantly, 99mTc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tissue. Results The affinity for human fibrin was 10−9 mol/L and there were >1015 receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9–22.6), DVT/muscle (31.1–89.4), PE/blood (1–155), and PE/lung (0.8–245) ratios. Thereafter, the PEs fragmented spontaneously below the spatial resolution of the γ-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. Conclusion 99mTc-TP850 with its modest affinity (10−9 mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis. PMID:16391200
NASA Astrophysics Data System (ADS)
Stevens, J.; Barbosa, F.; Bessuille, J.; Chudakov, E.; Dzhygadlo, R.; Fanelli, C.; Frye, J.; Hardin, J.; Kelsey, J.; Patsyuk, M.; Schwartz, C.; Schwiening, J.; Shepherd, M.; Whitlatch, T.; Williams, M.
The GlueX experiment was designed to search for and study the pattern of gluonic excitations in the meson spectrum produced through photoproduction reactions at a new tagged photon beam facility in Hall D at Jefferson Laboratory. The particle identification capabilities of the GlueX experiment will be enhanced by constructing a DIRC (Detection of Internally Reflected Cherenkov light) detector, utilizing components of the decommissioned BaBar DIRC. The DIRC will allow systematic studies of kaon final states that are essential for inferring the quark flavor content of both hybrid and conventional mesons. The design for the GlueX DIRC is presented, including the new expansion volumes that are currently under development.
Stevens, J.; Barbosa, F.; Bessuille, J.; Chudakov, E.; Dzhygadlo, R.; Fanelli, C.; Frye, J.; Hardin, J.; Kelsey, J.; Patsyuk, M.; et al
Here, the GlueX experiment was designed to search for and study the pattern of gluonic excitations in the meson spectrum produced through photoproduction reactions at a new tagged photon beam facility in Hall D at Jefferson Laboratory. The particle identification capabilities of the GlueX experiment will be enhanced by constructing a DIRC (Detection of Internally Reflected Cherenkov light) detector, utilizing components of the decommissioned BaBar DIRC. The DIRC will allow systematic studies of kaon final states that are essential for inferring the quark flavor content of both hybrid and conventional mesons. In this contribution, the design for the GlueX DIRCmore » will be discussed including new expansion volumes, read out with MaPMTs, that are currently under development.« less
Alexander Somov
The new experiment GlueX is being currently constructed at Jefferson Lab. The experiment was designed to search for hybrid mesons with exotic-quantum-numbers using a beam of linearly polarized photons incident on a liquid hydrogen target. We will discuss the discovery potential of the GlueX experiment and briefly overview its physics program. GlueX is a new experiment at Jefferson Lab. whose physics program is intended to improve our knowledge of strong interactions. The main goal of the experiment is to search for gluonic excitations in photoproduction. The experiment is expected to collect a data sample a few order of magnitudes larger than all existing photoproduction data. The physics topics of the experiment spans from light meson spectroscopy to Primakoff production of pseudoscalar mesons. The construction of the experiment has started in 2009 and the commissioning stage is expected to be finished in 2015.
[Mycelial wastes of penicillin fermentation as glue components].
Kadimaliev, D A; Revin, V V; Vatolin, A K; Groshev, V M; Bychkov, M V
A new trend in the rational use of micelial wastes after antibiotics fermentation was elaborated. The modification of P. chrysogenum micelium by means of acid and alkaline solutions allows to use it as bone glue component. As a result physico-mechanical characteristics of the mixture increase, while the ratio cost-price decreases. The obtained glue composition can be used in the production of glue paper tape, for paper and wood glue. PMID:12728627
Role of EVICEL Fibrin Sealant to Assist Hemostasis in Cranial and Spinal Epidural Space: A Neurosurgical Clinical Study.
Gazzeri, Roberto; Fiore, Claudio; Galarza, Marcelo
A variety of techniques have been used to stop venous bleeding from the cranial and spinal epidural space. These generally consist of packing with oxidized regenerated cellulose, fibrillar collagen, and so forth, and in cranial surgery, tack-up sutures. Bipolar coagulation may also be used to control bleeding from spinal venous plexus, but it may bear the risk of healthy nervous tissue injury: dissipation of heat from the tips of the bipolar forceps may induce thermal injury to adjacent neural structures. Quick and safe hemostasis reduces the duration of surgery. Efficient control of bleeding is also a prerequisite for the realization of the planned therapeutic procedure, that is, the result of surgery, and can thereby reduce perioperative morbidity. Fibrin sealant is safely used to increase hemostasis and to treat cerebrospinal leakage. Between January 2014 and March 2015, the authors used injection of fibrin sealant (EVICEL®, Johnson & Johnson Wound Management, Somerville, NJ) into the cranial and spinal epidural space to assist in hemostasis in 97 patients. EVICEL injection was used in 81 cases of cranial surgery and 16 cases of spinal surgery. When the venous bleeding continued from the epidural space after packing with classical hemostatic agents, fibrin sealant was used to stop venous bleeding. When arterial bleeding was present, fibrin sealant was not used. In all cases, the results were judged to be excellent with stoppage of epidural bleeding, or good with mild persistent oozing. During the 10-minute observation period, no patients treated with EVICEL required additional hemostatic measures. No complications related to the fibrin glue were encountered. PMID:26055033
Bell, D.; /Fermilab
I have reported most of the results of my adhesive testing to members of the VLPC design team at one time or another, usually verbally, but I am wnnng this summary as an easy reference to the results I obtained. The adhesives I tested were for two primary purposes. The first was adhering optical fibers to Torlon 7130; the other was for securing an aluminum nitride substrate to the same material. I have not had access to a scanning electron microscope and someone with the knowledge to determine actual failure mechanisms, so the deductions I have made about why some adhesives have worked well at low temperatures for some purposes and not for other applications while a different material never worked and another always worked are partially speculation. They should be taken merely at face value with no particular results 'carved in stone' so to speak. The first aspect of my testing was adhesion of optical fiber to torlon. Knowing that this is a very important joint, I tested a variety of glues of two primary types: acrylic and W cure. W cure adhesives are known to possess reasonably good properties at low temperatures and are quite convenient to use as long as a W source is available. The W cure adhesives I tested were: Loctite Utak 376 and also 7EN484(?), Master Bond 1 Component W 15-7, and Norland optical adhesive 61. I found them quite easy to use, and they were packaged in a way in which they were not likely to cause a mess. Lab 6 e Perimenters generally used the Loctite 376 optical cure adhesive in their research into connecting scintillating fibers to the standard type. The acrylics I tested were Loctite Speed Bonder 324 and Permabond Quick Bond 610. These worked reasonably well, but they require a considerably longer set time than the W cure adhesives and are more complicated to use. (5 minutes set time or so for the acrylics versus about 30 seconds for the W. The Loctite must have the activator applied about 5 minutes prior to the adhesive application and the
Sutureless cataract incision closure using laser-activated tissue glues
NASA Astrophysics Data System (ADS)
Eaton, Alexander M.; Bass, Lawrence S.; Libutti, Steven K.; Schubert, Herman D.; Treat, Michael R.
With the advent of phacoemulsification and foldable intraocular lenses, there is renewed interest in sutureless cataract wound. We report the use of laser activated tissue glues for the closure of scleral tunnel cataract incisions. Two glue mixtures were tested in enucleated porcine eyes. Glue A was composed of hyaluronic acid, human albumin, and indocyanine green dye. Glue B contained hyaluronic acid, chondroitin sulfate, human albumin, and indocyanine green dye. A Spectra Physics diode laser (808 nm) with a power density of 7-1 1 watts/cm2 was used for glue activation. Wound bursting pressures, as determined by the presence of fluid at the wound margin, was significantly higher with both glue combinations than without the glue (P
Zinc modulates thrombin adsorption to fibrin
Hopmeier, P.; Halbmayer, M.; Fischer, M.; Marx, G. )
Human thrombin with high affinity to Sepharose insolubilized fibrin monomers (high-affinity thrombin) was used to investigate the effect of Zn(II) on the thrombin adsorption to fibrin. Results showed that at Zn(II) concentrations exceeding 100 mumols/l, thrombin binding to fibrin was decreased concomitant with the Zn(II) concentration and time; at lower Zn(II) concentrations, thrombin adsorption was enhanced. Experimental results were identical by using 125I-labelled high-affinity alpha-thrombin or by measuring the thrombin activity either by chromogenic substrate or by a clotting time method. In contrast, Ca(II) alone (final conc. 3 mmol/l) or in combination with Zn(II) was not effective. However, at higher Ca(II) concentrations (7.5-15 mmol/l), thrombin adsorption was apparently decreased. Control experiments revealed that Zn(II) had no impact on the clottability of fibrinogen, and that the results of the experiments with Ca(II) were not altered by possible cross-linking of fibrin. We conclude that unlike Ca(II), Zn(II) is highly effective in modulating thrombin adsorption to fibrin.
The glue ear 'epidemic': a historical perspective.
Alderson, David
This paper explores the historical context of the dramatic rise in surgery for glue ear in the mid-20th century, and questions the published assertion that this represented a manufactured 'epidemic'. In examining historical sources, the reader's theoretical viewpoint greatly influences their conclusions: the sustained rise in treatment for glue ear may be seen as the advance of science in a golden age or the resistance of insular professionals to reason in the light of new scientific study methods. Current views on the practice of medicine, consumerism, science and standardisation, rationing and the nature of 'truth' all affect the way that we see this period. Technological advances clearly allowed better diagnosis and more effective treatment, but these did not appear to drive an 'epidemic', rather they were developed to meet the pre-existing challenges of otological practice. The proposition that an 'epidemic' was created does not appear to have any solid grounding. Society's perception of what constitutes disease and what needs treatment may have evolved, but the prevalence of other important diseases changed dramatically over this time period, and a real change in the epidemiology of glue ear cannot be dismissed. In defining the case for and against surgical treatment, a solely positivist, quantitative worldview cannot give us a complete picture of benefit and risk to individuals, families and society at large. PMID:21653931
Fibrin Architecture in Clots: A Quantitative Polarized Light Microscopy Analysis
Whittaker, Peter; Przyklenk, Karin
Fibrin plays a vital structural role in thrombus integrity. Thus, the ability to assess fibrin architecture has potential to provide insight into thrombosis and thrombolysis. Fibrin has an anisotropic molecular structure, which enables it to be seen with polarized light. Therefore, we aimed to determine if automated polarized light microscopy methods of quantifying two structural parameters; fibrin fiber bundle orientation and fibrin's optical retardation (OR: a measure of molecular anisotropy) could be used to assess thrombi. To compare fibrin fiber bundle orientation we analyzed picrosirius red-stained sections obtained from clots formed: (A) in vitro, (B) in injured and stenotic coronary arteries, and (C) in surgically created aortic aneurysms (n = 6 for each group). To assess potential changes in OR, we examined fibrin in picrosirius red-stained clots formed after ischemic preconditioning (10 minutes ischemia + 10 minutes reflow; a circumstance shown to enhance lysability) and in control clots (n = 8 each group). The degree of fibrin organization differed significantly according to the location of clot formation; fibrin was most aligned in the aneurysms and least aligned in vitro whereas fibrin in the coronary clots had an intermediate organization. The OR of fibrin in the clots formed after ischemic preconditioning was lower than that in controls (2.9 ± 0.5 nm versus 5.4 ± 1.0 nm, P < 0.05). The automated polarized light analysis methods not only enabled fibrin architecture to be assessed, but also revealed structural differences in clots formed under different circumstances. PMID:19054699
Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.
Mittermayr, Rainer; Branski, Ludwik; Moritz, Martina; Jeschke, Marc G; Herndon, David N; Traber, Daniel; Schense, Jason; Gampfer, Jörg; Goppelt, Andreas; Redl, Heinz
Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23723146
Autologous gastrointestinal reconstruction.
Bianchi, A
The patient with short bowel syndrome is essentially unable to absorb sufficient nutrients. This is caused by either short mucosal contact time, insufficient mucosal surface area (enterocyte mass), or a combination of the two. Management consists primarily in sustaining health and growth by intravenous nutrition and in enhancing the natural intestinal adaptation response. Surgery in the form of autologous gastrointestinal reconstruction (AGIR) is designed to redistribute the patient's own residual absorptive bowel to enhance adaptation and, possibly, to increase the absorptive mucosal surface by neomucosal growth. The alternative and ultimate fallback procedure in the management of intestinal failure is bowel transplantation, with its associated serious immunosuppression-related complications. Imaginative AGIR techniques provide new hope for the future. PMID:7728509
Encapsulation of cardiomyocytes in a fibrin hydrogel for cardiac tissue engineering.
Yuan Ye, Kathy; Sullivan, Kelly Elizabeth; Black, Lauren Deems
Culturing cells in a three dimensional hydrogel environment is an important technique for developing constructs for tissue engineering as well as studying cellular responses under various culture conditions in vitro. The three dimensional environment more closely mimics what the cells observe in vivo due to the application of mechanical and chemical stimuli in all dimensions (1). Three-dimensional hydrogels can either be made from synthetic polymers such as PEG-DA (2) and PLGA (3) or a number of naturally occurring proteins such as collagen (4), hyaluronic acid (5) or fibrin (6,7). Hydrogels created from fibrin, a naturally occurring blood clotting protein, can polymerize to form a mesh that is part of the body's natural wound healing processes (8). Fibrin is cell-degradable and potentially autologous (9), making it an ideal temporary scaffold for tissue engineering. Here we describe in detail the isolation of neonatal cardiomyocytes from three day old rat pups and the preparation of the cells for encapsulation in fibrin hydrogel constructs for tissue engineering. Neonatal myocytes are a common cell source used for in vitro studies in cardiac tissue formation and engineering (4). Fibrin gel is created by mixing fibrinogen with the enzyme thrombin. Thrombin cleaves fibrinopeptides FpA and FpB from fibrinogen, revealing binding sites that interact with other monomers (10). These interactions cause the monomers to self-assemble into fibers that form the hydrogel mesh. Because the timing of this enzymatic reaction can be adjusted by altering the ratio of thrombin to fibrinogen, or the ratio of calcium to thrombin, one can injection mold constructs with a number of different geometries (11,12). Further we can generate alignment of the resulting tissue by how we constrain the gel during culture (13). After culturing the engineered cardiac tissue constructs for two weeks under static conditions, the cardiac cells have begun to remodel the construct and can generate a
Dry-cured ham restructured with fibrin.
Romero de Ávila, M D; Hoz, L; Ordóñez, J A; Cambero, M I
The viability of a fibrinogen-thrombin system (FT) to bind fresh deboned hams for incorporation in the salting and ripening processes, to produce cured ham, was studied. The effects of the different processing variables (pH, NaCl concentration, temperature and gelation time) on FT, a meat emulsion mixed with FT, fresh pork portions and deboned hams restructured with FT were analyzed. The most stable and firmest fibrin gels were obtained after 6h of adding the FT, with less than 2% NaCl and pH 7-8.4. Scanning electron microscopy of the fibrin gel showed fibrillar structures with a high degree of cross-linking and a high density. Two structures were found in the binding area of restructured meat; one in the central part with similar characteristics to fibrin gels and, another in the area of contact between the meat surfaces, where a filamentous structure connected the fibrin gels with the muscle bundles. PMID:24767091
Platelets and fibrin strands during clot retraction.
Morgenstern, E; Korell, U; Richter, J
The ultrastructure of platelet fibrin contacts (PFC) and the course of the strands was investigated in serial sections of retracted clots with the help of specimen tilting. We found after retraction in a test tube as well as under isometric conditions in the resonance thrombograph, after HARTERT, an uniform type of PFC. The side to side contact between platelet surface and fibrin strands displayed a 15 nm wide space which was bridged of 10 - 30 nm by filamentary structure. In each case the direction of the fibrin strands changed on contact with the platelet surface (bend). These bends recurred if the adhering strands ran over a longer distance on the platelet surface. The bends can be explained by non-directional movement of the platelets or of their pseudopodia. Microfilaments (actomyosin) which run straight in pseudopodia and often also twisted in the platelet body support this assumption. The described mechanism - contact of the thrombin activated platelets with fibrin strands and simultaneous nondirectional movement of the platelets which bind further sections of the adhering strands to their surface - would provide a more satisfactory explanation for the retraction of the clot to 1/10 of its original volume. PMID:6539004
Autologous blood storage in obstetrics.
Herbert, W N; Owen, H G; Collins, M L
Autologous transfusion, storage of one's own blood for subsequent infusion if needed, is safe and effective in a variety of scheduled operative procedures. Obstetric involvement in such programs is very limited, however. Thirty pregnant women with placenta previa or other potential complications underwent 55 phlebotomies in an autologous transfusion program. Phlebotomies were performed at an average gestational age of 32.4 weeks (range 13-40). Changes in mean diastolic blood pressure and pulse were minimal. Electronic fetal monitoring tracings were normal during the 34 procedures in which it was used. The frequency of mild donor reactions (4%) was consistent with that in nonpregnant donors. After entry into this program, 15 patients received a total of 29 U of packed red blood cells (23 autologous; six homologous). Homologous transfusion was avoided in 86.7% of patients receiving blood. Selected pregnant women can participate safely in autologous blood collection programs, minimizing the need, and therefore the risks, of homologous transfusion. PMID:3292974
Impact of EmbryoGlue as the embryo transfer medium.
Hazlett, William David; Meyer, Liza R; Nasta, Tricia E; Mangan, Patricia A; Karande, Vishvanath C
Routine use of EmbryoGlue did not significantly improve pregnancy or implantation rates in nonselected patients receiving either a day 3 or day 5 embryo transfer compared with standard culture media. Future prospective randomized studies need to be performed to determine whether EmbryoGlue is beneficial in a selected patient population. PMID:17765233
Nicareta, Beatriz; Pereira, Luiz Haroldo; Sterodimas, Aris; Illouz, Yves Gérard
In the past 25 years, several different techniques of lipoinjection have been developed. The authors performed a prospective study to evaluate the patient satisfaction and the rate of complications after an autologous gluteal lipograft among 351 patients during January 2002 and January 2008. All the patients included in the study requested gluteal augmentation and were candidates for the procedure. Overall satisfaction with body appearance after gluteal fat augmentation was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5 (excellent). The evaluation was made at follow-up times of 12 and 24 months. The total amount of clean adipose tissue transplanted to the buttocks varied from 100 to 900 ml. In nine cases, liponecrosis was treated by aspiration with a large-bore needle connected to a 20-ml syringe, performed as an outpatient procedure. Infection of the grafted area also occurred for four patients and was treated by incision drainage and use of antibiotics. Of the 21 patients who expressed the desire of further gluteal augmentation, 16 had one more session of gluteal fat grafting. The remaining five patients did not have enough donor area and instead received gluteal silicone implants. At 12 months, 70% reported that their appearance after gluteal fat augmentation was "very good" to "excellent," and 23% responded that their appearance was "good." Only 7% of the patients thought their appearance was less than good. At 24 months, 66% reported that their appearance after gluteal fat augmentation was "very good" (36%) to "excellent" (30%), and 27% responded that their appearance was "good." However, 7% of the patients continued to think that their appearance was less than good. At this writing, the average follow-up time for this group of patients has been 4.9 years. The key to successful gluteal fat grafting is familiarity with the technique, knowledge of the gluteal topography, and understanding of the patient's goals. With experience, the
GlueX: Meson Spectroscopy in Photoproduction
Salgado, Carlos; Smith, Elton S.
The goal of the GlueX experiment \\cite{gluex} is to provide crucial data to help understand the soft gluonic fields responsible for binding quarks in hadrons. Hybrid mesons, and in particular exotic hybrid mesons, provide the ideal laboratory for testing QCD in the confinement regime since these mesons explicitly manifest the gluonic degrees of freedom. Photoproduction is expected to be effective in producing exotic hybrids but there is little data on the photoproduction of light mesons. GlueX will use the new 12-GeV electron beam at Jefferson Lab to produce a 9-GeV beam of linearly polarized photons using the technique of coherent bremsstrahlung. A solenoid-based hermetic detector is under construction, which will be used to collect data on meson production and decays. These data will also be used to study the spectrum of conventional mesons, including the poorly understood excited vector mesons. This talk will give an update on the experiment as well as describe theoretical developments \\cite{Dudek:2011bn} to help understand how these data can provide insights into the fundamental theory of strong interactions.
Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration
NASA Astrophysics Data System (ADS)
Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel
Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.
Autologous chondrocytes. Autologous chondrocyte implantation: more data needed.
There is no standard surgical treatment for young adults with persistent, incapacitating symptoms of knee cartilage damage. ChondroCelect is the first cell therapy product to be authorised in the European Union. It contains a dense suspension of chondrocytes cultured from a biopsy of the patient's knee cartilage for 4 weeks before being reimplanted. Clinical evaluation of Chondro-Celect only includes one trial, versus subchondral microfracture, in 118 patients. After 3 years of follow-up, there was no difference in the symptom score between the groups. Histological outcome was better after autologous chondrocyte implantation, but methodological problems make it difficult to interpret the observed difference. Long-term functional outcomes remain to be determined. More joint complications occurred after autologous chondrocyte implantation than after subchondral bone microfracture: more frequently symptomatic cartilage hypertrophy (27% versus 13%, possibly related to the implantation technique), joint swelling (22% versus 6.6%), joint effusion (24% versus 9.8%), and joint crepitations (18% versus 6.6%). Autologous chondrocyte implantation was sometimes associated with flu-like syndrome (in 7.8% of patients), which did not occur with the microfracture technique. Autologous chondrocyte implantation is more complex than microfracture. During routine use, there is a risk that one patient will inadvertently receive chondrocytes collected from another patient, leading to a risk of rejection. In practice, this autologous chondrocyte product should only be used by highly specialised teams, and its assessment must continue. PMID:21648176
Toward an understanding of fibrin branching structure
NASA Astrophysics Data System (ADS)
Fogelson, Aaron L.; Keener, James P.
The blood clotting enzyme thrombin converts fibrinogen molecules into fibrin monomers which polymerize to form a fibrous three-dimensional gel. The concentration of thrombin affects the architecture of the resulting gel, in particular, a higher concentration of thrombin produces a gel with more branch points per unit volume and with shorter fiber segments between branch points. We propose a mechanism by which fibrin branching can occur and show that this mechanism can lead to dependence of the gel's structure (at the time of gelation) on the rate at which monomer is supplied. A higher rate of monomer supply leads to a gel with a higher branch concentration and with shorter fiber segments between branch points. The origin of this dependence is explained.
Shulman, Sidney; Katz, Sidney; Ferry, John D.
1. Fibrin clots prepared in the absence of calcium can be dissolved in solutions of lithium chloride and bromide and sodium bromide and iodide, as well as of guanidine hydrochloride and urea. These salts do not denature fibrinogen under the same conditions of concentration, temperature, and time. Sedimentation experiments on the fibrin solutions show in each case a single sharp peak with a sedimentation constant close to that of fibrinogen. 2. At lower concentrations, these salts inhibit the clotting of fibrinogen by thrombin, but in the case of lithium bromide and sodium iodide, at least, allow an intermediate polymer to accumulate whose sedimentation constant is close to that of the polymer observed in systems inhibited by hexamethylene glycol or urea. PMID:13069679
Mechanisms of fibrin polymerization and clinical implications
Litvinov, Rustem I.
Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment. PMID:23305734
21 CFR 864.7300 - Fibrin monomer paracoagulation test.
Code of Federal Regulations, 2013 CFR
... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class...
21 CFR 864.7300 - Fibrin monomer paracoagulation test.
Code of Federal Regulations, 2010 CFR
... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class...
21 CFR 864.7300 - Fibrin monomer paracoagulation test.
Code of Federal Regulations, 2011 CFR
... clotting within a blood vessel) or in the differential diagnosis between disseminated intravascular coagulation and primary fibrinolysis (dissolution of the fibrin in a blood clot). (b) Classification. Class...
Scaffold architecture and fibrin gels promote meniscal cell proliferation
Pawelec, K. M. E-mail: email@example.com; Best, S. M.; Cameron, R. E.; Wardale, R. J. E-mail: firstname.lastname@example.com
Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. Metabolic activity was promoted by fibrin addition. Cellular proliferation, however, was significantly increased by both aligned architectures and fibrin addition. None of the constructs impaired collagen type I production or triggered adverse inflammatory responses. It was demonstrated that both fibrin gel addition and optimized scaffold architecture effectively promote meniscal cell proliferation.
Management of pulpal floor perforation and grade II Furcation involvement using mineral trioxide aggregate and platelet rich fibrin: A clinical report
Bains, Rhythm; Bains, Vivek K.; Loomba, Kapil; Verma, Kavita; Nasir, Afreena
To report the management of an iatrogenic perforation of pulpal floor in the furcation of mandibular first molar, using Mineral Trioxide Aggregate (MTA) and platelet rich fibrin (PRF). Unpredictable endodontic root/pulp chamber floor perforations resulting in unacceptable high rate of clinical failure has now been a lesser threat with the advent of new technologies and biocompatible materials that utilize the applications of basic research along with tissue engineering concept in clinical practice. Present case report illustrates the use of MTA and platelet rich fibrin (PRF) for the repair of the perforation defect and regeneration of the lost periodontium in furcation area. Although, histologic events and reaction of MTA with PRF is not studied so far, however, the autologous and biocompatible nature of the components used for present treatment modalities seems to be beneficial for the long term clinical results obtained in our case. PMID:23230369
Clinical effect of tetracycline demineralization and fibrin-fibronectin sealing system application on healing response following flap debridement surgery.
Trombelli, L; Scabbia, A; Scapoli, C; Calura, G
The aim of this controlled clinical trial was to assess the effect on healing following tetracycline (TTC) conditioning and fibrin-fibronectin sealing system (FFSS) application in association with flap debridement surgery (FDS) in 11 patients under treatment for moderate to severe periodontitis. Selection criteria included the presence of two bilateral, homologous, non-molar, interproximal sites with probing depth > or = 5 mm. The areas bilateral to the trial sites were matched for number and type of the teeth, and similar periodontal involvement. After initial therapy, a split-mouth design was used in which one area was treated by flap debridement surgery alone (control), and the contralateral area was treated following surgery with a 4-minute burnishing application of 100 mg/ml TTC solution and FFSS (test). Fibrin glue was applied with a syringe on the demineralized root surfaces and surrounding bone margins. Healing by primary intention was encouraged by flap repositioning with interrupted sutures left in place for 14 days. A monthly maintenance recall program was followed. Patients were clinically evaluated at baseline and 6 months and the following measurements were taken: gingival index, plaque control record, clinical attachment level, probing depth, recession, bleeding on probing. Statistical evaluation indicated that both approaches resulted in significant probing depth reduction and clinical attachment gain. However, the differences in healing between the test and control groups were not clinically nor statistically significant. These results suggest there is no additional benefit with TTC demineralization and topical FFSS application in conjunction with flap debridement surgery. PMID:8832480
The use of fibrin and gelatin fixation to repair a kinked internal carotid artery in carotid endarterectomy
Kubota, Hisashi; Sanada, Yasuhiro; Tanikawa, Rokuya; Kato, Amami
Background: The kinking of the internal carotid artery (ICA) after final closure in carotid endarterectomy (CEA) is thought to be uncommon. When it occurs, it is mandatory to reconstruct ICA to preserve normal blood flow. We herein present a case in which a fixation technique was applied to repair an ICA that became kinked during CEA. Case Description: A 68-year-old man presented with cerebral infarction due to an artery-to-artery embolism from the right cervical ICA stenosis. CEA was performed 12 days after admission. After final closure, a distal portion of ICA was found to have been kinked following plaque resection in CEA procedure. Fixation with fibrin glue and gelatin was used to reinforce the arterial wall and repair the kink. Postoperative magnetic resonance angiography demonstrated the release of the kink in ICA. Conclusion: Fixation with fibrin and gelatin is a salvage armamentarium that can be considered in CEA for the repair of kinked or tortuous ICA. PMID:27308092
Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey
UNDERSIDE FROM SOUTH BANKS; NOTICE NEW GLUE LAM CROSSBEAMS SISTERED TO OLDER BEAMS, NEW STRINGERS AND COMPONENTS MAKE UP A NEARLY NEW SUPPORT SYSTEM - Short Bridge, Spanning South Santiam River at High Deck Road, Cascadia, Linn County, OR
The GlueX Project at Jefferson Lab
Papandreou, Zisis
One of the main scientific questions that remains unanswered in subatomic physics is the nature and behaviour of the "Glue" which holds the quarks together. The puzzling feature of this construction is that quarks are never found free, but only in triplets or pairs, a phenomenon known as "confinement". Since gluons carry colour charge, they can form chromoelectric flux tubes, which may result in unusual objects, such as glue-balls or hybrid combinations of gluons and quarks. In certain models, the later can be produced with quantum numbers not allowed in the simple quark picture. An international experiment (GlueX) at Jefferson Lab, Virginia, is being designed to search for such exotic hybrid mesons and thus elucidate the phenomenon of confinement. GlueX is considered a 'discovery' experiment; its salient features, the planned methodology of partial- wave analysis, and the R&D progress of its detector subsystems will be
Rebooting autoimmunity with autologous HSCT.
Snowden, John A
Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT. PMID:26744435
Contaminating fibrin in CPD-blood: solubility in plasma and distribution in blood components following separation
Skjonsberg, O.H.; Kierulf, P.; Gravem, K.; Fagerhol, M.K.; Godal, H.C.
In order to estimate the solubility of contaminating fibrin in CPD-blood, thrombin induced fibrin polymerzation in CPD-plasma was examined by light scattering and fibrinopeptide A (FPA) determinations. In addition, I-125 fibrin monomer enriched CPD-blood was used to investigate fibrin monomer retention in blood bags and transfusion filters (170 microns) and fibrin distribution in blood components derived from CPD-blood. Initial fibrin polymerization in CPD-blood occurred after conversion of 15 per cent of the fibrinogen to fibrin, implying that substantial amounts of fibrin may be kept solubilized in CPD-blood bags. Only minor amounts of I-125 fibrin monomers were retained in blood bags (2.4 per cent) and in transfusion filters (2.9 per cent) after sham transfusions. After separating I-125-fibrin monomer enriched CPD-blood into its constituent components, the major part of fibrin (75.0 per cent) could be traced in the cryoprecipitate.
21 CFR 864.7300 - Fibrin monomer paracoagulation test.
Code of Federal Regulations, 2014 CFR
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fibrin monomer paracoagulation test. 864.7300 Section 864.7300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7300 Fibrin monomer paracoagulation test....
21 CFR 864.7300 - Fibrin monomer paracoagulation test.
Code of Federal Regulations, 2012 CFR
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fibrin monomer paracoagulation test. 864.7300 Section 864.7300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7300 Fibrin monomer paracoagulation test....
Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots
Zubairova, Laily D.; Nabiullina, Roza M.; Nagaswami, Chandrasekaran; Zuev, Yuriy F.; Mustafin, Ilshat G.; Litvinov, Rustem I.; Weisel, John W.
Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1–0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis. PMID:26635081
NASA Astrophysics Data System (ADS)
Pooser, Eric; GlueX Collaboration
The GlueX experiment will be one of the largest photo-production facilities in the world and is currently under construction. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been designed to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information. It is now under construction at Florida International University (FIU). This detector is designed to operate at photon intensities of up to 108 γ /s in the coherent peak. It consists of an array of 30 individual scintillators with ``pointed'' ends that bend toward the beam at the downstream end. SiPM detectors, which comprise the readout system, are placed as close as possible at the end of each scintillator. The EJ-200 scintillator is best suited for the timing studies with a fast decay time of 2.0 ns. The physical properties of the scintillators, configured to the desired geometry, have been studied extensively at FIU. Geant4 simulations are currently underway to replicate and to understand our experimental results. The results of these timing studies and simulations are discussed.
NASA Astrophysics Data System (ADS)
Pooser, Eric; GlueX Collaboration
The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 γ / s in the coherent peak and provide a timing resolution < 350 ps so as to provide successful identification of the electron beam buckets to within 99 % accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~ 90 % of 4 π hermeticity , and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the Start Counter have been studied extensively. The results of theses studies are discussed. This material is based upon work supported by the U.S. Department of Energy, Office of Science, and Office of Nuclear Physics under Contracts DE-AC05-06OR23177 & DE-FG02-99ER41065.
NASA Astrophysics Data System (ADS)
Pooser, Eric; GlueX Collaboration
The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 γ / s in the coherent peak and provide a timing resolution < 350ps so as to provide successful identification of the electron beam buckets to within 99 % accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~ 90 % of 4 π hermeticity , and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the Start Counter have been studied extensively. The results of theses studies are discussed. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics under Contracts DE-AC05-06OR23177 & DE-FG02-99ER41065.
NASA Astrophysics Data System (ADS)
Pooser, Eric; GlueX Collaboration
The GlueX experiment will study meson photoproduction with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 ns apart, and to provide accurate timing information which is used in the level-1 trigger of the experiment. This detector is designed to operate at photon intensities of up to 108 γ / s in the coherent peak and provide a timing resolution <350 ps so as to provide successful identification of the electron beam buckets to within 99% accuracy. Furthermore, the Start Counter detector will provide excellent solid angle coverage, ~90% of 4π hermeticity, and a high degree of segmentation for background rejection. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. Silicon PhotoMultiplier (SiPM) detectors have been selected as the readout system. The physical properties of the scintillators, have been studied extensively at FIU. The results of these studies are discussed.
NASA Astrophysics Data System (ADS)
Llodra, Anthony; Pooser, Eric; GlueX Collaboration
The GlueX experiment, which is online as of October of 2014, will study meson photo production with unprecedented precision. This experiment will use the coherent bremsstrahlung technique to produce a 9 GeV linearly polarized photon beam incident on a liquid H2 target kept at a few degrees Kelvin. A Start Counter detector has been fabricated to identify the accelerator electron beam buckets, approximately 2 nanoseconds apart, and to provide accurate timing information. This detector is designed to operate at photon intensities of up to 108 γ/s in the coherent peak and provide a timing resolution of less than 350 picoseconds so as to provide successful identification of the electron beam buckets. It consists of a cylindrical array of 30 scintillators with pointed ends that bend towards the beam at the downstream end. The EJ-200 scintillator is best suited for the Start Counter due to its fast decay time on the order of 2 nanoseconds and long attenuation length. Silicon Photo Multiplier (SiPM) detectors have been selected as the readout system and are to be placed as close as possible, less than 300 micron, to the upstream end of each scintillator. The methods/details of the assembly and the optimization of the surface quality of scintillator paddles are discussed. This work was supported in part by DoE Contracts DE-FG02-99ER41065 and DE-AC05-06OR23177.
Concentration of Fibrin and Presence of Plasminogen Affect Proliferation, Fibrinolytic Activity, and Morphology of Human Fibroblasts and Keratinocytes in 3D Fibrin Constructs
Reinertsen, Erik; Skinner, Michael; Wu, Benjamin
Fibrin is a hemostatic protein found in the clotting cascade. It is used in the operating room to stop bleeding and deliver cells and growth factors to heal wounds. However, formulations of clinically approved fibrin are optimized for hemostasis, and the extent to which biochemical and physical cues in fibrin mediate skin cell behavior is not fully understood nor utilized in the design of biomaterials. To determine if the concentration of fibrinogen and the presence of plasminogen affect cell behavior relevant to wound healing, we fabricated three-dimensional fibrin constructs made from 5, 10, or 20 mg/mL of clinical fibrin or plasminogen-depleted (PD) fibrin. We cultured dermal fibroblasts or epidermal keratinocytes in these constructs. Fibroblasts proliferated similarly in both types of fibrin, but keratinocytes proliferated more in low concentrations of clinical fibrin and less in PD fibrin. Clinical fibrin constructs with fibroblasts were less stiff and degraded faster than PD fibrin constructs with fibroblasts. Similarly, keratinocytes degraded clinical fibrin, but not PD fibrin. Fibroblast spreading varied with fibrin concentration in both types of fibrin. In conclusion, the concentration of fibrinogen and the presence of plasminogen affect fibroblast and keratinocyte proliferation, morphology, and fibrin degradation. Creating materials with heterogeneous regions of fibrin formulations and concentrations could be a novel strategy for controlling the phenotype of encapsulated fibroblasts and keratinocytes, and the subsequent biomechanical properties of the construct. However, other well-investigated aspects of wound healing remain to be utilized in the design of fibrin biomaterials, such as autocrine and paracrine signaling between fibroblasts, keratinocytes, and immune cells. PMID:24738616
Measurement of Fibrin Fiber Strength using AFM
NASA Astrophysics Data System (ADS)
Jawerth, Louise; Falvo, Mchael; Canning, Anthony; Matthews, Garrett; Superfine, Richard; Guthold, Martin
Blood clots usually form in the event of injury or damage to blood vessels to prevent the loss of blood. Moreover, as we age, blood clots often form in undesired locations, i.e. in blood vessels around the heart or brain, or in uninjured vessels resulting in heart attacks or strokes. Fibrin fibers, the skeleton of a blood clot, essentially perform the mechanical task of creating a blockage that stems blood flow. Thus, a better understanding of the mechanical properties of these fibers, such as the tensile strength and Young's modulus, will enhance our understanding of blood clots. For quantitative stress and strain measurements, we need to image the deformation of the fiber and measure the applied force simultaneously. For this reason, we are combining fluorescent microscopy with atomic force microscopy. Fibrin fibers were fluorescently labeled with streptavidin-coated quantum dots and deposited on a functionalized glass substrate, imaged and manipulated under buffer. We will describe our progress in obtaining quantitative lateral force measurements under buffer simultaneous with strain measurements from optical microscope images.
Kinetics of ligation of fibrin oligomers.
Nelb, G W; Kamykowski, G W; Ferry, J D
Human fibrinogen was treated with thrombin in the presence of fibrinoligase and calcium ion at pH 8.5, ionic strength 0.45, and the ensuring polymerization was interrupted at various time intervals (t) both before and after the clotting time (tc) by solubilization with a solution of sodium dodecyl sulfate and urea. Aliquots of the solubilized protein were subjected to gel electrophoresis on polyacrylamide gels after disulfide reduction by dithiothreitol and on agarose gels without reduction. The degree of gamma-gamma ligation was determined from the former and the size distribution of ligated oligomers, for degree of polymerization x from 1 to 10, from the latter. The degree of gamma-gamma ligation was calculated independently from the size distribution with the assumption that every junction between two fibrin monomers remaining intact after solubilization is ligated, and this agreed well with the direct determination. The size distribution at t/tc = 1.3 to 1.6 differed somewhat from that calculated by the classical theory of linear polycondensation on the assumption that all reactive sites react with equal probability and rate. Analysis of the difference suggests that ligation of a fibrin digomer is not a random process; the probability of ligation of a given junction between two monomers increases with the oligomer length. The number-average degree of polymerization, xn, of ligated oligomers increases approximately linearly with time up to a value of 1.6. PMID:7391026
Fibrin-mediated lentivirus gene transfer: implications for lentivirus microarrays
Raut, Shruti; Lei, Pedro; Padmashali, Roshan; Andreadis, Stelios T.
We employed fibrin hydrogel as bioactive matrix for lentivirus mediated gene transfer. Fibrin-mediated gene transfer was highly efficient and exhibited strong dependence on fibrinogen concentration. Efficient gene transfer was achieved with fibrinogen concentration between 3.75 – 7.5 mg/mL. Lower fibrinogen concentrations resulted in diffusion of virus out of the gel while higher concentrations led to ineffective fibrin degradation by target cells. Addition of fibrinolytic inhibitors decreased gene transfer in a dose-dependent manner suggesting that fibrin degradation by target cells may be necessary for successful gene delivery. Under these conditions transduction may be limited only to cells interacting with the matrix thereby providing a method for spatially localized gene delivery. Indeed, when lentivirus-containing fibrin microgels were spotted in an array format gene transfer was confined to virus-containing fibrin spots with minimal cross-contamination between neighboring sites. Collectively, our data suggest that fibrin may provide an effective matrix for spatially-localized gene delivery with potential applications in high-throughput lentiviral microarrays and in regenerative medicine. PMID:20153386
Revascularization Induced Maturogenesis of Non-Vital Immature Permanent Tooth Using Platelet-Rich-Fibrin: A Case Report.
Nagaveni, N B; Pathak, Sidhant; Poornima, P; Joshi, Jooie S
The aim of this report is to describe a novel method of revascularization therapy done in a non-vital, immature permanent tooth using Platelet-rich fibrin (PRF),in a recently developed scaffold material to overcome limitations associated with the traditional method of revascularization using natural blood clot. PRF prepared from autologous blood was placed in the root canal and patient was followed up regularly at one, three, six, nine and 12 months for detailed clinical and radiographic evaluation. At 12 months, radiographic examination revealed root elongation, root end closure, continued thickening of the root dentinal walls, obliteration of root canal space, and normal periradicular anatomy. However, more long term prospective trials and histological studies are highly needed before to testify PRF a panacea for the regenerative endodontic therapy in children. PMID:26696103
Interactions between ultrasound stimulated microbubbles and fibrin clots
NASA Astrophysics Data System (ADS)
Acconcia, Christopher; Leung, Ben Y. C.; Hynynen, Kullervo; Goertz, David E.
While it is well established that ultrasound stimulated microbubbles (USMBs) can potentiate blood clot lysis, the mechanisms are not well understood. Here we examine the interaction between USMBs and fibrin clots, which are comprised of fibrin networks that maintain the mechanical integrity of blood clots. High speed camera observations demonstrated that USMBs can penetrate fibrin clots. Two-photon microscopy revealed that penetrating bubbles can leave behind patent "tunnels" along their paths and that fluid can be transported into the clots. Finally, it is observed that primary radiation forces associated with USMBs can induce local deformation and macroscopic translation of clot boundaries.
Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment
Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro
The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma. PMID:27009516
Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P
New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in
[Autologous Fat Grafting in Scar Revision].
Yu, Pan-xi; Cai, Jing-long
Regenerative medicine is an emerging discipline. Adipose tissue is a rich source of fat cells and mesenchymal stem cells, and autologous fat grafting has increasingly been applied in plastic surgeries and dermatological treatments. This paper reviews the latest advances in autologous fat grafting in scar revision. PMID:27181904
Fibrin sealant use in pilonidal sinus: Systematic review
Kayaalp, Cuneyt; Ertugrul, Ismail; Tolan, Kerem; Sumer, Fatih
AIM: To review the current data about the success rates of fibrin sealant use in pilonidal disease. METHODS: Fibrin sealant can be used for different purposes in pilonidal sinus treatment, such as filling in the sinus tracts, covering the open wound after excision and lay-open treatment, or obliterating the subcutaneous dead space before skin closure. We searched Pubmed, Google-Scholar, Ebsco-Host, clinicaltrials, and Cochrane databases and found nine studies eligible for analysis; these studies included a total of 217 patients (84% male, mean age 24.2 ± 7.8). RESULTS: In cases where fibrin sealant was used to obliterate the subcutaneous dead space, there was no reduction in wound complication rates (9.8% vs 14.6%, P = 0.48). In cases where sealant was used to cover the laid-open area, the wound healing time and patient comfort were reported better than in previous studies (mean 17 d, 88% satisfaction). When fibrin sealant was used to fill the sinus tracts, the recurrence rate was around 20%, despite the highly selected grouping of patients. CONCLUSION: Consequently, using fibrin sealant to decrease the risk of seroma formation was determined to be an ineffective course of action. It was not advisable to fill the sinus tracts with fibrin sealant because it was not superior to other cost-effective and minimally invasive treatments. New comparative studies can be conducted to confirm the results of sealant use in covering the laid-open area. PMID:27022454
Alterations in Fibrin Structure in Patients with Liver Diseases.
Lisman, Ton; Ariëns, Robert A S
The hemostatic balance in patients with liver diseases is relatively well preserved due to concomitant alterations in pro- and antihemostatic pathways. Thrombin generation studies support the notion of hemostatic competence in liver diseases, but in such tests alterations in fibrinogen level and function are not taken into account. We have recently studied structural and functional properties of the fibrin clot in patients with liver diseases. Although we have confirmed previous findings that hypersialylation of the fibrinogen molecule in patients with liver diseases contributes to a defective fibrinogen-to-fibrin conversion, we have found that once the clot has been formed, it has a thrombogenic nature as assessed by permeability assays. These thrombogenic properties of the fibrin clot in cirrhosis relate to incompletely characterized intrinsic changes in the fibrinogen molecule, which may include oxidation and hypersialylation. In addition, in patients with nonalcoholic fatty liver disease thrombogenic properties of the fibrin clot are not only due to liver disease but also to obesity and the metabolic syndrome. During liver transplantation, the clot normalizes and becomes increasingly permeable, and the functional properties of the fibrin clot are markedly normalized by fibrinogen concentrate, when added to plasma samples in vitro. These new insights in the functional properties of the fibrin clot in patients with liver diseases facilitate a more rational approach to treatment and prevention of both bleeding and thrombotic complications. PMID:27071046
Multivalent Viral Capsids with Internal Cargo for Fibrin Imaging
Obermeyer, Allie C.; Capehart, Stacy L.; Jarman, John B.; Francis, Matthew B.
Thrombosis is the cause of many cardiovascular syndromes and is a significant contributor to life-threatening diseases, such as myocardial infarction and stroke. Thrombus targeted imaging agents have the capability to provide molecular information about pathological clots, potentially improving detection, risk stratification, and therapy of thrombosis-related diseases. Nanocarriers are a promising platform for the development of molecular imaging agents as they can be modified to have external targeting ligands and internal functional cargo. In this work, we report the synthesis and use of chemically functionalized bacteriophage MS2 capsids as biomolecule-based nanoparticles for fibrin imaging. The capsids were modified using an oxidative coupling reaction, conjugating ∼90 copies of a fibrin targeting peptide to the exterior of each protein shell. The ability of the multivalent, targeted capsids to bind fibrin was first demonstrated by determining the impact on thrombin-mediated clot formation. The modified capsids out-performed the free peptides and were shown to inhibit clot formation at effective concentrations over ten-fold lower than the monomeric peptide alone. The installation of near-infrared fluorophores on the interior surface of the capsids enabled optical detection of binding to fibrin clots. The targeted capsids bound to fibrin, exhibiting higher signal-to-background than control, non-targeted MS2-based nanoagents. The in vitro assessment of the capsids suggests that fibrin-targeted MS2 capsids could be used as delivery agents to thrombi for diagnostic or therapeutic applications. PMID:24960118
Platelet-derived microparticles associate with fibrin during thrombosis.
Siljander, P; Carpen, O; Lassila, R
Platelet-derived microparticles (MP) are reported to express both pro- and anticoagulant activities. Nevertheless, their functional significance has remained unresolved. The present study monitored the generation and fate of MP in an experimental model of thrombosis with costimulation of platelets by collagen and thrombin. When minimally anticoagulated (0.5 micromol/L PPACK) blood was perfused over immobilized fibrillar type I collagen in a flow chamber at a low shear rate (300 s(-1)), endogenous thrombin was generated, as evidenced by thrombin-antithrombin III complex. In contrast to full anticoagulation 150 micromol/L PPACK) and the absence of collagen, large platelet aggregates and fibrin ensued during perfusions over collagen in the presence of thrombin. In these thrombi, MP, defined as GPIIbIIIa- and P-selectin-positive vesicles (<1 micron), were found to align fibrin in immunofluorescence and scanning immunoelectron microscopy. Moreover, in sections of embolectomized thromboemboli from patients GPIIbIIIa- and P-selectin-positive material compatible with MP was detected in a fibrin strand-like pattern. In vitro binding studies showed that MP bound to fibrin and acted there as procoagulants. In summary, we show that MP generated during thrombus formation associate with local fibrin. This adhesive function fibrin could imply a sustained modulatory role for MP in evolving thrombi. PMID:8639834
Microporous Nanofibrous Fibrin-based Scaffolds for Bone Tissue Engineering
Osathanon, Thanaphum; Linnes, Michael L.; Rajachar, Rupak M.; Ratner, Buddy D.; Somerman, Martha J.; Giachelli, Cecilia M.
The fibrotic response of the body to synthetic polymers limits their success in tissue engineering and other applications. Though porous polymers have demonstrated improved healing, difficulty in controlling their pore sizes and pore interconnections has clouded the understanding of this phenomenon. In this study, a novel method to fabricate natural polymer/calcium phosphate composite scaffolds with tightly controllable pore size, pore interconnection, and calcium phosphate deposition was developed. Microporous, nanofibrous fibrin scaffolds were fabricated using sphere-templating methods. Composite scaffolds were created by solution deposition of calcium phosphate on fibrin surfaces or by direct incorporation of nanocrystalline hydroxyapatite (nHA). The SEM results showed that fibrin scaffolds exhibited a highly porous and interconnected structure. Osteoblast-like cells, obtained from murine calvaria, attached, spread and showed a polygonal morphology on the surface of the biomaterial. Multiple cell layers and fibrillar matrix deposition were observed. Moreover, cells seeded on mineralized fibrin scaffolds exhibited significantly higher alkaline phosphatase activity as well as osteoblast marker gene expression compared to fibrin scaffolds and nHA incorporated fibrin scaffolds (0.25 g and 0.5 g). All types of scaffolds were degraded both in vitro and in vivo. Furthermore, these scaffolds promoted bone formation in a mouse calvarial defect model and the bone formation was enhanced by addition of rhBMP-2. PMID:18640716
Fibrin Sealants in Dura Sealing: A Systematic Literature Review
Background Fibrin sealants are widely used in neurosurgery to seal the suture line, provide watertight closure, and prevent cerebrospinal fluid leaks. The aim of this systematic review is to summarize the current efficacy and safety literature of fibrin sealants in dura sealing and the prevention/treatment of cerebrospinal fluid leaks. Methods A comprehensive electronic literature search was run in the following databases: Cochrane Database of Systematic Reviews, Cochrane Central Resister of Controlled Trials, clinicaltrials.gov, MEDLINE/PubMed, and EMBASE. Titles and abstracts of potential articles of interest were reviewed independently by 3 of the authors. Results A total of 1006 database records and additional records were identified. After screening for duplicates and relevance, a total of 78 articles were assessed by the investigators for eligibility. Thirty-eight were excluded and the full-text of 40 articles were included in the qualitative synthesis. Seven of these included only safety data and were included in the safety assessment. The remaining 33 articles included findings from 32 studies that enrolled a total of 2935 patients who were exposed to fibrin sealant. Among these 33 studies there were only 3 randomized controlled trials, with the remaining being prospective cohort analysis, case controlled studies, prospective or retrospective case series. One randomized controlled trial, with 89 patients exposed to fibrin sealant, found a greater rate of intraoperative watertight dura closure in the fibrin sealant group than the control group (92.1% versus 38.0%, p<0.001); however, post-operative cerebrospinal fluid leakage occurred in more fibrin sealant than control patients (6.7% versus 2.0%, p>0.05). Other clinical trials evaluated the effect of fibrin sealant in the postoperative prevention of cerebrospinal fluid leaks. These were generally lower level evidence studies (ie, not prospective, randomized, controlled trials) that were not designed or
In the rat, citrullinated autologous fibrinogen is immunogenic but the induced autoimmune response is not arthritogenic
Duplan, V; Foulquier, C; Clavel, C; Al Badine, R; Serre, G; Saoudi, A; Sebbag, M
Conversion of arginyl to citrullyl residues (citrullination) is essential for the formation of the epitopes recognized by rheumatoid arthritis (RA)-associated autoantibodies to citrullinated proteins (ACPA). ACPA are secreted by plasma cells of the rheumatoid synovial tissue where their major target, citrullinated fibrin, is abundant. Although numerous arguments suggest that ACPA play an important role in RA, their pathological relevance remains to be established. In the present study, we assessed the immunogenicity and arthritogenicity of complete Freund's adjuvant-emulsified autologous citrullinated (C-rFBG) or non-citrullinated (NC-rFBG) fibrinogen in Lewis (LEW) and Brown–Norway rats, which exhibit drastic differences in their susceptibility to induced autoimmune diseases. NC-rFBG induced no antibody response. In contrast, a single injection of C-rFBG induced an IgG response directed mainly to citrullinated determinants of rFBG. However, all rat strains remained devoid of clinical and histological signs of arthritis up to 3 months after C-rFBG inoculation. Next, in LEW rats, we tested whether autoimmunity to C-rFBG could aggravate acute ankle arthritis triggered by intra-articular injection of incomplete Freund's adjuvant (IFA). However, such arthritis evolved identically in the presence or absence of anti-C-rFBG autoantibodies. However, IFA-injected joints were devoid of citrullinated fibrin deposits. Therefore, citrullination allows breakdown of immunological tolerance but the autoimmune response developed is not spontaneously arthritogenic. Whether or not it can aggravate arthritis with citrullinated fibrin deposits remains to be evaluated. PMID:16907920
Gravity: The Glue of the Universe. History and Activities.
ERIC Educational Resources Information Center
Gilbert, Harry; Smith, Diana Gilbert
This book presents a story of the history of gravity, the glue of the universe, and is based on two premises: (1) an understanding of mathematics is not required to grasp the concepts and implications of relativity; and (2) relativity has altered forever the perceptions of gravity, space, time, and how the universe works. A narrative text section…
Relevance of matter and glue dynamics for baryon number fluctuations
NASA Astrophysics Data System (ADS)
Fu, Wei-jie; Pawlowski, Jan M.
We investigate the impact of the matter and glue dynamics on baryon number fluctuations and the kurtosis of baryon number distribution. This is done within the framework of QCD-improved low-energy effective models. In particular, we include the momentum scale dependence of the quark-meson scattering and the nontrivial dispersions of both quarks and mesons. On the gluonic side, we take into account the backreaction of the matter sector on the glue dynamics. It is shown that the above fluctuations lead to a more rapid change of the baryon number fluctuations as well as the kurtosis of with the chiral crossover. We also study the signatures of quark confinement in low-energy QCD. It is shown that, contrary to the common picture, the effective thermal distribution in the presence of confining glue backgrounds does not tend towards the colorless baryonic one. Instead, the dominance of colorless hadronic states is obtained in a subtle interplay of quark and glue contributions to the canonical potential.
Mechanisms of vasculogenesis in 3D fibrin matrices mediated by the interaction of adipose-derived stem cells and endothelial cells.
Rohringer, Sabrina; Hofbauer, Pablo; Schneider, Karl H; Husa, Anna-Maria; Feichtinger, Georg; Peterbauer-Scherb, Anja; Redl, Heinz; Holnthoner, Wolfgang
Vascularization of tissue-engineered constructs is essential to provide sufficient nutrient supply and hemostasis after implantation into target sites. Co-cultures of adipose-derived stem cells (ASC) with outgrowth endothelial cells (OEC) in fibrin gels were shown to provide an effective possibility to induce vasculogenesis in vitro. However, the mechanisms of the interaction between these two cell types remain unclear so far. The aim of this study was to evaluate differences of direct and indirect stimulation of ASC-induced vasculogenesis, the influence of ASC on network stabilization and molecular mechanisms involved in vascular structure formation. Endothelial cells (EC) were embedded in fibrin gels either containing non-coated or ASC-coated microcarrier beads as well as ASC alone. Moreover, EC-seeded constructs incubated with ASC-conditioned medium were used in addition to constructs with ASC seeded on top. Vascular network formation was visualized by green fluorescent protein expressing cells or immunostaining for CD31 and quantified. RT-qPCR of cells derived from co-cultures in fibrin was performed to evaluate changes in the expression of EC marker genes during the first week of culture. Moreover, angiogenesis-related protein levels were measured by performing angiogenesis proteome profiler arrays. The results demonstrate that proximity of endothelial cells and ASC is required for network formation and ASC stabilize EC networks by developing pericyte characteristics. We further showed that ASC induce controlled vessel growth by secreting pro-angiogenic and regulatory proteins. This study reveals angiogenic protein profiles involved in EC/ASC interactions in fibrin matrices and confirms the usability of OEC/ASC co-cultures for autologous vascular tissue engineering. PMID:25086616
Tissue-Engineered Fibrin-Based Heart Valve with a Tubular Leaflet Design
Weber, Miriam; Heta, Eriona; Moreira, Ricardo; Gesche, Valentine N.; Schermer, Thomas; Frese, Julia
The general approach in heart valve tissue engineering is to mimic the shape of the native valve in the attempt to recreate the natural haemodynamics. In this article, we report the fabrication of the first tissue-engineered heart valve (TEHV) based on a tubular leaflet design, where the function of the leaflets of semilunar heart valves is performed by a simple tubular construct sutured along a circumferential line at the root and at three single points at the sinotubular junction. The tubular design is a recent development in pericardial (nonviable) bioprostheses, which has attracted interest because of the simplicity of the construction and the reliability of the implantation technique. Here we push the potential of the concept further from the fabrication and material point of view to realize the tube-in-tube valve: an autologous, living HV with remodelling and growing capability, physiological haemocompatibility, simple to construct and fast to implant. We developed two different fabrication/conditioning procedures and produced fibrin-based constructs embedding cells from the ovine umbilical cord artery according to the two different approaches. Tissue formation was confirmed by histology and immunohistology. The design of the tube-in-tube foresees the possibility of using a textile coscaffold (here demonstrated with a warp-knitted mesh) to achieve enhanced mechanical properties in vision of implantation in the aortic position. The tube-in-tube represents an attractive alternative to the conventional design of TEHVs aiming at reproducing the valvular geometry. PMID:23829551
One-step apexification using platelet rich fibrin matrix and mineral trioxide aggregate apical barrier.
Kumar, Anisha; Yadav, Amit; Shetty, Neeta
The absence of a natural apical constriction in a nonvital young permanent tooth makes endodontic treatment a challenge. There is a need to induce or create an apical barrier against, which the obturating material can be condensed. Traditionally, calcium hydroxide is the material of choice to induce apexification. Due to certain drawbacks such as prolonged treatment duration and unpredictable apical barrier formation, it is being replaced by materials, which have a more predictable outcome like mineral trioxide aggregate (MTA). One-step apexification with MTA reduces the treatment time when compared with traditional calcium hydroxide apexification, which requires an average time of 12-19 months. In one-step apexification using MTA, the technical problem encountered is controlling the overfill or underfill of MTA. The use of a matrix material helps to overcome this shortcoming. Platelet rich fibrin (PRF) is an immune platelet concentrate, which can be used as a matrix, it also promotes wound healing and repair. This case report presents a case of one step apexification using MTA as an apical barrier and autologous PRF as an internal matrix. PMID:25728119
A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo
Motley, Michael P.; Madsen, Daniel H.; Jürgensen, Henrik J.; Spencer, David E.; Szabo, Roman; Holmbeck, Kenn; Flick, Matthew J.; Lawrence, Daniel A.; Castellino, Francis J.; Weigert, Roberto
Extravascular fibrin deposition accompanies many human diseases and causes chronic inflammation and organ damage, unless removed in a timely manner. Here, we used intravital microscopy to investigate how fibrin is removed from extravascular space. Fibrin placed into the dermis of mice underwent cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin(ogen) receptors, αMβ2 and ICAM-1, the myeloid cell integrin-binding site on fibrin or the endocytic collagen receptor, the mannose receptor. The study identifies a novel fibrin endocytic pathway engaged in extravascular fibrin clearance and shows that interstitial fibrin and collagen are cleared by different subsets of macrophages employing distinct molecular pathways. PMID:26647393
A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo.
Motley, Michael P; Madsen, Daniel H; Jürgensen, Henrik J; Spencer, David E; Szabo, Roman; Holmbeck, Kenn; Flick, Matthew J; Lawrence, Daniel A; Castellino, Francis J; Weigert, Roberto; Bugge, Thomas H
Extravascular fibrin deposition accompanies many human diseases and causes chronic inflammation and organ damage, unless removed in a timely manner. Here, we used intravital microscopy to investigate how fibrin is removed from extravascular space. Fibrin placed into the dermis of mice underwent cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin(ogen) receptors, αMβ2 and ICAM-1, the myeloid cell integrin-binding site on fibrin or the endocytic collagen receptor, the mannose receptor. The study identifies a novel fibrin endocytic pathway engaged in extravascular fibrin clearance and shows that interstitial fibrin and collagen are cleared by different subsets of macrophages employing distinct molecular pathways. PMID:26647393
Foam-like compression behavior of fibrin networks.
Kim, Oleg V; Liang, Xiaojun; Litvinov, Rustem I; Weisel, John W; Alber, Mark S; Purohit, Prashant K
The rheological properties of fibrin networks have been of long-standing interest. As such there is a wealth of studies of their shear and tensile responses, but their compressive behavior remains unexplored. Here, by characterization of the network structure with synchronous measurement of the fibrin storage and loss moduli at increasing degrees of compression, we show that the compressive behavior of fibrin networks is similar to that of cellular solids. A nonlinear stress-strain response of fibrin consists of three regimes: (1) an initial linear regime, in which most fibers are straight, (2) a plateau regime, in which more and more fibers buckle and collapse, and (3) a markedly nonlinear regime, in which network densification occurs by bending of buckled fibers and inter-fiber contacts. Importantly, the spatially non-uniform network deformation included formation of a moving "compression front" along the axis of strain, which segregated the fibrin network into compartments with different fiber densities and structure. The Young's modulus of the linear phase depends quadratically on the fibrin volume fraction while that in the densified phase depends cubically on it. The viscoelastic plateau regime corresponds to a mixture of these two phases in which the fractions of the two phases change during compression. We model this regime using a continuum theory of phase transitions and analytically predict the storage and loss moduli which are in good agreement with the experimental data. Our work shows that fibrin networks are a member of a broad class of natural cellular materials which includes cancellous bone, wood and cork. PMID:25982442
Nano-thrombelastography of fibrin during blood plasma clotting.
Feller, Tímea; Kellermayer, Miklós S Z; Kiss, Balázs
Hemostasis is a complex process that relies on the sensitive balance between the formation and breakdown of the thrombus, a three-dimensional polymer network of the fibrous protein fibrin. Neither the details of the fibrinogen-fibrin transition, nor the exact mechanisms of fibrin degradation are fully understood at the molecular level. In the present work we investigated the nanoscale-changes in the viscoelasticity of the 3D-fibrin network during fibrinogenesis and streptokinase (STK)-induced fibrinolysis by using a novel application of force spectroscopy, named nano-thrombelastography. In this method the changes in the bending of an oscillating atomic-force-microscope (AFM) cantilever in human blood-plasma droplet were followed as a function of time. Whereas the global features of the time-dependent change in cantilever deflection corresponded well to a macroscopic thrombelastogram, the underlying force spectra revealed large, sample-dependent oscillations in the range of 3-50nN and allowed the separation of elastic and viscous components of fibrin behavior. Upon STK treatment the nano-thrombelastogram signal decayed gradually. The decay was driven by a decrease in thrombus elasticity, whereas thrombus viscosity decayed with a time delay. In scanning AFM images mature fibrin appeared as 17-nm-high and 12-196-nm-wide filaments. STK-treatment resulted in the decrease of filament height and the appearance of a surface roughness with 23.7nm discrete steps that corresponds well to the length of a fibrinogen monomer. Thus, the initial decay of thrombus elasticity during fibrinolysis may be caused by the axial rupture of fibrin fibers. PMID:24736106
Sepsis after autologous fat grafting.
Talbot, Simon G; Parrett, Brian M; Yaremchuk, Michael J
Autologous fat grafting is an increasingly popular technique, with numerous examples of excellent results. Adherence to key principles, including sterile technique and low-volume injection throughout layers of tissue, appears to be critical to obtaining good results. Reports of adverse outcomes are infrequent, but several case reports document both infectious and aesthetic complications. This case report represents an extreme complication, including abscess formation, life-threatening sepsis, and residual deformity. It serves as yet another reminder that early adoption of surgical procedures by those without a sound understanding of the underlying principles and techniques can have disastrous consequences. Furthermore, physicians operating on any patient must understand the potential for complications and be able to manage these appropriately when they occur. PMID:20885205
Fibrin(ogen)olytic activity of bumblebee venom serine protease
Qiu Yuling; Choo, Young Moo; Yoon, Hyung Joo; Jia Jingming; Cui Zheng; Wang Dong; Kim, Doh Hoon; Sohn, Hung Dae; Jin, Byung Rae
Bee venom is a rich source of pharmacologically active components; it has been used as an immunotherapy to treat bee venom hypersensitivity, and venom therapy has been applied as an alternative medicine. Here, we present evidence that the serine protease found in bumblebee venom exhibits fibrin(ogen)olytic activity. Compared to honeybee venom, bumblebee venom contains a higher content of serine protease, which is one of its major components. Venom serine proteases from bumblebees did not cross-react with antibodies against the honeybee venom serine protease. We provide functional evidence indicating that bumblebee (Bombus terrestris) venom serine protease (Bt-VSP) acts as a fibrin(ogen)olytic enzyme. Bt-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products. However, Bt-VSP is not a plasminogen activator, and its fibrinolytic activity is less than that of plasmin. Taken together, our results define roles for Bt-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings offer significant insight into the allergic reaction sequence that is initiated by bee venom serine protease and its potential usefulness as a clinical agent in the field of hemostasis and thrombosis. - Graphical abstract: Display Omitted Highlights: > Bumblebee venom serine protease (Bt-VSP) is a fibrin(ogen)olytic enzyme. > Bt-VSP activates prothrombin. > Bt-VSP directly degrades fibrinogen into fibrin degradation products. > Bt-VSP is a hemostatically active protein that is a potent clinical agent.
Phase-separated chitosan–fibrin microbeads for cell delivery
Chen, Zhewei; Wang, Limin; Stegemann, Jan P.
Matrix-enhanced delivery of cells is a promising approach to improving current cell therapies. Our objective was to create cell-laden composite microbeads that combine the attractive features of the natural polymers chitosan and fibrin. Liquid polydimethylsiloxane was used to emulsify a chitosan–fibrinogen solution containing suspended human fibroblast cells, followed by initiation of thrombin-mediated polymerization of fibrin and thermal/pH-mediated gelation of chitosan. Chitosan/fibrin weight percent (wt%) ratios of 100/0, 75/25, 50/50 and 25/75 were investigated. Microbead diameters ranged from 275 ± 99 μm to 38 ± 10 μm using impeller speeds from 600 to 1400 rpm. Fibroblasts remained viable on day 1 post-fabrication in all matrices, but cell viability was markedly higher in high-fibrin microbeads by day 8 post-fabrication. Cell spreading and interaction with the extracellular matrix was also markedly increased in high-fibrin matrices. Such composite microbeads containing viable entrapped cells have potential for minimally invasive delivery of cells for a variety of tissue repair applications. PMID:21736519
Fibrin network pattern changes of platelet-rich fibrin in young versus old age group of individuals: A cell block cytology study
Yajamanya, Shravanthi Raghav; Chatterjee, Anirban; Babu, Chaitanya Nischay; Karunanithi, Deepika
Background: To evaluate variations in fibrin network patterns of the platelet-rich fibrin (PRF) in different age groups. Materials and Methods: Ninety-five patients were divided into three age groups: Group 1: (20–39 years); Group 2: (40–59 years); and Group 3: (60 years and above). PRF was prepared from blood samples of all patients and were subjected to cell block cytology method of histological analysis and slides were prepared to histologically assess the age-related changes in (i) fibrin network patterns in terms of density and (ii) entrapment of platelets and white blood cells (WBCs) within fibrin meshwork. Results: Two types of fibrin network pattern arrangements noticed: Dense and loose types in three age groups. However, there was a noticeable decrease in the dense type of fibrin network with progressing age and increase in the loose type of fibrin arrangement. Furthermore, variation in a number of platelets and WBCs entrapped within fibrin network in relation to age was noticed. Conclusion: From the current study it can be concluded that age can be considered as one of the influencing factors on quality of PRF in terms of fibrin network patterns and hence, platelet and WBCs entrapment within these fibrin networks. PMID:27143826
[Nerve anastomoses. Sutures or fibrinogenic glue? Preliminary results].
Boedts, D; Bouckaert, J I
A comparative animal experiment was set up between two nerve anastomosis techniques, one by sealing nerve ends with a fibrinogen-thrombine glue and the other by classical perineural suturing. It was concluded that glueing nerve ends, from the surgical-technical point of view is a better method than suturing. It is an easy, time-sparing method which allows excellent coaptation of the severed nerves with minimal iatrogenic trauma. On the long run however some questions remain. There is the problem of induced fibrosis by using high doses of aprotinine and factor XIII at the site of the nerve junctions and on the other hand the influence of fibrinolysis in traumatized tissues, with early decrease of tensile strength at the junctions before nerve healing. So glued nerve ends should be completely free of tension, protected against secondary shearing forces, and also immobilization of the region is required. PMID:6385609
The Forward Calorimeter of the GlueX Experiment
NASA Astrophysics Data System (ADS)
Bennett, Daniel; GlueX Collaboration
The Forward Calorimeter (FCAL) of the GlueX experiment is a lead glass electromagnetic calorimeter currently being built in Hall D of Jefferson Lab. The GlueX experiment is a photoproduction experiment that will utilize coherent bremsstrahlung radiation to map out the light meson spectrum, including a search for hybrid mesons with exotic quantum numbers (JPC). The FCAL will detect photons between 1° and 10 .8° downstream from the target. The calorimeter is built out of 2800 elements, each of which consists of a lead glass block, an FEU 84-3 PMT, and a custom Cockcroft-Walton electronic base. In the Fall of 2011, a 25 element prototype detector was installed in Hall B of Jefferson Lab to measure the energy and timing resolution of the calorimeter using electrons between 100 and 250 MeV. The design and construction of FCAL and the results from the prototype test will be discussed.
Glue, steam and Clarivein--Best practice techniques and evidence.
Whiteley, Mark S
In July 2013, the National Institute of Health and Clinical Excellence (NICE) recommended "endothermal" ablation (meaning endovenous thermal ablation) is the first line treatment for truncal venous reflux in varicose veins. The initial endovenous thermoablation devices were radiofrequency ablation and endovenous laser ablation. More recently, Glue (cyanoacrylate), endovenous steam and Clarivein (mechanochemical ablation or MOCA) have entered the market as new endovenous techniques for the treatment of varicose veins. Glue and Clarivein do not require tumescent anaesthesia and do not use heat and therefore termed non-tumescent non-thermal (NTNT). Steam both requires tumescence and is also a thermal technique (TT). This article reviews the current position of these 3 new technologies in the treatment of varicose veins. PMID:26556699
Verification system for postoperative autologous blood retransfusion.
Yoshikawa, Takeki; Kimura, Eizen; Kobayashi, Shinji; Ishihara, Ken
Medical staff members should match blood products with patients using a barcode authentication system for blood transfusion to prevent medical accidents. However, our hospital only verifies the blood products of the Japanese Red Cross Society and the preserved autologous blood, not the autologous blood salvaged during the operation or from the oxygenator. In this study, we developed the barcode medication administration system and mobile device for verification. This system will prevent blood transfusion errors in the ward setting. PMID:23920751
[Adjusting gingival tissues morphology after dental implantation with fibrin use].
Maĭborodin, I V; Kolesnikov, I S; Sheplev, B V; Ragimova, T M; Kovyntsev, A N; Kovyntsev, D N; Shevela, A I
In gingival tissues of 62 patients after dental implantation of traditional type and with the use of thrombocyte rich fibrin preparation (TRFP) microcirculation and leucocytal infiltration were studied. It was disclosed that in all terms after titanium screw dental implant setting lymphostasis and leucocytal infiltration were seen as signs of active inflammatory process in gingival tissues. 3 months later after implants setting with the use of TRFP the lymphatic vessels status was normalized, the degree of leucocytal infiltration was reduced; when implantation was made without use of fibrin technologies in gingival tissues more leucocytes were found and lymphatic bed components were remained dilated. Besides fibrin preparation use in the process of dental implantation promoted quicker and stronger implant fixation, but granulomatous inflammatory process could develop and amount of eosinophils in gingival tissues could also increased. PMID:19365340
Fibrin self-assembly is adapted to oxidation.
Rosenfeld, Mark A; Bychkova, Anna V; Shchegolikhin, Alexander N; Leonova, Vera B; Kostanova, Elizaveta A; Biryukova, Marina I; Sultimova, Natalia B; Konstantinova, Marina L
Fibrinogen is extremely susceptible to attack by reactive oxygen species (ROS). Having been suffered an oxidative modification, the fibrinogen molecules, now with altered spatial structure and function of fibrin network, affect hemostasis differently. However, the potential effects of the oxidative stress on the early stages of the fibrin self-assembly process remain unexplored. To clarify the damaging influence of ROS on the knob 'A': hole 'a' and the D:D interactions, the both are operating on the early stages of the fibrin polymerization, we have used a novel approach based on exploration of FXIIIa-mediated self-assembly of the cross-linked fibrin oligomers dissolved in the moderately concentrated urea solutions. The oligomers were composed of monomeric desA fibrin molecules created by cleaving the fibrinopeptides A off the fibrinogen molecules with a thrombin-like enzyme, reptilase. According to the UV-absorbance and fluorescence measurements data, the employed low ozone/fibrinogen ratios have induced only a slight fibrinogen oxidative modification that was accompanied by modest chemical transformations of the aromatic amino acid residues of the protein. Else, a slight consumption of the accessible tyrosine residues has been observed due to intermolecular dityrosine cross-links formation. The set of experimental data gathered with the aid of electrophoresis, elastic light scattering and analytical centrifugation has clearly witnessed that the oxidation can serve as an effective promoter for the observed enhanced self-assembly of the covalently cross-linked oligomers. At urea concentration of 1.20M, the pristine and oxidized fibrin oligomers were found to comprise a heterogeneous set of the double-stranded protofibrils that are cross-linked only by γ-γ dimers and the fibers consisting on average of four strands that are additionally linked by α polymers. The amounts of the oxidized protofibrils and the fibers accumulated in the system were higher than those
Arthroscopic repair of acetabular chondral delamination with fibrin adhesive.
Tzaveas, Alexandros P; Villar, Richard N
Acetabular chondral delamination is a frequent finding at hip arthroscopy. The cartilage is macroscopically normal but disrupted from the subchondral bone. Excision of chondral flaps is the usual procedure for this type of lesion. However, we report 19 consecutive patients in whom the delaminated chondral flap was re-attached to the underlying subchondral bone with fibrin adhesive. We used the modified Harris hip score for assessment of pain and function. Improvement in pain and function was found to be statistically significant six months and one year after surgery. No local or general complications were noted. Three patients underwent further surgery for unrelated reasons. In each, the area of fibrin repair appeared intact and secure. Our results suggest that fibrin is a safe agent to use for acetabular chondral delamination. PMID:20235074
Search for Gluonic Excitations in Hadrons with GlueX
Igor Senderovich
The GlueX experiment will employ a linearly polarized 9 GeV tagged photon beam incident on a liquid hydrogen target to search for exotic states in the light meson spectrum. Optimized for this purpose, the detector has a highly uniform acceptance over nearly 4p solid angle, with high efficiency for both neutral and charged final state particles. An overview of the physics motivation and detector design will be given.
Superselective Embolization in Posttraumatic Priapism with Glubran 2 Acrylic Glue
Gandini, Roberto; Spinelli, Alessio; Konda, Daniel Reale, Carlo Andrea; Fabiano, Sebastiano; Pipitone, Vincenzo; Simonetti, Giovanni
Two patients with posttraumatic priapism underwent transcatheter embolization using microcoils, resulting in temporary penile detumescence and an apparent resolution of the artero-venous fistula. In both cases, priapism recurred 24 hours after the procedure and was successfully treated through selective transcatheter embolization of the nidus using acrylic glue (Glubran 2). The patients showed complete recovery of sexual activity within 30 days from the procedure and persistent exclusion of the artero-venous fistula after a 12-month follow-up.
[Autologous transfusion in obstetrics and fetal safety].
Rech, F; Patella, A; Cecchi, A; Ippolito, M; Indraccolo, S R
It is common knowledge that for modern medicine transfusion therapy represents a precious resource and an often mandatory option. It is equally known that autohemotransfusion (or autologous transfusion) provides further advantages: certainty of blood availability when necessary, absence of transfusion reactions, elimination of the risk of infections that is still associated with the traditional homologous transfusions. In its most widespread application, autotransfusion provides for the donation of one or more units of autologous blood, mostly before elective surgery. Even in obstetrics the practice of autologous blood donation with the aim of autotransfusion is finding increasing employment. However, there are still controversial aspects and the need is pointed out for more authoritative verifications as refers to the alleged innocuity to the fetus of acute maternal blood loss. The present study was performed to contribute personal experience to a better definition of the possible interactions between autologous blood donation during pregnancy and unborn child welfare. To this end, 80 term pregnant women underwent fetal heart rate electronic monitoring before, during and after the donation of one unit of autologous blood. Both during and after the phlebotomy there were no cardiotocographic signs of fetal hypo-oxygenation. Even the non stress tests performed at a distance of 24 hours and those that were periodically repeated afterwards were normal, confirming the safety of autologous predonation during pregnancy. However, the authors think that in obstetrics it is still premature to consider the experimental phase of autotransfusion as definitively exhausted. PMID:7936387
Fibrin activates GPVI in human and mouse platelets.
Alshehri, Osama M; Hughes, Craig E; Montague, Samantha; Watson, Stephanie K; Frampton, Jon; Bender, Markus; Watson, Steve P
The glycoprotein VI (GPVI)-Fc receptor γ (FcRγ) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRγ chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the αIIbβ3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRγ chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability. PMID:26282541
Fibrin activates GPVI in human and mouse platelets
Alshehri, Osama M.; Montague, Samantha; Watson, Stephanie K.; Frampton, Jon; Bender, Markus; Watson, Steve P.
The glycoprotein VI (GPVI)-Fc receptor γ (FcRγ) chain is the major platelet signaling receptor for collagen. Paradoxically, in a FeCl3 injury model, occlusion, but not initiation of thrombus formation, is delayed in GPVI-deficient and GPVI-depleted mice. In this study, we demonstrate that GPVI is a receptor for fibrin and speculate that this contributes to development of an occlusive thrombus. We observed a marked increase in tyrosine phosphorylation, including the FcRγ chain and Syk, in human and mouse platelets induced by thrombin in the presence of fibrinogen and the αIIbβ3 blocker eptifibatide. This was not seen in platelets stimulated by a protease activated receptor (PAR)-4 peptide, which is unable to generate fibrin from fibrinogen. The pattern of tyrosine phosphorylation was similar to that induced by activation of GPVI. Consistent with this, thrombin did not induce tyrosine phosphorylation of Syk and the FcRγ chain in GPVI-deficient mouse platelets. Mouse platelets underwent full spreading on fibrin but not fibrinogen, which was blocked in the presence of a Src kinase inhibitor or in the absence of GPVI. Spreading on fibrin was associated with phosphatidylserine exposure (procoagulant activity), and this too was blocked in GPVI-deficient platelets. The ectodomain of GPVI was shown to bind to immobilized monomeric and polymerized fibrin. A marked increase in embolization was seen following FeCl3 injury in GPVI-deficient mice, likely contributing to the delay in occlusion in this model. These results demonstrate that GPVI is a receptor for fibrin and provide evidence that this interaction contributes to thrombus growth and stability. PMID:26282541
Charged Particle Tracking for the GlueX Detector
NASA Astrophysics Data System (ADS)
Taylor, Simon; GlueX Collaboration
The GlueX experiment is a new experiment under construction at the Thomas Jefferson National Accelerator Facility designed to study gluonic degrees of freedom via the production of ``hybrid'' mesons with exotic quantum numbers. At full luminosity, the trigger rate is expected to be on the order of 150 kHz and the data rate to tape is expected to be on the order of 300 MB/s. In order to reduce the reconstruction time, the current GlueX analysis framework is multi-threaded such that multiple events can be analyzed in parallel on multi-core machines. The tracking code presents the largest bottleneck in the event reconstruction. By taking advantage of Single-Instruction, Multiple-Data (SIMD) instructions in the three-vector and matrix operations needed in the tracking code, the reconstruction can be sped up considerably. The current status of the tracking reconstruction for GlueX will be presented. This work was supported by the US Department of Energy contract DE-AC05-06OR23177, under which Jefferson Science Associates, LLC operates Thomas Jefferson National Accelerator Facility.
Profile of solvent abusers (glue sniffers) in East Malaysia.
Zabedah, M Y; Razak, M; Zakiah, I; Zuraidah, A B
Solvent abuse is deliberate sniffing of an organic solvent for the intention of altering the physiological state of the individual. It is also commonly known as glue sniffing because glue is the most commonly abused substance. This form of substance abuse is widespread throughout the world and usually popular among secondary school children and young adults because of its easy availability and it is cheaper compared with most drugs of abuse. In Malaysia this problem has been recognized especially among the children in East Malaysia. In this study, 37 children and young adults from or around Kota Kinabalu, Sabah were referred to Bukit Padang Psychiatric Hospital by the Anti-drug Task force for suspected solvent abuse. These children were interviewed using questionaire and examined physically. Blood and urine were analysed for toluene and hippuric acid. 27 of the children, age ranging between 8 and 20 years, willingly admitted to sniffing glue for a period between a few months to 2 years. Most of them were children of Fillipino illegal immigrants in Kota Kinabalu. Biochemical parameters were found to be normal. Two of them were pale with low hemoglobin and 7 had eosinophilia. Haematuria and proteinuria were found in 21 children (78%). 16 blood samples with toluene levels ranging from 0.3 to 41 microg/ml and 10 urine samples have elevated urinary hippuric acid levels ranging from 1.2 to 7.4 mg/ml. Strong positive correlation was noted between mean blood toluene levels and duration of abuse. PMID:12166590
Structural basis for the nonlinear mechanics of fibrin networks under compression.
Kim, Oleg V; Litvinov, Rustem I; Weisel, John W; Alber, Mark S
Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties. PMID:24840618
Structural basis for the nonlinear mechanics of fibrin networks under compression
Kim, Oleg V.; Litvinov, Rustem I.; Weisel, John W.; Alber, Mark S.
Fibrin is a protein polymer that forms a 3D filamentous network, a major structural component of protective physiological blood clots as well as life threatening pathological thrombi. It plays an important role in wound healing, tissue regeneration and is widely employed in surgery as a sealant and in tissue engineering as a scaffold. The goal of this study was to establish correlations between structural changes and mechanical responses of fibrin networks exposed to compressive loads. Rheological measurements revealed nonlinear changes of fibrin network viscoelastic properties under dynamic compression, resulting in network softening followed by its dramatic hardening. Repeated compression/decompression enhanced fibrin clot stiffening. Combining fibrin network rheology with simultaneous confocal microscopy provided direct evidence of structural modulations underlying nonlinear viscoelasticity of compressed fibrin networks. Fibrin clot softening in response to compression strongly correlated with fiber buckling and bending, while hardening was associated with fibrin network densification. Our results suggest a complex interplay of entropic and enthalpic mechanisms accompanying structural changes and accounting for the nonlinear mechanical response in fibrin networks undergoing compressive deformations. These findings provide new insight into the fibrin clot structural mechanics and can be useful for designing fibrin-based biomaterials with modulated viscoelastic properties. PMID:24840618
Enhanced Neurite Growth from Mammalian Neurons in Three-Dimensional Salmon Fibrin Gels
Ju, Yo-El; Janmey, Paul A.; McCormick, Margaret; Sawyer, Evelyn S.; Flanagan, Lisa A.
Three-dimensional fibrin matrices have been used as cellular substrates in vitro and as bridging materials for central nervous system repair. Cells can be embedded within fibrin gels since the polymerization process is non-toxic, making fibrin an attractive scaffold for transplanted cells. Most studies have utilized fibrin prepared from human or bovine blood proteins. However, fish fibrin may be well suited for neuronal growth since fish undergo remarkable central nervous system regeneration and molecules implicated in this process are present in fibrin. We assessed the growth of mammalian central nervous system neurons in bovine, human, and salmon fibrin and found that salmon fibrin gels encouraged the greatest degree of neurite (dendrite and axon) growth and were the most resistant to degradation by cellular proteases. The neurite growth-promoting effect was not due to the thrombin used to polymerize the gels or to any copurifying plasminogen. Co-purified fibronectin partially accounted for the effect on neurites, and blockade of fibrinogen/fibrin-binding integrins markedly decreased neurite growth. Anion exchange chromatography revealed different elution profiles for salmon and mammalian fibrinogens. These data demonstrate that salmon fibrin encourages the growth of neurites from mammalian neurons and suggest that salmon fibrin may be a beneficial scaffold for neuronal regrowth after CNS injury. PMID:17258313
Comparative evaluation of the biological properties of fibrin for bone regeneration
Oh, Joung-Hwan; Kim, Hye-Jin; Kim, Tae-Il; Woo, Kyung Mi
Fibrin is a natural provisional matrix found in wound healing, while type I collagen is a major organic component of bone matrix. Despite the frequent use of fibrin and type I collagen in bone regenerative approaches, their comparative efficacies have not yet been evaluated. In the present study, we compared the effects of fibrin and collagen on the proliferation and differentiation of osteoblasts and protein adsorption. Compared to collagen, fibrin adsorbed approximately 6.7 times more serum fibronectin. Moreover, fibrin allowed the proliferation of larger MC3T3-E1 pre-osteoblasts, especially at a low cell density. Fibrin promoted osteoblast differentiation at higher levels than collagen, as confirmed by Runx2 expression and transcriptional activity, alkaline phosphatase activity, and calcium deposition. The results of the present study suggest that fibrin is superior to collagen in the support of bone regeneration. [BMB Reports 2014; 47(2): 110-114] PMID:24257120
Potential of nanocrystalline cellulose-fibrin nanocomposites for artificial vascular graft applications.
Brown, Elvie E; Hu, Dehong; Abu Lail, Nehal; Zhang, Xiao
The potential of synthesizing new nanocomposites from nanocrystalline cellulose (NCC) and fibrin for small-diameter replacement vascular graft (SDRVG) application was demonstrated. Periodate oxidation of NCC can augment reactive carbonyl groups on NCC and facilitate its cross-linking with fibrin. NCC-fibrin nanocomposites were synthesized, composed of homogeneously dispersed oxidized NCC (ONCC) in a fibrin matrix, with fibrin providing elasticity and ONCC providing strength. The maximum strength and elongation of the nanocomposites were determined by Atomic Force Microscopy (AFM) and compared with a native blood vessel. The manipulation of degree of oxidation of NCC and the NCC-to-fibrin ratio resulted in the variation of strength and elongation of the nanocomposites, indicating that the nanocomposites can be tailored to conform to the diverse mechanical properties of native blood vessels. A mechanistic understanding of the molecular interactions of ONCC and fibrin was illustrated. This study established fundamental information to utilizing NCC for SDRVG applications. PMID:23421631
Fiber optic immunosensor for cross-linked fibrin concentration
NASA Astrophysics Data System (ADS)
Moskowitz, Samuel E.
Working with calcium ions in the blood, platelets produce thromboplastin which transforms prothrombin into thrombin. Removing peptides, thrombin changes fibrinogen into fibrin. Cross-linked insoluble fibrin polymers are solubilized by enzyme plasmin found in blood plasma. Resulting D-dimers are elevated in patients with intravascular coagulation, deep venous thrombosis, pulmonary embolism, myocardial infarction, multiple trauma, cancer, impaired renal and liver functions, and sepsis. Consisting principally of a NIR 780 nm GaAlAs laser diode and a 800 nm avalanche photodiode (APD), the fiber-optic immunosensor can determined D-dimer concentration to levels <0.1 ng/ml. A capture monoclonal antibody to the antigen soluble cross-linked fibrin is employed. Immobilized at the tip of an optical fiber by avidin-biotin, the captured antigen is detected by a second antibody which is labeled with NN 382 fluorescent dye. An evanescent wave traveling on an excitation optical fiber excites the antibody-antigen fluorophore complex. Concentration of cross-linked fibrin is directly proportional to the APD measured intensity of fluorescence. NIR fluorescence has advantages of low background interference, short fluorescence lifetime, and large difference between excitation and emission peaks. Competitive ELISA test for D-dimer concentration requires trained personnel performing a time consuming operation.
Investigating the interaction between acoustically stimulated microbubbles and fibrin clots
NASA Astrophysics Data System (ADS)
Acconcia, Christopher; Leung, Ben; Hynynen, Kullervo; Goertz, David
While it is well established that ultrasound stimulated microbubbles can potentiate thrombolysis, the mechanisms of action are poorly understood. The objective of this work was to gain a more fundamental understanding of how acoustically stimulated microbubbles interact with and potentially degrade fibrin clots. Owing to their optical transparency, the use of fibrin clots allowed to optically observe microbubbles interacting with the clot boundary and any resultant disruption of the fluorescently tagged fibrin network. It was found that microbubbles could readily penetrate into fibrin clots with velocities up to 0.2 m/s and to depths related to the number of pulses applied. At lower pressures (0.2-0.55 MPa), microbubbles as small as 3μm were observed to penetrate, whereas higher pressures (>0.9 MPa) caused the penetration of larger microbubbles (10-30μm), formed by coalescence prior to entry. In some cases, patent 'tunnels' remained along the path taken by penetrating microbubbles. Tunnel diameters ranged between 9-35μm depending largely on pressure and pulse duration. Two-photon microscopy indicated either patent tunnels or paths of disrupted fibers consistent with collapsed tunnel. Fluid flow within the clot was observed to accompany penetrating microbubbles, which may have implications for lytic enzyme penetration.
Oriented fibrin gels formed by polymerization in strong magnetic fields
NASA Astrophysics Data System (ADS)
Torbet, J.
Fibrinogen is a soluble plasma protein which, after cleavage by the specific proteolytic enzyme thrombin, polymerizes to form the filamentous fibrin network during blood clotting (see refs 1 and 2 for reviews). Fibrinogen has a molecular weight of 340,000 and is composed of two identical halves, each containing three peptide chains designated Aα, Bβ and γ. Fibrin monomers are produced by thrombin which releases the small negatively charged fibrinopeptides A and B. The overall shape of the fibrinogen molecule has not been unequivocally established1,2. The trinodular, elongated (~450 Å long) structure proposed by Hall and Slayter3 is the most widely accepted model and it has obtained additional support from recent work4-6. Fibrin monomers are also about 450 Å long7 and in fibres they probably have a half-staggered arrangement along the axis7,8. The fibres are an assembly of protofibrils whose structure and packing are not reliably known. We report here that highly oriented fibrin gels are formed when polymerization takes place slowly in a strong magnetic field. It is shown that the protofibrils pack into a three-dimensional crystalline lattice. We introduce magnetically induced birefringence as a potential tool for studying polymerization and briefly speculate on the applications of strong magnetic fields.
Cutaneous collagenous vasculopathy associated with intravascular occlusive fibrin thrombi.
Salama, Samih; Chorneyko, Kathy; Belovic, Brian
Cutaneous collagenous vasculopathy (CCV) is a rare cutaneous microangiopathy that clinically resembles generalized essential telangiectasia with only 12 cases reported to date. The perivascular fibrosis is thought to be due to production of abnormal collagen by veil cells in the outer vessel walls as a result of unknown factors. This report is of an 84-year-old male with progressive telangiectasia. Biopsies showed characteristic features of CCV. In addition, there were multiple intravascular fibrin thrombi, some organizing and associated with endothelial cell hyperplasia with recanalization reminiscent of glomeruloid bodies and simulating reactive angioendotheliomatosis (RAE). Histochemically and ultrastructurally fibrin was noted within the vessel walls integrating into the fibrous tissue around the vessels; however, the patient had no evidence of coagulation disorder, cryoglobulinemia or cold agglutinemia. Immunofluorescence showed fibrinogen within the vessel walls but no immunoglobulins or C3. As well, there were minimal inflammatory cells. This suggests pauci-inflammatory injury to the endothelial cells by unknown angiogenic factors causing local intravascular fibrin thrombi with fibrin leaking and incorporating into the vessel walls, eventually leading to reparative perivascular fibrosis. This case suggests that some cases of CCV are related to a primary local intravascular occlusive thrombotic microangiopathy. However, the primary triggering factor causing the endothelial cell damage has yet to be elucidated. PMID:24350781
Fibrin polymerization as a phase transition wave: A mathematical model
NASA Astrophysics Data System (ADS)
Lobanov, A. I.
A mathematical model of fibrin polymerization is described. The problem of the propagation of phase transition wave is reduced to a nonlinear Stefan problem. A one-dimensional discontinuity fitting difference scheme is described, and the results of one-dimensional computations are presented.
Generation of a Fibrin Based Three-Layered Skin Substitute.
Kober, Johanna; Gugerell, Alfred; Schmid, Melanie; Kamolz, Lars-Peter; Keck, Maike
A variety of skin substitutes that restore epidermal and dermal structures are currently available on the market. However, the main focus in research and clinical application lies on dermal and epidermal substitutes whereas the development of a subcutaneous replacement (hypodermis) is often disregarded. In this study we used fibrin sealant as hydrogel scaffold to generate a three-layered skin substitute. For the hypodermal layer adipose-derived stem cells (ASCs) and mature adipocytes were embedded in the fibrin hydrogel and were combined with another fibrin clot with fibroblasts for the construction of the dermal layer. Keratinocytes were added on top of the two-layered construct to form the epidermal layer. The three-layered construct was cultivated for up to 3 weeks. Our results show that ASCs and fibroblasts were viable, proliferated normally, and showed physiological morphology in the skin substitute. ASCs were able to differentiate into mature adipocytes during the course of four weeks and showed morphological resemblance to native adipose tissue. On the surface keratinocytes formed an epithelial-like layer. For the first time we were able to generate a three-layered skin substitute based on a fibrin hydrogel not only serving as a dermal and epidermal substitute but also including the hypodermis. PMID:26236715
Effect of Allogeneic Platelet Lysate and Cyanoacrylate Tissue Glue on the Fibrovascularization of the Porous Polyethylene Implant.
Ozturk, Sinan; Sahin, Cihan; Tas, Arzu Caputcu; Muftuoglu, Tuba; Karagoz, Huseyin
Because of limited autogenous tissue sources, donor site morbidity, and difficulty of shaping the autologous tissue, surgeons often need to use alloplastic frameworks in reconstruction of 3-dimensional tissue defects. Synthetic porous polyethylene (PP) implant is widely used in plastic surgery for 3-dimensional reconstruction of the lost or highly deformed tissues. One of the main factors of PP implant exposure is delayed fibrovascular ingrowth. In the present study, the authors investigated the effect allogeneic plateletlysate (PL) and cyanoacrylate tissue glue (CTG) (2-octyl cyanoacrylate) on the fibrovascularization of the PP implant.Twenty adult female Wistar rats were divided into 4 groups equally, according to the different surgical techniques and implanted materials used. Only PP implant was implanted subcutaneously through a skin incision on the chest wall skin of the rats in the control group; however, CTG was applied with PP implant in the cyanoacrylate group, PL was applied with PP implant in the platelet group, CTG and platelet was applied together with PP implant in the combination group. All of the implants in each group were histologically assessed at postoperative second week. Determination of the collagen density in the tissues, inflammation, and necrosis and vascularization status was assessed semiquantitatively.A denser collagen structure, low inflammation, and necrosis were found in PL groups. There was, however, a significant decrease in vascular density with PL-treated groups. PL treatment may have a potential to reduce complications related to PP implants. PMID:26703066
Postoperative Autologous Reinfusion in Total Knee Replacement
Crescibene, A.; Martire, F.; Gigliotti, P.; Rende, A.; Candela, M.
Surgeries for total knee replacement (TKR) are increasing and in this context there is a need to develop new protocols for management and use of blood transfusion therapy. Autologous blood reduces the need for allogeneic blood transfusion and the aim of the present study was to verify the safety and the clinical efficacy. An observational retrospective study has been conducted on 124 patients, undergoing cemented total knee prosthesis replacement. Observed population was stratified into two groups: the first group received reinfusion of autologous blood collected in the postoperative surgery and the second group did not receive autologous blood reinfusion. Analysis of data shows that patients undergoing autologous blood reinfusion received less homologous blood bags (10.6% versus 30%; p = 0.08) and reduced days of hospitalization (7.88 ± 0.7 days versus 8.96 ± 2.47 days for the control group; p = 0.03). Microbiological tests were negative in all postoperatively salvaged and reinfused units. Our results emphasize the effectiveness of this procedure and have the characteristics of simplicity, low cost (€97.53 versus €103.79; p < 0.01), and easy reproducibility. Use of autologous drainage system postoperatively is a procedure that allows reducing transfusion of homologous blood bags in patients undergoing TKR. PMID:26442168
Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition
Bernik, Maria B.
Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways—affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis. PMID:4266421
First results from the GlueX experiment
NASA Astrophysics Data System (ADS)
Al Ghoul, H.; Anassontzis, E. G.; Barbosa, F.; Barnes, A.; Beattie, T. D.; Bennett, D. W.; Berdnikov, V. V.; Black, T.; Boeglin, W.; Brooks, W. K.; Cannon, B.; Chernyshov, O.; Chudakov, E.; Crede, V.; Dalton, M. M.; Deur, A.; Dobbs, S.; Dolgolenko, A.; Dugger, M.; Egiyan, H.; Eugenio, P.; Foda, A. M.; Frye, J.; Furletov, S.; Gan, L.; Gasparian, A.; Gerasimov, A.; Gevorgyan, N.; Goryachev, V. S.; Guegan, B.; Guo, L.; Hakobyan, H.; Hakobyan, H.; Hardin, J.; Huber, G. M.; Ireland, D.; Ito, M. M.; Jarvis, N. S.; Jones, R. T.; Kakoyan, V.; Kamel, M.; Klein, F. J.; Kourkoumeli, C.; Kuleshov, S.; Lara, M.; Larin, I.; Lawrence, D.; Leckey, J.; Levine, W. I.; Livingston, K.; Lolos, G. J.; Mack, D.; Mattione, P. T.; Matveev, V.; McCaughan, M.; McGinley, W.; McIntyre, J.; Mendez, R.; Meyer, C. A.; Miskimen, R.; Mitchell, R. E.; Mokaya, F.; Moriya, K.; Nigmatkulov, G.; Ochoa, N.; Ostrovidov, A. I.; Papandreou, Z.; Pedroni, R.; Pennington, M.; Pentchev, L.; Ponosov, A.; Pooser, E.; Pratt, B.; Qiang, Y.; Reinhold, J.; Ritchie, B. G.; Robison, L.; Romanov, D.; Salgado, C.; Schumacher, R. A.; Semenov, A. Yu.; Semenova, I. A.; Senderovich, I.; Seth, K. K.; Shepherd, M. R.; Smith, E. S.; Sober, D. I.; Somov, A.; Somov, S.; Soto, O.; Sparks, N.; Staib, M. J.; Stevens, J. R.; Subedi, A.; Tarasov, V.; Taylor, S.; Tolstukhin, I.; Tomaradze, A.; Toro, A.; Tsaris, A.; Vasileiadis, G.; Vega, I.; Voulgaris, G.; Walford, N. K.; Whitlatch, T.; Williams, M.; Wolin, E.; Xiao, T.; Zarling, J.; Zihlmann, B.
The GlueX experiment at Jefferson Lab ran with its first commissioning beam in late 2014 and the spring of 2015. Data were collected on both plastic and liquid hydrogen targets, and much of the detector has been commissioned. All of the detector systems are now performing at or near design specifications and events are being fully reconstructed, including exclusive production of π0, η and ω mesons. Linearly-polarized photons were successfully produced through coherent bremsstrahlung and polarization transfer to the ρ has been observed.
Silicon photomultiplier characterization for the GlueX barrel calorimeter
F. Barbosa, J.E. McKisson, J. McKisson, Y. Qiang, E. Smith, C. Zorn
GlueX is a new detector being constructed at Jefferson Laboratory to study gluonic excitations and confinement via the detection of exotic meson states. The hermetic detector includes a barrel calorimeter where the photodetectors must operate in a high magnetic field exceeding 0.5 T. After extensive tests with a variety of sensors, the chosen photodetector will be a custom silicon photomultiplier (SiPM) array manufactured by Hamamatsu Corporation. This paper will focus on the characterization of the first 80 production samples of these SiPMs, including dark rate, photodetection efficiency (PDE), crosstalk, response uniformity and radiation tolerance.
Polyions act as an electrostatic glue for mesoscopic particle aggregates
NASA Astrophysics Data System (ADS)
Bordi, F.; Cametti, C.; Sennato, S.
Although complexation of charged particles induced by polyions of opposite charge is a well-known phenomenon, the possibility of obtaining equilibrium clusters stuck together by flexible polyions, which act as an electrostatic glue, is not completely recognized. In this Letter, we call attention towards the behavior of polyions in attaching together charged particles, by means of controlled electrostatic interactions. As an example, we present some features of equilibrium clusters composed of cationic liposomes built up by DOTAP and glued up by an anionic polyion, polyacrylate sodium salt. We discuss briefly some applications in nanostructure science and biotechnology.
Transcatheter glue arterial embolization of a mass in the hind limb of a dog
de La Villeon, Guillaume; Louvet, Arnaud; Behr, Luc; Borenstein, Nicolas
This article reports the use of transarterial glue embolization in the treatment of a soft-tissue mass in the hind limb of a dog that was referred for a > 15-cm diameter soft tissue mass in the caudal thigh. Clinical improvement showed that the percutaneous therapeutic cyanoacrylate glue embolization procedure was technically feasible and useful. PMID:21629422
Spiritual and Religious Supports Part 8: Church G.L.U.E.
ERIC Educational Resources Information Center
Newman, Barbara J.
CLC Network is an organization that partners with churches, schools, and families to help promote and build inclusive and interdependent communities for those with disabilities. This article describes CLC Network's most recent tool--a book entitled the G.L.U.E. Training Manual. G.L.U.E. is an adhesive process to allow each individual to be firmly…
GLUE!: An Architecture for the Integration of External Tools in Virtual Learning Environments
ERIC Educational Resources Information Center
Alario-Hoyos, Carlos; Bote-Lorenzo, Miguel L.; Gomez-Sanchez, Eduardo; Asensio-Perez, Juan I.; Vega-Gorgojo, Guillermo; Ruiz-Calleja, Adolfo
The integration of external tools in Virtual Learning Environments (VLEs) aims at enriching the learning activities that educational practitioners may design and enact. This paper presents GLUE!, an architecture that enables the lightweight integration of multiple existing external tools in multiple existing VLEs. GLUE! fosters this integration by…
Elastic Behavior and Platelet Retraction in Low- and High-Density Fibrin Gels
Wufsus, Adam R.; Rana, Kuldeepsinh; Brown, Andrea; Dorgan, John R.; Liberatore, Matthew W.; Neeves, Keith B.
Fibrin is a biopolymer that gives thrombi the mechanical strength to withstand the forces imparted on them by blood flow. Importantly, fibrin is highly extensible, but strain hardens at low deformation rates. The density of fibrin in clots, especially arterial clots, is higher than that in gels made at plasma concentrations of fibrinogen (3–10 mg/mL), where most rheology studies have been conducted. Our objective in this study was to measure and characterize the elastic regimes of low (3–10 mg/mL) and high (30–100 mg/mL) density fibrin gels using shear and extensional rheology. Confocal microscopy of the gels shows that fiber density increases with fibrinogen concentration. At low strains, fibrin gels act as thermal networks independent of fibrinogen concentration. Within the low-strain regime, one can predict the mesh size of fibrin gels by the elastic modulus using semiflexible polymer theory. Significantly, this provides a link between gel mechanics and interstitial fluid flow. At moderate strains, we find that low-density fibrin gels act as nonaffine mechanical networks and transition to affine mechanical networks with increasing strains within the moderate regime, whereas high-density fibrin gels only act as affine mechanical networks. At high strains, the backbone of individual fibrin fibers stretches for all fibrin gels. Platelets can retract low-density gels by >80% of their initial volumes, but retraction is attenuated in high-density fibrin gels and with decreasing platelet density. Taken together, these results show that the nature of fibrin deformation is a strong function of fibrin fiber density, which has ramifications for the growth, embolization, and lysis of thrombi. PMID:25564864
Elastic behavior and platelet retraction in low- and high-density fibrin gels.
Wufsus, Adam R; Rana, Kuldeepsinh; Brown, Andrea; Dorgan, John R; Liberatore, Matthew W; Neeves, Keith B
Fibrin is a biopolymer that gives thrombi the mechanical strength to withstand the forces imparted on them by blood flow. Importantly, fibrin is highly extensible, but strain hardens at low deformation rates. The density of fibrin in clots, especially arterial clots, is higher than that in gels made at plasma concentrations of fibrinogen (3-10 mg/mL), where most rheology studies have been conducted. Our objective in this study was to measure and characterize the elastic regimes of low (3-10 mg/mL) and high (30-100 mg/mL) density fibrin gels using shear and extensional rheology. Confocal microscopy of the gels shows that fiber density increases with fibrinogen concentration. At low strains, fibrin gels act as thermal networks independent of fibrinogen concentration. Within the low-strain regime, one can predict the mesh size of fibrin gels by the elastic modulus using semiflexible polymer theory. Significantly, this provides a link between gel mechanics and interstitial fluid flow. At moderate strains, we find that low-density fibrin gels act as nonaffine mechanical networks and transition to affine mechanical networks with increasing strains within the moderate regime, whereas high-density fibrin gels only act as affine mechanical networks. At high strains, the backbone of individual fibrin fibers stretches for all fibrin gels. Platelets can retract low-density gels by >80% of their initial volumes, but retraction is attenuated in high-density fibrin gels and with decreasing platelet density. Taken together, these results show that the nature of fibrin deformation is a strong function of fibrin fiber density, which has ramifications for the growth, embolization, and lysis of thrombi. PMID:25564864
Spray- and laser-assisted biomaterial processing for fast and efficient autologous cell-plus-matrix tissue engineering.
Klopsch, Christian; Gäbel, Ralf; Kaminski, Alexander; Mark, Peter; Wang, Weiwei; Toelk, Anita; Delyagina, Evgenya; Kleiner, Gabriela; Koch, Lothar; Chichkov, Boris; Mela, Petra; Jockenhoevel, Stefan; Ma, Nan; Steinhoff, Gustav
At present, intensive investigation aims at the creation of optimal valvular prostheses. We introduced and tested the applicability and functionality of two advanced cell-plus-matrix seeding technologies, spray-assisted bioprocessing (SaBP) and laser-assisted bioprocessing (LaBP), for autologous tissue engineering (TE) of bioresorbable artificial grafts. For SaBP, human mesenchymal stem cells (HMSCs), umbilical cord vein endothelial cells (HUVECs) and fibrin were simultaneously spray-administered on poly(ε-caprolactone) (PCL) substrates. For LaBP, HUVECs and HMSCs were separately laser-printed in stripes, followed by fibrin sealing. Three-leaflet valves were manufactured following TE of electrospun PCL tissue equivalents. Grafts were monitored in vitro under static and dynamic conditions in bioreactors. SaBP and LaBP resulted in TE of grafts with homogeneous cell distribution and accurate cell pattern, respectively. The engineered valves demonstrated immediate sufficient performance, complete cell coating, proliferation, engraftment, HUVEC-mediated invasion, HMSC differentiation and extracellular matrix deposition. SaBP revealed higher efficiency, with at least 12-fold shorter processing time than the applied LaBP set-up. LaBP realized coating with higher cell density and minimal cell-scaffold distance. Fibrin and PCL stability remain issues for improvement. The introduced TE technologies resulted in complete valvular cell-plus-matrix coating, excellent engraftment and HMSCs differentiation. SaBP might have potential for intraoperative table-side TE considering the procedural duration and ease of implementation. LaBP might accelerate engraftment with precise patterns. PMID:23208947
The mechanics of fibrin networks and their alterations by platelets
NASA Astrophysics Data System (ADS)
Jawerth, Louise Marie
Fibrin is a biopolymer that assembles into a network during blood coagulation to become the structural scaffold of a blood clot. The precise mechanics of this network are crucial for a blood clot to properly stem the flow of blood at the site of vascular injury while still remaining pliable enough to avoid dislocation. A hallmark of fibrin's mechanical response is strain-stiffening: at small strains, its response is low and linear; while at high strains, its stiffness increases non-linearly with increasing strain. The physical origins of strain-stiffening have been studied for other biopolymer systems but have remained elusive for biopolymer networks composed of stiff filaments, such as fibrin. To understand the origins of this intriguing behavior, we directly observe and quantify the motion of all of the fibers in the fibrin networks as they undergo shear in 3D using confocal microscopy. We show that the strain-stiffening response of a clot is a result of the full network deformation rather than an intrinsic strain-stiffening response of the individual fibers. We observe a distinct transition from a linear, low-strain regime, where all fibers avoid any internal stretching, to a non-linear, high-strain regime, where an increasing number of fibers become stretched. This transition is characterized by a high degree of non-affine motion. Moreover, we are able to precisely calculate the non-linear stress-strain response of the network by using the strains on each fiber measured directly with confocal microscopy and by assuming the fibers behave like linearly elastic beams. This result confirms that it is the network deformation that causes the strain-stiffening behavior of fibrin clots. These data are consistent with predictions for low-connectivity networks with soft, bending, or floppy modes. Moreover, we show that the addition of small contractile cells, platelets, increases the low-strain stiffness of the network while the high-strain stiffness is independent of
Beam Test Results of the GlueX Forward Calorimeter
NASA Astrophysics Data System (ADS)
Bauer, Kevin; Moriya, Kei; Shepherd, Matthew
GlueX is an experiment to begin running in the near future at Jefferson Lab. Our research group is responsible for the forward calorimeter (FCAL) that is designed to measure the energy of photons produced from the decays of mesons. Recently, we conducted a beam test at Jefferson Lab using a prototype of the FCAL. Its goal was to experimentally verify the energy resolution of the FCAL as a function of beam energy. The prototype was tested with recoil electrons ranging in energy from 113MeV to 277MeV. We obtained the resolution by comparing the reconstructed energy to the known energy. In addition, we corrected our measured resolution for multiple scattering and energy loss based on a GEANT4 simulation of the prototype. Another important goal of the beam test was to measure the timing resolution of the channels on our flash analog to digital converters (fADCs). For GlueX, we need to require the timing resolution to be much less than the bunch spacing (2ns). The results of our studies indicate that the energy resolution of the FCAL is consistent with our predictions. We also found the timing resolution as a function of signal size and the results agreed with a similar study. For signals of about at least 75mV, the timing resolution achieved was significantly lower than 2ns.
Sweet Syndrome After Autologous Stem Cell Transplant.
Alkan, Ali; İdemen, Celal; Okçu Heper, Aylin; Utkan, Güngör
Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare clinical entity characterized by skin lesions, neutrophilia, fever, and neutrophilic infiltration of the dermis. It may be a consequence of malignant disease, comorbidities, or drugs. We present a case of acute febrile neutrophilic dermatosis in a patient after autologous stem cell transplant. PMID:25748978
Cord Blood Banking Standards: Autologous Versus Altruistic
Armitage, Sue
Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485
Cord Blood Banking Standards: Autologous Versus Altruistic.
Armitage, Sue
Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485
Potential of nanocrystalline cellulose-fibrin nanocomposites for artificial vascular graft applications
Brown, Elvie; Hu, Dehong; Abu-Lail, Nehal; Zhang, Xiao
Nanocrystalline cellulose, a new bio-nanomaterial is utilized as a reinforcing material for biocompatible fibrin matrix to form into a nanocomposite for small-diameter replacement vascular graft application (SDRVG). The periodate oxidation of NCC, which provided it with a reactive carbonyl group, allowed molecular interaction between NCC and fibrin. Such interaction resulted into an effective mechanical reinforcement indicated by the improvement of max. force, elongation at break and modulus when oxidized NCC (ONCC) was incorporated into fibrin. The nanocomposite's mechanical properties can be manipulated to conform to the native blood vessel by varying the ONCC to fibrin ratio and/or by controlling the degree of oxidation of NCC. Using atomic force microscopy had provided fundamental information on the effects of molecular interactions to the nanolevel mechanical properties of NCC/fibrin nanocomposites. This fundamental information established the positive feasibility and commenced continuing investigation for the practical SDRVG application of NCC/fibrin nanocomposite.
Interaction of Fibrin with the VLDL Receptor: Further Characterization and Localization of the Fibrin-Binding Site
Yakovlev, Sergiy; Medved, Leonid
Our recent study revealed that fibrin interacts with the VLDL receptor (VLDLR) on endothelial cells through its βN-domains and this interaction promotes transendothelial migration of leukocytes and thereby inflammation. The major aims of the present study were to further characterize this interaction and localize fibrin-binding site in the VLDL receptor. To localize the fibrin-binding site, we expressed a soluble extracellular portion of this receptor, sVLDLRHT, its N- and C-terminal regions, VLDLR(1–8)HT and des(1–8)VLDLRHT, respectively, and a number of VLDLR fragments containing various combinations of CR-domains, and confirmed their proper folding by fluorescence spectroscopy. Interaction of these fragments with the (β15–66)2 fragment corresponding to a pair of VLDLR-binding βN-domains of fibrin was tested by different methods. Our experiments performed by ELISA and surface plasmon resonance revealed that the VLDLR(1–8)HT fragment containing eight CR-domain of VLDLR and its sub-fragments, VLDLR(1–4)HT and VLDLR(2–4)HT, interact with (β15–66)2 with practically the same affinity as sVLDLRHT while the affinity of VLDLR(2–3)HT was about 2-fold lower. In contrast, des(1–8)VLDLRHT exhibited no binding. Complex formation in solution between the fibrin-binding fragments of VLDLR and (β15–66)2 was detected by fluorescence spectroscopy. In addition, formation of a complex between VLDLR(2–4)HT and (β15–66)2 in solution was confirmed by size-exclusion chromatography. Thus, the results obtained indicate that minimal fibrin-binding structures are located within the second and third CR-domains of the VLDL receptor and the presence of the fourth CR-domain is required for the high affinity binding. They also indicate that tryptophan residues of CR-domains are involved in this binding. PMID:26153297
Obstructive fibrinous tracheal pseudomembrane: a rare condition in postextubation stridor.
Nakwan, Narongwit
Obstructive fibrinous tracheal pseudomembrane (OFTP) is an airway complication that occurs after endotracheal intubation. It originates from superficial mucosal abrasion and desquamation of necrotic tracheal epithelium at the site of cuff pressure. This condition is a rare cause of postextubation stridor. We present a case of postextubation stridor secondary to OFTP, resulting in clinical features of upper airway obstruction > 8 h after extubation. The case features complete obstruction at the tip of the endotracheal tube from OFTP. PMID:24170917
Altered plasma fibrin clot properties in essential thrombocythemia.
Małecki, Rafał; Gacka, Małgorzata; Kuliszkiewicz-Janus, Małgorzata; Jakobsche-Policht, Urszula; Kwiatkowski, Jacek; Adamiec, Rajmund; Undas, Anetta
Patients with increased thromboembolic risk tend to form denser fibrin clots which are relatively resistant to lysis. We sought to investigate whether essential thrombocythemia (ET) is associated with altered fibrin clot properties in plasma. Ex vivo plasma fibrin clot permeability coefficient (Ks), turbidimetry and clot lysis time (CLT) were measured in 43 consecutive patients with ET (platelet count from 245 to 991 × 10(3)/µL) and 50 control subjects matched for age, sex and comorbidities. Fibrinolysis proteins and inhibitors together with platelet activation markers were determined. Reduced Ks (-38%, p < 0.0001) and prolonged CLT (+34%, p < 0.0001) were observed in ET. The differences remained significant after adjustment for fibrinogen and platelet count. ET was associated with a slightly shorter lag phase (-5%, p = 0.01) and higher maximum absorbency of the turbidimetric curve (+6%, p < 0.001). The ET patients had higher plasma P-selectin by 193% (p < 0.00001) and platelet factor 4 (PF4) by 173% (p < 0.00001), with higher P-selectin observed in 19 (44%) patients with JAK-2 gene V617F mutation. Higher t-PA (+20%, p < 0.001), 23% higher plasminogen activator inhibitor-1, PAI-1 (+23%, p < 0.01) and unaltered thrombin-activatable fibrinolysis inhibitor, plasminogen and α2-antiplasmin activity were found in the ET group. Ks inversely correlated with fibrinogen, PF4 and C-reactive protein. CLT positively correlated only with PAI-1. Patients with ET display prothrombotic plasma fibrin clot phenotype including impaired fibrinolysis, which represents a new prothrombotic mechanism in this disease. PMID:25989112
Dialysis catheter fibrin sheath stripping: a useful technique after failed catheter exchange.
Mohamad Ali, Af; Uhwut, E; Liew, Sk
Fibrin sheath formation around long-term haemodialysis catheter is a common cause of failed dialysis access. Treatment options include pharmacological and mechanical methods. This paper reports a case of failed dialysis access due to fibrin sheath encasement. Pharmacologic thrombolysis, mechanical disruption using guide wire and catheter exchange had failed to address the issue. Eventually, fibrin sheath stripping using the loop snare technique was able to successfully restore the catheter function. PMID:22970064
Physical Determinants of Fibrinolysis in Single Fibrin Fibers
Bucay, Igal; O'Brien, E. Tim; Wulfe, Steven D.; Superfine, Richard; Wolberg, Alisa S.; Falvo, Michael R.; Hudson, Nathan E.
Fibrin fibers form the structural backbone of blood clots; fibrinolysis is the process in which plasmin digests fibrin fibers, effectively regulating the size and duration of a clot. To understand blood clot dissolution, the influence of clot structure and fiber properties must be separated from the effects of enzyme kinetics and perfusion rates into clots. Using an inverted optical microscope and fluorescently-labeled fibers suspended between micropatterned ridges, we have directly measured the lysis of individual fibrin fibers. We found that during lysis 64 ± 6% of fibers were transected at one point, but 29 ± 3% of fibers increase in length rather than dissolving or being transected. Thrombin and plasmin dose-response experiments showed that the elongation behavior was independent of plasmin concentration, but was instead dependent on the concentration of thrombin used during fiber polymerization, which correlated inversely with fiber diameter. Thinner fibers were more likely to lyse, while fibers greater than 200 ± 30 nm in diameter were more likely to elongate. Because lysis rates were greatly reduced in elongated fibers, we hypothesize that plasmin activity depends on fiber strain. Using polymer physics- and continuum mechanics-based mathematical models, we show that fibers polymerize in a strained state and that thicker fibers lose their prestrain more rapidly than thinner fibers during lysis, which may explain why thick fibers elongate and thin fibers lyse. These results highlight how subtle differences in the diameter and prestrain of fibers could lead to dramatically different lytic susceptibilities. PMID:25714359
Extraction Socket Management Utilizing Platelet Rich Fibrin: A Proof-of-Principle Study of the "Accelerated-Early Implant Placement" Concept.
Kotsakis, Georgios A; Boufidou, Foteini; Hinrichs, James E; Prasad, Hari S; Rohrer, Michael; Tosios, Kostantinos I
Dental implants are widely accepted as the golden standard for the rehabilitation of an edentulous site following the extraction of a tooth. The ideal time for implant placement is dependent on the time required for partial or complete tissue healing and the adequacy of socket dimensions. The use of autologous growth factors is a promising new concept that aids clinicians in minimizing treatment time and increasing patient satisfaction. The purpose of this paper is to introduce a protocol for "accelerated-early" implant placement. In this protocol, platelet rich fibrin is employed to accelerate soft and hard tissue healing and to provide a better-healed recipient site for accelerated, early implant placement. Histological analysis revealed that at 6 weeks postextraction, the application of our approach resulted in delicate newly formed bone showing intense osteoblastic activity surrounded by connective tissue as well as areas of mineralized tissue. The present study is a proof-of-principle study of the acceleration of the physiologic postextraction healing sequelae with the use of autologous growth factors. The accelerated-early implant placement concept is a bioengineered protocol that may aid clinicians to achieve increased primary stability, by placing implants in ridges in an advanced stage of bone healing, while offering patients the benefits associated with early implant placement. Controlled studies are warranted to verify the reproducibility of this treatment concept and identify specific indications where the use of the presented technique can lead to significant clinical results. PMID:26389580
21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.
Code of Federal Regulations, 2013 CFR
... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards)....
21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.
Code of Federal Regulations, 2010 CFR
... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards)....
21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.
Code of Federal Regulations, 2011 CFR
... dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels). (b) Classification. Class II (performance standards)....
Comparison of the fibrin-binding activities in the N- and C-termini of fibronectin.
Rostagno, A A; Schwarzbauer, J E; Gold, L I
Fibronectin (Fn) binds to fibrin in clots by covalent and non-covalent interactions. The N- and C-termini of Fn each contain one non-covalent fibrin-binding site, which are composed of type 1 (F1) structural repeats. We have previously localized the N-terminal site to the fourth and fifth F1 repeats (4F1.5F1). In the current studies, using proteolytic and recombinant proteins representing both the N- and C-terminal fibrin-binding regions, we localized and characterized the C-terminal fibrin-binding site, compared the relative fibrin-binding activities of both sites and determined the contribution of each site to the fibrin-binding activity of intact Fn. By fibrin-affinity chromatography, a protein composed of the 10F1 repeat through to the C-terminus of Fn (10F1-COOH), expressed in COS-1 cells, and 10F1-12F1, produced in Saccharomyces cerevisiae, displayed fibrin-binding activity. However, since 10F1 and 10F1.11F1 were not active, the presence of 12F1 is required for fibrin binding. A proteolytic fragment of 14.4 kDa, beginning 14 residues N-terminal to 10F1, was isolated from the fibrin-affinity matrix. Radio-iodinated 14.4 kDa fibrin-binding peptide/protein (FBP) demonstrated a dose-dependent and saturable binding to fibrin-coated wells that was both competitively inhibited and reversed by unlabelled 14.4 kDa FBP. Comparison of the fibrin-binding affinities of proteolytic FBPs from the N-terminus (25.9 kDa FBP), the C-terminus (14.4 kDa) and intact Fn by ELISA yielded estimated Kd values of 216, 18 and 2.1 nM, respectively. The higher fibrin-binding affinity of the N-terminus was substantiated by the ability of both a recombinant 4F1.5F1 and a monoclonal antibody (mAb) to this site to maximally inhibit biotinylated Fn binding to fibrin by 80%, and by blocking the 90% inhibitory activity of a polyclonal anti-Fn, by absorption with the 25.9 kDa FBP. We propose that whereas the N-terminal site appears to contribute to most of the binding activity of native Fn to
Optical imaging of fibrin deposition to elucidate participation of mast cells in foreign body responses
Weng, Hong; Tang, Ewin N.; Baker, David W.; Tang, Liping
Mast cell activation has been shown to be an initiator and a key determinant of foreign body reactions. However, there is no non-invasive method that can quantify the degree of implant-associated mast cell activation. Taking advantage of the fact that fibrin deposition is a hallmark of mast cell activation around biomaterial implants, a near infrared probe was fabricated to have high affinity to fibrin. Subsequent in vitro testing confirmed that this probe has high affinity to fibrin. Using a subcutaneous particle implantation model, we found significant accumulation of fibrin-affinity probes at the implant sites as early as 15 min following particle implantation. The accumulation of fibrin-affinity probes at the implantation sites could also be substantially reduced if anti-coagulant – heparin was administered at the implant sites. Further studies have shown that subcutaneous administration of mast cell activator – compound 48/80 – prompted the accumulation of fibrin-affinity probes. However, implant-associated fibrin-affinity probe accumulation was substantially reduced in mice with mast cell deficiency. The results show that our fibrin-affinity probes may serve as a powerful tool to monitor and measure the extent of biomaterial-mediated fibrin deposition and mast cell activation in vivo. PMID:24342726
The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering.
Bacakova, Marketa; Musilkova, Jana; Riedel, Tomas; Stranska, Denisa; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie
Fibrin plays an important role during wound healing and skin regeneration. It is often applied in clinical practice for treatment of skin injuries or as a component of skin substitutes. We prepared electrospun nanofibrous membranes made from poly(l-lactide) modified with a thin fibrin nanocoating. Fibrin surrounded the individual fibers in the membrane and also formed a thin fibrous mesh on several places on the membrane surface. The cell-free fibrin nanocoating remained stable in the cell culture medium for 14 days and did not change its morphology. On membranes populated with human dermal fibroblasts, the rate of fibrin degradation correlated with the degree of cell proliferation. The cell spreading, mitochondrial activity, and cell population density were significantly higher on membranes coated with fibrin than on nonmodified membranes, and this cell performance was further improved by the addition of ascorbic acid in the cell culture medium. Similarly, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts, and this effect was further enhanced by ascorbic acid. The expression of beta1-integrins was also improved by fibrin, and on pure polylactide membranes, it was slightly enhanced by ascorbic acid. In addition, ascorbic acid promoted deposition of collagen I in the form of a fibrous extracellular matrix. Thus, the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acid seems to be particularly advantageous for skin tissue engineering. PMID:26955273
Immunohistological assessment of fibrin deposition and thrombus formation in canine mammary neoplasia.
Golombiewski, A; Gutberlet, K; Rudolph, R
A commercially available monoclonal antibody against human fibrin was used to detect fibrin in canine formalin-fixed, paraffin wax-embedded tissue by applying a slightly modified alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Twenty-eight mammary tumours from six bitches were examined for the presence of fibrin. Thrombi and extravascular fibrin deposits were detected in 15 tumours (12 complex adenocarcinomas, one adenocarcinoma, two solid carcinomas), and a single thrombus was detected in one adenoma; 12 tumours (three adenomas, one complex adenoma, four complex adenocarcinomas and four adenocarcinomas) did not show any staining reaction. PMID:9352443
The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering
Bacakova, Marketa; Musilkova, Jana; Riedel, Tomas; Stranska, Denisa; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie
Fibrin plays an important role during wound healing and skin regeneration. It is often applied in clinical practice for treatment of skin injuries or as a component of skin substitutes. We prepared electrospun nanofibrous membranes made from poly(l-lactide) modified with a thin fibrin nanocoating. Fibrin surrounded the individual fibers in the membrane and also formed a thin fibrous mesh on several places on the membrane surface. The cell-free fibrin nanocoating remained stable in the cell culture medium for 14 days and did not change its morphology. On membranes populated with human dermal fibroblasts, the rate of fibrin degradation correlated with the degree of cell proliferation. The cell spreading, mitochondrial activity, and cell population density were significantly higher on membranes coated with fibrin than on nonmodified membranes, and this cell performance was further improved by the addition of ascorbic acid in the cell culture medium. Similarly, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts, and this effect was further enhanced by ascorbic acid. The expression of beta1-integrins was also improved by fibrin, and on pure polylactide membranes, it was slightly enhanced by ascorbic acid. In addition, ascorbic acid promoted deposition of collagen I in the form of a fibrous extracellular matrix. Thus, the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acid seems to be particularly advantageous for skin tissue engineering. PMID:26955273
The conversion of fibrinogen to fibrin. XIII. Dissolution of fibrin and inhibition of clotting by various neutral salts.
1. Fibrin clots prepared in the absence of calcium can be dissolved in solutions of lithium chloride and bromide and sodium bromide and iodide, as well as of guanidine hydrochloride and urea. These salts do not denature fibrinogen under the same conditions of concentration, temperature, and time. Sedimentation experiments on the fibrin solutions show in each case a single sharp peak with a sedimentation constant close to that of fibrinogen. 2. At lower concentrations, these salts inhibit the clotting of fibrinogen by thrombin, but in the case of lithium bromide and sodium iodide, at least, allow an intermediate polymer to accumulate whose sedimentation constant is close to that of the polymer observed in systems inhibited by hexamethylene glycol or urea. PMID:13069679
Surgical Re-entry of an Intentionally Replanted Periodontally Compromised Tooth Treated with Platelet Rich Fibrin (PRF): Hopeless to Hopeful.
Ryana, Haneet Kour; Srinath, Rashmi; Prakash, Shobha
Intentional replantation is generally contraindicated in periodontally compromised teeth however, there are reports suggesting that it can be a successful treatment alternative for periodontally involved hopeless teeth. Currently there is dearth of evidence regarding the success of this therapy, especially evidence for the effectiveness of autologous platelet rich fibrin is lacking. We present a case report of a 23-year-old male patient with periodontally hopeless left maxillary central incisor having bone loss extending beyond root apex. The tooth was gently extracted and replanted utilizing root conditioning and combined regenerative therapy (Xenograft, PRF and Type I Collagen Membrane). Surgical re-entry at nine months revealed bone formation in the apical third of the tooth. At one year, 87% radiographic bone gain was accomplished. The improvement in the clinical and radiographic parameters reinforced by the re-entry surgery findings strongly suggest that intentional replantation may be a cost-effective substitute to implants and tooth supported prosthesis in situations where conventional periodontal therapy would yield compromised outcomes. PMID:27504421
Evaluation of intrabony defects treated with platelet-rich fibrin or autogenous bone graft: A comparative analysis
Mathur, Ashish; Bains, Vivek Kumar; Gupta, Vivek; Jhingran, Rajesh; Singh, G. P.
Objective: The primary objective of this study was to compare clinically and radiographically the efficacy of autologous platelet rich fibrin (PRF) and autogenous bone graft (ABG) obtained using bone scrapper in the treatment of intrabony periodontal defects. Materials and Methods: Thirty-eight intrabony defects (IBDs) were treated with either open flap debridement (OFD) with PRF or OFD with ABG. Clinical parameters were recorded at baseline and 6 months postoperatively. The defect-fill and defect resolution at baseline and 6 months were calculated radiographically (intraoral periapical radiographs [IOPA] and orthopantomogram [OPG]). Results: Significant probing pocket depth (PPD) reduction, clinical attachment level (CAL) gain, defect fill and defect resolution at both PRF and ABG treated sites with OFD was observed. However, inter-group comparison was non-significant (P > 0.05). The bivariate correlation results revealed that any of the two radiographic techniques (IOPA and OPG) can be used for analysis of the regenerative therapy in IBDs. Conclusion: The use of either PRF or ABG were effective in the treatment of three wall IBDs with an uneventful healing of the sites. PMID:25713492
Surgical Re-entry of an Intentionally Replanted Periodontally Compromised Tooth Treated with Platelet Rich Fibrin (PRF): Hopeless to Hopeful
Srinath, Rashmi; Prakash, Shobha
Intentional replantation is generally contraindicated in periodontally compromised teeth however, there are reports suggesting that it can be a successful treatment alternative for periodontally involved hopeless teeth. Currently there is dearth of evidence regarding the success of this therapy, especially evidence for the effectiveness of autologous platelet rich fibrin is lacking. We present a case report of a 23-year-old male patient with periodontally hopeless left maxillary central incisor having bone loss extending beyond root apex. The tooth was gently extracted and replanted utilizing root conditioning and combined regenerative therapy (Xenograft, PRF and Type I Collagen Membrane). Surgical re-entry at nine months revealed bone formation in the apical third of the tooth. At one year, 87% radiographic bone gain was accomplished. The improvement in the clinical and radiographic parameters reinforced by the re-entry surgery findings strongly suggest that intentional replantation may be a cost-effective substitute to implants and tooth supported prosthesis in situations where conventional periodontal therapy would yield compromised outcomes. PMID:27504421
Platelet-Rich Fibrin Promotes an Accelerated Healing of Achilles Tendon When Compared to Platelet-Rich Plasma in Rat
Dietrich, Franciele; L. Duré, Gustavo; P. Klein, Caroline; F. Bampi, Vinícius; V. Padoin, Alexandre; D. Silva, Vinícius; Braga-Silva, Jefferson
BACKGROUND Autologous platelet concentrate has been used to improve the function and regeneration of injured tissues. Tendinopathies are common in clinical practice, although long-term treatment is required. On the basis of lead time, we compared the effect of using platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in repairing rat Achilles tendon. METHODS The effectiveness of using PRP and PRF was evaluated after 14 and 28 postoperative days by histological analysis. The quantification of collagen types I and III was performed by Sirius red staining. Qualitatively, the data were verified with hematoxylin-eosin (H&E) staining. RESULTS In Sirius red staining, no significant treatment differences were found between groups. Statistical difference was observed only between PRP (37.2% collagen) and the control group (16.2%) 14 days after treatment. Intra-groups compared twice showed a difference for collagen I (27.8% and 47.7%) and III (66.9% and 46.0%) in the PRF group. The control group showed differences only in collagen I (14.2% and 40.9%) and no other finding was observed in the PRP group. In H&E staining, PRF showed a better cellular organization when compared to the other groups at 28 days. CONCLUSION Our study suggests that PRF promotes accelerated regeneration of the Achilles tendon in rats, offering promising prospects for future clinical use. PMID:26284178
Fibrin gel-immobilized primary osteoblasts in calcium phosphate bone cement: in vivo evaluation with regard to application as injectable biological bone substitute.
Kneser, U; Voogd, A; Ohnolz, J; Buettner, O; Stangenberg, L; Zhang, Y H; Stark, G B; Schaefer, D J
Osteogenic injectable bone substitutes may be useful for many applications. We developed a novel injectable bone substitute based on osteoblast-fibrin glue suspension and calcium phosphate bone cement (BC). Human osteoblasts were isolated from trabecular bone samples and cultured under standard conditions. Osteoblasts were suspended in fibrinogen solution (FS). BC was cured with thrombin solution. 8 x 4 mm injectable bone discs were prepared using silicon molds and a custom-made applicator device. Discs containing BC, BC/FS, or BC/FS/osteoblasts were implanted subcutaneously into athymic nude mice. After 3, 9 and 24 weeks, specimens were explanted and subjected to morphologic and biomechanical evaluation. In vitro fibrin gel-embedded osteoblasts displayed a differentiated phenotype as evidenced by alkaline phosphatase, collagen type 1 and von Kossa stains. A proportion of osteoblasts appeared morphologically intact over a 3-day in vitro period following application into the BC. BC/FS and BC/FS/osteoblast discs were sparsely infiltrated with vascularized connective tissue. There was no bone formation in implants from all groups. However, positive von Kossa staining only in BC/FS/osteoblast groups suggests engraftment of at least some of the transplanted cells. Biomechanical evaluation demonstrated initial stability of the composites. Young's modulus and maximal load did not differ significantly in the BC/FS and BC/FS/osteoblast groups. The practicability of osteoblast-containing injectable bone could be demonstrated. The dense microstructure and the suboptimal initial vascularization of the composites may explain the lack of bone formation. Modifications with regard to enhanced osteoblast survival are mandatory for a possible application as injectable osteogenic bone replacement system. PMID:16046862
Socket preservation by beta-tri-calcium phosphate with collagen compared to platelet-rich fibrin: A clinico-radiographic study
Das, Swati; Jhingran, Rajesh; Bains, Vivek Kumar; Madan, Rohit; Srivastava, Ruchi; Rizvi, Iram
Objectives: This study was primarily designed to determine the clinico-radiographic efficacy of platelet-rich fibrin (PRF) and beta-tri-calcium phosphate with collagen (β-TCP-Cl) in preserving extraction sockets. Materials and Methods: For Group I (PRF), residual sockets (n = 15) were filled with autologous PRF obtained from patients' blood; and for Group II (β-TCP-Cl), residual sockets (n = 15) were filled with β-TCP-Cl. For the sockets randomly selected for Group II (β-TCP-Cl), the reshaped Resorbable Tissue Replacement cone was inserted into the socket. Results: Clinically, there was a significantly greater decrease in relative socket depth, but apposition in midcrestal height in Group II (β-TCP-Cl) as compared to Group I (PRF), whereas more decrease in buccolingual width of Group I (PRF) than Group II (β-TCP-Cl) after 6 months. Radiographically, the mean difference in socket height, residual ridge, and width (coronal, middle, and apical third of socket) after 6 months was higher in Group I (PRF) as compared to Group II (β-TCP-Cl). The mean density (in Hounsfield Units) at coronal, middle, and apical third of socket was higher in Group I (PRF) as compared to Group II (β-TCP-Cl). There were statistically significant apposition and resorption for Group I (PRF) whereas nonsignificant resorption and significant apposition for Group II (β-TCP-Cl) in buccal and lingual/palatal cortical plate, respectively, at 6 months on computerized tomography scan. Conclusion: The use of either autologous PRF or β-TCP-Cl was effective in socket preservation. Results obtained from PRF were almost similar to β-TCP-Cl; therefore being autologous, nonimmune, cost-effective, easily procurable regenerative biomaterial, PRF proves to be an insight into the future biofuel for regeneration. PMID:27095909
Relative Gain Monitoring of the GlueX Calorimeters
Anassontzis, Efstratios G.; Kourkoumelis, C.; Vasileiadis, G.; Voulgaris, G.; Kappos, E.; Beattie, T.; Krueger, S.; Lolos, G. J.; Papandreou, Z.; Semenov, A. Yu.; Frye, John M.; Leckey, John P.; Shepherd, Matt; Bogart, T.; Smith, Elton S.
The relative gain of the photodetectors for the GlueX Barrel and Forward calorimeters will be monitored using modular LED driver systems. The BCAL system consists of a global controller that feeds power, bias voltage and trigger signals to 96 local controllers situated at the ends of the 48 BCAL modules, which drive 40 LEDs associated with the 40 light guides at the end of each module. The FCAL system consists also of a global controller, a local controller for each acrylic quadrant covering the face of the FCAL, and ten 4-LED pulser boards per local controller connected in a star configuration along the edges of the acrylic panes. The respective systems are currently being installed on the detectors and their tested performance is presented herein.
Bioorthogonal Click Chemistry-Based Synthetic Cell Glue.
Koo, Heebeom; Choi, Myunghwan; Kim, Eunha; Hahn, Sei Kwang; Weissleder, Ralph; Yun, Seok Hyun
Artificial methods of cell adhesion can be effective in building functional cell complexes in vitro, but methods for in vivo use are currently lacking. Here, a chemical cell glue based on bioorthogonal click chemistry with high stability and robustness is introduced. Tetrazine (Tz) and trans-cyclooctene (TCO) conjugated to the cell surface form covalent bonds between cells within 10 min in aqueous conditions. Glued, homogeneous, or heterogeneous cell pairs remain viable and stably attached in a microfluidic flow channel at a shear stress of 20 dyn cm(-2) . Upon intravenous injection of assembled Jurkat T cells into live mice, fluorescence microscopy shows the trafficking of cell pairs in circulation and their infiltration into lung tissues. These results demonstrate the promising potential of chemically glued cell pairs for various applications ranging from delivering therapeutic cells to studying cell-cell interactions in vivo. PMID:26768353
Quark and Glue Components of the Proton Spin from Lattice Calculation
NASA Astrophysics Data System (ADS)
Liu, Keh-Fei
The status of lattice calculations of the quark spin, the quark orbital angular momentum, the glue angular momentum and glue spin in the nucleon is summarized. The quark spin calculation is recently carried out from the anomalous Ward identity with chiral fermions and is found to be small mainly due to the large negative anomaly term which is believed to be the source of the 'proton spin crisis'. We also present the first calculation of the glue spin at finite nucleon momenta.
Increased fibrin formation and impaired fibrinolytic capacity in severe chronic kidney disease.
Mörtberg, Josefin; Blombäck, Margareta; Wallén, Åkan; He, Shu; Jacobson, Stefan H; Spaak, Jonas
Chronic kidney disease (CKD) is associated with a concurrent increased risk of thrombosis and bleeding. We aimed to investigate whether CKD is associated with increased fibrin formation, impaired fibrin degradation, or both. Twenty-one patients with CKD stage 4 (CKD 4), 15 haemodialysis patients, and 13 controls (C) without kidney disease were studied. We used a global assay to determine fibrin formation and degradation in plasma. Fibrin turbidity was measured over time to obtain a value of the coagulation activation profile (Cp) and the fibrinolysis activation profile (Fp), and the amount of fibrin formed, termed fibrin optical density sum (fibrin OD-sum). We used scanning electron microscopy (SEM) to visualize the fibrin network. Plasminogen activator inhibitor type-1 antigen, thrombin-activatable fibrinolysis inhibitor activity, fibrinogen, von Willebrand factor, antithrombin, albumin, and C-reactive protein were measured in plasma. Fibrin OD-sum was significantly elevated in haemodialysis patients [312 a.u.; 278-435 (median; interquartile range); P < 0.0013] and in CKD 4 (293 a.u.; 169-434; P = 0.0119) compared with controls (115 a.u.; 82-234). SEM showed a tight fibrin network in haemodialysis and CKD 4 patients. Fp was lower in the haemodialysis group than in controls (P = 0.030). Plasminogen activator inhibitor type-1 was lower in haemodialysis patients (P = 0.034). Thrombin-activatable fibrinolysis inhibitor activity, Cp, antithrombin, and C-reactive protein did not differ between groups. Fibrinogen was significantly elevated and albumin decreased in both haemodialysis and CKD 4 patients compared with controls. Von Willebrand factor was elevated in haemodialysis patients compared with controls (P = 0.010). The prothrombotic state in severe CKD is characterized by impaired fibrinolysis in association with increased fibrin formation despite normal levels of endogenous fibrinolysis inhibitors. PMID:26650459
Autologous Fat Grafting Improves Facial Nerve Function
Klinger, Marco; Lisa, Andrea; Caviggioli, Fabio; Maione, Luca; Murolo, Matteo; Vinci, Valeriano; Klinger, Francesco Maria
We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman's technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function. PMID:26167327
Achieving ideal breast aesthetics with autologous reconstruction
Achieving ideal breast aesthetic has become a top priority for women considering breast reconstruction following mastectomy. The use of autologous tissue is generally regarded as providing the most natural results because donor tissues quality and consistency is similar to that of the native breast. There are several donor sites that are particularly useful for autologous reconstruction that include the abdomen, gluteal region, posterior thorax, and the thigh. Traditional and microsurgical techniques can be used. Shaping is a critical component and involves a basic understanding of the footprint, conus, and skin envelope. This manuscript will review many aspects of breast shaping in-order to achieve aesthetically pleasing results in a predictable manner. PMID:26005645
The effect of an autologous cellular gel-matrix integrated implant system on wound healing
Background This manuscript reports the production and preclinical studies to examine the tolerance and efficacy of an autologous cellular gel-matrix integrated implant system (IIS) aimed to treat full-thickness skin lesions. Methods The best concentration of fibrinogen and thrombin was experimentally determined by employing 28 formula ratios of thrombin and fibrinogen and checking clot formation and apparent stability. IIS was formed by integrating skin cells by means of the in situ gelification of fibrin into a porous crosslinked scaffold composed of chitosan, gelatin and hyaluronic acid. The in vitro cell proliferation within the IIS was examined by the MTT assay and PCNA expression. An experimental rabbit model consisting of six circular lesions was utilized to test each of the components of the IIS. Then, the IIS was utilized in an animal model to cover a 35% body surface full thickness lesion. Results The preclinical assays in rabbits demonstrated that the IIS was well tolerated and also that IIS-treated rabbit with lesions of 35% of their body surface, exhibited a better survival rate (p = 0,06). Conclusion IIS should be further studied as a new wound dressing which shows promising properties, being the most remarkable its good biological tolerance and cell growth promotion properties. PMID:20565787
Cryptococcal meningitis post autologous stem cell transplantation.
Chaaban, S; Wheat, L J; Assi, M
Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving. PMID:24750320
[Nutritional pathway for autologous stem cell transplantation].
Aoyama, Takashi; Imataki, Osamu; Inoue, Naomi; Katsumata, Mina; Katsuta, Tomoko; Kataoka, Tomomi; Yoshida, Takashi; Mochizuki, Takahiro; Motokawa, Satoshi; Tamai, Yotaro; Hagiwara, Shotaro; Kawakami, Kimihiro
We developed a nutritional pathway for autologous stem cell transplantation (SCT) to be applied in our transplantation unit. We performed autologous SCT for 37 patients with malignant lymphoma and multiple myeloma during from April 2003 to July 2005. For 10 of them who underwent SCT since 2005,we intervened with nutritional support using our original nutritional pathway,to monitor the clinical course of SCT from the aspect of dietetics with a dietician making assessments of the individual nutrition status. From comparing the 2 groups with (n=27) or without (n=10) the nutritional pathway, oral intake at day 14 was significantly increased from 1,038 kcal to 1,440 kcal,and at discharge developed from 1,167 kcal to 1,446 kcal without statistical significance. Patients whose body weight decreased more than 5% were reduced from 52%(14/27) to 10%(1/10),and 3 days reduction of the CVC insertion period was observed after the intervention. Although the long-term clinical outcome was not fully evaluated, the efficacy of nutritional pathway for autologous SCT was suggested. PMID:17687206
Magnetic resonance profiling studies of the drying of film-forming aqueous dispersions and glue layers.
Bennett, G; Gorce, J-P; Keddie, J L; McDonald, P J; Berglind, H
We report magnetic resonance profiling experiments to monitor (i) the drying of alkyd emulsion layers, (ii) the cure of wood glue layers and (iii) water transport through glue lines. The alkyd drying is a two stage process. We report new results which support previous evidence that the alkyd drops do not coalesce until the water fraction is below circa 0.02. The profiles recorded from glue layers suggest that MR is a sensitive probe of the curing process and barrier properties of the glue. The measurements were made using GARField (stray field, STRAFI like) magnetic resonance profiling and an improved GARField magnet design characterized by two values of the gradient-to-field strength ratio at two locations offering the same field strength is also reported. PMID:12850713
Event based uncertainty assessment in urban drainage modelling, applying the GLUE methodology
NASA Astrophysics Data System (ADS)
Thorndahl, S.; Beven, K. J.; Jensen, J. B.; Schaarup-Jensen, K.
SummaryIn the present paper an uncertainty analysis on an application of the commercial urban drainage model MOUSE is conducted. Applying the Generalized Likelihood Uncertainty Estimation (GLUE) methodology the model is conditioned on observation time series from two flow gauges as well as the occurrence of combined sewer overflow. The GLUE methodology is used to test different conceptual setups in order to determine if one model setup gives a better goodness of fit conditional on the observations than the other. Moreover, different methodological investigations of GLUE are conducted in order to test if the uncertainty analysis is unambiguous. It is shown that the GLUE methodology is very applicable in uncertainty analysis of this application of an urban drainage model, although it was shown to be quite difficult to get good fits of the whole time series.
Nonlinear temperature dependence of glue-induced birefringence in polarization maintaining FBG sensors
NASA Astrophysics Data System (ADS)
Hopf, Barbara; Koch, Alexander W.; Roths, Johannes
Glue-induced stresses decrease the accuracy of surface-mounted fiber Bragg gratings (FBG). Significant temperature dependent glue-induced birefringence was verified when a thermally cured epoxy-based bonding technique had been used. Determining the peak separation of two azimuthally aligned FBGs in PM fibers combined with a polarization resolved measurement set-up in a temperature range between -30°C and 150°C revealed high glue-induced stresses at low temperatures. Peak separations of about 60 pm and a nonlinear temperature dependence of the glue-induced birefringence due to stress relaxation processes and a visco-elastic behavior of the used adhesive have been shown.
21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.
Code of Federal Regulations, 2012 CFR
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fibrinogen/fibrin degradation products assay. 864.7320 Section 864.7320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7320 Fibrinogen/fibrin degradation...
21 CFR 864.7320 - Fibrinogen/fibrin degradation products assay.
Code of Federal Regulations, 2014 CFR
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fibrinogen/fibrin degradation products assay. 864.7320 Section 864.7320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7320 Fibrinogen/fibrin degradation...
Modification of fibrin network ultrastructure by Fab fragments specific for different domain of fibrinogen.
Cierniewski, C S; Janiak, A; Wyroba, E
Kinetics of inhibition of fibrin monomer polymerization produced by Fab fragments prepared from immunochemically purified monospecific antibodies to the surface epitopes of different domains of fibrinogen molecule has been correlated with electron microscopic observations of resulting specimens. Fab fragments prepared from anti FgD antisera were the most efficient inhibitors of thrombin-catalysed conversion of fibrinogen to fibrin; polymerization of fibrin monomers as detected spectrophotometrically was abolished at 2:1 molar ratio of anti FgD Fab fragments to fibra monomer. These Fab fragments acting as a steric hindrance of polymerization sites inhibited the first stage of fibrin monomer aggregation. Interaction of Fab fragments derived from antibodies specific for alpha 239-476 with corresponding segment of fibrinogen molecule resulted in a weak inhibition of fibrin monomer polymerization. However, fibrin obtained in the presence of these Fab fragments was significantly modified and showed no periodicity. This observation may suggest that anti alpha 239-476 Fab impaired the course of the second stage of fibrin monomer polymerization, i.e. lateral association of fibrin fibrils. PMID:2433859
Simultaneous measurement of thrombin generation and fibrin formation in whole blood under flow conditions.
Kelchtermans, Hilde; Pelkmans, Leonie; Bouwhuis, Anne; Schurgers, Evelien; Lindhout, Theo; Huskens, Dana; Miszta, Adam; Hemker, H Coenraad; Lancé, Marcus D; de Laat, Bas
Assays based on the formation of thrombin and fibrin are frequently used, and results are considered exchangeable in research/clinical settings. However, thrombin generation and fibrin formation do not always go hand in hand and flow profoundly influences thrombus formation. We describe the technical/clinical evaluation of an assay to simultaneously measure thrombin generation and fibrin formation under conditions of flow. Introduction of a fluorometer into a 'cone and base principle'-based rheometer allowed the measurement of thrombin generation (using a thrombin-sensitive substrate) and fibrin formation (changes in viscosity), while applying a linear shear flow. Increasing shear rates inversely related with thrombin generation and fibrin formation. Increasing fibrinogen concentrations in defibrinated plasma resulted in increased thrombin generation and fibrin formation. In pre-operative samples of 70 patients undergoing cardiothoracic surgery, fibrin formation and thrombin generation parameters correlated with fibrinogen content, rotational thromboelastometry (ROTEM) and whole blood Calibrated Automated Thrombinography (CAT) parameters, respectively. Upon dividing patients into two groups based on the median clot strength, a significant difference in perioperative/total blood loss was established. In conclusion, we clinically evaluated a method capable of simultaneously measuring thrombin generation and fibrin formation in plasma/whole blood under continuous flow, rendering our method one step closer to physiology. Importantly, our test proved to be indicative for the amount of blood loss during/after cardiothoracic surgery. PMID:27074907
Role of fibrinopeptide B release: comparison of fibrins produced by thrombin and Ancrod.
Shen, L L; Hermans, J; McDonagh, J; McDonagh, R P
The gelation time, opacity, light scattering, and elastic moduli of human fibrin gels clotted in the presence of thrombin, Ancrod, and Reptilase have been compared. At low ionic strength lateral association to thick fibers is observed in all cases. At all ionic strengths thrombin fibrin forms thicker fibers than does Ancrod fibrin. We have demonstrated that an increase in the extent of lateral association is linked to an increase in its velocity and to a decrease in the gelation time. One may consider the removal of fibrinopeptide B to act as a switch: after it is removed fibrin assembles rapidly to thick fibers and gelation is fast; but when this peptide is still attached, there is a slow assembly of thin fibers, and gelation, especially of dilute fibrin, is delayed. We believe that this delay is critical for the complete digestion by plasmin of fibrin formed during in vivo defibrination with Ancrod and of fibrin produced by very small amounts of thrombin (which would still contain fibrinopeptide B), and that slow release of fibrinopeptide B is part of a control mechanism for the regulation of fibrin formation and the prevention of intravascular coagulation. PMID:879301
Aprotinin extends mechanical integrity time of cell-seeded fibrin sutures.
Coffin, Spencer T; Gaudette, Glenn R
Cell therapy has the potential to treat different pathologies, including myocardial infarctions (heart attacks), although cell engraftment remains elusive with most delivery methods. Biological sutures composed of fibrin have been shown to effectively deliver human mesenchymal stem cell (MSC) to infarcted hearts. However, human MSCs rapidly degrade fibrin making cell seeding and delivery time sensitive. To delay the degradation process, we propose using Aprotinin, a proteolytic enzyme inhibitor that has been shown to slow fibrinolysis. Human MSCs seeded on fibrin sutures and incubated with Aprotinin demonstrated similar cell viability, examined using a LIVE/DEAD stain, to controls. No differences in proliferation, as determined by Ki-67 presence, were observed. Human MSCs incubated in Aprotinin differentiated into adipocytes, osteocytes, and chondrocytes, confirming multipotency. The number of cells adhered to fibrin sutures increased through Aprotinin supplementation at 2, 3, and 5 day time points. Uniaxial tensile testing was used to examine the effect of Aprotinin on suture integrity. Sutures exposed to Aprotinin had higher ultimate tensile strength and modulus when compared to sutures exposed to standard growth media. Fibrin sutures incubated in Aprotinin had larger diameters and less fibrin degradation products compared to the controls, confirming decreased fibrinolysis. These data suggest that Aprotinin can reduce degradation of fibrin sutures without significant effects on MSC function, providing a novel method for extending the implantation window and increasing the number of cells delivered via fibrin sutures. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2271-2279, 2016. PMID:27101153
Influence of a constant magnetic field on the fibrinogen-fibrin system. [in blood coagulation process
NASA Technical Reports Server (NTRS)
Matskevichene, V. B.; Platonova, A. T.
The effect of a constant magnetic field with a strength of 2500 oersteds on the fibrinogen-fibrin system was studied in the organism of healthy rabbits with exposure times of 1 and 5 hours. The results obtained indicate disruptions in the stage of conversion of fibrinogen to fibrin and an increase in the amount of fibrinogen.
Protein unfolding accounts for the unusual mechanical behavior of fibrin networks
Purohit, Prashant K.; Litvinov, Rustem I.; Brown, Andre E. X.; Discher, Dennis E.; Weisel, John W.
We describe the mechanical behavior of isotropic fibrin networks at the macroscopic scale in terms of the nanoscale force response of fibrin molecules that are its basic building blocks. We show that the remarkable extensibility and compressibility of fibrin networks have their origins in the unfolding of fibrin molecules. The force-stretch behavior of a single fibrin fiber is described using a two-state model in which the fiber has a linear force-stretch relation in the folded phase and behaves like a worm-like-chain in the unfolded phase. The nanoscale force-stretch response is connected to the macro-scale stress-stretch response by means of the eight-chain model. This model is able to capture the macroscopic response of a fibrin network in uniaxial tension and appears remarkably simple given the molecular complexity. We use the eight-chain model to explain why fibrin networks have negative compressibility and Poisson's ratio greater than one due to unfolding of fibrin molecules. PMID:21342665
Dystrophic calcifications after autologous fat injection on face.
Kim, Dai Hyun; Jang, Hee Won; Kim, Hee Joo; Son, Sang Wook
Autologous fat injection is widely used procedure for various functional and aesthetic purposes. However, it could result in many immediate or delayed complications including dystrophic calcifications. Almost all of the case reports about dystrophic calcification after autologous fat injection were result from the iatrogenic tissue trauma of breast augmentation. This is a report of a 30-year-old patient who developed pathologically proven multiple dystrophic calcifications on the face after autologous fat injection. PMID:24131074
Double Coaxial Microcatheter Technique for Glue Embolization of Renal Arteriovenous Malformations
Uchikawa, Yoko; Mori, Kensaku; Shiigai, Masanari; Konishi, Takahiro; Hoshiai, Sodai; Ishigro, Toshitaka Hiyama, Takashi; Nakai, Yasunobu; Minami, Manabu
PurposeTo demonstrate the technical benefit of the double coaxial microcatheter technique for embolization of renal arteriovenous malformations (AVMs) with n-butyl cyanoacrylate and iodized oil (glue).Materials and MethodsSix consecutive patients (1 man and 5 women; mean age 61 years; range 44–77 years) with renal AVMs were included. Five patients had hematuria, and one had a risk of heart failure due to a large intrarenal arteriovenous shunt. All patients underwent transarterial embolization using glue and the double coaxial microcatheter technique with outer 2.6F and inner 1.9F microcatheters. After glue injection, the inner microcatheter was retracted, while the outer microcatheter was retained. We assessed the complications and clinical outcomes of this technique.ResultsTechnical success was achieved in all patients. In 9 sessions, 34 feeding arteries were embolized with glue using the double coaxial microcatheter technique, 1 was embolized with glue using a single microcatheter, and 2 were embolized with coils. The double coaxial microcatheter technique was useful for selecting small tortuous feeding arteries, preventing glue reflux to the proximal arteries, and approaching multiple feeding arteries without complete retraction of the microcatheters. As a minor complication, glue migrated into the venous system in four patients without any sequelae. In all patients, favorable clinical outcomes, including hematuria cessation in five patients and improvement of the large intrarenal arteriovenous shunt in one patient, were obtained without deterioration of renal function.ConclusionGlue embolization with the double coaxial microcatheter technique was useful for treating renal AVMs with multiple tortuous feeding arteries.
The presence of γ' chain impairs fibrin polymerization
Gersh, Kathryn C.; Nagaswami, Chandrasekaran; Weisel, John W.; Lord, Susan T.
Introduction A fraction of fibrinogen molecules contain an alternatively spliced variant chain called γ'. Plasma levels of this variant have been associated with both myocardial infarction and venous thrombosis. Because clot structure has been associated with cardiovascular risk, we examined the effect of γ' chain on clot structure. Materials and Methods We expressed three fibrinogen variants in Chinese hamster ovary (CHO) cells: γ/γ homodimer, γ/γ' heterodimer, and γ'/γ' homodimer. We observed thrombin-catalyzed fibrinopeptide release by HPLC, fibrin polymerization by turbidity, and clot structure by scanning electron microscopy. We characterized post-translational modifications by mass spectrometry. Results Fibrinopeptide A was released at the same rate for all three fibrinogens, while fibrinopeptide B was released faster from the γ'/γ' homodimer. The rise in turbidity was slower and final absorbance was lower during polymerization of γ'-containing fibrinogens than for γ/γ fibrinogen. Micrographs showed that γ'/γ' fibrin clots are composed of very thin fibers, while the diameter of γ/γ' fibers is similar to γ/γ fibers. Further, the fiber networks formed from γ'-containing samples were non-uniform. Mass spectrometry showed heterogeneous addition of N-glycans and tyrosine sulfation in the γ' chain. Conclusions The presence of γ' chains slows lateral aggregation and alters fibrin structure. We suggest these changes are likely due to charge-charge repulsion, such that polymerization of the γ'/γ' homodimer is more impaired than the heterodimer since these repulsions are partially offset by incorporation of γ chains in the γ/γ' heterodimer. PMID:19138790
Fibrin-based biomaterials: Modulation of macroscopic properties through rational design at the molecular level
Brown, Ashley C.; Barker, Thomas H.
Fibrinogen is one of the primary components of the coagulation cascade and rapidly forms an insoluble matrix following tissue injury. In addition to its important role in hemostasis, fibrin acts as a scaffold for tissue repair and provides important cues for directing cell phenotype following injury. Because of these properties and the ease of polymerization of the material, fibrin has been widely utilized as a biomaterial for over a century. Modifying the macroscopic properties of fibrin, such as elasticity and porosity, has been somewhat elusive until recently, yet with a molecular-level rational design approach can now be somewhat easily modified through alterations of molecular interactions key to the protein's polymerization process. This review outlines the biochemistry of fibrin and discusses methods for modification of molecular interactions and their application to fibrin based biomaterials. PMID:24056097
Fibrin Clots Are Equilibrium Polymers That Can Be Remodeled Without Proteolytic Digestion
NASA Astrophysics Data System (ADS)
Chernysh, Irina N.; Nagaswami, Chandrasekaran; Purohit, Prashant K.; Weisel, John W.
Fibrin polymerization is a necessary part of hemostasis but clots can obstruct blood vessels and cause heart attacks and strokes. The polymerization reactions are specific and controlled, involving strong knob-into-hole interactions to convert soluble fibrinogen into insoluble fibrin. It has long been assumed that clots and thrombi are stable structures until proteolytic digestion. On the contrary, using the technique of fluorescence recovery after photobleaching, we demonstrate here that there is turnover of fibrin in an uncrosslinked clot. A peptide representing the knobs involved in fibrin polymerization can compete for the holes and dissolve a preformed fibrin clot, or increase the fraction of soluble oligomers, with striking rearrangements in clot structure. These results imply that in vivo clots or thrombi are more dynamic structures than previously believed that may be remodeled as a result of local environmental conditions, may account for some embolization, and suggest a target for therapeutic intervention.
Transurethral Use of Evicel® Fibrin Sealant
Masel, Jonathan L.
Transurethral resection of bladder tumor remains the most common procedure for the diagnosis, management, and treatment of bladder cancer. Deep resection of the detrusor muscle for the correct staging of bladder cancer can increase the risk of hemorrhage that can be difficult to control with standard transurethral surgical maneuvers. Evicel® Fibrin Sealant was applied transurethrally to manage difficult hemorrhage following transurethral resection of bladder tumor in two surgically complex bladder cancer patients. Our early experience suggests Evicel® can be an effective tool in managing difficult to control hemorrhage associated with TURBT. Further clinical investigation is to be encouraged. PMID:26793564
Fibrinous anterior uveitis following laser in situ keratomileusis.
Parmar, Pragya; Salman, Amjad; Rajmohan, M; Jesudasan, Nelson C A
A 29-year-old woman who underwent laser in situ keratomileusis (LASIK) for myopic astigmatism in both eyes presented with severe pain, photophobia and decreased visual acuity in the left eye eight days after surgery. Examination revealed severe anterior uveitis with fibrinous exudates in the anterior chamber, flap edema and epithelial bullae. Laboratory investigations for uveitis were negative and the patient required systemic and intensive topical steroids with cycloplegics to control the inflammation. This case demonstrates that severe anterior uveitis may develop after LASIK and needs prompt and vigorous management for resolution. PMID:19574707
Platelet-rich fibrin application in dentistry: a literature review
Borie, Eduardo; Oliví, Daniel García; Orsi, Iara Augusta; Garlet, Katia; Weber, Benjamín; Beltrán, Víctor; Fuentes, Ramón
The development of bioactive surgical additives to regulate the inflammation and increase the speed of healing process is one of the great challenges in clinical research. In this sense, platelet rich fibrin (PRF) appears as a natural and satisfactory alternative with favorable results and low risks. The following review attempts to summarize the relevant literature regarding the technique of using PRF, focusing on its preparation, advantages, and disadvantages of using it in clinical applications. PRF alone or in combination with other biomaterials seems to have several advantages and indications both for medicine and dentistry, due it is a minimally invasive technique with low risks and satisfactory clinical results. PMID:26221349
Evidence from Multiple Species that Spider Silk Glue Component ASG2 is a Spidroin.
Collin, Matthew A; Clarke, Thomas H; Ayoub, Nadia A; Hayashi, Cheryl Y
Spiders in the superfamily Araneoidea produce viscous glue from aggregate silk glands. Aggregate glue coats prey-capture threads and hampers the escape of prey from webs, thereby increasing the foraging success of spiders. cDNAs for Aggregate Spider Glue 1 (ASG1) and 2 (ASG2) have been previously described from the golden orb-weaver, Nephila clavipes, and Western black widow, Latrodectus hesperus. To further investigate aggregate glues, we assembled ASG1 and ASG2 from genomic target capture libraries constructed from three species of cob-web weavers and three species of orb-web weavers, all araneoids. We show that ASG1 is unlikely to be a glue, but rather is part of a widespread arthropod gene family, the peritrophic matrix proteins. For ASG2, we demonstrate its remarkable architectural and sequence similarities to spider silk fibroins, indicating that ASG2 is a member of the spidroin gene family. Thus, spidroins have diversified into glues in addition to task-specific, high performance fibers. PMID:26875681
Dynamics of spider glue adhesion: effect of surface energy and contact area
NASA Astrophysics Data System (ADS)
Amarpuri, Gaurav; Chen, Yizhou; Blackledge, Todd; Dhinojwala, Ali
Spider glue is a unique biological adhesive which is humidity responsive such that the adhesion continues to increase upto 100% relative humidity (RH) for some species. This is unlike synthetic adhesives that significantly drop in adhesion with an increase in humidity. However, most of adhesion data reported in literature have used clean hydrophilic glass substrate, unlike the hydrophobic, and charged insect cuticle surface that adheres to spider glue in nature. Previously, we have reported that the spider glue viscosity changes over five orders of magnitude with humidity. Here, we vary the surface energy and surface charge of the substrate to test the change in Larnioides cornutus spider glue adhesion with humidity. We find that an increase in both surface energy and surface charge density increases the droplet spreading and there exists an optimum droplet contact area where adhesion is maximized. Moreover, spider glue droplets act as reusable adhesive for low energy hydrophobic surface at the optimum humidity. These results explain why certain prey are caught more efficiently by spiders in their habitat. The mechanism by which spider species tune its glue adhesion for local prey capture can inspire new generation smart adhesives.
Evidence from Multiple Species that Spider Silk Glue Component ASG2 is a Spidroin
Collin, Matthew A.; Clarke, Thomas H.; Ayoub, Nadia A.; Hayashi, Cheryl Y.
Spiders in the superfamily Araneoidea produce viscous glue from aggregate silk glands. Aggregate glue coats prey-capture threads and hampers the escape of prey from webs, thereby increasing the foraging success of spiders. cDNAs for Aggregate Spider Glue 1 (ASG1) and 2 (ASG2) have been previously described from the golden orb-weaver, Nephila clavipes, and Western black widow, Latrodectus hesperus. To further investigate aggregate glues, we assembled ASG1 and ASG2 from genomic target capture libraries constructed from three species of cob-web weavers and three species of orb-web weavers, all araneoids. We show that ASG1 is unlikely to be a glue, but rather is part of a widespread arthropod gene family, the peritrophic matrix proteins. For ASG2, we demonstrate its remarkable architectural and sequence similarities to spider silk fibroins, indicating that ASG2 is a member of the spidroin gene family. Thus, spidroins have diversified into glues in addition to task-specific, high performance fibers. PMID:26875681
Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation.
Sharp, Kelli G; Dickson, Amanda R; Marchenko, Steve A; Yee, Kelly M; Emery, Pauline N; Laidmåe, Ivo; Uibo, Raivo; Sawyer, Evelyn S; Steward, Oswald; Flanagan, Lisa A
The neural degeneration caused by spinal cord injury leaves a cavity at the injury site that greatly inhibits repair. One approach to promoting repair is to fill the cavity with a scaffold to limit further damage and encourage regrowth. Injectable materials are advantageous scaffolds because they can be placed as a liquid in the lesion site then form a solid in vivo that precisely matches the contours of the lesion. Fibrin is one type of injectable scaffold, but risk of infection from blood borne pathogens has limited its use. We investigated the potential utility of salmon fibrin as an injectable scaffold to treat spinal cord injury since it lacks mammalian infectious agents and encourages greater neuronal extension in vitro than mammalian fibrin or Matrigel®, another injectable material. Female rats received a T9 dorsal hemisection injury and were treated with either salmon or human fibrin at the time of injury while a third group served as untreated controls. Locomotor function was assessed using the BBB scale, bladder function was analyzed by measuring residual urine, and sensory responses were tested by mechanical stimulation (von Frey hairs). Histological analyses quantified the glial scar, lesion volume, and serotonergic fiber density. Rats that received salmon fibrin exhibited significantly improved recovery of both locomotor and bladder function and a greater density of serotonergic innervation caudal to the lesion site without exacerbation of pain. Rats treated with salmon fibrin also exhibited less autophagia than those treated with human fibrin, potentially pointing to amelioration of sensory dysfunction. Glial scar formation and lesion size did not differ significantly among groups. The pattern and timing of salmon fibrin's effects suggest that it acts on neuronal populations but not by stimulating long tract regeneration. Salmon fibrin clearly has properties distinct from those of mammalian fibrin and is a beneficial injectable scaffold for treatment
Effects of a fibrin-fibronectin sealing system on proliferation and type I collagen synthesis of human PDL fibroblasts in vitro.
Fabris, G; Trombelli, L; Schincaglia, G P; Cavallini, R; Calura, G; del Senno, L
Fibrin glue (FG) is an agent widely used in many surgical disciplines for achieving hemostasis and tissue adhesion. The aim of this investigation was to determine the effectiveness of a highly concentrated FG (Tissucol) on the growth and phenotypic expression of human periodontal ligament (PDL) fibroblasts. PDL fibroblast strains were established from cells scraped from PDL, and cultured in the presence and absence of FG for 48 and 72 h. Cell proliferation was studied by counting cells and mitoses, and by immunocytochemical detection of the proliferation-associated Ki-67 nuclear antigen. Type-I collagen production was assessed by radioimmunological assay of the procollagen C-terminal peptide. Results showed that FG treatment was compatible with PDL fibroblast growth and type-I collagen synthesis, although a reduced trend in cell proliferation and collagen production was found in FG-supplemented cultures compared to control cultures. We conclude that FG may represent a suitable substrate for supporting PDL fibroblast growth and function. PMID:9477014
The origins of strain stiffening in fibrin networks
NASA Astrophysics Data System (ADS)
Jawerth, Louise; Muenster, Stefan; Weitz, David
Fibrin networks form the structural scaffold of blood clots; their non-linear mechanical properties are crucial to stem the flow of blood at a site of vascular injury. A hallmark of these networks is strain stiffening: a stiffness that increases non-linearly as a network is strained. Deformations of the fibers and the network combine to control the mechanical properties of the bulk and must lead to the strain stiffening behavior of the networks; however, the details of this process are unknown. Here, we study fibrin networks undergoing shear on a confocal microscope and compare this to bulk rheological measurements. We track individual fiber branchpoints as function of system strain. We characterize the non-affinity of the motion and show that the low strain, linear regime corresponds to highly non-affine motion while the high strain, nonlinear regime corresponds to affine motion. Moreover, we show that the non-linear bulk response can be well approximated by considering the fibers to be linear elastic elements with soft compressive behavior and, therefore, is a result of the topology of the network itself rather than nonlinearity of its constituents.
Fibrin solubilizing properties of certain anionic and cationic detergents.
Chakrabarty, S
The fibrinolytic (fibrin dissolving) properties of several anionic, cationic, nonionic and zwitterionic detergents were assessed in an in vitro fibrin agarose assay. Of the 4 anionic detergents tested, only sodium dodecyl sulfate (SDS) was found to be fibrinolytic. SDS was fibrinolytic either in the absence or presence of factor XIII. Four other cationic detergents were found to possess similar fibrinolytic properties. These cationic detergents were cetyltrimethylammonium bromide (CTAB), mix alkyltrimethyl ammonium bromide (MTAB), hexadecyltrimethylammonium bromide (HTAB) and cetylpyridium chloride (CPC). The nonionic (digitonin, triton X-100/tween 20) and zeitterionic (CHAPS, zeittergent 3-08) detergents were not fibrinolytic. Detergents mediated fibrinolysis, unlike that of tissue type plasminogen activator and urokinase, was independent of the presence of plasminogen. Non-detergents such as polyethylene glycol and highly charged compounds such as poly-1-lysine and poly-1-glutamic acid were not fibrinolytic. Fibrinolytic activity was observed for SDS and the cationic detergents at concentrations ranging from 0.1-10 percent. The effects of these fibrinolytic detergents (SDS, CTAB, MTAB, HTAB and CPC) on clot formation and on pre-formed clots were then assessed, using freshly drawn human venous blood. Incorporation of these detergents into blood inhibited the formation of clots in a concentration dependent manner. The detergents were also able to dissolve pre-formed clots in a similar fashion. SDS was found to be most potent in these properties. PMID:2510356
Soft fibrin gels promote selection and growth of tumorigenic cells
NASA Astrophysics Data System (ADS)
Liu, Jing; Tan, Youhua; Zhang, Huafeng; Zhang, Yi; Xu, Pingwei; Chen, Junwei; Poh, Yeh-Chuin; Tang, Ke; Wang, Ning; Huang, Bo
The identification of stem-cell-like cancer cells through conventional methods that depend on stem cell markers is often unreliable. We developed a mechanical method for selecting tumorigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe combined immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as ten such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.
Migration of keratinocytes through tunnels of digested fibrin
NASA Astrophysics Data System (ADS)
Ronfard, Vincent; Barrandon, Yann
We report here a hitherto undescribed form of cell migration. When a suspension of human keratinocytes is plated on a fibrin matrix, single cells invade the matrix and progress through it as rounded cells by dissolving the fibrin and thereby creating tunnels. These tunnels are cylindrical or helical, the latter being the result of constant change in the path of cellular advance around the helical axis. Helical tunnel formation is strongly promoted by epidermal growth factor. The rate of migration of the cell through the track of a helical tunnel (up to 2.1 mm per day) is about 7-fold greater than through a cylindrical tunnel. Pericellular fibrinolysis leading to tunnel formation depends on the presence of plasminogen in the medium and its conversion to plasmin by a cellular activator. Formation of tunnels requires that plasminogen activator be localized on the advancing surface of the keratinocyte; we propose that the tunnel is cylindrical when the site of release of plasmin is located at a fixed point on the cell surface and helical when the site of release precesses.
Suicide reconstruction by glue-lift of gunshot residue.
Basu, S; Ferriss, S; Horn, R
Based upon the recently developed glue-lift collection of gunshot residue particles for examination in the scanning electron microscope with energy dispersive X-rays, this laboratory has undertaken a research program to determine if reconstruction of gunshot deaths is feasible. Because undisturbed conditions of suicide victims may help in securing unambiguous results and high success rates, the program has been carried out to reconstruct suicides only. Data obtained from 13 firearms suicides and their laboratory reconstruction which involved primarily shotguns and handguns, indicate that reconstruction can be immensely useful to interpretation of the gunshot residue distributions on a suspect's or victim's hands. This reports outlines the basic experiments performed to relate the residue emission from the gun to the deposits found on the firing hand(s) and a description of the reconstruction technique that uses a target to simulate a human body. The technique can determine the specifics of a victim's hand position at the time of firing and which hand was used to pull the trigger. Because the technique is sensitive to the nature of the grasp of the firing hand and of the supporting hand, in the case of a shotgun, it has been possible in all cases to date, to determine which one of the potential eight hand positions existed at the time of shooting. PMID:6747586
Performance of the GlueX Barrel Calorimeter
NASA Astrophysics Data System (ADS)
Smith, Elton; Dalton, Mark; McGinley, William; Papandreou, Zisis; GlueX Collaboration
The GlueX experiment at Jefferson Lab will search for exotic hybrid mesons, a new form of hadronic matter that exhibits gluonic degrees of freedom. We have taken data to commission the experiment and report here on the construction and performance of the electromagnetic barrel calorimeter (BCAL). The BCAL is a ``spaghetti calorimeter,'' consisting of layers of corrugated lead sheets, interleaved with planes of 1-mm-diameter, double-clad, scintillating fibers, bonded in the lead grooves using optical epoxy. This detector consists of 48 modules that are readout using 3,840 large-area Multi-Photon Pixel counter (MPPC) arrays. The measured width of the π0 mass peak is approximately 10 MeV, only slightly higher than projections based on prototypes. Systematic studies are underway to understand the contributions to the resolution and improve its performance. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics under Contract DE-AC05-06OR23177.
From glue to gasoline: how competition turns perspective takers unethical.
Pierce, Jason R; Kilduff, Gavin J; Galinsky, Adam D; Sivanathan, Niro
Perspective taking is often the glue that binds people together. However, we propose that in competitive contexts, perspective taking is akin to adding gasoline to a fire: It inflames already-aroused competitive impulses and leads people to protect themselves from the potentially insidious actions of their competitors. Overall, we suggest that perspective taking functions as a relational amplifier. In cooperative contexts, it creates the foundation for prosocial impulses, but in competitive contexts, it triggers hypercompetition, leading people to prophylactically engage in unethical behavior to prevent themselves from being exploited. The experiments reported here establish that perspective taking interacts with the relational context--cooperative or competitive--to predict unethical behavior, from using insidious negotiation tactics to materially deceiving one's partner to cheating on an anagram task. In the context of competition, perspective taking can pervert the age-old axiom "do unto others as you would have them do unto you" into "do unto others as you think they will try to do unto you." PMID:23955353
Autologous bone marrow transplantation by photodynamic therapy
NASA Astrophysics Data System (ADS)
Gulliya, Kirpal S.
Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.
The configuration of fibrin clots determines capillary morphogenesis and endothelial cell migration.
Nehls, V; Herrmann, R
In the living organism, capillary growth frequently occurs in a fibrin-rich extracellular matrix. The structure and the mechanical properties of fibrin clots are influenced by various macromolecules (i.e., hyaluronic acid and thrombospondin) and also by pH, ionic strength, and thrombin concentrations of the milieu in which they polymerize. The configuration (three-dimensional architecture) and the rigidity of fibrin clots correlate with their opacity measured by spectrophotometric absorbance readings at 350 nm. By using bovine pulmonary artery endothelial cells and bovine fibrinogen, we show here that transparent fibrin clots (A(350) < 1.0), polymerized at > or = pH 7.5 or in the presence of increased thrombin or sodium chloride concentrations, strongly stimulated capillary morphogenesis in vitro. In contrast, opaque fibrin gels (A(350) > 1.5), polymerized at pH 7.2 or in the presence of dextran, stimulated only the migration of endothelial cells but not capillary morphogenesis. We demonstrate that the angiomorphogenic effects of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are strongly dependent on the structure of the fibrin clots. Our findings suggest that bFGF/VEGF primarily stimulate the proliferation of endothelial cells, whereas the three-dimensional architecture of the fibrin matrix is decisive for capillary morphogenesis. PMID:8992233
Quantification and macroscopic modeling of the nonlinear viscoelastic behavior of strained gels with varying fibrin concentrations.
Benkherourou, M; Guméry, P Y; Tranqui, L; Tracqui, P
The mechanical properties of fibrin gels under uniaxial strains have been analyzed for low fibrin concentrations using a free-floating gel device. We were able to quantify the viscous and elastic moduli of gels with fibrin concentration ranging from 0.5 to 3 mg/ml, reporting significant differences of biogels moduli and dynamical response according to fibrin concentration. Furthermore, considering sequences of successively imposed step strains has revealed the strain-hardening properties of fibrin gels for strain amplitude below 5%. This nonlinear viscoelastic behavior of the gels has been precisely analyzed through numerical simulations of the overall gel response to the strain steps sequences. Phenomenological power laws relating the instantaneous and relaxed elasticity moduli to fibrin concentration have been validated, with concentration exponent in the order of 1.2 and 1.0, respectively. This continuous description of strain-dependent mechanical moduli was then used to simulate the biogel behavior when continuously time-varying strains are applied. We discuss how this experimental setup and associated macroscopic modeling of fibrin gels enable a further quantification of cell traction forces and mechanotransduction processes induced by biogel compaction or stretching. PMID:11077740
Detection of accessory spleens with indium 111-labeled autologous platelets
Davis, H.H., II; Varki, A.; Heaton, W.A.; Siegel, B.A.
In two patients with recurrent immune thrombocytopenia, accessory splenic tissue was demonstrated by radionuclide imaging following administration of indium 111-labeled autologous platelets. In one of these patients, no accessory splenic tissue was seen on images obtained with technetium 99m sulfur colloid. This new technique provides a simple means for demonstrating accessory spleens and simultaneously evaluating the life-span of autologous platelets.
Platelet glycoprotein VI binds to polymerized fibrin and promotes thrombin generation.
Mammadova-Bach, Elmina; Ollivier, Véronique; Loyau, Stéphane; Schaff, Mathieu; Dumont, Bénédicte; Favier, Rémi; Freyburger, Geneviève; Latger-Cannard, Véronique; Nieswandt, Bernhard; Gachet, Christian; Mangin, Pierre H; Jandrot-Perrus, Martine
Fibrin, the coagulation end product, consolidates the platelet plug at sites of vascular injury and supports the recruitment of circulating platelets. In addition to integrin αIIbβ3, another as-yet-unidentified receptor is thought to mediate platelet interaction with fibrin. Platelet glycoprotein VI (GPVI) interacts with collagen and several other adhesive macromolecules. We evaluated the hypothesis that GPVI could be a functional platelet receptor for fibrin. Calibrated thrombin assays using platelet-rich plasma (PRP) showed that tissue factor-triggered thrombin generation was impaired in GPVI-deficient patients and reduced by the anti-GPVI Fab 9O12. Assays on reconstituted PRP and PRP from fibrinogen-deficient patients revealed a fibrinogen-dependent enhancement of thrombin generation, which relied on functional GPVI. The effect of GPVI was found to depend on fibrin polymerization. A binding assay showed a specific interaction between GPVI-Fc and fibrin, inhibited by the Fab 9O12. This Fab also reduced platelet adhesion to fibrin at low (300 s(-1)) and high (1500 s(-1)) wall shear rates. Platelets adherent to fibrin displayed shape change, exposure of procoagulant phospholipids, and the formation of small clots. When hirudinated blood was perfused at 1500 s(-1) over preformed fibrin-rich clots, the Fab 9O12 decreased the recruitment of platelets by up to 85%. This study identifies GPVI as a platelet receptor for polymerized fibrin with 2 major functions: (1) amplification of thrombin generation and (2) recruitment of circulating platelets to clots. These so-far-unrecognized properties of GPVI confer on it a key role in thrombus growth and stabilization. PMID:25977585
Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*
Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas
Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443
Fibrin hydrogels for lentiviral gene delivery in vitro and in vivo
Kidd, Martha; Shin, Seungjin; Shea, Lonnie D.
Gene delivery from hydrogels represents a versatile approach for localized expression of tissue inductive factors than can promote cellular processes that lead to regeneration. Lentiviral gene therapy vectors were entrapped within fibrin hydrogels, either alone or complexes with hydroxylapatite (HA) nanoparticles. The inclusion of HA into the hydrogel led to the formation of small aggregates distributed throughout the hydrogel, with no obvious alteration of the pore structure outside the aggregates. The presence of HA slowed hydrogel degradation by collagenase and plasmin relative to fibrin alone, and also decreased the rate of cell migration. Lentivirus had similar release from the fibrin hydrogels formed with or without HA. The altered hydrogel properties suggest an interaction between the nanoparticle and fibrin, which may displace the virus from the particle leading to similar release profiles. Transgene expression by cells migrating into the hydrogel in vitro was reduced in the presence of HA, consistent with the role of cell migration on transgene expression. In vivo, lentivirus loaded fibrin hydrogels promoted localized transgene expression that increased through day 9 and decreased through day 14. For the fibrin only hydrogels, expression continued to decline after day 14. However, hydrogels with HA maintained this transgene expression level for an additional two weeks before declining. Immunostaining identified transgene primarily outside the fibrin-HA gel at day 9; however, at day 21, transgene expression was observed primarily within the fibrin-HA gel. The localized delivery of lentivirus provides an opportunity to enhance the bioactivity of fibrin hydrogels for a wide range of applications in regenerative medicine. PMID:21907251
Fibrin Accumulation Secondary to Loss of Plasmin-Mediated Fibrinolysis Drives Inflammatory Osteoporosis in Mice
Cole, Heather A.; Ohba, Tetsuro; Nyman, Jeffry S.; Hirotaka, Haro; Cates, Justin M. M.; Flick, Matthew J.; Degen, Jay L.; Schoenecker, Jonathan G.
Objective Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related co-morbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Methods Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αMβ2 binding motif. Results Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αMβ2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αMβ2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Conclusion Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. PMID:24664548
Fibronectin provides a conduit for fibroblast transmigration from collagenous stroma into fibrin clot provisional matrix.
Greiling, D; Clark, R A
After injury, the wound space is filled with a fibrin/fibronectin clot containing growth factors released by platelets and monocytes. In response to these factors, fibroblasts migrate into the fibrin clot and contribute to the formation of granulation tissue. The functional mechanisms allowing fibroblasts to leave the collagenous matrix of normal connective tissue and invade the provisional matrix of the fibrin clot have not been fully defined. To investigate these mechanisms we established a new in vitro model which simulates specific aspects of early wound healing, that is, the migration of fibroblasts from a three-dimensional collagen matrix into a fibrin clot. This transmigration could be induced by physiological concentrations of platelet releasate or platelet-derived growth factor BB (PDGF-BB) in a concentration-dependent manner. At 24 hours irradiated fibroblasts invaded the fibrin gel almost as well as non-irradiated cells, indicating that transmigration was independent of proliferation. Plasminogen and its activators appear to be necessary for invasion of the fibrin clot since protease inhibitors decreased the amount of migration. These serine proteases, however, were not necessary for exit from the collagen gel as fibroblasts migrated out of the collagen gel onto a surface coated with fibrin fibrils even in the presence of inhibitors. Removal of fibronectin (FN) from either the collagen gel or the fibrin gel markedly decreased the number of migrating cells, suggesting that FN provides a conduit for transmigration. Cell movement in the in vitro model was inhibited by RGD peptide, and by monoclonal antibodies against the subunits of the alpha5 beta1 and alpha v beta3 integrin receptor. Thus, the functional requirements for fibroblast transmigration from collagen-rich to fibrin-rich matrices, such as occurs in early wound healing, have been partially defined using an in vitro paradigm of this important biologic process. PMID:9133673
Autologous Graft-versus-Tumor Effect: Reality or Fiction?
In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients.
The relevance of Choukroun's platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft. Part II: implant surgery, prosthodontics, and survival.
Simonpieri, Alain; Del Corso, Marco; Sammartino, Gilberto; Dohan Ehrenfest, David M
Extensive bone grafting remains a delicate procedure, due to the slow and difficult integration of the grafted material into the physiological architecture. The recent use of platelet concentrates aims to improve this process of integration by accelerating bone and mucosal healing. Choukroun's platelet-rich fibrin (PRF) is a healing biomaterial that concentrates in a single autologous fibrin membrane, most platelets, leukocytes, and cytokines from a 10-mL blood harvest, without artificial biochemical modification (no anticoagulant, no bovine thrombin). In this second part, we describe the implant and prosthetic phases of a complex maxillary rehabilitation, after preimplant bone grafting using allograft, Choukroun's PRF membranes, and metronidazole. Twenty patients were treated using this new technique and followed up during 2.1 years (1-5 years). Finally, 184 dental implants were placed, including 54 classical screw implants (3I, Palm Beach Gardens, FL) and 130 implants with microthreaded collar (46 from AstraTech, Mölndal, Sweden; 84 from Intra-Lock, Boca Raton, FL). No implant or graft was lost in this case series, confirming the validity of this reconstructive protocol. However, the number of implants used per maxillary rehabilitation was always higher with simple screw implants than with microthreaded implants, the latter presenting a stronger initial implant stability. Finally, during complex implant rehabilitations, PRF membranes are particularly helpful for periosteum healing and maturation. The thick peri-implant gingiva is related to several healing phases on a PRF membrane layer and could explain the low marginal bone loss observed in this series. Microthreaded collar and platform-switching concept even improved this result. Multiple healing on PRF membranes seems a new opportunity to improve the final esthetic result. PMID:19509532
Implantation of rAAV5-IGF-I transduced autologous chondrocytes improves cartilage repair in full-thickness defects in the equine model.
Ortved, Kyla F; Begum, Laila; Mohammed, Hussni O; Nixon, Alan J
Cartilage injury often precipitates osteoarthritis which has driven research to bolster repair in cartilage impact damage. Autologous chondrocytes transduced with rAAV5-IGF-I were evaluated in chondral defects in a well-established large animal model. Cartilage was harvested from the talus of 24 horses; chondrocytes were isolated and stored frozen. Twenty million cells were cultured and transduced with 10(5) AAV vg/cell prior to implantation. Chondrocytes from eight horses were transduced with rAAV5-IGF-I, chondrocytes from eight horses with rAAV5-GFP, and chondrocytes from eight horses were not transduced. A 15 mm full-thickness chondral defect was created arthroscopically in the lateral trochlear ridge of the femur in both femoropatellar joints. Treated defects were filled with naive or gene-enhanced chondrocytes, in fibrin vehicle. Control defects in the opposite limb received fibrin alone. rAAV5-IGF-I transduced chondrocytes resulted in significantly better healing at 8 week arthroscopy and 8 month necropsy examination when compared to controls. At 8 months, defects implanted with cells expressing IGF-I had better histological scores compared to control defects and defects repaired with naive chondrocytes. This included increased chondrocyte predominance and collagen type II, both features of hyaline-like repair tissue. The equine model closely approximates human cartilage healing, indicating AAV-mediated genetic modification of chondrocytes may be clinically beneficial to humans. PMID:25311491
Acute fibrinous and organizing pneumonia: A rare form of nonbacterial pneumonia.
Saxena, Prashant; Kumar, Kuldeep; Mittal, Sarita; Goyal, Nidhi; Trikha, Sahil; Vashisth, Arti
Acute fibrinous and organizing pneumonia (AFOP) is a rare disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of "fibrin balls." Here, we report a 43-year-old female with complaints of fever, dry cough, and shortness of breath with hypoxemia. High-resolution computed tomography thorax revealed diffuse confluent consolidation in bilateral lung zones. Bronchoscopy and transbronchial biopsy revealed features of AFOP. With prednisolone treatment, there was an improvement in her condition. AFOP is a rare disease and should be taken into consideration and differential diagnosis of severe acute pneumonias with no significant comorbidities. PMID:27303141
Acute fibrinous and organizing pneumonia: A rare form of nonbacterial pneumonia
Saxena, Prashant; Kumar, Kuldeep; Mittal, Sarita; Goyal, Nidhi; Trikha, Sahil; Vashisth, Arti
Acute fibrinous and organizing pneumonia (AFOP) is a rare disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of "fibrin balls." Here, we report a 43-year-old female with complaints of fever, dry cough, and shortness of breath with hypoxemia. High-resolution computed tomography thorax revealed diffuse confluent consolidation in bilateral lung zones. Bronchoscopy and transbronchial biopsy revealed features of AFOP. With prednisolone treatment, there was an improvement in her condition. AFOP is a rare disease and should be taken into consideration and differential diagnosis of severe acute pneumonias with no significant comorbidities. PMID:27303141
Breast Augmentation With Autologous Fat Injection
Li, Fa-Cheng; Chen, Bing; Cheng, Lin
Introduction Autologous fat transplantation has attracted great interest in breast augmentation for cosmetic purpose. In the present study, we reported our experience in fat grafting in breast in 105 cases, and some detailed procedure concerning efficacy and safety of grafting was evaluated. Methods Fat was harvested using 20-mL syringe attached to a 3-hole blunt cannula in a diameter not beyond 3 mm. After washing with cool normal saline to remove blood, the fat was managed with open method using cotton towel as a platform for concentration fat tissue and separating them from fluids, oil, and debris. A 14-gauge, 1-hole blunt cannula was used to place the fat through 3-mm incision on inframammary fold. The fat was infiltrated into the breast from deep to superficial subcutaneous plane. Results Between July 2002 and August 2010, 105 patients have undergone this procedure. The age distribution of the patients ranged from 18 to 45 years, with a mean of 31.3 years. Grafted fat volume has ranged from 120 to 250 mL (average, 205 mL) per breast per session. All women had a significant improvement in their breast size and shape postoperatively, and the breasts were soft and natural in appearance. Conclusions Liposuction and autologous fat transplantation is a suitable approach for augmentation mammaplasty. PMID:25003461
Autologous stem cells for personalised medicine.
Prasongchean, Weerapong; Ferretti, Patrizia
Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention. PMID:22561284
Meniscal Repair of Degenerative Horizontal Cleavage Tears Using Fibrin Clots
Kamimura, Tamiko; Kimura, Masashi
Background: Presently, the treatment options available for patients with horizontal degenerative cleavage tears of the meniscus are limited. These tears are considered an indication for partial or subtotal meniscectomy because when the tear is located within an avascular area, it is difficult to induce healing. However, meniscectomy is not ideal because it disrupts the normal anatomical structure and function of the meniscus. Purpose: To examine the clinical and arthroscopic outcomes following meniscal repair of degenerative horizontal cleavage tears using fibrin clots. Study Design: Case series; Level of evidence, 4. Methods: Vertical sutures were placed in the meniscal tear, and the cleft was filled with fibrin clots before the sutures were tightened. We repaired 18 menisci in 18 consecutive eligible patients using a previously described technique. Three patients with anterior cruciate ligament (ACL) injury who underwent simultaneous ACL reconstruction and 5 patients who did not undergo follow-up arthroscopy within 12 months were excluded. The remaining 10 menisci in 10 patients were evaluated in this study. The mean age of the patients was 35.8 ± 16.5 years, and the mean postoperative follow-up time was 40.8 ± 5.4 months. Pre- and postoperative Lysholm scores, International Knee Documentation Committee (IKDC) subjective scores, and Tegner activity levels were compared. The arthroscopy findings were evaluated at a mean postoperative time of 6.7 ± 2.9 months. Results: The mean Lysholm score improved significantly from 69.3 ± 16.3 points preoperatively to 95.4 ± 3.6 points postoperatively (P < .005). The mean IKDC subjective score also improved significantly from 26.5% ± 19.0% preoperatively to 87.8% ± 7.5% postoperatively (P < .001). The Tegner activity level recovered to the preinjury level in 6 patients and to 1 level below the preinjury level in 4 patients. The follow-up arthroscopies showed complete healing in 7 patients (70%) and incomplete healing in
The polymerization and thrombin-binding properties of des-(B beta 1-42)-fibrin.
Siebenlist, K R; DiOrio, J P; Budzynski, A Z; Mosesson, M W
Multiple factors affect the thrombin-catalyzed conversion of fibrinogen to fibrin, including: fibrinopeptide (FPA and FPB) release leading to exposure of two types of polymerization domains ("A" and "B," respectively) in the central portion of the molecule, and exposure of a noncatalytic "secondary" thrombin-binding site in fibrin. Fibrinogen containing the FPA sequence but lacking the B beta 1-42 sequence ("des-(B beta 1-42)-fibrinogen"), was compared to native fibrinogen (containing both FPA and FPB) to investigate the role played by B beta 1-42 in the polymerization of alpha-fibrin (i.e. fibrin lacking FPA), to compare reptilase and thrombin cleavage of FPA from fibrinogen, and to explore the location and function of the secondary thrombin-binding site. Electron microscopy of evolving polymer structures (mu, 0.14; pH 7.4) plus turbidity measurements, showed that early thin fibril formation as well as subsequent lateral fibril associations were impaired in des-(B beta 1-42)-alpha-fibrin, thus indicating that the B beta 1-42 sequence contributes to the A polymerization site. Reptilase-activated des-(B beta 1-42)-alpha-fibrin polymerized even more slowly than thrombin-activated des-(B beta 1-42)-alpha-fibrin, differences that disappeared when repolymerization of preformed fibrin monomers was carried out. Since existing data indicate that thrombin releases FPA in a concerted manner, resulting in relatively rapid evolution of fully functional divalent alpha-fibrin monomers, it can be inferred that delayed fibrin assembly of reptilase fibrin is due to slower formation of divalent alpha-fibrin monomers. Thrombin-activated des-(B beta 1-42)-alpha-fibrin polymerized more rapidly at low ionic strength (mu, 0.04) than did native alpha,beta-fibrin, a reversal of their behavior at physiological ionic strength (mu, 0.14). Concomitant measurement of FPA release revealed modest slowing of release at low ionic strength from des-(B beta 1-42)-fibrinogen (t1/2, 36.5 versus 21
Ubiquitous distribution of salts and proteins in spider glue enhances spider silk adhesion
NASA Astrophysics Data System (ADS)
Amarpuri, Gaurav; Chaurasia, Vishal; Jain, Dharamdeep; Blackledge, Todd A.; Dhinojwala, Ali
Modern orb-weaving spiders use micron-sized glue droplets on their viscid silk to retain prey in webs. A combination of low molecular weight salts and proteins makes the glue viscoelastic and humidity responsive in a way not easily achieved by synthetic adhesives. Optically, the glue droplet shows a heterogeneous structure, but the spatial arrangement of its chemical components is poorly understood. Here, we use optical and confocal Raman microscopy to show that salts and proteins are present ubiquitously throughout the droplet. The distribution of adhesive proteins in the peripheral region explains the superior prey capture performance of orb webs as it enables the entire surface area of the glue droplet to act as a site for prey capture. The presence of salts throughout the droplet explains the recent Solid-State NMR results that show salts directly facilitate protein mobility. Understanding the function of individual glue components and the role of the droplet's macro-structure can help in designing better synthetic adhesives for humid environments.
Daily streamflow prediction with uncertainty in ephemeral catchments using the GLUE methodology
NASA Astrophysics Data System (ADS)
Viola, F.; Noto, L. V.; Cannarozzo, M.; La Loggia, G.
The Generalised Likelihood Uncertainty Estimation (GLUE) approach is presented here as a tool for estimating the predictive uncertainty of a rainfall-runoff model. The GLUE methodology allows to recognise the possible equifinality of different parameter sets and assesses the likelihood of a parameters set being acceptable simulator when model predictions are compared to observed field data. The results of the GLUE methodology depend greatly on the choice of the likelihood measure and on the choice of the threshold which determines if a parameters set is behavioural or not. Moreover the sampling size has a strong influence on the uncertainty assessment of the response of a rainfall-runoff model. This is one of the most controversial and criticized aspect of the GLUE methodology, because it seems that this procedure does not learn from observations. Following these premises, this paper investigated first on the effect of different likelihood measures on the uncertainty analysis in the rainfall-runoff modelling of a mediterranean catchment. Performance of individual parameter sets has been assessed using three likelihood measures with a shaping factor. The acceptability threshold influence on the uncertainty analysis has been also evaluated. Finally it can be demonstrated how, using the GLUE, the predictive uncertainty grows with the streamflow variance while remains almost the same with the sampling size. In order to overcome these inconsistencies, a new simple likelihood measure, which explicitly takes into account the sample variance and extension, is here proposed.
Ubiquitous distribution of salts and proteins in spider glue enhances spider silk adhesion
Amarpuri, Gaurav; Chaurasia, Vishal; Jain, Dharamdeep; Blackledge, Todd A.; Dhinojwala, Ali
Modern orb-weaving spiders use micron-sized glue droplets on their viscid silk to retain prey in webs. A combination of low molecular weight salts and proteins makes the glue viscoelastic and humidity responsive in a way not easily achieved by synthetic adhesives. Optically, the glue droplet shows a heterogeneous structure, but the spatial arrangement of its chemical components is poorly understood. Here, we use optical and confocal Raman microscopy to show that salts and proteins are present ubiquitously throughout the droplet. The distribution of adhesive proteins in the peripheral region explains the superior prey capture performance of orb webs as it enables the entire surface area of the glue droplet to act as a site for prey capture. The presence of salts throughout the droplet explains the recent Solid-State NMR results that show salts directly facilitate protein mobility. Understanding the function of individual glue components and the role of the droplet's macro-structure can help in designing better synthetic adhesives for humid environments. PMID:25761668
The application of a new cyanoacrylate glue in pediatric surgery for fistula closure.
Hosseini, Seyed Mohammad Vahid; Bahador, Ali; Foroutan, Hamid Reza; Sabet, Babak; Geramizadeh, Bita; Zarenezhad, Mohammad
Surgical glues have been used in pediatric surgery because of the fragility of tissue, and to prevent major surgeries. The present report describes our experience with using a new cyanoacrylate Glubran 2 (Viareggio, Italy) in the treatment of five cases of tracheoesophageal atresia with fistula (one fistula protection, three recurrent fistula, and one unstable patients), two cases of hypospadias, one case of vesicutanouse fistula after bladder extrophy, and one case of cloacal extrophy from January-December 2008. Three cases of recurrent tracheoesophageal atresia with fistula were treated by bronchoscpic glue injection. The other two cases benefited from glue through its ability to plug the fistula and to act as a protecting layer on anastomosis. In two cases with hypospadias excessive use of the glue caused skin necrosis, which was repaired. The wounds of cloacal extrophy were protected from nearby colostomy contamination and infection, and the vesicocutanouse fistula was closed by deepithelialization and sealing with glue. Based on the outcomes of the cases, it may be possible to suggest that Glubran 2 may be used safely in Pediatric Surgery as a sealant for the prevention and treatment of fistulas. PMID:23365480
The Application of a New Cyanoacrylate Glue in Pediatric Surgery for Fistula Closure
Hosseini, Seyed Mohammad Vahid; Bahador, Ali; Foroutan, Hamid Reza; Sabet, Babak; Geramizadeh, Bita; Zarenezhad, Mohammad
Surgical glues have been used in pediatric surgery because of the fragility of tissue, and to prevent major surgeries. The present report describes our experience with using a new cyanoacrylate Glubran 2 (Viareggio, Italy) in the treatment of five cases of tracheoesophageal atresia with fistula (one fistula protection, three recurrent fistula, and one unstable patients), two cases of hypospadias, one case of vesicutanouse fistula after bladder extrophy, and one case of cloacal extrophy from January–December 2008. Three cases of recurrent tracheoesophageal atresia with fistula were treated by bronchoscpic glue injection. The other two cases benefited from glue through its ability to plug the fistula and to act as a protecting layer on anastomosis. In two cases with hypospadias excessive use of the glue caused skin necrosis, which was repaired. The wounds of cloacal extrophy were protected from nearby colostomy contamination and infection, and the vesicocutanouse fistula was closed by deepithelialization and sealing with glue. Based on the outcomes of the cases, it may be possible to suggest that Glubran 2 may be used safely in Pediatric Surgery as a sealant for the prevention and treatment of fistulas. PMID:23365480
Nabiullina, R M; Mustafin, I G; Ataullakhanov, F I; Litvinov, R I; Zubairova, L D
The effects of blood microparticles (MPs) on the dynamics of fibrin polymerization, clot structure and susceptibility to fibrinolysis were studied. Kinetics of fibrin polymerization, fibrinolysis, thrombin generation in platelet-free, microparticle-depleted and microparticle-depleted plasma replenished with cephalin, from healthy donors were analyzed in parallel. MPs have profound effects on all stages of fibrin formation, decrease its turbidity. All parameters obtained in the absence of MPs were recovered after reconstitution of phospholipids. Thrombin generation rates were reduced in the absence of MPs. In the presence of MPs the fibrin networks had less poro us structures with thinner fibers, while clots formed in the absence of MPs had larger pores and were built of thicker fibers. Clots formed in the presence of MPs were significantly more resistant to fibrinolysis. Results show that normally circulating MPs can support the formation of stable clots at the sites of vascular injury. PMID:26591054
Fibrin Clot Structure and Mechanics Associated with Specific Oxidation of Methionine Residues in Fibrinogen
Weigandt, Katie M.; White, Nathan; Chung, Dominic; Ellingson, Erica; Wang, Yi; Fu, Xiaoyun; Pozzo, Danilo C.
Using a combination of structural and mechanical characterization, we examine the effect of fibrinogen oxidation on the formation of fibrin clots. We find that treatment with hypochlorous acid preferentially oxidizes specific methionine residues on the α, β, and γ chains of fibrinogen. Oxidation is associated with the formation of a dense network of thin fibers after activation by thrombin. Additionally, both the linear and nonlinear mechanical properties of oxidized fibrin gels are found to be altered with oxidation. Finally, the structural modifications induced by oxidation are associated with delayed fibrin lysis via plasminogen and tissue plasminogen activator. Based on these results, we speculate that methionine oxidation of specific residues may be related to hindered lateral aggregation of protofibrils in fibrin gels. PMID:23283239
An analysis of a preoperative pediatric autologous blood donation program
Letts, Merv; Perng, Richard; Luke, Brian; Jarvis, James; Lawton, Louis; Hoey, Steve
Objective To determine the efficacy of a pediatric autologous blood donation program. Design A retrospective study of patient charts and blood-bank records. Setting The Children's Hospital of Eastern Ontario, Ottawa, a tertiary care, pediatric centre. Patients One hundred and seventy-three children who received blood transfusions for a total of 182 procedures between June 1987 and June 1997. Interventions Autologous and homologous blood transfusion required for major surgical intervention, primarily spinal fusion. Main outcome measures Surgeons' accuracy in predicting the number of autologous blood units required for a given procedure, compliance rate (children's ability to donate the requested volume of blood), utilization rate of autologous units and rate of allogeneic transfusion. Results The surgeons' accuracy in predicting the number of autologous units required for a given procedure was 53.8%. The compliance rate of children to donate the requested amount of blood was 80.3%. In children below the standard age and weight criteria for blood donation the compliance rate was 75.5%. The utilization rate of autologous units obtained was 84.4% and the incidence of allogeneic transfusion was 26.6%. Conclusions There was a high rate of compliance and utilization of predonated autologous blood in the children in the study. Preoperative blood donation programs are safe and effective in children, even in those below the standard age and weight criteria of 10 years and 40 kg. PMID:10812347
Photoclickable dendritic molecular glue: noncovalent-to-covalent photochemical transformation of protein hybrids.
Uchida, Noriyuki; Okuro, Kou; Niitani, Yamato; Ling, Xiao; Ariga, Takayuki; Tomishige, Michio; Aida, Takuzo
A water-soluble dendron with a fluorescein isothiocyanate (FITC) fluorescent label and bearing nine pendant guanidinium ion (Gu(+))/benzophenone (BP) pairs at its periphery (Glue(BP)-FITC) serves as a "photoclickable molecular glue". By multivalent salt-bridge formation between Gu(+) ions and oxyanions, Glue(BP)-FITC temporarily adheres to a kinesin/microtubule hybrid. Upon subsequent exposure to UV light, this noncovalent binding is made permanent via a cross-linking reaction mediated by carbon radicals derived from the photoexcited BP units. This temporal-to-permanent transformation by light occurs quickly and efficiently in this preorganized state, allowing the movements of microtubules on a kinesin-coated glass plate to be photochemically controlled. A fundamental difference between such temporal and permanent bindings was visualized by the use of "optical tweezers". PMID:23477460
Application of the silicon photomultipliers for detectors in the GlueX experiment
Somov, Sergey V.; Tolstukhin, Ivan; Somov, Alexander S.
The GlueX detector in Hall D at Jefferson Lab is instrumented with about 5000 Silicon Photomultipliers (SiPM) manufactured by Hamamatsu Corporation [2]. These photo sensors have properties similar to conventional photomultipliers but can be operated at high magnetic fields. Silicon photomultipliers with a sensitive area of 3x3 mm2 are used to detect light from the following GlueX scintillator detectors: the tagger microscope, pair spectrometer, and start counter. Arrays of 4x4 SiPMs sensors were chosen for the instrumentation of the barrel electromagnetic calorimeter. The tagger microscope must operate at high rates (up to 2.5 MHz) and provide time measurements with a resolution better than 0.3 ns. The paper will describe some results of the characterization of SiPMs for various GlueX sub-detectors.
Exotic Hybrid Meson Spectroscopy with the GlueX detector at Jlab
Lawrence, David W.
The GlueX experiment is scheduled to begin taking data in 2015. The goal is to discover evidence for the existence of exotic hybrid mesons and to map out their spectrum in the light quark sector. Recent theoretical developments using Lattice QCD predict exotic hybrid states in a mass range accessible using the newly upgraded 12GeV electron accelerator at Jefferson Lab. Hybrid mesons, and in particular exotic hybrid mesons, provide the ideal laboratory for testing QCD in the confinement regime since these mesons explicitly manifest the gluonic degrees of freedom. The experiment will use 9 GeV linearly polarized photons produced via coherent bremsstrahlung to produce the exotic hybrids. The decay products will be detected in the solenoid-based GlueX detector currently under construction at Jefferson Lab. The status of the GlueX experiment including detector parameters will be presented along with theoretical motivation for the experiment.
Bioengineered fibrin-based niche to direct outgrowth of circulating progenitors into neuron-like cells for potential use in cellular therapy
NASA Astrophysics Data System (ADS)
Tara, S.; Krishnan, Lissy K.
Objective. Autologous cells are considered to be the best choice for use in transplantation therapy. However, the challenges and risks associated with the harvest of transplantable autologous cells limit their successful therapeutic application. The current study explores the possibility of isolating neural progenitor cells from circulating multipotent adult progenitor cells for potential use in cell-based and patient-specific therapy for neurological diseases. Approach. To enable the selection of neural progenitor cells from human peripheral blood mononuclear cells, and to support their lineage maintenance, the composition of a fibrin-based niche was optimized. Morphological examination and specific marker analysis were carried out, employing a qualitative/quantitative polymerase chain reaction followed by immunocytochemistry to: (i) characterize neural progenitor cells in culture; (ii) monitor proliferation/survival; and (iii) track their differentiation status. Main results. The presence of neural progenitors in circulation was confirmed by the presence of nestin+ cells at the commencement of the culture. The isolation, proliferation and differentiation of circulating neural progenitors to neuron-like cells were directed by the engineered niche. Neural cell isolation to near homogeneity was confirmed by the expression of β-III tubulin in ∼95% of cells, whereas microtubule associated protein-2 expression confirmed their ability to differentiate. The concentration of potassium chloride in the niche was found to favour neuron-like cell lengthening, cell-cell contact, and expressions of synaptophysin and tyrosine hydroxylase. Significance. The purpose of this research was to find out if peripheral blood could serve as a potential source of neural progenitors for cell based therapy. The study established that neural progenitors could be selectively isolated from peripheral blood mononuclear cells using a biomimetic niche. The selected cells could multiply and
Potential dental pulp revascularization and odonto-/osteogenic capacity of a novel transplant combined with dental pulp stem cells and platelet-rich fibrin.
Chen, Yong-Jin; Zhao, Yin-Hua; Zhao, Ya-Juan; Liu, Nan-Xia; Lv, Xin; Li, Qiang; Chen, Fa-Ming; Zhang, Min
Our aim is to investigate the cytobiological effects of autologous platelet-rich fibrin (PRF) on dental pulp stem cells (DPSCs) and to explore the ectopic and orthotopic possibilities of dental pulp revascularization and pulp-dentin complex regeneration along the root canal cavities of the tooth by using a novel tissue-engineered transplant composed of cell-sheet fragments of DPSCs and PRF granules. Canine DPSCs were isolated and characterized by assaying their colony-forming ability and by determining their cell surface markers and osteogenic/adipogenic differentiation potential. The biological effects of autologous PRF on DPSCs, including cell proliferation, alkaline phosphatase (ALP) activity and odonto-/osteogenic gene expression, were then investigated and quantified. A novel transplant consisting of cell-sheet fragments of DPSCs and PRF granules was adopted to regenerate pulp-dentin-like tissues in the root canal, both subcutaneously in nude mice and in the roots of canines. PRF promoted the proliferation of DPSCs in a dose- and time-dependent manner and induced the differentiation of DPSCs to odonto-/osteoblastic fates by increasing the expression of the Alp, Dspp, Dmp1 and Bsp genes. Transplantation of the DPSC/PRF construct led both to a favorable regeneration of homogeneous and compact pulp-like tissues with abundantly distributed blood capillaries and to the deposition of regenerated dentin along the intracanal walls at 8 weeks post-operation. Thus, the application of DPSC/PRF tissue constructs might serve as a potential therapy in regenerative endodontics for pulp revitalization or revascularization. PMID:25797716
Aydinova, P R; Aliyev, E A
Results of surgical treatment of 21 patients, suffering high transsphincteric and extrasphincteric rectal fistulas, were studied. In patients of Group I the fistula passage was closed, using fistula plug obturator; and in patients of Group II--by the same, but preprocessed by fibrin adhesive. The fistula aperture germeticity, prophylaxis of rude cicatrices development in operative wound zone, promotion of better fixation of bioplastic material were guaranteed, using fistula plug obturator with preprocessing, using fibrin adhesive. PMID:26419026
Efficient therapy of ischaemic lesions with VEGF121-fibrin in an animal model of systemic sclerosis
Allipour Birgani, Shadab; Mailänder, Marion; Wasle, Ines; Dietrich, Hermann; Gruber, Johann; Distler, Oliver; Sgonc, Roswitha
Background In systemic sclerosis (SSc), chronic and uncontrolled overexpression of vascular endothelial growth factor (VEGF) results in chaotic vessels, and intractable fingertip ulcers. Vice versa, VEGF is a potent mediator of angiogenesis if temporally and spatially controlled. We have addressed this therapeutic dilemma in SSc by a novel approach using a VEGF121 variant that covalently binds to fibrin and gets released on demand by cellular enzymatic activity. Using University of California at Davis (UCD)-206 chickens, we tested the hypothesis that cell-demanded release of fibrin-bound VEGF121 leads to the formation of stable blood vessels, and clinical improvement of ischaemic lesions. Methods Ninety-one early and late ischaemic comb and neck skin lesions of UCD-206 chickens were treated locally with VEGF121-fibrin, fibrin alone, or left untreated. After 1 week of treatment the clinical outcome was assessed. Angiogenesis was studied by immunofluorescence staining of vascular markers quantitatively analysed using TissueQuest. Results Overall, 79.3% of the lesions treated with VEGF121-fibrin showed clinical improvement, whereas 71.0% of fibrin treated controls, and 93.1% of untreated lesions deteriorated. This was accompanied by significantly increased growth of stable microvessels, upregulation of the proangiogenic VEGFR-2 and its regulator TAL-1, and increase of endogenous endothelial VEGF expression. Conclusions Our findings in the avian model of SSc suggest that cell-demanded release of VEGF121 from fibrin matrix induces controlled angiogenesis by differential regulation of VEGFR-1 and VEGFR-2 expression, shifting the balance towards the proangiogenic VEGFR-2. The study shows the potential of covalently conjugated VEGF-fibrin matrices for the therapy of ischaemic lesions such as fingertip ulcers. PMID:26362758
Molecular imaging of fibrin in a breast cancer xenograft mouse model
Uppal, Ritika; Medarova, Zdravka; Farrar, Christian T.; Dai, Guangping; Moore, Anna; Caravan, Peter
Rationale and objectives Fibrin deposition has been indicated within the stroma of a majority of solid tumors. Here we assess the feasibility of using the established fibrin-specific probe EP-2104R for the noninvasive imaging of fibrin in the context of breast cancer. Methods EP-2104R, untargeted Gd-DTPA and a newly synthesized non-fibrin binding control linear peptide (CLP) were compared using steady-state and dynamic contrast enhanced MR imaging in a breast cancer xenograft mouse model at 9.4T. Results EP-2104R transiently enhanced both the tumor core and periphery, but only the enhancement in the tumor periphery persisted even 90 min after EP-2104R administration. However, untargeted Gd-DTPA and CLP are not retained in the tumor periphery. The half-life of EP-2104R in the tumor periphery (103±18 min) is significantly longer (p<0.05) than either Gd-DTPA (29.6±2.4 min) or CLP (42.4±1.5 min), but the rate of clearance is similar for all the three probes from the tumor core. The presence of high concentrations of fibrin in the tumor periphery was corroborated using immuno-histochemistry with a fibrin-specific antibody. Conclusions The persistent enhancement observed in the tumor periphery with EP-2104R is likely a result of its fibrin-specific binding rather than its size and demonstrates the feasibility of EP-2104R for molecular imaging of fibrin in tumor stroma. PMID:22960948
Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.
Bouchatta, Otmane; Ouhaz, Zakaria; Ba-Mhamed, Saadia; Kerekes, Nóra; Bennis, Mohamed
Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice. PMID:26969766
Role of autologous bladder-neck slings: a urogynecology perspective.
Zoorob, Dani; Karram, Mickey
The concept of the autologous pubovaginal sling involves supporting the proximal urethra and bladder neck with a piece of graft material, achieving continence either by providing a direct compressive force on the urethra/bladder outlet or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during transmission of increased abdominal pressure. Pubovaginal slings using a biological sling material (whether autologous, allograft, or xenograft) can be used successfully to manage primary or recurrent stress incontinence. This article addresses the indications for the use of an autologous bladder-neck sling, describes the surgical techniques, and discusses outcomes and technical considerations. PMID:22877713
Indium-111 autologous leukocyte imaging in pancreatitis
Anderson, J.R.; Spence, R.A.; Laird, J.D.; Ferguson, W.R.; Kennedy, T.L.
Thirty-nine patients with acute pancreatitis have been assessed using a prognostic factor grading system, abdominal ultrasound, and autologous leukocyte imaging. Both prognostic factor grading and leukocyte imaging can accurately assess the severity of the disease early in its course. All patients with a negative indium-labeled leukocyte image recovered without sequelae, whereas five of the 12 patients with a positive image developed complications, including two deaths. Abdominal ultrasound is of no value in assessing severity, but is a useful method of detecting those patients with gallstone-associated disease. In patients with suspected abscess formation following acute pancreatitis, indium leukocyte imaging does not differentiate between fat necrosis and abscess formation. In this situation, computerized tomography should be carried out before laparotomy is undertaken.
The α-Helix to β-Sheet Transition in Stretched and Compressed Hydrated Fibrin Clots
Litvinov, Rustem I.; Faizullin, Dzhigangir A.; Zuev, Yuriy F.; Weisel, John W.
Fibrin is a protein polymer that forms the viscoelastic scaffold of blood clots and thrombi. Despite the critical importance of fibrin deformability for outcomes of bleeding and thrombosis, the structural origins of the clot's elasticity and plasticity remain largely unknown. However, there is substantial evidence that unfolding of fibrin is an important part of the mechanism. We used Fourier transform infrared spectroscopy to reveal force-induced changes in the secondary structure of hydrated fibrin clots made of human blood plasma in vitro. When extended or compressed, fibrin showed a shift of absorbance intensity mainly in the amide I band (1600–1700 cm−1) as well as in the amide II and III bands, indicating an increase of the β-sheets and a corresponding reduction of the α-helices. The structural conversions correlated directly with the strain or pressure and were partially reversible at the conditions applied. The additional absorbance observed at 1612–1624 cm−1 was characteristic of the nascent interchain β-sheets, consistent with protein aggregation and fiber bundling during clot deformation observed using scanning electron microscopy. We conclude that under extension and/or compression an α-helix to β-sheet conversion of the coiled-coils occurs in the fibrin clot as a part of forced protein unfolding. PMID:23009851
Inhibition of thrombin generation in plasma by fibrin formation (Antithrombin I).
de Bosch, N B; Mosesson, M W; Ruiz-Sáez, A; Echenagucia, M; Rodriguez-Lemoin, A
The adsorption of thrombin to fibrin during clotting defines "Antithrombin I" activity. We confirmed that thrombin generation in afibrinogenemic or in Reptilase defibrinated normal plasma was higher than in normal plasma. Repletion of these fibrinogen-deficient plasmas with fibrinogen 1 (gamma A/gamma A), whose fibrin has two "low affinity" non-substrate thrombin binding sites, resulted in moderately reduced thrombin generation by 29-37%. Repletion with fibrinogen 2 (gamma'/gamma A), which in addition to low affinity thrombin-binding sites in fibrin, has a "high affinity" non-substrate thrombin binding site in the carboxy-terminal region of its gamma' chain, was even more effective and reduced thrombin generation by 57-67%. Adding peptides that compete for thrombin binding to fibrin [S-Hir53-64 (hirugen) or gamma'414-427] caused a transient delay in the onset of otherwise robust thrombin generation, indicating that fibrin formation is necessary for full expression of Antithrombin I activity. Considered together, 1) the increased thrombin generation in afibrinogenemic or fibrinogen-depleted normal plasma that is mitigated by fibrinogen replacement; 2) evidence that prothrombin activation is increased in afibrinogenemia and normalized by fibrinogen replacement; 3) the severe thrombophilia that is associated with defective thrombin-binding in dysfibrinogenemias Naples I and New York I, and 4) the association of afibrinogenemia or hypofibrinogenemia with venous or arterial thromboembolism, indicate that Antithrombin I (fibrin) modulates thromboembolic potential by inhibiting thrombin generation in blood. PMID:12195697
Endothelial Cells Organize Fibrin Clots into Structures That Are More Resistant to Lysis
NASA Astrophysics Data System (ADS)
Gray Jerome, W.; Handt, Stefan; Hantgan, Roy R.
Acute myocardial infarction is a major cause of death and disability in the United States. Introducing thrombolytic agents into the clot to dissolve occlusive coronary artery thrombi is one method of treatment. However, despite advances in our knowledge of thrombosis and thrombolysis, survival rates following thrombolytic therapy have not improved substantially. This failure highlights the need for further study of the factors mediating clot stabilization. Using laser scanning confocal microscopy of clots formed from fluorescein-labeled fibrinogen, we investigated what effect binding of fibrin to the endothelial surface has on clot structure and resistance to lysis. Fluorescent fibrin clots were produced over human umbilical vein endothelial cells (HUVEC) and the clot structure analyzed. In the presence of HUVEC, fibrin near the endothelial surface was more organized and occurred in tighter bundles compared to fibrin just 50 [mu]m above. The HUVEC influence on fibrin architecture was blocked by inhibitory concentrations of antibodies to [alpha]V or [beta]3 integrin subunits. The regions of the clots associated with endothelial cells were more resistant to lysis than the more homogenous regions distal to endothelium. Thus, our data show that binding of fibrin to integrins on endothelial surfaces produces clots that are more resistant to lysis.
Enhanced Viability of Endothelial Colony Forming Cells in Fibrin Microbeads for Sensor Vascularization
Gandhi, Jarel K.; Zivkovic, Lada; Fisher, John P.; Yoder, Mervin C.; Brey, Eric M.
Enhanced vascularization at sensor interfaces can improve long-term function. Fibrin, a natural polymer, has shown promise as a biomaterial for sensor coating due to its ability to sustain endothelial cell growth and promote local vascularization. However, the culture of cells, particularly endothelial cells (EC), within 3D scaffolds for more than a few days is challenging due to rapid loss of EC viability. In this manuscript, a robust method for developing fibrin microbead scaffolds for long-term culture of encapsulated ECs is described. Fibrin microbeads are formed using sodium alginate as a structural template. The size, swelling and structural properties of the microbeads were varied with needle gauge and composition and concentration of the pre-gel solution. Endothelial colony-forming cells (ECFCs) were suspended in the fibrin beads and cultured within a perfusion bioreactor system. The perfusion bioreactor enhanced ECFCs viability and genome stability in fibrin beads relative to static culture. Perfusion bioreactors enable 3D culture of ECs within fibrin beads for potential application as a sensor coating. PMID:26393602
Fibrin Sealant: The Only Approved Hemostat, Sealant, and Adhesive—a Laboratory and Clinical Perspective
Spotnitz, William D.
Background. Fibrin sealant became the first modern era material approved as a hemostat in the United States in 1998. It is the only agent presently approved as a hemostat, sealant, and adhesive by the Food and Drug Administration (FDA). The product is now supplied as patches in addition to the original liquid formulations. Both laboratory and clinical uses of fibrin sealant continue to grow. The new literature on this material also continues to proliferate rapidly (approximately 200 papers/year). Methods. An overview of current fibrin sealant products and their approved uses and a comprehensive PubMed based review of the recent literature (February 2012, through March 2013) on the laboratory and clinical use of fibrin sealant are provided. Product information is organized into sections based on a classification system for commercially available materials. Publications are presented in sections based on both laboratory research and clinical topics are listed in order of decreasing frequency. Results. Fibrin sealant remains useful hemostat, sealant, and adhesive. New formulations and applications continue to be developed. Conclusions. This agent remains clinically important with the recent introduction of new commercially available products. Fibrin sealant has multiple new uses that should result in further improvements in patient care. PMID:24729902
Fibrin Networks Support Recurring Mechanical Loads by Adapting their Structure across Multiple Scales.
Kurniawan, Nicholas A; Vos, Bart E; Biebricher, Andreas; Wuite, Gijs J L; Peterman, Erwin J G; Koenderink, Gijsje H
Tissues and cells sustain recurring mechanical loads that span a wide range of loading amplitudes and timescales as a consequence of exposure to blood flow, muscle activity, and external impact. Both tissues and cells derive their mechanical strength from fibrous protein scaffolds, which typically have a complex hierarchical structure. In this study, we focus on a prototypical hierarchical biomaterial, fibrin, which is one of the most resilient naturally occurring biopolymers and forms the structural scaffold of blood clots. We show how fibrous networks composed of fibrin utilize irreversible changes in their hierarchical structure at different scales to maintain reversible stress stiffening up to large strains. To trace the origin of this paradoxical resilience, we systematically tuned the microstructural parameters of fibrin and used a combination of optical tweezers and fluorescence microscopy to measure the interactions of single fibrin fibers for the first time, to our knowledge. We demonstrate that fibrin networks adapt to moderate strains by remodeling at the network scale through the spontaneous formation of new bonds between fibers, whereas they adapt to high strains by plastic remodeling of the fibers themselves. This multiscale adaptation mechanism endows fibrin gels with the remarkable ability to sustain recurring loads due to shear flows and wound stretching. Our findings therefore reveal a microscopic mechanism by which tissues and cells can balance elastic nonlinearity and plasticity, and thus can provide microstructural insights into cell-driven remodeling of tissues. PMID:27602730
Fibrin Gel as an Injectable Biodegradable Scaffold and Cell Carrier for Tissue Engineering
Li, Yuting; Meng, Hao; Liu, Yuan
Due to the increasing needs for organ transplantation and a universal shortage of donated tissues, tissue engineering emerges as a useful approach to engineer functional tissues. Although different synthetic materials have been used to fabricate tissue engineering scaffolds, they have many limitations such as the biocompatibility concerns, the inability to support cell attachment, and undesirable degradation rate. Fibrin gel, a biopolymeric material, provides numerous advantages over synthetic materials in functioning as a tissue engineering scaffold and a cell carrier. Fibrin gel exhibits excellent biocompatibility, promotes cell attachment, and can degrade in a controllable manner. Additionally, fibrin gel mimics the natural blood-clotting process and self-assembles into a polymer network. The ability for fibrin to cure in situ has been exploited to develop injectable scaffolds for the repair of damaged cardiac and cartilage tissues. Additionally, fibrin gel has been utilized as a cell carrier to protect cells from the forces during the application and cell delivery processes while enhancing the cell viability and tissue regeneration. Here, we review the recent advancement in developing fibrin-based biomaterials for the development of injectable tissue engineering scaffold and cell carriers. PMID:25853146
Fibrin-Loaded Porous Poly(Ethylene Glycol) Hydrogels as Scaffold Materials for Vascularized Tissue Formation
Jiang, Bin; Waller, Thomas M.; Larson, Jeffery C.; Appel, Alyssa A.
Vascular network formation within biomaterial scaffolds is essential for the generation of properly functioning engineered tissues. In this study, a method is described for generating composite hydrogels in which porous poly(ethylene glycol) (PEG) hydrogels serve as scaffolds for mechanical and structural support, and fibrin is loaded within the pores to induce vascularized tissue formation. Porous PEG hydrogels were generated by a salt leaching technique with 100–150-μm pore size and thrombin (Tb) preloaded within the scaffold. Fibrinogen (Fg) was loaded into pores with varying concentrations and polymerized into fibrin due to the presence of Tb, with loading efficiencies ranging from 79.9% to 82.4%. Fibrin was distributed throughout the entire porous hydrogels, lasted for greater than 20 days, and increased hydrogel mechanical stiffness. A rodent subcutaneous implant model was used to evaluate the influence of fibrin loading on in vivo response. At weeks 1, 2, and 3, all hydrogels had significant tissue invasion, but no difference in the depth of invasion was found with the Fg concentration. Hydrogels with fibrin loading induced more vascularization, with a significantly higher vascular density at 20 mg/mL (week 1) and 40 mg/mL (weeks 2 and 3) Fg concentration compared to hydrogels without fibrin. In conclusion, we have developed a composite hydrogel that supports rapid vascularized tissue ingrowth, and thus holds great potential for tissue engineering applications. PMID:23003671
Bandwidth-Tunable Fiber Bragg Gratings Based on UV Glue Technique
NASA Astrophysics Data System (ADS)
Fu, Ming-Yue; Liu, Wen-Feng; Chen, Hsin-Tsang; Chuang, Chia-Wei; Bor, Sheau-Shong; Tien, Chuen-Lin
In this study, we have demonstrated that a uniform fiber Bragg grating (FBG) can be transformed into a chirped fiber grating by a simple UV glue adhesive technique without shifting the reflection band with respect to the center wavelength of the FBG. The technique is based on the induced strain of an FBG due to the UV glue adhesive force on the fiber surface that causes a grating period variation and an effective index change. This technique can provide a fast and simple method of obtaining the required chirp value of a grating for applications in the dispersion compensators, gain flattening in erbium-doped fiber amplifiers (EDFAs) or optical filters.
Gastric outflow obstruction after ingestion of wood glue in a dog.
Horstman, Christopher L; Eubig, Paul A; Cornell, Karen K; Khan, Safdar A; Selcer, Barbara A
A 2-year-old, male, mixed-breed dog presented with a 12-day history of vomiting, depression, and weight loss after ingestion of industrial-strength wood glue containing diphenylmethane diisocyanate as its active ingredient. A diagnosis of gastric foreign body was made from survey abdominal radiographs. A large aggregate of solidified wood glue was surgically removed, and the dog recovered uneventfully. Fourteen other cases have been reported to the Animal Poison Control Center at the American Society for the Prevention of Cruelty to Animals (ASPCA). Eight of those 14 cases required surgical intervention. All cases recovered completely. PMID:12549613
Photocurable surgical tissue adhesive glues composed of photoreactive gelatin and poly(ethylene glycol) diacrylate.
Nakayama, Y; Matsuda, T
This article presents a novel photochemically driven surgical tissue adhesive technology using photoreactive gelatins and a water-soluble difunctional macromer (poly(ethylene glycol) diacrylate: PEGDA).The gelatins were partially derivatized with photoreactive groups, such as ultraviolet light (UV)-reactive benzophenone and visible light-reactive xanthene dye (e.g., fluorescein sodium salt, eosin Y, and rose bengal). A series of the prepared photocurable tissue adhesive glues, consisting of the photoreactive gelatin, PEGDA, and a saline solution with or without ascorbic acid as a reducing agent, were viscous solutions under warming, and their effectiveness was evaluated as hemostasis- and anastomosis-aid in cardiovascular surgery. Regardless of the type of photoreactive groups, the irradiation of the photocurable tissue adhesive glues by UV or visible light within 1 min produced water-swollen gels, which had a high adhesive strength to wet collagen film. These were due to the synergistic action of photoreactive group-initiated photo-cross-linking and photograft polymerization. An increase in the irradiation time resulted in increased gel yield and reduced water swellability. A decrease in the molecular weight of PEGDA and an increase in concentration of both gelatin and PEGDA resulted in reduced water swellability and increased tensile and burst strengths of the resultant gels. In rats whose livers were injured with a trephine in laparotomy, the bleeding spots were coated with the photocurable adhesive glue and irradiated through an optical fiber. The coated solution was immediately converted to a swollen gel. The gel was tightly adhered to the liver tissue presumably by interpenetration, and concomitantly hemostasis was completed. The anastomosis treatment with the photocurable glue in the canine abdominal or thoracic aortas incised with a knife resulted in little bleeding under pulsatile flow after declamping. Histological examination showed that the glues
[Fibrinogen glue in osteochondral fractures with small fragments of the upper limb].
Zilch, H; Talke, M
Fibrin sealant presents a satisfactory possibility for reconstruction of the joint surface, especially in cases of little osteochondral fragments. Our experience in 16 patients is detailed. The patients average age was 23 years. 34 osteochondral fragments had been glued in these 16 cases, 10 times at the finger joints, 4 times at the caput radii and 2 times at the trochlea humeri. The patients, who had been operated on from June 1979 to December 1984 have been followed up at an average of 2,1 years after the fibrin gluing. This method can avoid an early arthrodesis or oversized osteosynthetic material. PMID:2447845
In Vivo Evaluation of Different Surgical Procedures for Autologous Chondrocyte Implantation
Maréchal, Marina; Van Hauwermeiren, Hadewych; Neys, Johan; Vanderlinden, Gert
Objective: Autologous chondrocyte implantation (ACI) involves the application of a chondrocyte suspension into a membrane-sealed cartilage defect. Recently, "cell-seeded collagen matrix-supported" ACI has been developed wherein chondrocytes are seeded on a biomembrane. This study aimed at preclinically comparing 4 variant ACI techniques in a refined goat model: 2 traditional procedures, whereby the defect is sealed by a periosteal flap or collagen membrane, and 2 cell-seeding methods, with the collagen membrane either sutured or glued into the defect. Design: The efficacy of the surgical techniques was evaluated in an acute critical size chondral defect in the medial condyle of 32 skeletally mature goats, randomly assigned to 1 of the 4 aforementioned treatment groups. After 10 weeks in vivo, the quality of the repair was graded histologically by 2 independent, blinded readers using the "modified O'Driscoll" score. Results: The cell-seeding procedure whereby the membrane is sutured into the defect has a similar structural repair capacity than traditional ACI techniques. However, when the cell-seeded membrane was glued into the defect, the outcome appeared inferior. Conclusion: These findings indicate that optimizing the goat model and the postoperative recovery does allow preclinical evaluation of ACI-based cartilage implants in a load-bearing setting. This preclinical observation provides support to the clinical utilization of the sutured membrane-seeded (ACI-CS) technique, provided sutures, but not fibrin sealants, are used to fix the cell-seeded membrane in the defect bed. PMID:26069652
The clinical efficacy of using autologous platelet rich plasma in hip arthroplasty: A retrospective comparative study
Safdar, Atif; Shaaban, Hamid; Tibayan, Restituto; Miller, Richard; Boairdo, Richard; Guron, Gunwant
Background: Platelet rich plasma (PRP) is a blood derivative concentrate of platelets, fibrin and growth factors obtained through withdrawal and centrifugation of autologous blood and use for its inherent hemostatic and adhesive properties to promote wound healing. Hip arthroplasty is often associated with significant perioperative complications including blood loss necessitating blood transfusions, which can lead to multiple adverse reactions, infection transmission, and longer hospital stay. Materials and Methods: We conducted this retrospective comparative study to determine whether the use of PRP can reduce the bleeding complications in hip replacement surgeries and therefore decrease analgesic requirements and shorten the hospital stay. Results: Sixty patients had consecutive hip replacement surgeries. The study group (n=23) received PRP applications while the control group (n=37) were operated without PRP applications. Postoperative drop of hemoglobin, number of red blood cell (RBC) transfusions, analgesic requirements, and duration of hospital stay were recorded. There was no significant difference in the drop of hemoglobin preoperatively and postoperatively comparing study and control groups (P=0.75). There was no difference in transfusion requirements between the two groups (P=0.16) but there was trend toward less transfusion in the PRP-treated group. There were also no statistical differences in analgesic use (P=0.83) and lengths of hospitalization (P=0.68) between the two groups. Conclusion: We concluded that there is no clinical efficacy in using PRP in hip replacement surgeries. We recommend a larger prospective study be conducted to determine its clinical utility as an optimization strategy to improve outcome after hip arthroplasty PMID:25810634
Application of atelocollagen sheet for sellar reconstruction.
Goto, Yuko; Oshino, Satoru; Shimizu, Takeshi; Saitoh, Youichi
We aimed to evaluate combined use of atelocollagen sheet and fibrin glue for sellar reconstruction. Experiment 1: A plastic chamber was prepared with a hydroxyapatite lid with a hole of 10mm in diameter at its center, covered with a Gore-Tex sheet (W.L. Gore & Associates, Tokyo, Japan) 15mm in diameter and sealed with a combination of fibrin glue sealant and either atelocollagen sheet or polyglycolic acid (PGA) sheet. Air was injected into the chamber and the pressure at which air leakage occurred was measured under each situation. Mean (±standard deviation) leakage pressure was 816±162mmH2O for atelocollagen sheet (n=5), significantly higher than the 557±130mmH2O for PGA sheet (n=5, p<0.05, Wilcoxon test). Experiment 2: Bilateral 5mm bone windows were made in the temporal bone in eight rats. The surgical cavities were filled with one of four materials (fibrin glue only; fibrin glue and atelocollagen sheet; PGA sheet; or autologous fat tissue). Histological changes including the status of implanted materials and inflammatory responses were investigated 2 and 5weeks after the procedures. Both atelocollagen and PGA sheets remained at 5weeks after implantation, whereas fibrin glue and fat tissue were absorbed and undetectable at 2weeks. Inflammatory cell accumulation was less around the atelocollagen sheet compared to the PGA sheet. The combination of atelocollagen sheet and fibrin glue sealant showed sufficient adhesion force and favorable tissue affinity, suggesting this combination as a feasible material in sellar reconstruction. PMID:26778360
Autologous and allogeneic serum eye drops. The Dutch perspective.
van der Meer, Pieter F; Seghatchian, Jerard; de Korte, Dirk
If regular artificial tears are ineffective for treatment of ocular surface disorders (including extreme dry eye syndrome), serum eye drops (SEDs) may provide a way to relieve the symptoms. However, not all patients are eligible to donate blood to produce autologous SEDs. Therefore, the use of allogeneic SEDs (obtained from voluntary blood donors) should be explored as an alternative for autologous SEDs. The Dutch blood bank organization is currently looking into the possibilities to provide allogeneic SEDs, as (GMP) regulations become stricter, making it for hospitals more difficult to provide autologous SEDs. To demonstrate effectiveness of both autologous and allogeneic SEDs, a clinical trial is planned. The current status of SEDs in The Netherlands is described. This paper is based on summary of the presentation given at the DGTI meeting in Dresden. PMID:26138910
9 CFR 95.10 - Glue stock; importations permitted subject to restrictions.
Code of Federal Regulations, 2011 CFR
... disinfection by such method or methods as the Deputy Administrator, Veterinary Services may prescribe unless... permission by the Deputy Administrator, Veterinary Services glue stock may be stored for a temporary period... persons authorized by the Deputy Administrator, Veterinary Services so to do, or without sealing...
9 CFR 95.10 - Glue stock; importations permitted subject to restrictions.
Code of Federal Regulations, 2010 CFR
... disinfection by such method or methods as the Deputy Administrator, Veterinary Services may prescribe unless... permission by the Deputy Administrator, Veterinary Services glue stock may be stored for a temporary period... persons authorized by the Deputy Administrator, Veterinary Services so to do, or without sealing...
9 CFR 95.10 - Glue stock; importations permitted subject to restrictions.
Code of Federal Regulations, 2012 CFR
... disinfection by such method or methods as the Deputy Administrator, Veterinary Services may prescribe unless... permission by the Deputy Administrator, Veterinary Services glue stock may be stored for a temporary period... persons authorized by the Deputy Administrator, Veterinary Services so to do, or without sealing...
9 CFR 95.10 - Glue stock; importations permitted subject to restrictions.
Code of Federal Regulations, 2013 CFR
... disinfection by such method or methods as the Deputy Administrator, Veterinary Services may prescribe unless... permission by the Deputy Administrator, Veterinary Services glue stock may be stored for a temporary period... persons authorized by the Deputy Administrator, Veterinary Services so to do, or without sealing...
Transcatheter Embolization of a Large Symptomatic Pelvic Arteriovenous Malformation with Glubran 2 Acrylic Glue
Gandini, R.; Angelopoulos, G. Konda, D.; Messina, M.; Chiocchi, M.; Perretta, T.; Simonetti, G.
A young patient affected by a pelvic arteriovenous malformation (pAVM) with recurrent episodes of hematuria following exercise, underwent transcatheter embolization using Glubran 2 acrylic glue (GEM, Viareggio, Italy). All branches of the pAVM were successfully occluded. The patient showed prompt resolution of symptoms and persistent occlusion of the pAVM at the 6 month follow-up.
9 CFR 95.10 - Glue stock; importations permitted subject to restrictions.
Code of Federal Regulations, 2014 CFR
... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Glue stock; importations permitted subject to restrictions. 95.10 Section 95.10 Animals and Animal Products ANIMAL AND PLANT HEALTH... ANIMAL PRODUCTS SANITARY CONTROL OF ANIMAL BYPRODUCTS (EXCEPT CASINGS), AND HAY AND STRAW, OFFERED...
Prosthodontic self-treatment with acrylic resin super glue: a case report.
Winkler, Sheldon; Wood, Robert; Facchiano, Anne M; Boberick, Kenneth G; Patel, Amita R
A case history is presented of a patient who fabricated 3 prostheses from autopolymerizing acrylic resin intended for fingernail augmentation and then cemented them into her mouth with super glue. Patients must be warned not to attempt self-treatment for esthetics with self-fabricated prostheses because severe adverse and irreversible hard and soft tissue reactions may occur. PMID:16836177
Glueballs, gluon condensate, and pure glue QCD below T{sub c}
Buisseret, F.
A quasiparticle description of pure glue QCD below T{sub c} is presented. It is shown that the strong decrease of both the gluon condensate and the lightest glueball masses when approaching T{sub c} might be the trigger of the phase transition. The proposed model compares favorably with recent lattice data.
A unique and unexplained ricochet leak post PCI – Successfully treated with intra-coronary glue
Goel, Pravin K.; Syal, Sanjeev K.
We herein describe a unique case of coronary artery perforation treated with covered stent with repeat cardiac tamponade resulting out of a fresh unexplained leak from a remote vessel (Ricochet) and successfully treated with intra-coronary injection of sterile synthetic glue, cyanoacrylate. PMID:24581110
A unique and unexplained ricochet leak post PCI - successfully treated with intra-coronary glue.
Goel, Pravin K; Syal, Sanjeev K
We herein describe a unique case of coronary artery perforation treated with covered stent with repeat cardiac tamponade resulting out of a fresh unexplained leak from a remote vessel (Ricochet) and successfully treated with intra-coronary injection of sterile synthetic glue, cyanoacrylate. PMID:24581110
Large-area silicon photomultipliers as readout candidates for the GlueX experiment
NASA Astrophysics Data System (ADS)
Papandreou, Zisis; Janzen, Kathryn; Lolos, George; Semenov, Andrei; Zorn, Carl
The core mission of the GlueX experiment involves a search for exotic hybrid mesons as evidence of gluonic excitations in an effort to understand confinement in QCD. A key subsystem of the GlueX detector is the electromagnetic barrel calorimeter (BCAL) located inside a 2.5 Tesla superconducting solenoid. Due to this arrangement, light sensors are required that can operate in the high magnetic field environment. Among these, Silicon photomultipliers (SiPMs) are very promising candidates as front-end detectors. To date, routine use of SiPMs has been limited to those with an active area of a few mm^2. GlueX will require 2300 large-area SiPMs, each composed of sixteen 3x3 mm^2 cells arranged in a 4x4 array for a total area of ˜144 mm^2 per array. This has placed the GlueX collaboration in the unique position of driving the technology for such larger-area sensors. In this talk I will present tests carried out at Regina and Jefferson Lab regarding performance parameters of prototype SiPM arrays and their micro subcomponents.
Magnetic Retraction of Bowel by Intraluminal Injectable Cyanoacrylate-Based Magnetic Glue
Brown, Andrew; André, Pascal; Brown, Stuart I.; Florence, Gordon J.; Cuschieri, Alfred
Magnetic retraction offers advantages over physical retraction by graspers because of reduced tissue trauma. The objectives of this study are to investigate a novel method of magnetisation of bowel segments by intraluminal injection of magnetic glue and to demonstrate the feasibility of magnetic retraction of bowel with sufficient force during minimal access surgery. Following an initial materials characterisation study, selected microparticles of stainless steel (SS410-μPs) were mixed with chosen cyanoacrylate glue (Loctite 4014). During intraluminal injection of the magnetic glue using ex vivo porcine colonic segments, a magnetic probe placed at the injected site ensured that the SS410-μPs aggregated during glue polymerisation to form an intraluminal mucosally adherent coagulum. The magnetised colonic segments were retracted by magnetic probes (5 and 10 mm) placed external to the bowel wall. A tensiometer was used to record the retraction force. With an injected volume of 2 mL in a particle concentration of 1 g/mL, this technique produced maximal magnetic retraction forces of 2.24 ± 0.23 N and 5.11 ± 0.34 N (n = 20), with use of 5 and 10 mm probes, respectively. The results indicate that the formation of an intraluminal coagulum based on SS410-μPs and Loctite 4014 produces sufficient magnetic retraction for bowel retraction. PMID:24319684
Embolization with Histoacryl Glue of an Anastomotic Pseudoaneurysm following Surgical Repair of Abdominal Aortic Aneurysm
Walid, Ayesha; Ul Haq, Tanveer; Ur Rehman, Zia
We report a 62-year-old female who had surgical repair of abdominal aortic aneurysm with a bifurcated graft 2 years ago. She presented with a distal anastomotic pseudoaneurysm which was successfully embolized with histoacryl glue. Only one such similar case has been reported in the literature so far (Yamagami et al. (2006)). PMID:23476883
[Fixing of osteochondral fragments with fibrinogen glue. Clinical experiences (author's transl)].
Zilch, H; Friedebold, G
Small osteochondral fragments are well fixed with the fibrinogen glue. This method is really a progress in comparison with the traditional fixation by screws or K-wires. The fragments were revascularized early. This is demonstrated by 31 glued osteochondral fragments which healed well. The joints must be immobilized during a period of 3 weeks. PMID:6118021
A safe and efficient method to retrieve mesenchymal stem cells from three-dimensional fibrin gels.
Carrion, Bita; Janson, Isaac A; Kong, Yen P; Putnam, Andrew J
Mesenchymal stem cells (MSCs) display multipotent characteristics that make them ideal for potential therapeutic applications. MSCs are typically cultured as monolayers on tissue culture plastic, but there is increasing evidence suggesting that they may lose their multipotency over time in vitro and eventually cease to retain any resemblance to in vivo resident MSCs. Three-dimensional (3D) culture systems that more closely recapitulate the physiological environment of MSCs and other cell types are increasingly explored for their capacity to support and maintain the cell phenotypes. In much of our own work, we have utilized fibrin, a natural protein-based material that serves as the provisional extracellular matrix during wound healing. Fibrin has proven to be useful in numerous tissue engineering applications and has been used clinically as a hemostatic material. Its rapid self-assembly driven by thrombin-mediated alteration of fibrinogen makes fibrin an attractive 3D substrate, in which cells can adhere, spread, proliferate, and undergo complex morphogenetic programs. However, there is a significant need for simple cost-effective methods to safely retrieve cells encapsulated within fibrin hydrogels to perform additional analyses or use the cells for therapy. Here, we present a safe and efficient protocol for the isolation of MSCs from 3D fibrin gels. The key ingredient of our successful extraction method is nattokinase, a serine protease of the subtilisin family that has a strong fibrinolytic activity. Our data show that MSCs recovered from 3D fibrin gels using nattokinase are not only viable but also retain their proliferative and multilineage potentials. Demonstrated for MSCs, this method can be readily adapted to retrieve any other cell type from 3D fibrin gel constructs for various applications, including expansion, bioassays, and in vivo implantation. PMID:23808842
A Safe and Efficient Method to Retrieve Mesenchymal Stem Cells from Three-Dimensional Fibrin Gels
Carrion, Bita; Janson, Isaac A.; Kong, Yen P.
Mesenchymal stem cells (MSCs) display multipotent characteristics that make them ideal for potential therapeutic applications. MSCs are typically cultured as monolayers on tissue culture plastic, but there is increasing evidence suggesting that they may lose their multipotency over time in vitro and eventually cease to retain any resemblance to in vivo resident MSCs. Three-dimensional (3D) culture systems that more closely recapitulate the physiological environment of MSCs and other cell types are increasingly explored for their capacity to support and maintain the cell phenotypes. In much of our own work, we have utilized fibrin, a natural protein-based material that serves as the provisional extracellular matrix during wound healing. Fibrin has proven to be useful in numerous tissue engineering applications and has been used clinically as a hemostatic material. Its rapid self-assembly driven by thrombin-mediated alteration of fibrinogen makes fibrin an attractive 3D substrate, in which cells can adhere, spread, proliferate, and undergo complex morphogenetic programs. However, there is a significant need for simple cost-effective methods to safely retrieve cells encapsulated within fibrin hydrogels to perform additional analyses or use the cells for therapy. Here, we present a safe and efficient protocol for the isolation of MSCs from 3D fibrin gels. The key ingredient of our successful extraction method is nattokinase, a serine protease of the subtilisin family that has a strong fibrinolytic activity. Our data show that MSCs recovered from 3D fibrin gels using nattokinase are not only viable but also retain their proliferative and multilineage potentials. Demonstrated for MSCs, this method can be readily adapted to retrieve any other cell type from 3D fibrin gel constructs for various applications, including expansion, bioassays, and in vivo implantation. PMID:23808842
Schek, R.M.; Michalek, A.J.; Iatridis, J.C.
Treatment of damaged intervertebral discs is a significant clinical problem and, despite advances in the repair and replacement of the nucleus pulposus, there are few effective strategies to restore defects in the annulus fibrosus. An annular repair material should meet three specifications: have a modulus similar to the native annulus tissue, support the growth of disc cells, and maintain adhesion to tissue under physiological strain levels. We hypothesized that a genipin crosslinked fibrin gel could meet these requirements. Our mechanical results showed that genipin crosslinked fibrin gels could be created with a modulus in the range of native annular tissue. We also demonstrated that this material is compatible with the in vitro growth of human disc cells, when genipin:fibrin ratios were 0.25:1 or less, although cell proliferation was slower and cell morphology more rounded than for fibrin alone. Finally, lap tests were performed to evaluate adhesion between fibrin gels and pieces of annular tissue. Specimens created without genipin had poor handling properties and readily delaminated, while genipin crosslinked fibrin gels remained adhered to the tissue pieces at strains exceeding physiological levels and failed at 15–30%. This study demonstrated that genipin crosslinked fibrin gels show promise as a gap-filling adhesive biomaterial with tunable material properties, yet the slow cell proliferation suggests this biomaterial may be best suited as a sealant for small annulus fibrosus defects or as an adhesive to augment large annulus repairs. Future studies will evaluate degradation rate, fatigue behaviors, and long-term biocompatibility. PMID:21503869
The influence of type 2 diabetes on fibrin clot properties in patients with coronary artery disease.
Neergaard-Petersen, S; Hvas, A-M; Kristensen, S D; Grove, E L; Larsen, S B; Phoenix, F; Kurdee, Z; Grant, P J; Ajjan, R A
Type 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered fibrin clot properties. However, the influence of T2DM on fibrin clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on fibrin clot properties in patients with CAD. Fibrin clot structure and fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p< 0.001), but clots made from purified fibrinogen showed no differences in fibrin properties in the two populations. Adjusting for fibrinogen levels, T2DM was associated with C-reactive protein and complement C3 plasma levels, with the former correlating with clot maximum absorbance (r=0.24, p< 0.0001) and the latter with lysis time (r=0.30, p< 0.0001). Independent of fibrinogen levels, females had more compact clots with prolonged lysis time compared with males (all p-values< 0.001). In conclusion, T2DM is associated with prothrombotic changes in fibrin clot properties in patients with CAD. This is related to quantitative rather than qualitative changes in fibrinogen with a possible role for inflammatory proteins. PMID:25187394
Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results
Kreuz, Peter C; Müller, Sebastian; Ossendorf, Christian; Kaps, Christian; Erggelet, Christoph
Introduction Second-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed®-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee. Methods Clinical outcome after 4-year clinical follow-up was assessed in 19 patients with preoperatively radiologically confirmed osteoarthritis and a Kellgren-Lawrence score of 2 or more. Clinical scoring was performed before implantation of the graft and 6, 12, and 48 months after implantation using the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) score, and the International Cartilage Repair Society (ICRS) score. Cartilage regeneration and articular resurfacing were assessed by magnetic resonance imaging (MRI) 4 years after implantation of the autologous cartilage graft. Results Significant improvement (P < 0.05) of the Lysholm and ICRS scores was observed as early as 6 months after implantation of BioSeed®-C and remained stable during follow-up. The IKDC score showed significant improvement compared with the preoperative situation at 12 and 48 months (P < 0.05). The KOOS showed significant improvement in the subclasses pain, activities of daily living, and knee-related quality of life 6 months as well as 1 and 4 years after implantation of BioSeed®-C in osteoarthritic defects (P < 0.05). MRI analysis showed moderate to complete defect filling with a normal to incidentally hyperintense signal in 16 out of 19 patients treated with BioSeed®-C. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years. Conclusions The results show that the good clinical
Photoinduced Bioorthogonal 1,3-Dipolar Poly-cycloaddition Promoted by Oxyanionic Substrates for Spatiotemporal Operation of Molecular Glues.
Hatano, Junichi; Okuro, Kou; Aida, Takuzo
PGlue(PZ), a pyrazoline (PZ)-based fluorescent adhesive which can be generated spatiotemporally in living systems, was developed. Since PGlue(PZ) carries many guanidinium ion (Gu(+)) pendants, it strongly adheres to various oxyanionic substrates through a multivalent salt-bridge interaction. PGlue(PZ) is given by bioorthogonal photopolymerization of a Gu(+)-appended monomer (Glue(TZ)), bearing tetrazole (TZ) and olefinic termini. Upon exposure to UV light, Glue(TZ) transforms into a nitrileimine (NI) intermediate (Glue(NI)), which is eligible for 1,3-dipolar polycycloaddition. However, Glue(NI) in aqueous media can concomitantly be deactivated into Glue(WA) by the addition of water, and the polymerization hardly occurs unless Glue(NI) is concentrated. We found that, even under high dilution, Glue(NI) is concentrated on oxyanionic substrates to a sufficient level for the polymerization, so that their surfaces can be point-specifically functionalized with PGlue(PZ) by the use of a focused beam of UV light. PMID:26530322
Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting
Alexander, Robert W; Harrell, David B
Objectives Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF) for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG) with use of disposable, microcannula systems. Design Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are available as safe, sterile, disposable, compact systems for acquiring high-quality AFG. Presented is a detailed, step-by-step, proven protocol for performing quality autologous structural adipose
Enhancement of withstanding pressure of fibrin sealant by modified mixing ratio of fibrin sealant components for skull base reconstruction: technical note.
Saitoh, Youichi; Oshino, Satoru
A method to enhance the withstanding pressure of fibrin sealant in gasket-seal closure to prevent cerebrospinal fluid (CSF) leakage after extended transsphenoidal surgery (ETSS) was investigated by adjusting the mixing ratio of the components. A plastic chamber (200 ml) was constructed with a lid made of hydroxyapatite with a hole 10 mm in diameter. The chamber could be pressurized via an opening in the side wall. The hole in the hydroxyapatite lid was covered with a Gore-Tex sheet, 15 mm in diameter. The margin of the sheet was free. Solutions A (fibrinogen 80 mg/ml) and B (thrombin 250 units/ml) of fibrin sealant were mixed in volume ratios of 1:1, 2:1, and 5:1, and applied to the Gore-Tex sheet, then water was introduced to cover the fibrin sealant. The pressure was measured at which air leakage occurred from the side of the Gore-Tex sheet. The pressure values for A/B ratios of 1:1, 2:1, and 5:1 were 117 ± 23.8 mmH(2)O (mean ± standard error) (n = 5), 234 ± 38.8 mmH(2)O (n = 5), and 345 ± 36.4 mmH(2)O (n = 5), respectively, in the acute phase (5 minutes after application of fibrin sealant). Pressures were increased after 24 hours, and that for 5:1 was the highest (373 ± 40.4 mmH(2)O, n = 5). The use of devices such as syringes specially designed to mix solutions A and B in the ratio of 5:1 can easily enhance the preventive effect of fibrin sealant against CSF leakage in ETSS. PMID:23358175
Endoscopic variceal ligation caused massive bleeding due to laceration of an esophageal varicose vein with tissue glue emboli
Wei, Xiu-Qing; Gu, Hua-Ying; Wu, Zhi-E; Miao, Hui-Biao; Wang, Pei-Qi; Wen, Zhuo-Fu; Wu, Bin
Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed. PMID:25400482
Endoscopic variceal ligation caused massive bleeding due to laceration of an esophageal varicose vein with tissue glue emboli.
Wei, Xiu-Qing; Gu, Hua-Ying; Wu, Zhi-E; Miao, Hui-Biao; Wang, Pei-Qi; Wen, Zhuo-Fu; Wu, Bin
Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed. PMID:25400482
Using blocking peptides to control and analyze the mechanical properties of single fibrin fibers
NASA Astrophysics Data System (ADS)
Maddi, Pranav; O'Brien, E. Tim, III; Gorkun, Oleg; Falvo, Michael R.
Fibrin is the main structural protein involved in blood clotting, and exhibits high strength and elasticity. Fibrin study traditionally focuses on fully formed clots, whereas we employ new AFM nanoManipulation techniques to study single fibrin fiber mechanics. We used 4 and 10 residue peptides to interfere with the knob-hole and αC interactions involved in fibrin polymerization to evaluate the contribution of each interaction to the fiber's mechanical properties. We varied the concentration of each peptide present during polymerization to find the concentration that inhibited polymerization by half. The presence of either peptide during fibrin polymerization did not affect single fiber breaking strain (δLL0). The breaking force of all treated fibers reduced from 10-50nN to 2-10nN, suggesting treated fibers are thinner or are the same diameter with some inhibition of interactions. Fibers polymerized with the knob-hole targeting peptide visibly lost elasticity after 100% strain, while fibers polymerized with the αC targeting peptide lost elasticity after reaching 150% strain, suggesting that the knob-hole interactions control single fiber elasticity.
A comparative study of skin cell activities in collagen and fibrin constructs.
Law, Jia Xian; Musa, Faiza; Ruszymah, Bt Hj Idrus; El Haj, Alicia J; Yang, Ying
Collagen and fibrin are widely used in tissue engineering due to their excellent biocompatibility and bioactivities that support in vivo tissue formation. These two hydrogels naturally present in different wound healing stages with different regulatory effects on cells, and both of them are mechanically weak in the reconstructed hydrogels. We conducted a comparative study by the growth of rat dermal fibroblasts or dermal fibroblasts and epidermal keratinocytes together in collagen and fibrin constructs respectively with and without the reinforcement of electrospun poly(lactic acid) nanofiber mesh. Cell proliferation, gel contraction and elastic modulus of the constructs were measured on the same gels at multiple time points during the 22 day culturing period using multiple non-destructive techniques. The results demonstrated considerably different cellular activities within the two types of constructs. Co-culturing keratinocytes with fibroblasts in the collagen constructs reduced the fibroblast proliferation, collagen contraction and mechanical strength at late culture point regardless of the presence of nanofibers. Co-culturing keratinocytes with fibroblasts in the fibrin constructs promoted fibroblast proliferation but exerted no influence on fibrin contraction and mechanical strength. The presence of nanofibers in the collagen and fibrin constructs played a favorable role on the fibroblast proliferation when keratinocytes were absent. Thus, this study exhibited new evidence of the strong cross-talk between keratinocytes and fibroblasts, which can be used to control fibroblast proliferation and construct contraction. This cross-talk activity is extracellular matrix-dependent in terms of the fibrous network morphology, density and strength. PMID:27349492
Flow and delta-P dictate where thrombin, fibrin, and von Willebrand Factor will be found.
Diamond, Scott L
Hemostasis occurs in two different topological scenarios: complete severing of a vessel or disruption of the vessel wall. Either to meet the daily rigors of active life or during an acute trauma, hemostasis involves the regulated and self-limiting production of thrombin to stop bleeding. In contrast, arterial and venous thrombosis typically involves the unregulated, intraluminal growth of a clot, in the absence of bleeding. For either hemostasis or thrombosis, the presence of flow and pressure gradients (delta-P, ΔP) dictates when and where thrombin and fibrin are located and in what quantity. For hemostatic clots, fibrin formation helped limit clot growth. We found that γ'-fibrinogen had a role in limiting clot growth via anti-thrombin activity at venous, but not arterial conditions. For hemophilic blood, severe factor deficiency (<1% healthy) led to a defect in both platelet and fibrin deposition under flow. However, moderate deficiency, which is associated with a less severe bleeding phenotype, had normalized platelet function but still lacked fibrin production. We conclude signaling levels of thrombin can be generated during moderate hemophilia to sufficiently activate platelets to achieve primary hemostasis, even if fibrin formation remains defective. Finally, as a clot grows, shear stresses can become sufficiently extreme in diseased arteries to drive von Willebrand Factor self-association into massive fibers, potentially the final burst of clot growth towards full thrombotic occlusion. PMID:27207416
Dynamic behaviors of astrocytes in chemically modified fibrin and collagen hydrogels.
Seyedhassantehrani, Negar; Li, Yongchao; Yao, Li
Astrocytes play a critical role in supporting the normal physiological function of neurons in the central nervous system (CNS). Astrocyte transplantation can potentially promote axonal regeneration and functional recovery after spinal cord injury (SCI). Fibrin and collagen hydrogels provide growth-permissive substrates and serve as carriers for therapeutic cell transplantation into an injured spinal cord. However, the application of fibrin and collagen hydrogels may be limited due to their relatively rapid degradation rate in vivo. In this study, immature astrocytes isolated from neonatal rats were grown in fibrin hydrogels containing aprotinin and collagen hydrogels crosslinked with poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG), and the cell behavior in these hydrogels was studied. The cell viability of astrocytes in the hydrogels was tested using the LIVE/DEAD® assay and the AlamarBlue® assay, and this study showed that astrocytes maintained good viability in these hydrogels. The cell migration study showed that astrocytes migrated in the fibrin and collagen hydrogels, and the migration speed is similar in these hydrogels. The crosslinking of collagen hydrogels with 4S-StarPEG did not change the astrocyte migration speed. However, the addition of aprotinin in the fibrin hydrogel inhibited astrocyte migration. The expression of chondroitin sulfate proteoglycan (CSPG), including NG2, neurocan, and versican, by astrocytes grown in the hydrogels was analyzed by quantitative RT-PCR. The expression of NG2, neurocan, and versican by the cells in these hydrogels was not significantly different. PMID:27079938
Fabrication of electrospun poly (lactide-co-glycolide)-fibrin multiscale scaffold for myocardial regeneration in vitro.
Sreerekha, Perumcherry Raman; Menon, Deepthy; Nair, Shantikumar V; Chennazhi, Krishna Prasad
Myocardial tissue engineering is one of the most promising treatment strategies to restore heart function after a massive heart attack. The biomaterials, cells, and scaffold design play important roles in engineering of heart tissue. In this study, we have developed a fibrin-based multiscale electrospun composite scaffold for myocardial regeneration. Fibrin is the natural wound-healing matrix having angiogenic potential and comprehensively used for tissue engineering applications. It provides a natural environment for cell attachment, migration, and proliferation. Morphological, chemical, and mechanical characterization of the scaffolds was done by scanning electron microscopy, fibrin-specific phosphotungstic acid hematoxylin staining, and mechanical testing. The fiber diameters of fibrin nanofibers range from 50 to 300 nm and that of poly (lactide-co-glycolide) microfibers range from 2 to 4 μm, which mimics the structural hierarchy of native myocardial tissue. Our results indicate that this scaffold enhances the differentiation of mesenchymal stem cells into cardiomyocytes. The cardiac phenotype of the cells was confirmed by the presence of cardiac-specific proteins like α-sarcomeric actinin, troponin, tropomyosin, desmin, and atrial natriuretic peptide Estimation of D-Dimer in the culture supernatant for 2 weeks and analysis of scaffold for 3 weeks of in vitro culture of cardiomyocytes indicated the degradation of fibrin and presence of newly synthesized collagen respectively. Our results demonstrate the promising potential of this scaffold for myocardial tissue engineering applications. PMID:23083104
Effect of Age and Diabetes on the Response of Mesenchymal Progenitor Cells to Fibrin Matrices
Stolzing, A.; Colley, H.; Scutt, A.
Mesenchymal stem cells are showing increasing promise in applications such as tissue engineering and cell therapy. MSC are low in number in bone marrow, and therefore in vitro expansion is often necessary. In vivo, stem cells often reside within a niche acting to protect the cells. These niches are composed of niche cells, stem cells, and extracellular matrix. When blood vessels are damaged, a fibrin clot forms as part of the wound healing response. The clot constitutes a form of stem cell niche as it appears to maintain the stem cell phenotype while supporting MSC proliferation and differentiation during healing. This is particularly appropriate as fibrin is increasingly being suggested as a scaffold meaning that fibrin-based tissue engineering may to some extent recapitulate wound healing. Here, we describe how fibrin modulates the clonogenic capacity of MSC derived from young/old human donors and normal/diabetic rats. Fibrin was prepared using different concentrations to modulate the stiffness of the substrate. MSC were expanded on these scaffolds and analysed. MSC showed an increased self-renewal on soft surfaces. Old and diabetic cells lost the ability to react to these signals and can no longer adapt to the changed environment. PMID:22194749
Treatment of gingival recession using free gingival graft with fibrin fibronectin sealing system: A novel approach.
Srinivas, B V V; Rupa, N; Halini Kumari, K V; Rajender, A; Reddy, M Narendra
Periodontal plastic surgery is the branch of periodontology that is focused mainly on the correction or elimination of mucogingival problems associated with lack of attached gingiva, a shallow vestibule and aberrant frenum. Various mucogingival surgical procedures are used to halt the progression of the gingival recession and to correct poor esthetic appearance. Free gingival autograft is one of the most common techniques used for a gingival recession in areas of inadequate attached gingiva in the mandibular anterior region. Fibrin sealants are human plasma derivatives that mimic the final stages of blood coagulation, forming a fibrin clot. Fibrin Sealants enhances the overall outcome of surgical intervention because of their hemostatic, adhesive, and healing properties. These properties of fibrin sealants may reduce operating time, prevent complications, and enhance the overall outcome of many surgical interventions. Hence, this case report aims to investigate the clinical effectiveness of free gingival graft along with the commercially available fibrin-fibronectin sealing system (Tissucol(®)) in the treatment of Miller's class II gingival recession. PMID:26538956
Improved Growth Factor Directed Vascularization into Fibrin Constructs Through Inclusion of Additional Extracellular Molecules
Smith, JD; Melhem, ME; Magge, KT; Waggoner, AS; Campbell, PG
Using the chick chorioallantoic membrane assay (CAM) and a novel histological technique we investigated the ability of blood vessels to directly invade fibrin-based scaffolds. In our initial experiments utilizing vascular endothelial growth factor (VEGF165) we found no direct invasion. Instead, the fibrin was completely degraded and replaced with highly vascularized new tissue. Addition of fibroblast growth factor-2 (FGF-2), bone morphogenic protein-2 (BMP-2), or platelet-derived growth factor-BB (PDGF-BB) to the fibrin construct also did not result in construct vascularization. Because natural and regenerating tissues exhibit complex extracellular matrices (ECMs), we hypothesized that a more complex scaffold may improve blood vessel invasion. Addition of fibronectin, hyaluronic acid, and collagen type I within 20 mg/mL fibrin constructs resulted in no significant improvement. However, the same additive concentrations within 10 mg/mL fibrin constructs resulted in dramatic improvements, specifically with hyaluronic acid. Overall, we believe these results indicate the importance of structural and functional cues of not only in the initial scaffold but also as the construct is degraded and remodeled. Furthermore, the CAM assay may represent a useful model for understanding ECM interactions as well as for screening and designing tissue engineered scaffolds. PMID:17223139
A Synthetic Fibrin-Crosslinking Polymer for Modulating Clot Properties and Inducing Hemostasis
Chan, Leslie W.-G.; Wang, Xu; Wei, Hua; Pozzo, Lilo D.; White, Nathan J.; Pun, Suzie H.
Clotting factor replacement is the standard management of acute bleeding in congenital and acquired bleeding disorders. We present a synthetic approach to hemostasis using an engineered hemostatic polymer (PolySTAT) that circulates innocuously in the blood, identifies sites of vascular injury, and promotes clot formation to stop bleeding. PolySTAT induces hemostasis by crosslinking the fibrin matrix within clots, mimicking the function of the transglutaminase Factor XIII. Furthermore, synthetic PolySTAT binds specifically to fibrin monomers and is uniformly integrated into fibrin fibers during fibrin polymerization, resulting in a fortified, hybrid polymer network with enhanced resistance to enzymatic degradation. In vivo hemostatic activity was confirmed in a rat model of trauma and fluid resuscitation in which intravenous administration of PolySTAT improved survival by reducing blood loss and resuscitation fluid requirements. PolySTAT-induced fibrin crosslinking is a novel approach to hemostasis utilizing synthetic polymers for non-invasive modulation of clot architecture with potentially wide-ranging therapeutic applications. PMID:25739763
Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator
de Giorgio-Miller, Alexander; Bottoms, Steve; Laurent, Geoffrey; Carmeliet, Peter; Herrick, Sarah
The deposition of fibrin is an integral part of the tissue repair process, but its persistence is also associated with a number of fibrotic conditions. This study addressed the hypothesis that reduced fibrinolysis and fibrin persistence are associated with an enhanced accumulation of collagen and the development of skin fibrosis. Decreased fibrinolysis was confirmed in fibrin gel cultures that contained human dermal fibroblasts plus the specific plasmin inhibitor α2-antiplasmin or dermal fibroblasts isolated from plasminogen activator (PA)-deficient mice. Collagen accumulation was significantly increased in the presence of inhibitor and in tPA-deficient, but not uPA-deficient, fibroblasts compared with controls. These findings were also confirmed using a skin fibrosis model in which multiple injections of fibrin were given subcutaneously to PA-deficient mice. Injection sites from tPA-deficient mice displayed significantly increased collagen levels compared with uPA-deficient mice and wild-type controls. Up-regulation of fibroblast procollagen gene expression and reduced activation of pro-MMP-1 appeared to mediate the increase in collagen by human dermal fibroblasts in the presence of α2-antiplasmin. These findings suggest that persistent fibrin is associated with enhanced collagen accumulation that may result in the development of fibrotic skin disorders in which reduced fibrinolysis is a feature. PMID:16127152
Characterization of Fibrin and Collagen Gels for Engineering Wound Healing Models
Moreno-Arotzena, Oihana; Meier, Johann G.; del Amo, Cristina; García-Aznar, José Manuel
Hydrogels are used for 3D in vitro assays and tissue engineering and regeneration purposes. For a thorough interpretation of this technology, an integral biomechanical characterization of the materials is required. In this work, we characterize the mechanical and functional behavior of two specific hydrogels that play critical roles in wound healing, collagen and fibrin. A coherent and complementary characterization was performed using a generalized and standard composition of each hydrogel and a combination of techniques. Microstructural analysis was performed by scanning electron microscopy and confocal reflection imaging. Permeability was measured using a microfluidic-based experimental set-up, and mechanical responses were analyzed by rheology. We measured a pore size of 2.84 and 1.69 μm for collagen and fibrin, respectively. Correspondingly, the permeability of the gels was 1.00·10−12 and 5.73·10−13 m2. The shear modulus in the linear viscoelastic regime was 15 Pa for collagen and 300 Pa for fibrin. The gels exhibited strain-hardening behavior at ca. 10% and 50% strain for fibrin and collagen, respectively. This consistent biomechanical characterization provides a detailed and robust starting point for different 3D in vitro bioapplications, such as collagen and/or fibrin gels. These features may have major implications for 3D cellular behavior by inducing divergent microenvironmental cues. PMID:26290683
Low cost biological lung volume reduction therapy for advanced emphysema
Bakeer, Mostafa; Abdelgawad, Taha Taha; El-Metwaly, Raed; El-Morsi, Ahmed; El-Badrawy, Mohammad Khairy; El-Sharawy, Solafa
Background Bronchoscopic lung volume reduction (BLVR), using biological agents, is one of the new alternatives to lung volume reduction surgery. Objectives To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue. Methods Enrolled patients were divided into two groups: group A (seven patients) in which autologous blood was used and group B (eight patients) in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications. Results In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted) (P-value: <0.001 and 0.038, respectively). In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted) (P-value: 0.005 and 0.004, respectively). All patients tolerated the procedure with no mortality. Conclusion BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. PMID:27536091
Second autologous stem cell transplant for multiply relapsed Hodgkin's disease.
Lin, T S; Avalos, B R; Penza, S L; Marcucci, G; Elder, P J; Copelan, E A
Therapeutic options for patients with Hodgkin's disease who relapse after high-dose chemotherapy with autologous stem cell support are limited. Salvage chemotherapy is not curative, and allogeneic stem cell transplantation in this setting is associated with mortality rates of 40-65%. We report our institution's experience with second autologous transplants in this patient population. Five patients (median age 36) with relapsed Hodgkin's disease underwent a second autologous stem cell transplant at a median of 66 months after first transplant. Four patients received CBV, and one patient received BuCy as conditioning. Neutrophil and platelet engraftment occurred by days +10 and +16, respectively. All patients achieved a complete response, and no relapses have occurred after a median follow-up of 42 months. All four patients who received CBV developed interstitial pneumonitis, and two patients died of pulmonary complications 37 and 48 months following second transplant. Three patients remain alive and disease-free 41, 42 and 155 months after second transplant. These data indicate that second autologous transplantation should be considered for selected patients who relapse after a prolonged response to first autologous transplant. However, BCNU pneumonitis is the major toxicity in patients who have undergone previous mantle radiation and received busulfan with first transplant. PMID:12040474
Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma)
NASA Astrophysics Data System (ADS)
Ebine, Kunio
Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.
Chimeric autologous/allogeneic constructs for skin regeneration.
Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn
The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. PMID:25102552
Autologous Blood Transfusion in Sports: Emerging Biomarkers.
Salamin, Olivier; De Angelis, Sara; Tissot, Jean-Daniel; Saugy, Martial; Leuenberger, Nicolas
Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. PMID:27260108
Autologous splenic transplantation for splenic trauma.
Pisters, P W; Pachter, H L
OBJECTIVE: The authors reviewed the experimental evidence, surgical technique, complications, and results of clinical trials evaluating the role of autologous splenic transplantation for splenic trauma. SUMMARY BACKGROUND DATA: Splenorrhaphy and nonoperative management of splenic injuries have now become routine aspects in the management of splenic trauma. Unfortunately, not all splenic injuries are readily amenable to conventional spleen-conserving approaches. Heterotopic splenic autotransplantation has been advocated for patients with severe grade IV and V injuries that would otherwise mandate splenectomy. For this subset of patients, splenic salvage by autotransplantation would theoretically preserve the critical role the spleen plays in the host's defense against infection. METHODS: The relevant literature relating to experimental or clinical aspects of splenic autotransplantation was identified and reviewed. Data are presented on the experimental evaluation of autogenous splenic transplantation, methods and complications of autotransplantation, choice of anatomic site and autograft size, and results of clinical trials in humans. RESULTS: The most commonly used technique of autotransplantation in humans involves implanting tissue homogenates or sections of splenic parenchyma into pouches created in the gastrocolic omentum. Most authors have observed evidence of splenic function with normalization of postsplenectomy thrombocytosis, immunoglobulin M levels, and peripheral blood smears. Some degree of immune function of transplanted grafts has been demonstrated with in vivo assays, but the full extent of immunoprotection provided by human splenic autotransplants is currently unknown. CONCLUSIONS: Multiple human and animal studies have established that splenic autotransplantation is a relatively safe and easily performed procedure that results in the return of some hematologic and immunologic parameters to baseline levels. Some aspects of reticuloendothelial
Enhancing Osteoconductivity of Fibrin Gels with Apatite-Coated Polymer Microspheres
Davis, Hillary E.; Binder, Bernard Y.K.; Schaecher, Phillip; Yakoobinsky, Dana D.; Bhat, Archana
Fibrin gels are a promising material for use in promoting bone repair and regeneration due to their ease of implant formation, tailorability, biocompatibility, and degradation by natural processes. However, these materials lack necessary osteoconductivity to nucleate calcium, integrate with surrounding bone, and promote bone formation. Polymeric substrata formed from poly(lactide-co-glycolide) (PLG) are widely used in bone tissue engineering. A carbonated apatite layer of bone-like mineral can be successfully grown on the surface of PLG microspheres after a multiday incubation process in modified simulated body fluid. Such coatings improve the osteoconductivity of the polymer, provide nucleation sites for cell-secreted calcium, and enhance the potential osseointegration with host tissue. We examined the capacity of mineralized polymeric microspheres suspended within fibrin hydrogels to enhance the osteoconductivity of fibrin gels and increase the osteogenic potential of these materials. The inclusion of microparticles, both nonmineralized and mineralized, reduced the capacity of mesenchymal stem cells (MSCs) to contract the gel. When cultured in osteogenic media, we detected a near linear increase in both calcium and phosphate incorporation in gels containing mineralized microspheres and entrapped MSCs. The osteoconductivity of acellular fibrin gels with mineralized and nonmineralized microspheres was assessed in a rodent calvarial bone defect over 12 weeks. Compared to untreated rodent calvarial bone defects, we detected significant increases in early vascularization when treated with fibrin gels, with greater vascularization, on average, occurring with gels containing microspheres. We detected a trend for increased bone mineral density in gels containing mineralized microspheres after 12 weeks. These findings demonstrate that the osteoconductivity of fibrin gels can be increased by inclusion of mineralized microspheres, but additional signals may be required to
Fibrin nanoconstructs: a novel processing method and their use as controlled delivery agents
NASA Astrophysics Data System (ADS)
Praveen, G.; Sreerekha, P. R.; Menon, Deepthy; Nair, Shantikumar V.; Prasad Chennazhi, Krishna
Fibrin nanoconstructs (FNCs) were prepared through a modified water-in-oil emulsification-diffusion route without the use of any surfactants, resulting in a high yield synthesis of fibrin nanotubes (FNTs) and fibrin nanoparticles (FNPs). The fibrin nanoconstructs formed an aligned structure with self-assembled nanotubes with closed heads that eventually formed spherical nanoparticles of size ˜250 nm. The nanotubes were typically ˜700 nm long and 150-300 nm in diameter, with a wall thickness of ˜50 nm and pore diameter of about 150-250 nm. These constructs showed high stability against aggregation indicated by a zeta potential of -44 mV and an excellent temperature stability upto 200 °C. Furthermore, they were found to be enzymatically degradable, thereby precluding any long term toxicity effects. These unique fibrin nanostructures were analyzed for their ability to deliver tacrolimus, an immunosuppressive drug that is used widely to prevent the initial phase of tissue rejection during allogenic transplantation surgeries. Upon conjugation with tacrolimus, a drug encapsulation efficiency of 66% was achieved, with the in vitro release studies in PBS depicting a sustained and complete drug release over a period of one week at the physiological pH of 7.4. At a more acidic pH, the drug release was very slow, suggesting their potential for oral-intestinal drug administration as well. The in vivo drug absorption rates analyzed in Sprague Dawley rats further confirmed the sustained release pattern of tacrolimus for both oral and parenteral delivery routes. The novel fibrin nanoconstructs developed using a green chemistry approach thus proved to be excellent biodegradable nanocarriers for oral as well as parenteral administrations, with remarkable potential also for delivering specific growth factors in tissue engineering scaffolds.
C-reactive protein and fibrin clot strength measured by thrombelastography after coronary stenting
Kreutz, Rolf P.; Owens, Janelle; Breall, Jeffrey A.; Lu, Deshun; von der Lohe, Elisabeth; Bolad, Islam; Sinha, Anjan; Flockhart, David A.
Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma fibrin clot strength in patients after coronary stenting. Plasma fibrin clot strength was measured by TEG in 54 patients 16–24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma fibrin clot strength measured by TEG (P < 0.001) and increasing BMI (P =0.04). Patients in the highest quartile of CRP had significantly higher maximal fibrin clot strength (G) than the patients in the lowest quartile (G: 3438 ± 623 vs. 2184 ± 576 dyn/cm2, P < 0.0001). Fibrinogen concentration was not significantly different across quartiles of CRP (P =0.97). Patients with established coronary artery disease undergoing coronary stenting who have elevated CRP after PCI exhibit heightened maximal plasma fibrin clot strength as compared with those with low CRP. Thrombotic risk associated with elevated CRP may be linked to procoagulant changes and high tensile fibrin clot strength independent of fibrinogen concentration. PMID:23429252
C-reactive protein and fibrin clot strength measured by thrombelastography after coronary stenting.
Kreutz, Rolf P; Owens, Janelle; Breall, Jeffrey A; Lu, Deshun; von der Lohe, Elisabeth; Bolad, Islam; Sinha, Anjan; Flockhart, David A
Inflammation is implicated in the progression of coronary artery disease and the molecular processes of inflammation and thrombosis are closely intertwined. Elevated levels of C-reactive protein (CRP) have been associated with an elevated risk of adverse ischaemic events after coronary stenting and hypercoagulability. Heightened whole blood clot strength measured by thrombelastography (TEG) has been associated with adverse ischaemic events after stenting. We intended to examine the relationship of CRP to plasma fibrin clot strength in patients after coronary stenting. Plasma fibrin clot strength was measured by TEG in 54 patients 16-24 h after undergoing elective percutaneous coronary intervention (PCI). Coagulation was induced in citrated plasma by addition of kaolin and CaCl2. Plasma levels of CRP and fibrinogen were measured by enzyme-linked immunoassay. Increasing quartiles of CRP were associated with increasing levels of maximal plasma fibrin clot strength measured by TEG (P < 0.001) and increasing BMI (P = 0.04). Patients in the highest quartile of CRP had significantly higher maximal fibrin clot strength (G) than the patients in the lowest quartile (G: 3438 ± 623 vs. 2184 ± 576 dyn/cm, P < 0.0001). Fibrinogen concentration was not significantly different across quartiles of CRP (P = 0.97). Patients with established coronary artery disease undergoing coronary stenting who have elevated CRP after PCI exhibit heightened maximal plasma fibrin clot strength as compared with those with low CRP. Thrombotic risk associated with elevated CRP may be linked to procoagulant changes and high tensile fibrin clot strength independent of fibrinogen concentration. PMID:23429252
Mesenchymal stromal cells form vascular tubes when placed in fibrin sealant and accelerate wound healing in vivo.
Mendez, Julio J; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum O; Steinbacher, Derek M; Leffell, David J; Niklason, Laura E
Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608
Thrombus on Indwelling Central Venous Catheters: The Histopathology of 'Fibrin Sheaths'
Suojanen, James Norman; Brophy, David Paul; Nasser, Imad
Purpose: Central venous catheters (CVC) may fail for many reasons, though 'fibrin sheaths' blocking catheter ports are usually implicated. We examined the sheaths removed from dialysis catheters to determine their histopathology.Methods: Ten catheter strippings were performed and the removed material was studied grossly and microscopically.Results: The histologic specimens showed thrombus both with and without a proteinaceous sheath.Conclusion: Dialysis catheters fail because of thrombus formation. This can occur in either the absence or presence of a protein coating on the catheter, the so-called 'fibrin sheath.'.
Plasma fibrin clot phenotype independently affects intracoronary thrombus ultrastructure in patients with acute myocardial infarction.
Zalewski, Jaroslaw; Bogaert, Jan; Sadowski, Marcin; Woznicka, Olga; Doulaptsis, Konstantinos; Ntoumpanaki, Maria; Ząbczyk, Michal; Nessler, Jadwiga; Undas, Anetta
Determinants of intracoronary thrombus (ICT) composition in patients with ST-elevation myocardial infarction (STEMI) are largely unknown. We sought to investigate whether plasma fibrin phenotype and platelet reactivity affect ICT ultrastructure. We assessed the content of fibrin, platelets and erythrocytes including polyhedrocytes by scanning electron microscopy on the surface and inside ICT aspirated from 80 STEMI patients within 12 hours since chest pain onset. Plasma fibrin clot permeability (Ks), which indicates the average pore size, lysis time (t50 %), platelet reactivity index (PRI) and ADP-induced platelet aggregation (ADP5, 20µM) were evaluated on admission. All patients received aspirin and 45 (56.3 %) 600 mg of clopidogrel, 80 (60-120) min prior to aspiration. Higher content of fibrin (61.6 vs 34.3 %, P< 0.0001) and platelets (8.2 vs 4.8 %, P=0.018) and lower erythrocyte content (15.8 vs 42.9 %, P< 0.0001) were found on ICT surface compared with its inner part. After adjustment for fibrinogen, in both ICT parts fibrin content was correlated with Ks (r≤-0.55, P< 0.0001) and t50 % (r≥ 0.29, P≤ 0.02) but not with PRI and ADP5,20µM. Polyhedrocytes were observed in 16 (20 %) patients and their large amount expressed as ≥ 50 % fields of view covered by polyhedrocytes was associated with the lower PRI values (40 vs 69 %, P=0.015), but not Ks or t50 %. By multivariate regression, Ks (β=-0.62, P< 0.0001), clopidogrel pretreatment (β=-0.36, P< 0.001), ischemia time (β=0.19, P=0.044) and family history (β=0.18, P=0.049) independently predicted fibrin content in the whole ICT (R²=0.65, P< 0.0001). Formation of denser plasma fibrin clots is independently associated with high fibrin content within the ICT in STEMI. PMID:25739375
Autologous blood donation in support of cardiac surgery: a preliminary report on a hospital-based autologous donor programme.
Pinkerton, P H
The purpose of this study was to assess the success or otherwise of the introduction of an autologous blood programme in support of cardiac surgery in reducing patient exposure to allogeneic blood products and to assess the guideline of two units as the collection schedule for such patients. Sixty-six patients were enrolled in the programme provided they met defined clinical conditions and donated one, two or three units of blood at seven-day intervals, using isovolaemic conditions. One minor vasovagal adverse reaction was recorded. Of the 66 patients, 51 (77%) avoided allogeneic red cells and 42 (64%) received no allogeneic product. If each patient deposited two units, 51 (77%) would have required no allogeneic red cells; if three units were deposited, 57 (86%) patients would have required no allogeneic red cells, but 60 units would be surplus to requirements. Comparison of 52 patients for coronary artery bypass grafting who were autologous donors, with 130 patients undergoing the procedure before the availability of autologous blood, supports the suggestions that there is increased readiness to initiate transfusion of autologous blood and that exposure to allogeneic red cells is reduced. However, exposure to allogeneic products of all kinds is not reduced. It is concluded that the collection of two units of autologous blood is appropriate for most eligible patients and that this reduces exposure to allogeneic red cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7828248
Autologous blood injection for the treatment of recurrent mandibular dislocation.
Coser, R; da Silveira, H; Medeiros, P; Ritto, F G
The purpose of the present study was to evaluate the effectiveness of autologous blood injection in the treatment of recurrent temporomandibular joint dislocation. Eleven patients diagnosed with recurrent dislocation of the joint that could not be self-reduced, received bilateral injections of autologous blood in the superior joint compartment and pericapsular region. During a follow-up period ranging from 24 to 35 months (average 29.6 months), eight patients (72.7%) did not show new episodes of dislocation. The most advocated treatment for recurrent dislocation is eminectomy, which involves a skin incision, with the risk of damaging the facial nerve, requires general anaesthesia, and presents an average success rate of 85% according to the literature. Autologous blood injection is a simple, rapid, minimally invasive, and cost-effective technique, with a low possibility of complications, and is a feasible alternative treatment before surgical intervention. PMID:26022511
Improving diagnosis of appendicitis. Early autologous leukocyte scanning
DeLaney, A.R.; Raviola, C.A.; Weber, P.N.; McDonald, P.T.; Navarro, D.A.; Jasko, I. )
A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of appendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging In 111 oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.
Therapeutic Potential of Autologous Stem Cell Transplantation for Cerebral Palsy
Purandare, Chaitanya; Shitole, D. G.; Belle, Vaijayantee; Kedari, Aarti; Bora, Neeta; Joshi, Meghnad
Background. Cerebral palsy (CP) is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs) transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R) scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient. PMID:23259143
Study of nano imprinting using soft lithography on Krafty glue and PVDF polymer thin films
Sankar, M. S. Ravi Gangineni, Ramesh Babu
The present work reveals soft lithography strategy based on self assembly and replica molding for carrying out micro and nanofabrication. It provides a convenient, effective and very low cost method for the formation and manufacturing of micro and nano structures. Al-layer of compact disc (sony CD-R) used as a stamp with patterned relief structures to generate patterns and structures with pattern size of 100nm height, 1.7 μm wide. In literature, PDMS (Polydimethylsiloxane) solution is widely used to get negative copy of the Al-layer. In this work, we have used inexpensive white glue (Polyvinylacetate + water), 15gm (□5) and PVDF (Polyvinylidene difluoride) spin coated films and successfully transferred the nano patterns of Al layer on to white glue and PVDF films.
Development of silicon photomultipliers and their applications to GlueX calorimetry
NASA Astrophysics Data System (ADS)
Smith, Elton S.
The GlueX experiment is a photoproduction experiment in Hall D at Jefferson Lab that is being commissioned for use with the new 12 GeV accelerator. The purpose of the experiment is to search for Hybrid mesons, which are mesons with quark and gluon degrees of freedom. The barrel calorimeter of GlueX is instrumented with 4000 large-area (1.2 × 1.2 cm2) silicon photomultipliers (SiPMs). These photon sensors have properties similar to vacuum photomultipliers, but are unaffected by high magnetic fields. In our experiment they operate in magnetic fields exceeding 1T. After extensive tests with a variety of sensors, we chose the S12045(X) custom SiPM arrays manufactured by Hamamatsu Corporation, also known as multi-pixel photon counters (MPPCs). We will give an overview of this new technology as well as the experience gained during two commissioning periods with beam.
Successful percutaneous angioembolisation of bleeding jejunal varix by acrylate glue and coils
Haq, Tanveer Ul; AlQamari, Nauman; Sayani, Raza; Hilal, Kiran
Portal hypertension is a common disease worldwide. One of its rare complications is bleeding jejunal varices which is usually asymptomatic and may present with gastrointestinal bleeding. We present a case of a jejunal bleeding that was successfully embolised with acrylate glue and embolisation coils. A middle-aged woman with a history of multiple abdominal surgeries for adenocarcinoma of right ovary, presented to us with multiple episodes of haematochezia. On a CT scan of the abdomen, she was diagnosed with chronic liver disease with portal hypertension, multiple varices at porto-systemic anastomosis and ectopic jejunal varix. She was treated by interventional radiologists by percutaneous embolisation of bleeding varix using glue and embolisation coils through a portal venous approach. PMID:24158303
The Research of Improving the Particleboard Glue Dosing Process Based on TRIZ Analysis
NASA Astrophysics Data System (ADS)
Yu, Huiling; Fan, Delin; Zhang, Yizhuo
This research creates a design methodology by synthesizing the Theory of Inventive Problem Solving (TRIZ) and cascade control based on Smith predictor. The particleboard glue supplying and dosing system case study defines the problem and the solution using the methodology proposed in the paper. Status difference existing in the gluing dosing process of particleboard production usually causes gluing volume inaccurately. In order to solve the problem above, we applied the TRIZ technical contradiction and inventive principle to improve the key process of particleboard production. The improving method mapped inaccurate problem to TRIZ technical contradiction, the prior action proposed Smith predictor as the control algorithm in the glue dosing system. This research examines the usefulness of a TRIZ based problem-solving process designed to improve the problem-solving ability of users in addressing difficult or reoccurring problems and also testify TRIZ is practicality and validity. Several suggestions are presented on how to approach this problem.
Critical Speed of The Glass Glue Machine's Creep and Influence Factors Analysis
NASA Astrophysics Data System (ADS)
Yang, Jianxi; Huang, Jian; Wang, Liying; Shi, Jintai
When automatic glass glue machine works, two questions of the machine starting vibrating and stick-slip motion are existing. These problems should be solved. According to these questions, a glue machine's model for studying stick-slip is established. Based on the dynamics system describing of the model, mathematical expression is presented. The creep critical speed expression is constructed referring to existing research achievement and a new conclusion is found. The influencing factors of stiffness, dampness, mass, velocity, difference of static and kinetic coefficient of friction are analyzed through Matlab simulation. Research shows that reasonable choice of influence parameters can improve the creep phenomenon. These all supply the theory evidence for improving the machine's motion stability.
Full thickness burns caused by cyanoacrylate nail glue: A case series.
Kelemen, Noemi; Karagergou, Eleni; Jones, Sarah L; Morritt, Andrew N
Artificial (acrylic) nails are popular cosmetic enhancements that provide the user with the appearance of manicured nails, do not chip or crack, and are generally considered very safe to apply. We report three cases where full thickness thermal burns were sustained from nail glue adhesive (cyanoacrylate) during the application of artificial nails. All three cases underwent surgical debridement and split skin graft reconstruction. We carried out an experiment to characterize the exothermic reaction between nail glue and cotton leggings. The average high temperature produced was 68°C which was sustained for 12.2s which is more than sufficient to cause full thickness burns on skin. We report these cases to increase both professional and public awareness of this serious potential complication associated with the application of artificial nails. PMID:26777605
Dendrimeric nano-glue material for localized surface plasmon resonance-based fiber-optic sensors
NASA Astrophysics Data System (ADS)
Satija, Jitendra; Mukherji, Soumyo
In this study, we have investigated dendrimeric architecture as "nano-glue" material for RI-sensitive fiber-optic sensors. Dendrimers are immobilized on fiber-optic probes using a simple method that includes dipping, rinsing and drying of probes at room temperature. Dendrimer binding was confirmed by contact angle measurement and fluorescein isothiocyanate binding studies. These functionalized probes were coated with gold nanoparticles to develop localized surface plasmon resonance-based refractive index sensor. RI sensitivity measurement revealed that the dendrimeric matrix enhanced the RI sensitivity by 1.4-fold compared to two-dimensional amino-silanized sensor matrices. This suggests that dendrimer molecules are better choice as "nano-glue" material for fiber-optic sensors.
Efficacy and Limitations of Transarterial Acrylic Glue Embolization for Intracranial Dural Arteriovenous Fistulas
MIYAMOTO, Naoko; NAITO, Isao; SHIMIZU, Tatsuya; YOSHIMOTO, Yuhei
The efficacy and limitations of transarterial acrylic glue embolization for the treatment of intracranial dural arteriovenous fistulas (DAVFs) were investigated. Thirty-four DAVFs treated by transarterial embolization using n-butyl cyanoacrylate were retrospectively reviewed. The locations of DAVFs were the transverse-sigmoid sinus in 11, tentorium in 10, cranial vault in 9, and superior sagittal sinus, jugular bulb, foramen magnum, and middle cranial fossa in 1 each. Borden classification was type I in 7, type II in 3, and type III in 24. Eight patients had undergone prior transvenous coil embolization. Complete obliteration rate was 56% immediately after embolization, 71% at follow-up angiography, and 85% after additional treatments (1 transvenous embolization and 4 direct surgery). Complications occurred in three patients, consisting of asymptomatic vessel perforations during cannulation in two patients and leakage of contrast medium resulting in medullary infarction in one patient. Transarterial glue embolization is highly effective for Borden type III DAVF with direct cortical venous drainage, but has limitations for Borden type I and II DAVFs in which the affected sinus is part of the normal venous circulation. Onyx is a new liquid embolic material and is becoming the treatment of choice for DAVF. The benefits of glue embolization compared to Onyx embolization are high thrombogenicity, and relatively low risks of cranial nerve palsies and of excessive migration into the draining veins of high flow fistula. Transarterial glue embolization continues to be useful for selected patients, and complete cure can be expected in most patients with fewer complications if combined with transvenous embolization or direct surgery. PMID:25746311
Percutaneous Cyanoacrylate Glue Injection into the Renal Pseudoaneurysm to Control Intractable Hematuria After Percutaneous Nephrolithotomy
Lal, Anupam Kumar, Ajay; Prakash, Mahesh; Singhal, Manphool; Agarwal, Mayank Mohan; Sarkar, Debansu; Khandelwal, Niranjan
We report a case of a 43-year-old man who developed intractable hematuria after percutaneous nephrolithotomy. Angiography detected a pseudoaneurysm arising from the lower polar artery; however, embolization could not be performed because of unfavorable vascular anatomy. A percutaneous thrombin injection under ultrasound guidance initially controlled the bleeding, but hematuria subsequently recurred as a result of recanalization of the aneurysm. The case was successfully managed with ultrasound- and fluoroscopic-guided direct injection of cyanoacrylate glue into the pseudoaneurysm.
A drift detector system with anode and cathode readout in the GlueX experiment
Berdnikov, V V; Somov, S V; Pentchev, L; Zihlmann, B
A drift detector system designed to detect charged particle tracks in the GlueX experiment dedicated to study the nature of confinement is described. The key design features of the drift chambers associated with the requirement of a minimum material budget in the path of secondary particles are presented. The spatial resolution and the detection efficiency have been measured with cosmic rays using the automatic data acquisition system.
Techniques of autologous pericardial leaflet replacement for aortic valve reconstruction.
Rankin, J Scott; Nöbauer, Christian; Crooke, Philip S; Schreiber, Christian; Lange, Rüdiger; Mazzitelli, Domenico
Glutaraldehyde-fixed autologous pericardium rarely calcifies or retracts, and it is a useful substitute for cardiac valve leaflets. Current understanding of aortic valve geometry provides good models for aortic leaflet design, and pericardial leaflet construction is illustrated in this article for bicuspid and tri-leaflet valves. Outcomes have been characterized by low valve-related complication rates, and results of recent series are encouraging. Perhaps sufficient data are available to consider autologous pericardial leaflet replacement in highly selected younger patients with irreparable leaflets and contraindications to warfarin. PMID:25087813
A review of the application of autologous blood transfusion.
Zhou, J
Autologous blood transfusion (ABT) has been gradually attracting more attention due to the increasingly prominent problem of blood transfusion safety and blood shortage in recent years. With the rapid development of blood conservation techniques, blood component separation technology, blood transfusion medicine and a constant increase in clinical needs, ABT technology has been expanded and innovated to a large degree. In this study, the development of preoperative autologous blood donation (PABD), acute normovolemic hemodilution (ANH), intraoperative and postoperative autotransfusion, and other new technologies and theories are reviewed and existing questions are analyzed. Challenges and applications are also discussed in order to provide reference for peers. PMID:27533770
Autologous hematopoietic stem cell transplantation for mediastinal extramedullary plasmocytoma.
Abdelkefi, Abderrahmene; Ben Othman, Tarek; Torjman, Lamia; Ladeb, Saloua; Ben Ghorbel, Imed; Lakhal, Amed; Ben Amor, Ramzi; Miled, Mohamed; Kchir, Mohamed-Nidhameddine; Ben Abdeladhim, Abdeladhim
Extramedullary plasmocytoma (EMP) is a rare cell neoplasm most frequently localised in the upper respiratory tract. We report the case of a 43 year-old-man, with an unusual presentation of EMP developing in the mediastinum, two years after a diagnosis of solitary plasmocytoma of the bone which was successfully treated by local irradiation. In this aggressive presentation, we decided to perform an autologous hematopoietic stem cell transplantation. Two months after transplantation, CT scan showed disappearance of the mediastinal mass and immunofixation of the serum was normal. Selected cases of diffuse EMP, could benefit from intensive treatment followed by autologous hematopoietic stem cell transplantation. PMID:14534964
A review of the application of autologous blood transfusion
Zhou, J.
Autologous blood transfusion (ABT) has been gradually attracting more attention due to the increasingly prominent problem of blood transfusion safety and blood shortage in recent years. With the rapid development of blood conservation techniques, blood component separation technology, blood transfusion medicine and a constant increase in clinical needs, ABT technology has been expanded and innovated to a large degree. In this study, the development of preoperative autologous blood donation (PABD), acute normovolemic hemodilution (ANH), intraoperative and postoperative autotransfusion, and other new technologies and theories are reviewed and existing questions are analyzed. Challenges and applications are also discussed in order to provide reference for peers. PMID:27533770
The impact of UVB radiation on the glycoprotein glue of orb-weaving spider capture thread.
Stellwagen, Sarah D; Opell, Brent D; Clouse, Mary E
Many spider orb-webs are exposed to sunlight and the potentially damaging effects of ultraviolet B (UVB) radiation. We examined the effect of UVB on the viscoelastic glycoprotein core of glue droplets deposited on the prey capture threads of these webs, hypothesizing that webs built by species that occupy sunny habitats are less susceptible to UVB damage than are webs built by species that prefer shaded forest habitats or by nocturnal species. Threads were tested shortly after being collected in the early morning and after being exposed to UVB energy equivalent to a day of summer sun and three times this amount. Droplets kept in a dark chamber allowed us to evaluate post-production changes. Droplet volume was unaffected by treatments, indicating that UVB did not damage the hygroscopic compounds in the aqueous layer that covers droplets. UVB exposure did not affect energies of droplet extension for species from exposed and partially to mostly shaded habitats (Argiope aurantia, Leucauge venusta and Verrucosa arenata). However, UVB exposure reduced the energy of droplet extension in Micrathena gracilis from shaded forests and Neoscona crucifera, which forages at night. Only in L. venusta did the energy of droplet extension increase after the dark treatment, suggesting endogenous molecular alignment. This study adds UVB irradiation to the list of factors (humidity, temperature and strain rate) known to affect the performance of spider glycoprotein glue, factors that must be more fully understood if adhesives that mimic spider glycoprotein glue are to be produced. PMID:26333924
Composition and Function of Spider Glues Maintained During the Evolution of Cobwebs.
Jain, Dharamdeep; Zhang, Ci; Cool, Lydia Rose; Blackledge, Todd A; Wesdemiotis, Chrys; Miyoshi, Toshikazu; Dhinojwala, Ali
Capture silks are an interesting class of biological glues that help spiders subdue their prey. Viscid capture silk produced by the orb web spiders is a combination of hygroscopic salts that aid in water uptake and interact with adhesive glycoproteins to make them soft and sticky. The orb was a stepping stone to the evolution of new web types, but little is known about the adhesives in these webs. For instance, cobweb spiders evolved from orb-weaving ancestors and utilize glue in specialized sticky gumfoot threads rather than an elastic spiral. Early investigation suggests that gumfoot adhesives are quite different viscid glues because they lack a visible glycoprotein core, act as viscoelastic fluids rather than solids, and are largely invariant to humidity. Here, we use spectroscopic and staining methods to show that the gumfoot silk produced by Latrodectus hesperus (western black widow) is composed of hygroscopic organic salts and water insoluble glycoproteins, similar to viscid silk, in addition to a low concentration of spider coating peptides reported before. Our adhesion studies reveal that the organic salts play an important role in adhesion, similar to that seen in orb web spiders, but modulating function at much lower humidity. Our work shows more similarities in the viscid silk produced by orb web and cobweb spiders than previously anticipated and provide guidelines for developing synthetic adhesives that can work in dry to humid environments. PMID:26322742
Rapid cultivation of aerobic granular sludge by bone glue augmentation and contaminant removal characteristics.
Wang, Shuo; Shi, Wenxin; Yu, Shuili; Yi, Xuesong
To achieve a quick start-up and stable operation, aerobic granular sludge (AGS) was cultivated in a sequencing batch airlift reactor (SBAR) with the addition of bone glue augmentation. Adding an amount of bone glue (40 mg L(-1)) can accelerate granulation, which advanced by 10 d on average. Aerobic granules of size 0.5-3.0 mm were dominant in the SBAR and the settling velocity acquired a better correlation with the size of the AGS. In addition, the content of total polysaccharides was 19.54 mg gMLSS(-1) (grams of mixed liquor suspended solids) (an increase of 34.0%), the content of total protein was 60.59 mg gMLSS(-1) (an increase of a factor of 33) and the total proteins/total polysaccharides ratio was 3.3. The relatively high protein content was an essential feature for cultivation of AGS, which may indicate that extracellular polymeric substance was the mechanism for granulation due to the adhesion of microorganisms by bone glue. AGS possessed better chemical oxygen demand, NH4(+)-N and PO4(3-)-P removal efficiency (of 86.7, 90.6 and 93.8%, respectively) and no nitrite accumulation was observed in the whole process. PMID:23552254
A Self-assembly Model of Time-Dependent Glue Strength
NASA Astrophysics Data System (ADS)
Sahu, Sudheer; Yin, Peng; Reif, John H.
Self-assembly is a ubiquitous process in which small objects self-organize into larger and complex structures. In 2000, Rothemund and Winfree proposed a Tile Assembly Model as a mathematical model for theoretical studies of self-assembly. We propose a refined self-assembly model in which the glue strength between two juxtaposed tiles is a function of the time they have been in neighboring positions. We then present an implementation of our model using strand displacement reactions on DNA tiles. Under our model, we can demonstrate and study catalysis and self-replication in the tile assembly. We then study the tile complexity for assembling shapes in our model and show that a thin rectangle of size k×N can be assembled using O((log (N))/log log (N)) types of tiles, demonstrating the glue model has additional capabilities over the prior tiling assembly model. We also describe a method to implement with DNA tiles our model of time-dependant glue strength.
Avetikov, D; Loza, K; Starchenko, I; Loza, E; Marushchak, M
We aimed to investigate the morphological features of healing of postoperative wounds in the early stages of reparative process in the experiment, depending on the used type of the wound closure. It is proved that the nature and type of the scar depends on the processes that occur in the wound at the early postoperative stage, which in turn greatly affects the form of suture material used. The experiment included 20 male rats, weighing 180-200 g. All rats were anesthetized by a single intraperitoneal injection of sodium thiopental. After the shaving operative field, 2 cm full-thickness incision wound was made on the anterior surface of the abdomen in the longitudinal direction. As suture material for wound closure in the 1st experimental group (10 rats) we used surgical filament "Polyamide 4-0». In the 2nd experimental group (10 rats) wounds were closured by using skin glue "Dermabond". According from our experiment, the usage of skin glue creates better conditions for wound healing. Thus, to achieve a more aesthetic scar, we recommend applying skin glue instead of using nodal joints. PMID:26177141
Glue-induced birefringence in surface-attached FBG strain sensors
NASA Astrophysics Data System (ADS)
Helminger, Dominik; Daitche, Alexej; Roths, Johannes
The influence of the gluing process on the birefringence of surface-glued FBGs that were inscribed in highly birefringence (HiBi) optical fibers of type Panda was studied by monitoring the variation of the birefringence during the gluing procedure. The isothermal curing process at 100°C of the epoxy-based adhesive is characterized by the reduction of birefringence during curing. Significant transversal strain is introduced into the fiber during the cool down period, which is due to different thermal expansion coefficients of the silica and the glue. When the slow axis of the HiBi fiber is oriented parallel to the surface, the glue-induced transversal strain reduces the birefringence of the fiber by ΔB = -6.6 10-5 and when it is perpendicular to the surface, it is increased by ΔB = 1.1 10-5. It can be estimated that for conventional FBGs in single mode fibers a glue-induced birefringence in the order of ΔB = 3.4 10-5 can be expected, which has to be taken into account if in surface-mounted FBG-based strain measurements a high accuracy has to be achieved.
Bone Glue Modified Asphalt: A Step towards Energy Conservation and Environment Friendly Modified Asphalts
Rizvi, Hashim Raza; Gallo, August A.
Asphalt has been modified for the past several decades using various additives, including synthetic polymers. Polymer modification improves structural and engineering characteristics of the binder, which is a result of improvement in rheological characteristics of binder as well as its adhesion capability with the aggregate. Such enhancement inevitably enhances the performance characteristics of hot mix asphalts (HMA) such as fatigue life, resistance to rutting, and thermal cracking. Even though polymer-modified HMA is popular in North America and European countries, its use is still limited in developing countries of Southeast Asia due to high costs associated with its manufacturing, processing, and energy consumption. In this study, a new kind of asphalt modifier derived from animal wastes, such as bones, hides, and flesh commonly known as Bone Glue, is studied. This biomaterial which is a by-product of food and cattle industries is cheap, conveniently available, and produced locally in developing countries. The results of the research study showed that the bone glue can easily be mixed with asphalt without significantly altering the asphalt binder's viscosity and mixing and compaction temperatures of HMA. Additionally, improvements in complex shear modulus for a range of temperatures were also determined and it was found that complex shear modulus was improved by bone glue modification. PMID:27437456
Percutaneous Glue Embolization of a Visceral Artery Pseudoaneurysm in a Case of Sickle Cell Anemia
Gulati, Gurpreet S.; Gulati, Manpreet S. Makharia, Govind; Hatimota, Pradeep; Saikia, Nripen; Paul, Shashi B.; Acharya, Subrat
Although aneurysmal complications of sickle cell anemia have been described in the intracranial circulation, visceral artery pseudoaneurysms in this disease entity have not previously been reported in the literature. Conventional treatment of visceral pseudoaneurysms has been surgical ligation or resection of the aneurysm. Transcatheter embolization has emerged as an attractive, minimally invasive alternative to surgery in the treatment of these lesions. In certain situations, however, due to the unfavorable angiographic anatomy precluding safe transcatheter embolization, direct percutaneous glue injection of the pseudoaneurysm sac may be considered to achieve successful occlusion of the sac. The procedure may be rendered safer by simultaneous balloon protection of the parent artery. We describe this novel treatment modality in a case of inferior pancreaticoduodenal artery pseudoaneurysm in a patient with sickle cell anemia. Although a complication in the form of glue reflux into the parent vessel occurred that necessitated surgery, this treatment modality may be used in very selected cases (where conventional endovascular embolization techniques are not applicable) after careful selection of the balloon diameter and appropriate concentration of the glue-lipiodol mixture.
Proteinaceous adhesive secretions from insects, and in particular the egg attachment glue of Opodiphthera sp. moths.
Li, Dongmei; Huson, Mickey G; Graham, Lloyd D
Biochemical and electrophoretic screening of 29 adhesive secretions from Australian insects identified six types that appeared to consist largely of protein. Most were involved in terrestrial egg attachment. Hydrogel glues were subjected to gravimetric analyses and assessed for overall amino acid composition. When 32 proteins in glues from eight insect species were analyzed individually, many proved to be rich in Gly, Ser, and/or Pro, and some contained substantial levels of 4-hydroxyproline. A few proteins were heavily glycosylated. Abundant protein-based secretions were tested as adhesives, mainly by measuring dry shear strength on wood. The strongest (1-2 MPa) was an egg attachment glue produced by saturniid gum moths of the genus Opodiphthera. It was harvested from female colleterial gland reservoirs as a treacle-like liquid that underwent irreversible gelation, and recovered from the capsules of laid eggs as a highly elastic orange-brown hydrogel that could also display high tack. Its protein-based nature was confirmed and explored by spectroscopy, enzymatic degradation, and 2D gel electrophoresis. Its proteins are mostly 80-95 kDa, and sequences (almost all novel) were established for 23 tryptic peptides. Scanning probe microscopy of Opodiphthera hydrogel in water returned median values of 0.83 nN for adhesion, 63 kPa for modulus, and 87% for resilience. Recombinant mimics of this material might be useful as biodegradable commodity adhesives or as specialty biomedical products. PMID:18780346
Autologous serum eye drops for dry eye
Pan, Qing; Angelina, Adla; Zambrano, Andrea; Marrone, Michael; Stark, Walter J; Heflin, Thomas; Tang, Li; Akpek, Esen K
Background Theoretically, autologous serum eye drops (AS) have a potential advantage over traditional therapies based on the assumption that AS serve not only as a lacrimal substitute to provide lubrication, but also contain other biochemical components mimicking natural tears more closely. The application of AS in dry eye treatment has gained popularity as a second-line therapy in the treatment of dry eye. Published studies on the subject indicate that autologous serum could be an effective treatment for dry eye. Objectives To evaluate the efficacy and safety of AS compared to artificial tears for treating dry eye. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLD MEDLINE, (January 1950 to April 2013), EMBASE (January 1980 to April 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to April 2013), the meta Register of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (September 2013) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 April 2013. Selection criteria We included randomized controlled trials (RCTs) in which AS was compared to artificial tears in the treatment of dry eye in adults. Data collection and analysis Two review authors independently screened all titles and abstracts and assessed full-text articles of potentially eligible trials. Two review authors extracted data and assessed the methodological quality and characteristics of the included trials.We contacted investigators for missing data
Repair of Segmental Load-Bearing Bone Defect by Autologous Mesenchymal Stem Cells and Plasma-Derived Fibrin Impregnated Ceramic Block Results in Early Recovery of Limb Function
Ng, Min Hwei; Duski, Suryasmi; Tan, Kok Keong; Yusof, Mohd Reusmaazran; Low, Kiat Cheong; Mohamed Rose, Isa; Mohamed, Zahiah; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj
Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function. PMID:25165699
[Quantification of D-dimer and soluble fibrin in blood plasma of people with ischemic heart disease and hypertension].
Lugovskoĭ, E V; Kolesnikova, I N; Lugovskaia, N E; Litvinova, L M; Gritsenko, P G; Gogolinskaia, G K; Liashko, E D; Kostiuchenko, E P; Remizovskiĭ, G A; Pedchenko, V N; Komisarenko, S V
The method of D-dimer quantification in the human blood plasma has been developed using monoclonal antibodies 111-3b and II-4d. The method has been verified on the blood plasma of the patients with ischemic heart disease with and without stenocardia and with hypertension. The results showed that at ischemic heart disease with and without stenocardia and at hypertension the quantities of D-dimer in the blood plasma were generally less than the highest normal level 500 ng/ml (64.3%, 76.2% and 95%, correspondingly). The semiquantitative measurements of soluble fibrin levels in blood plasmas of the patients with ischemic heart disease and hypertension have been performed. It has been shown that the quantity of soluble fibrin at these diseases range greatly from < 0.03 mg/ml to 0.15 mg/ml. There was no correlation between the quantities of D-dimer and soluble fibrin in blood plasmas of the patients. Electrophoresis in PAAG with SDS showed that the soluble fibrin at these diseases had the mo- lecular mass of the fibrin (ogen). Thus the soluble fibrin in blood plasmas analysed consisted mainly of fibrin desAA oligomers (may be with fibrinogen incorporation) which are not stabilized by the factor XIIIa. PMID:16350758
Optimization of acidic fibroblast growth factor (FGF-1) and its delivery through a modified degradable fibrin scaffold
NASA Astrophysics Data System (ADS)
Pandit, Abhay Smashikant
The aim of this investigation was to develop a degradable fibrin wound dressing that can deliver an optimized dose of acidic fibroblast growth factor (FGF-1). This aim led to three distinct phases of study. In the first phase, a structurally modified fibrin degradable scaffold was developed and tested in a rabbit ear ulcer model. A significant increase in the angiogenic and fibroblastic response with a corresponding decrease in healing time was seen in the modified fibrin-treated ulcers as compared with untreated ulcers and ulcers treated with non-modified fibrin systems. In the second phase of the study, a biochemical factor, FGF-1, was added to this scaffold. An optimal dose of 8 mug of FGF-1 was determined to be required to initiate a desired wound-healing response in a rabbit ear ulcer model, based on an enhanced angiogenic and fibroblastic response and an increased epithelialization rate. The objective of the last phase was to investigate the efficacy of a modified scaffold as a vehicle for FGF-1. In vivo testing was conducted in a full-thickness defect model in a rabbit. Improvements were seen in the angiogenic and fibroblastic responses in the FGF-1/modified fibrin treatment group and, hence, FGF-1/modified fibrin was the preferred treatment. In conclusion, the modified fibrin/FGF-1 matrix served as a suitable vehicle for the growth factor, providing a desired healing response and a desirable release rate and, thus, was determined to be an effective scaffold.
Formation and stability of interpenetrating polymer network hydrogels consisting of fibrin and hyaluronic acid for tissue engineering.
Lee, Fan; Kurisawa, Motoichi
Fibrin gel is widely used as a tissue engineering scaffold. However, it has poor mechanical properties, which often result in rapid contraction and degradation of the scaffold. An interpenetrating polymer network (IPN) hydrogel composed of fibrin and hyaluronic acid-tyramine (HA-Tyr) was developed to improve the mechanical properties. The fibrin network was formed by cleaving fibrinogen with thrombin, producing fibrin monomers that rapidly polymerize. The HA network was formed through the coupling of tyramine moieties using horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂). The degree of crosslinking of the HA-Tyr network can be tuned by varying the H₂O₂ concentration, producing IPN hydrogels with different storage moduli (G'). While fibrin gels were completely degraded in the presence of plasmin and contracted when embedded with cells, the shape of the IPN hydrogels was maintained due to structural support by the HA-Tyr networks. Cell proliferation and capillary formation occurred in IPN hydrogels and were found to decrease with increasing G' of the hydrogels. The results suggest that fibrin-HA-Tyr IPN hydrogels are a potential alternative to fibrin gels as scaffolds for tissue engineering applications that require shape stability. PMID:22943886
[Propolis. The bee glue as presented by the Graeco-Roman literature].
Golder, Werner
The bee glue, commonly known as propolis, has been employed for medical purposes already in teh ancient world. More than 15 Greek and Roman authors report on the preparation and application of the so-called third natural product of the bees (besides honey and wax). Aristoteles described the fundamental issues of its biology in his 'Historia Animalium' correctly. The bulk of propolis is obtained from the barks of poplars. Once carried in the hives, the glue is used to stabilize the cells and honeycombs and to protect the bees against invaders and cold weather. Propolis has been chiefly employed for the preparation of ointment and plasters. For this purpose, the viscous raw material was purified, moulded and boiled. In most preparations, the bee glue was only one of many (up to 20) pharmacologically active constituents and came to five to 20% of the mixture. Only rarely, a single drug therapy was using propolis was carried out. The application of the glue was most successful in general surgery and casualties. In that respect, the ancient physicians took advantage of the anti-edematous and anti-infectious properties of the substance. Thus, it was used to treat bumps, indurations, and slow-healing wounds. Moreover, cataplasms against swollen cervical nodes and indurations of the female breast often contained propolis. Finally, bee glue proved successful for the treatment of chronic backache and pain in the hip as well as fresh injuries of muscles and tendons. In the sector of skin diseases, lichens and condylomata were found to respond well to propolis. ALl this indications have been a matter of several records. However, the successful use of propolis in diseases of the stomach and liver has ben reported solely by Alexander of Tralles (6th century AD). Not counting the internal diseases, the spectrum of indications for propolis has not substantially changed as compared to the classical antiquity. Interestingly, radiation therapists have adopted the ancient remedy and
Fundamental Investigations of the Extracellular Proteins Fibrin and Collagen in Microchannel Devices
NASA Astrophysics Data System (ADS)
Evans, Heather M.; Koester, Sarah; Pfohl, Thomas
Microfluidic structures are particularly amenable to controlled investigations of protein bundle and network formation. Hydrodynamic focusing is utilized to create a diffusion-controlled gradient of reactants, enabling non-equilibrium investigations. We present studies of the blood clotting protein fibrin, a three-dimensional network formed from the enzymatic cleavage of fibrinogen monomers by the protein thrombin. Fibrin is a vital component of blood clots, and has been implicated in a variety of diseases. Real-time fluorescence microscopy and x-ray micro-diffraction are used to quantify supramolecular assembly and provide snapshots of the evolution of fibrin network formation. We also show that collagen, a ubiquitous extracellular protein, can be bundled in situ through the use of a pH gradient. An outlook toward artificial blood vessels arises from the insight that both fibrin and collagen can easily be used to coat microchannel structures. The resulting mesh forms an ideal environment for red blood cells and other cell types.
Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair.
Perussi Biscola, Natalia; Politti Cartarozzi, Luciana; Ferreira Junior, Rui Seabra; Barraviera, Benedito; Leite Rodrigues de Oliveira, Alexandre
Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons. PMID:27446617
A Comparison of the Mechanical and Structural Properties of Fibrin Fibers with Other Protein Fibers
Guthold, M.; Liu, W.; Sparks, E. A.; Jawerth, L. M.; Peng, L.; Falvo, M.; Superfine, R.; Hantgan, R. R.; Lord, S. T.
In the past few years a great deal of progress has been made in studying the mechanical and structural properties of biological protein fibers. Here, we compare and review the stiffness (Young's modulus, E) and breaking strain (also called rupture strain or extensibility, εmax) of numerous biological protein fibers in light of the recently reported mechanical properties of fibrin fibers. Emphasis is also placed on the structural features and molecular mechanisms that endow biological protein fibers with their respective mechanical properties. Generally, stiff biological protein fibers have a Young's modulus on the order of a few Gigapascal and are not very extensible (εmax < 20%). They also display a very regular arrangement of their monomeric units. Soft biological protein fibers have a Young's modulus on the order of a few Megapascal and are very extensible (εmax > 100%). These soft, extensible fibers employ a variety of molecular mechanisms, such as extending amorphous regions or unfolding protein domains, to accommodate large strains. We conclude our review by proposing a novel model of how fibrin fibers might achieve their extremely large extensibility, despite the regular arrangement of the monomeric fibrin units within a fiber. We propose that fibrin fibers accommodate large strains by two major mechanisms: (1) an α-helix to β-strand conversion of the coiled coils; (2) a partial unfolding of the globular C-terminal domain of the γ-chain. PMID:17952642
Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Fan, Natalie K.; Keegan, Philip M.; Platt, Manu O.; Averett, Rodney D.
Fibrin is an extracellular matrix protein that is responsible for maintaining the structural integrity of blood clots. Much research has been done on fibrin in the past years to include the investigation of synthesis, structure-function, and lysis of clots. However, there is still much unknown about the morphological and structural features of clots that ensue from patients with disease. In this research study, experimental techniques are presented that allow for the examination of morphological differences of abnormal clot structures due to diseased states such as diabetes and sickle cell anemia. Our study focuses on the preparation and evaluation of fibrin clots in order to assess morphological differences using various experimental assays and confocal microscopy. In addition, a method is also described that allows for continuous, real-time calculation of lysis rates in fibrin clots. The techniques described herein are important for researchers and clinicians seeking to elucidate comorbid thrombotic pathologies such as myocardial infarctions, ischemic heart disease, and strokes in patients with diabetes or sickle cell disease. PMID:25867016
Immobilization of alkaline phosphatase on microporous nanofibrous fibrin scaffolds for bone tissue engineering.
Osathanon, Thanaphum; Giachelli, Cecilia M; Somerman, Martha J
Alkaline phosphatase (ALP) promotes bone formation by degrading inorganic pyrophosphate (PP(i)), an inhibitor of hydroxyapatite formation, and generating inorganic phosphate (P(i)), an inducer of hydroxyapatite formation. P(i) is a crucial molecule in differentiation and mineralization of osteoblasts. In this study, a method to immobilize ALP on fibrin scaffolds with tightly controllable pore size and pore interconnection was developed, and the biological properties of these scaffolds were characterized both in vitro and in vivo. Microporous, nanofibrous fibrin scaffolds (FS) were fabricated using a sphere-templating method. ALP was covalently immobilized on the fibrin scaffolds using 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (EDC). Scanning electron microscopic observation (SEM) showed that mineral was deposited on immobilized alkaline phosphatase fibrin scaffolds (immobilized ALP/FS) when incubated in medium supplemented with beta-glycerophosphate, suggesting that the immobilized ALP was active. Primary calvarial cells attached, spread and formed multiple layers on the surface of the scaffolds. Mineral deposition was also observed when calvarial cells were seeded on immobilized ALP/FS. Furthermore, cells seeded on immobilized ALP/FS exhibited higher osteoblast marker gene expression compared to control FS. Upon implantation in mouse calvarial defects, both the immobilized ALP/FS and FS alone treated group had higher bone volume in the defect compared to the empty defect control. Furthermore, bone formation in the immobilized ALP/FS treated group was statistically significant compared to FS alone group. However, the response was not robust. PMID:19501906
Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair
Ferreira Junior, Rui Seabra
Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons. PMID:27446617
Lyophilized platelet-rich fibrin (PRF) promotes craniofacial bone regeneration through Runx2.
Li, Qi; Reed, David A; Min, Liu; Gopinathan, Gokul; Li, Steve; Dangaria, Smit J; Li, Leo; Geng, Yajun; Galang, Maria-Therese; Gajendrareddy, Praveen; Zhou, Yanmin; Luan, Xianghong; Diekwisch, Thomas G H
Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold±0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold±0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p<0.001) when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering. PMID:24830554
Plasma fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion.
Malik, Gunjan; Knowles, Lynn M; Dhir, Rajiv; Xu, Shuping; Yang, Shuting; Ruoslahti, Erkki; Pilch, Jan
The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating plasma fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin alphavbeta3. In vitro studies showed that fibrin-fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-fibronectin complexes to induce the activation of integrin alphavbeta3. Our findings reveal an important contribution of plasma fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a fibronectin-alphavbeta3 integrin axis, in which plasma fibronectin has to be incorporated into the blood clot. PMID:20501851
Lyophilized Platelet-Rich Fibrin (PRF) Promotes Craniofacial Bone Regeneration through Runx2
Li, Qi; Reed, David A.; Min, Liu; Gopinathan, Gokul; Li, Steve; Dangaria, Smit J.; Li, Leo; Geng, Yajun; Galang, Maria-Therese; Gajendrareddy, Praveen; Zhou, Yanmin; Luan, Xianghong; Diekwisch, Thomas G. H.
Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold ± 0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold ± 0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p < 0.001) when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering. PMID:24830554
Platelet Rich Fibrin Matrix Improves Wound Angiogenesis via Inducing Endothelial Cell Proliferation
Roy, Sashwati; Driggs, Jason; Elgharably, Haytham; Biswas, Sabyasachi; Findley, Muna; Khanna, Savita; Gnyawali, Urmila; Bergdall, Valerie K.; Sen, Chandan K.
The economic, social and public health burden of chronic ulcers and other compromised wounds are enormous and rapidly increasing with the aging population. The growth factors derived from platelets play an important role in tissue remodeling including neovascularization. Platelet-rich plasma (PRP) has been utilized and studied for the last four decades. Platelet gel and fibrin sealant, derived from PRP mixed with thrombin and calcium chloride, have been exogenously applied to tissues to promote wound healing, bone growth, hemostasis and tissue sealing. In this study we first characterized recovery and viability of as well as growth factor release from platelets in a novel preparation of platelet gel and fibrin matrix, namely, platelet rich fibrin matrix (PRFM). Next, the effect of PRFM application in a delayed model of ischemic wound angiogenesis was investigated. The study for the first-time shows the kinetics of the viability of platelet embedded fibrin matrix. A slow and steady release of growth factors from PRFM was observed. The VEGF released from PRFM was primarily responsible for endothelial mitogenic response via ERK activation pathway. Finally, this preparation of PRFM effectively induced endothelial cell proliferation and improved wound angiogenesis in chronic wounds, providing evidence of probable mechanisms of action of PRFM in healing of chronic ulcers. PMID:22092846
Therapeutic assessment of mesenchymal stem cells delivered within a PEGylated fibrin gel following an ischemic injury.
Ricles, Laura M; Hsieh, Pei-Ling; Dana, Nicholas; Rybalko, Viktoriya; Kraynak, Chelsea; Farrar, Roger P; Suggs, Laura J
The intent of the current study was to investigate the therapeutic contribution of MSCs to vascular regeneration and functional recovery of ischemic tissue. We used a rodent hind limb ischemia model and intramuscularly delivered MSCs within a PEGylated fibrin gel matrix. Within this model, we demonstrated that MSC therapy, when delivered in PEGylated fibrin, results in significantly higher mature blood vessel formation, which allows for greater functional recovery of skeletal muscle tissue as assessed using force production measurements. We observed initial signs of vascular repair at early time points when MSCs were delivered without PEGylated fibrin, but this did not persist or lead to recovery of the tissue in the long-term. Furthermore, animals which were treated with PEGylated fibrin alone exhibited a greater number of mature blood vessels, but they did not arterialize and did not show improvements in force production. These results demonstrate that revascularization of ischemic tissue may be a necessary but not sufficient step to complete functional repair of the injured tissue. This work has implications on stem cell therapies for ischemic diseases and also potentially on how such therapies are evaluated. PMID:27318932
Bioreactor Conditioning for Accelerated Remodeling of Fibrin-Based Tissue Engineered Heart Valves
NASA Astrophysics Data System (ADS)
Schmidt, Jillian Beth
Fibrin is a promising scaffold material for tissue engineered heart valves, as it is completely biological, allows for engineered matrix alignment, and is able to be degraded and replaced with collagen by entrapped cells. However, the initial fibrin matrix is mechanically weak, and extensive in vitro culture is required to create valves with sufficient mechanical strength and stiffness for in vivo function. Culture in bioreactor systems, which provide cyclic stretching and enhance nutrient transport, has been shown to increase collagen production by cells entrapped in a fibrin scaffold, accelerating strengthening of the tissue and reducing the required culture time. In the present work, steps were taken to improve bioreactor culture conditions with the goal of accelerating collagen production in fibrin-based tissue engineered heart valves using two approaches: (i) optimizing the cyclic stretching protocol and (ii) developing a novel bioreactor system that permits transmural and lumenal flow of culture medium for improved nutrient transport. The results indicated that incrementally increasing strain amplitude cyclic stretching with small, frequent increments in strain amplitude was optimal for collagen production in our system. In addition, proof of concept studies were performed in the novel bioreactor system and increased cellularity and collagen deposition near the lumenal surface of the tissue were observed.
Role of clot-associated (-derived) thrombin in cell proliferation induced by fibrin clots in vitro
Gandossi, E; Lunven, C; Berry, C N
Thrombin is a potent mitogenic agent. Clot-associated thrombin retains its amidolytic and pro-aggregant activity. We therefore studied the ability of fibrin clots to induce proliferation in CCL39 cells (Chinese hamster lung fibroblasts), in the absence and presence of the thrombin inhibitors PPACK, recombinant hirudin (rHV2 Lys47) and heparin:antithrombin III. Fibrin clots incubated for 48 h with CCL39 cells led to significant cell proliferation, which was dependent on the concentration of thrombin used to prepare the clots. Thus, clots prepared with 91 nmol l−1 thrombin produced a similar proliferation (231±21%) to that obtained with 50 nmol l−1 thrombin in solution (213±29%). Rabbit plasma clots led to a 499±41% increase in cell number under identical conditions. Fibrin clot-induced cell proliferation was inhibited by all three thrombin inhibitors with no difference in IC50 values compared to those obtained against thrombin in solution, suggesting that cell proliferation be due to thrombin leaching from the clots. We found a time-dependent increase in thrombin release from the clots attaining a plateau at 24 h (∼61% of the total thrombin used in clot formation). Clots separated from the cells using porous cell culture chamber inserts led to similar proliferation to that of clots in contact with the cells. Thus fibrin-clot induced CCL39 proliferation is due to thrombin released from the clots. PMID:10696104
Human umbilical cord stem cell encapsulation in novel macroporous and injectable fibrin for muscle tissue engineering.
Liu, Jun; Xu, Hockin H K; Zhou, Hongzhi; Weir, Michael D; Chen, Qianming; Trotman, Carroll Ann
There has been little research on the seeding of human umbilical cord mesenchymal stem cells (hUCMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were: (i) to seed hUCMSCs in a fibrin hydrogel containing fast-degradable microbeads (dMBs) to create macropores to enhance cell viability; and (ii) to investigate the encapsulated cell proliferation and myogenic differentiation for muscle tissue engineering. Mass fractions of 0-80% of dMBs were tested, and 35% of dMBs in fibrin was shown to avoid fibrin shrinkage while creating macropores and promoting cell viability. This construct was referred to as "dMB35". Fibrin without dMBs was termed "dMB0". Microbead degradation created macropores in fibrin and improved cell viability. The percentage of live cells in dMB35 reached 91% at 16 days, higher than the 81% in dMB0 (p<0.05). Live cell density in dMB35 was 1.6-fold that of dMB0 (p<0.05). The encapsulated hUCMSCs proliferated, increasing the cell density by 2.6 times in dMB35 from 1 to 16 days. MTT activity for dMB35 was substantially higher than that for dMB0 at 16 days (p<0.05). hUCMSCs in dMB35 had high gene expressions of myotube markers of myosin heavy chain 1 (MYH1) and alpha-actinin 3 (ACTN3). Elongated, multinucleated cells were formed with positive staining of myogenic specific proteins including myogenin, MYH, ACTN and actin alpha 1. Moreover, a significant increase in cell fusion was detected with myogenic induction. In conclusion, hUCMSCs were encapsulated in fibrin with degradable microbeads for the first time, achieving greatly enhanced cell viability and successful myogenic differentiation with formation of multinucleated myotubes. The injectable and macroporous fibrin-dMB-hUCMSC construct may be promising for muscle tissue engineering applications. PMID:22902812
Fibrin deposition following bile duct injury limits fibrosis through an αMβ2-dependent mechanism.
Joshi, Nikita; Kopec, Anna K; Ray, Jessica L; Cline-Fedewa, Holly; Nawabi, Atta; Schmitt, Timothy; Nault, Rance; Zacharewski, Timothy R; Rockwell, Cheryl E; Flick, Matthew J; Luyendyk, James P
Coagulation cascade activation and fibrin deposits have been implicated or observed in diverse forms of liver damage. Given that fibrin amplifies pathological inflammation in several diseases through the integrin receptor αMβ2, we tested the hypothesis that disruption of the fibrin(ogen)-αMβ2 interaction in Fibγ(390-396A) mice would reduce hepatic inflammation and fibrosis in an experimental setting of chemical liver injury. Contrary to our hypothesis, α-naphthylisothiocyanate (ANIT)-induced liver fibrosis increased in Fibγ(390-396A) mice, whereas inflammatory cytokine expression and hepatic necrosis were similar to ANIT-challenged wild-type (WT) mice. Increased fibrosis in Fibγ(390-396A) mice appeared to be independent of coagulation factor 13 (FXIII) transglutaminase, as ANIT challenge in FXIII-deficient mice resulted in a distinct pathological phenotype characterized by increased hepatic necrosis. Rather, bile duct proliferation underpinned the increased fibrosis in ANIT-exposed Fibγ(390-396A) mice. The mechanism of fibrin-mediated fibrosis was linked to interferon (IFN)γ induction of inducible nitric oxide synthase (iNOS), a gene linked to bile duct hyperplasia and liver fibrosis. Expression of iNOS messenger RNA was significantly increased in livers of ANIT-exposed Fibγ(390-396A) mice. Fibrin(ogen)-αMβ2 interaction inhibited iNOS induction in macrophages stimulated with IFNγ in vitro and ANIT-challenged IFNγ-deficient mice had reduced iNOS induction, bile duct hyperplasia, and liver fibrosis. Further, ANIT-induced iNOS expression, liver fibrosis, and bile duct hyperplasia were significantly reduced in WT mice administered leukadherin-1, a small molecule that allosterically enhances αMβ2-dependent cell adhesion to fibrin. These studies characterize a novel mechanism whereby the fibrin(ogen)-integrin-αMβ2 interaction reduces biliary fibrosis and suggests a novel putative therapeutic target for this difficult-to-treat fibrotic disease. PMID
Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector
NASA Astrophysics Data System (ADS)
Poley, L.; Bloch, I.; Edwards, S.; Friedrich, C.; Gregor, I.-M.; Jones, T.; Lacker, H.; Pyatt, S.; Rehnisch, L.; Sperlich, D.; Wilson, J.
The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive used initially between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). However, this glue has several disadvantages, which motivated the search for an alternative. This paper presents a study of six ultra-violet (UV) cure glues and a glue pad for possible use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, thermal conduction and shear strength. Samples were thermally cycled, radiation hardness and corrosion resistance were also determined. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives than silver loaded glue. Results from electrical tests of first prototype modules constructed using these glues are presented.
How Effective is Autologous Serum Therapy in Chronic Autoimmune Urticaria
Majid, Imran; Shah, Shazia; Hassan, Altaf; Aleem, Saima; Aziz, Khalid
Background: Chronic autoimmune urticaria (CAU) is one of the most challenging therapeutic problems faced by a dermatologist. Recently, weekly autologous serum injections have been shown to induce a prolonged remission in this disease. Aim: To evaluate the efficacy of repeated autologous serum injections in patients with CAU. Materials and Methods: Seventy patients of CAU were prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a post-intervention follow-up of 12 weeks. Total urticaria severity score (TSS) was monitored at the baseline, at the end of treatment and lastly at the end of 12 weeks of follow up. Response to treatment was judged by the percentage reduction in baseline TSS at the end of treatment and again at the end of 12 weeks-follow-up. Results: Out of the 70 patients enrolled, 11 dropped out of the injection treatment after one or the first few doses only. Among the rest of 59 patients, only 7 patients (12%) went into a partial or complete remission and remained so over the follow-up period of 12 weeks. Forty patients (68%) did not demonstrate any significant reduction in TSS at the end of the treatment period. Rest of the 12 patients showed either a good or excellent response while on weekly injection treatment, but all of them relapsed over the follow-up period of 12 weeks. Conclusion: Autologous serum therapy does not seem to lead to any prolonged remission in patients of CAU. PMID:25657418
Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.
Martins, Deborah B; Farias-Eisner, Gina; Mandelbaum, Rachel S; Hoang, Han; Bradley, James P; Lee, Justine C
Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction. PMID:27579233
Potential of autologous NK cell therapy to eradicate leukemia
Abdel-Azim, Hisham; Heisterkamp, Nora
B-precursor acute lymphoblastic leukemia (BP-ALL) patients are immunocompromised. We recently reported that functional natural killer (NK) cells can be grown from patient bone marrow and blood samples at diagnosis. Surprisingly, such NK cells exhibit cytotoxicity against autologous BP-ALL cells. Here, we outline unanswered questions, challenges and possible applications associated with these findings. PMID:25949882
Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction
Martins, Deborah B.; Farias-Eisner, Gina; Mandelbaum, Rachel S.; Hoang, Han; Bradley, James P.
Summary: Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction. PMID:27579233
Label-free, sensitivity detection of fibrillar fibrin using gold nanoparticle-based chemiluminescence system.
Zhang, Yuanfu; Liu, Jifeng; Liu, Ting; Li, Haibo; Xue, Qingwang; Li, Rui; Wang, Lei; Yue, Qiaoli; Wang, Shuhao
A novel, label-free, gold nanoparticles (AuNPs)-based chemiluminescence assay has been developed for the detection of fibrillar fibrin. The method relied on the interaction of fibrinogen (Fib) with AuNPs and the aggregated AuNPs induce a strong luminol-H2O2 chemiluminesecence (CL) signal. We prepared the 12-nm-diameter AuNPs which well dispersed in the solution. Fib was absorbed on the surface of AuNPs against the aggregation of AuNPs in 1.0M NaCl. Otherwise, Fib was catalyzed to form fibrillar fibrin in the presence of thrombin. The fibrin induced AuNPs aggregated in the presence of NaCl solution. The catalytic activity of aggregated AuNPs on the luminol-H2O2 CL reaction is greatly enhanced. This allows us to utilize the luminol-H2O2 CL system for quantitative analysis of thrombin, which was used to denote fibrosis degree of Fib. The assay showed a linear toward fibrillar fibrin concentration in the range of 2.7 × 10(-15)-2.7 × 10(-13)M with a correlation of 0.9920. The limit of detection for fibrin was experimentally determined to be 1 fM, based on a signal-to-noise ratio (S/N) of 3. Relative to conventional methods, this method offers the advantages of higher sensitivity and selectivity and lower cost, showing great potential for medical diagnosis. PMID:26397422
The role of leukocytes in the pathogenesis of fibrin deposition in bovine acute lung injury.
Car, B. D.; Suyemoto, M. M.; Neilsen, N. R.; Slauson, D. O.
The peculiarly fibrinous nature of bovine acute lung injury due to infection with Pasteurella haemolytica A1 suggests an imbalance between leukocyte-directed procoagulant and profibrinolytic influences in the inflamed bovine lung. Calves with experimental pneumonia produced by intratracheal inoculation with P. haemolytica A1 developed acute locally extensive cranioventral fibrinopurulent bronchopneumonia. Pulmonary alveolar macrophages (PAM) recovered by segmental lavage from affected lung lobes were 30 times more procoagulant than PAM obtained from unaffected lung lobes and 37-fold more procoagulant than PAM from control calf lungs. Unlike the enhancement of procoagulant activity, profibrinolytic activity (plasminogen activator amidolysis) of total lung leukocytes (PAM and plasminogen activator neutrophils [PMN]) was decreased 23 times in cells obtained from affected lung lobes and also was decreased four times in cells obtained from unaffected lobes of infected animals. This marked imbalance in cellular procoagulant and fibrinolytic activity probably contributes significantly to enhanced fibrin deposition and retarded fibrin removal. In addition, PAM from inflamed lungs were strongly positive for bovine tissue factor antigen as demonstrated by immunocytochemistry. Intensely tissue factor-positive PAM enmeshed in fibrinocellular exudates and positive alveolar walls were situated such that they were likely to have, in concert, initiated extrinsic activation of coagulation in the acutely inflamed lung. These data collectively suggest that enhanced PAM-directed procoagulant activity and diminished PAM- and PMN-directed profibrinolytic activity represent important modifications of local leukocyte function in bovine acute lung injury that are central to the pathogenesis of lesion development with extensive fibrin deposition and retarded fibrin removal. Images Figure 2 Figure 3 PMID:2024707
Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas.
de la Fuente, Cristian; Pumarola, Martí; Blasco, Ester; Fernández, Francisco; Viu, Judit; Añor, Sònia
In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas. PMID:24745770
Regeneration of Tissues and Organs Using Autologous Cells
Anthony Atala
The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the native
Inhibition of fibrin polymerization by fragment d is affected by calcium, Gly-Pro-Arg and Gly-His-Arg.
Furlan, M; Rupp, C; Beck, E A
Fibrinopeptides A and B were removed from purified human fibrinogen by bovine thrombin, whereas the snake venom protease batroxobin only split fibrinopeptide A from fibrinogen. Aggregation of the resulting desAB- and desA-fibrin monomers was evaluated by recording the turbidity of incubation mixtures. Fibrin assembly was strongly accelerated by increasing the calcium concentration from 10(-5) to 10(-3) M. Fragment D was obtained from fibrinogen by proteolytic degradation with plasmin in the presence of Ca2+. At a 4-fold molar concentration relative to fibrinogen, fragment D dramatically inhibited fibrin polymerization at up to 10(-4) M Ca2+. This anticlotting activity was, however, much less pronounced at 10(-3) M Ca2+. The thrombin clotting time, measured on human plasma, was prolonged by fragment D in a dose-dependent manner. In citrate-containing plasma, the fibrinogen clotting was significantly delayed by an equimolar concentration of fragment D. In barium sulfate-adsorbed oxalated plasma, containing 2.5 mM Ca2+, the same amount of fragment D hardly affected fibrin polymerization. We conclude that fragment D has no important anticlotting effect under physiological conditions. The synthetic peptide Gly-Pro-Arg, corresponding to the amino-terminal sequence of the fibrin alpha-chain, inhibited aggregation of both desA-fibrin and desAB-fibrin at 10(-3) M Ca2+. The inhibition of desAB-fibrin polymerization by Gly-Pro-Arg was abolished at 10(-5) M Ca2+. In addition, Gly-Pro-Arg depressed the anticlotting activity of fragment D at low calcium concentration. An analogue of the amino-terminus of fibrin beta-chain, Gly-His-Arg, strongly accelerated aggregation of desA-fibrin monomers, but only moderately enhanced polymerization of desAB-fibrin monomers at 10(-5) M Ca2+, both in the presence and in the absence of fragment D. This activating effect of Gly-His-Arg was abolished at 10(-3) M Ca2+. It is suggested that the binding of calcium, Gly-His-Arg, and possibly also Gly
Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction
Manimaran, K.; Sharma, Rohini; Sankaranarayanan, S.; Perumal, S. Mahendra
Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1st month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10th month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor.
Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction.
Manimaran, K; Sharma, Rohini; Sankaranarayanan, S; Perumal, S Mahendra
Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. PMID:27563616
Comparative Evaluation of Platelet-Rich Fibrin Biomaterial and Open Flap Debridement in the Treatment of Two and Three Wall Intrabony Defects
Ajwani, Himanshu; Shetty, Sharath; Gopalakrishnan, Dharmarajan; Kathariya, Rahul; Kulloli, Anita; Dolas, R S; Pradeep, A R
Background: Platelet-rich concentrates are the most widely used regenerative biomaterials. Stimulation and acceleration of soft and hard tissue healing are due to local and continuous delivery of growth factors and proteins, mimicking the needs of the physiological wound healing and reparative tissue processes. This article aims to evaluate the clinical efficacy of open flap debridement (OFD) with or without platelet-rich fibrin (PRF) in the treatment of intrabony defects. Materials and Methods: Twenty subjects with forty intrabony defects were treated with either autologous PRF with open-flap debridement (test, n = 20) or open-flap debridement alone (control, n = 20). Soft tissue parameters included: Plaque index, sulcus bleeding index, probing depth, relative attachment level and gingival marginal level (GML). The hard tissue parameters included-distances from: Cement enamel junction to the base of the defect (CEJ-BOD): Alveolar crest to the base of the defect (AC-BOD): And CEJ to AC. The parameters were recorded at baseline and at 9 months postoperatively calculated using standardized radiographs by image-analysis software. Results: Statistically significant (0.005*) intragroup improvements were seen with all the hard and soft parameters in both test and control groups, except for GML. Statistically significant improvements were seen with the mean defect fill (CEJ-BOD and AC-BOD) (P = 0.003*) when intergroup comparisons were made. Conclusions: Adjunctive use of PRF with OFD significantly improves defect fill when compared to OFD alone. PRF has consistently been showing regenerative potential; it is simple, easy and inexpensive biomaterial compared with bone grafts. PMID:25954068
Quantitative analysis of AgNOR proteins in buccal epithelial cells of Indian street boys addicted to gasp 'golden glue'.
Mondal, Nandan Kumar; Ghosh, Sreenita; Ray, Manas Ranjan
The effect of glue snuffle on the expression of argyrophilic nucleolar organizer regions (AgNORs), an indicator of ribosome biosynthesis, in epithelial cells of oral mucosa has been investigated. AgNOR was evaluated by cytochemical staining in 148 Indian street boys (median age 12 year) who had different bad addictions like tobacco smoking, chewing and most importantly inhaling glue and 20 age- and body mass index-matched school boys who had no such type of bad habit. Compared with school boys, glue addicted street boys showed remarkably increased number of AgNOR dots per nucleus (9.38±1.84 vs. 3.12±0.87, p<0.001), AgNOR size (1.34±0.52 vs. 0.43±0.02 μm(2), p<0.001) and percentage of AgNOR occupied nuclear area (9.38±2.12 vs. 0.99±0.03%, p<0.001). Increase in number and size of the dots is also higher in tobacco smokers and chewers when compared with school boys but a remarkable difference was recorded in glue addicted boys. The changes in AgNOR expression were positively associated with years of addiction after controlling potential confounders. Thus, glue snuffle appeared to be a risk factor for abnormal cell growth via up-regulation of ribosome biogenesis. PMID:20541922
Comparison of a CO2 (Carbon Dioxide) Laser and Tissue Glue with Conventional Surgical Techniques in Circumcision
Mungnirandr, Akkrapol; Wiriyakamolphan, Suwanna; Ruangtrakool, Ravit; Ngerncham, Monawat; Tumrongsombutsakul, Sureerat; Leumcharoen, Bungorn
Introduction: CO2 (Carbon Dioxide) laser application in circumcision, for cutting and coagulation, has been reported to have excellent results. Also, tissue glue has been reported to have advantages over sutures for approximation of wound edges. Most previous studies focused on comparisons between CO2 laser and scalpel, or between tissue glue and sutures. This study prospectively compared the results and complications CO2 laser and tissue glue, with standard surgical techniques in circumcision. Methods: Thirty boys were prospectively divided into two groups. Group 1 (n = 17) underwent circumcision by scalpel with approximation of the wound edges using chromic catgut sutures. Group 2 (n = 13) underwent circumcision with CO2 laser and approximation of the wound edges using tissue glue. Patient age, indications for surgery, operative time, wound swelling, bleeding, wound infection, local irritation, pain score, and cosmetic appearance were recorded. Results: Group 1 had a significantly longer operative time (P= 0.011), higher rate of local irritation (P= 0.016), and poorer cosmetic appearance (P< 0.001) than group 2. Bleeding only occurred in one patient in group 1. There were no significant differences in pain score, wound infection rate, or cost of surgery between the two groups. Conclusions: CO2 laser and tissue glue have advantages over standard surgical techniques in circumcision, with a significantly shorter operative time, lower rate of local irritation, and better cosmetic appearance. The cost of surgery is similar between the two groups. PMID:25699165
Identification of animal glue species in artworks using proteomics: application to a 18th century gilt sample.
Dallongeville, Sophie; Koperska, Monika; Garnier, Nicolas; Reille-Taillefert, Geneviève; Rolando, Christian; Tokarski, Caroline
This study proposes a proteomic-based strategy for the identification of the origin species of glues used as binding media and adhesives in artworks. The methodology, based on FTICR high resolution mass spectrometry, was evaluated on glues from different animal origin (i.e., bovine, rabbit, and fish). The analysis of the peptide mixture resulting from the enzymatic hydrolysis of the proteins led to the identification of species-specific peptides. Up to 15 specific peptides were identified for the bovine species and three for the rabbit species and, in the case of sturgeon glue, three fish-specific peptides were found by sequence homology to the rainbow trout. Then, the method was applied to authenticate different rabbit skin glue samples, including a 100 year-old sample named "Colle à Doreurs" coming from the "Maison Totin-Frères". For this sample, two specific peptides of rabbit collagen were identified. To evaluate the method in a complex matrix, model paints composed of lead white, linseed oil, and animal glue were prepared. Species-specific peptides were identified in each paint sample. Finally, a gilt sample from St Maximin church dating from the eighteenth century was analyzed, and 13 peptides specific to bovine collagens were identified starting from very low sample amount (50 μg). PMID:22014085
Tandem autologous versus autologous/allogeneic transplantation for multiple myeloma: propensity score analysis.
Kawamura, Koji; Ikeda, Takashi; Hagiwara, Shotaro; Mori, Takehiko; Shinagawa, Atsushi; Nishiwaki, Kaichi; Ohashi, Kazuteru; Kubonishi, Shiro; Fukuda, Takahiro; Ito, Toshiro; Tomita, Naoto; Ichinohe, Tatsuo; Kato, Koji; Morishima, Yasuo; Atsuta, Yoshiko; Sunami, Kazutaka; Kanda, Yoshinobu
Autologous hematopoietic stem cell transplantation (auto-HCT) is considered a standard therapy for transplant-eligible patients with multiple myeloma, while allogeneic HCT (allo-HCT) is controversial. We retrospectively analyzed 765 patients with myeloma who underwent tandem transplantation between 1998 and 2012 using Japanese registry data. We evaluated the clinical outcomes of tandem auto-HCT (n = 676) and auto/allo-HCT (n = 89). To adjust for a selection bias, we compared overall survival (OS) between the two groups by a propensity score analysis. The probability of OS at six years was 58.5% for the tandem auto-HCT group and 54.4% for the tandem auto/allo-HCT group (p = 0.47). In a matched-pair analysis based on the propensity score, the difference in survival between the two groups was not statistically significant, although the survival curve appeared to reach a plateau beyond five years in the auto/allo group. Further strategies to reduce treatment-related mortality and enhance a graft-versus-myeloma effect are necessary to improve OS. PMID:26961137
A Novel Technique Using a Protection Filter During Fibrin Sheath Removal for Implanted Venous Access Device Dysfunction.
Sotiriadis, Charalampos; Hajdu, Steven David; Degrauwe, Sophie; Barras, Heloise; Qanadli, Salah Dine
With the increased use of implanted venous access devices (IVADs) for continuous long-term venous access, several techniques such as percutaneous endovascular fibrin sheath removal, have been described, to maintain catheter function. Most standard techniques do not capture the stripped fibrin sheath, which is subsequently released in the pulmonary circulation and may lead to symptomatic pulmonary embolism. The presented case describes an endovascular technique which includes stripping, capture, and removal of fibrin sheath using a novel filter device. A 64-year-old woman presented with IVAD dysfunction. Stripping was performed using a co-axial snare to the filter to capture the fibrin sheath. The captured fragment was subsequently removed for visual and pathological verification. No immediate complication was observed and the patient was discharged the day of the procedure. PMID:27016091
Non-Covalent Interaction of α2-Antiplasmin with Fibrin(ogen): Localization of α2-Antiplasmin Binding Sites
Tsurupa, Galina; Yakovlev, Sergiy; McKee, Patrick; Medved, Leonid
Covalent incorporation (cross-linking) of plasmin inhibitor α2-antiplasmin (α2-AP) into fibrin clots increases their resistance to fibrinolysis. We hypothesized that α2-AP may also interact non-covalently with fibrin prior to its covalent cross-linking. To test this hypothesis, we studied binding of α2-AP to fibrin(ogen) and its fragments by ELISA and Surface Plasmon Resonance. The experiments revealed that α2-AP binds to polymeric fibrin and surface-adsorbed fibrin(ogen) while no binding was observed with fibrinogen in solution. To localize the α2-AP-binding sites, we studied the interaction of α2-AP with the fibrin(ogen)-derived D1, D-D and E3 fragments, and the recombinant αC region and its constituents, αC-connector and αC-domain and its sub-domains, which together encompass practically the whole fibrin(ogen) molecule. In ELISA, α2-AP bound to immobilized D1, D-D, αC region, αC-domain and its C-terminal sub-domain. The binding was Lys-independent and was not inhibited by plasminogen or tPA. Furthermore, the affinity of α2-AP to D-D was significantly increased in the presence of plasminogen while that to the αC-domain remained unaffected. Altogether, these results indicate that the fibrin(ogen) D region and the C-terminal sub-domain of the αC-domain contain high affinity α2-AP-binding sites that are cryptic in fibrinogen and exposed in fibrin or adsorbed fibrinogen, and the presence of plasminogen facilitates interaction of α2-AP with the D regions. The discovered non-covalent interaction of α2-AP with fibrin may contribute to regulation of the initial stage of fibrinolysis and provide proper orientation of the cross-linking sites to facilitate covalent cross-linking of α2-AP to the fibrin clot. PMID:20687529
A Blinded, Randomised, Controlled Trial of Stapled Versus Tissue Glue Closure of Neck Surgery Incisions
Ridgway, DM; Mahmood, F; Moore, L; Bramley, D; Moore, PJ
INTRODUCTION Cosmetic acceptability of scar and neck mobility are important outcomes after collar line incision for neck surgery. This randomised, controlled trial compares these parameters in closures using tissue glue (Dermabond™, Ethicon, UK) and skin staples. PATIENTS AND METHODS Patients requiring a collar line incision were randomised to receiving tissue glue or staples for skin closure. Time for closure to be completed was recorded. Mobility of the neck was assessed using a visual analogue scale at 48 h and 1 week after surgery. At 6 weeks, cosmetic appearance was assessed using a linear 1–10 visual analogue scale by the patient, surgeon and an independent blinded assessor. Results were compared using appropriate statistical tests. RESULTS Glued (n = 14) and stapled (n = 15) closures were performed for hemithyroidectomy (n = 8 versus 6), sub-total thyroidectomy (n = 2 versus 4), total thyroidectomy (n = 1 versus 4) and parathyroidectomy (n = 3 versus 1). Closure with tissue glue took significantly longer than with staples (mean, 95 versus 28 s; P < 0.001). Neck mobility scores were comparable at 48 h and 1 week (mean, 4.8 versus 4.4; P = 0.552: and 2.7 versus 2.6; P = 0.886). Cosmetic appearance at 6 weeks was comparable when patient (mean, 1.7 versus 1.8; P = 0.898), surgeon (mean, 2.6 versus 2.3; P = 0.633) and independent assessment (mean, 1.4 versus 1.9; P = 0.365) was performed. CONCLUSIONS The use of glued skin closure may increase the duration of surgery but acceptable neck mobility and wound cosmesis can be achieved by the more rapid application of stapled skin closure in cervicotomy incisions. PMID:17394707
Fibrin Sealant: A Review of the History, Biomechanics, and Current Applications for Prosthetic Fixation in Hernia Repair.
Watson, Jefferson Tyler; Webb, David L; Stoikes, Nathaniel F N; Voeller, Guy R
The role of surgical adhesives in hernia repair has continued to evolve. The purpose of this chapter is to review the role of fibrin sealant and its application in general surgery for mesh fixation, specifically the history, biomechanics, and clinical utilization. The utilization of fibrin sealant for repair of groin hernias, both open and laparoscopic, ventral hernias, and hiatal hernias will be discussed. PMID:26696538
Uncertainty and sensitivity assessments of an agricultural-hydrological model (RZWQM2) using the GLUE method
NASA Astrophysics Data System (ADS)
Sun, Mei; Zhang, Xiaolin; Huo, Zailin; Feng, Shaoyuan; Huang, Guanhua; Mao, Xiaomin
Quantitatively ascertaining and analyzing the effects of model uncertainty on model reliability is a focal point for agricultural-hydrological models due to more uncertainties of inputs and processes. In this study, the generalized likelihood uncertainty estimation (GLUE) method with Latin hypercube sampling (LHS) was used to evaluate the uncertainty of the RZWQM-DSSAT (RZWQM2) model outputs responses and the sensitivity of 25 parameters related to soil properties, nutrient transport and crop genetics. To avoid the one-sided risk of model prediction caused by using a single calibration criterion, the combined likelihood (CL) function integrated information concerning water, nitrogen, and crop production was introduced in GLUE analysis for the predictions of the following four model output responses: the total amount of water content (T-SWC) and the nitrate nitrogen (T-NIT) within the 1-m soil profile, the seed yields of waxy maize (Y-Maize) and winter wheat (Y-Wheat). In the process of evaluating RZWQM2, measurements and meteorological data were obtained from a field experiment that involved a winter wheat and waxy maize crop rotation system conducted from 2003 to 2004 in southern Beijing. The calibration and validation results indicated that RZWQM2 model can be used to simulate the crop growth and water-nitrogen migration and transformation in wheat-maize crop rotation planting system. The results of uncertainty analysis using of GLUE method showed T-NIT was sensitive to parameters relative to nitrification coefficient, maize growth characteristics on seedling period, wheat vernalization period, and wheat photoperiod. Parameters on soil saturated hydraulic conductivity, nitrogen nitrification and denitrification, and urea hydrolysis played an important role in crop yield component. The prediction errors for RZWQM2 outputs with CL function were relatively lower and uniform compared with other likelihood functions composed of individual calibration criterion. This
[Use of Tissucol, a tissue glue, in reconstructive surgery of large scleral defects].
Karel, I; Dolezalová, J
In a 14-year-old female patient the postoperative course of myectomy of the musculus rectus oculi externus on account of concomittant strabism was complicated by necrosis of the sclera (diameter 9 mm) at the site of intrascleral stitches and exudation into the anterior chamber and the vitreous body. For fixation of the transplant from lyophilized sclera the tissue glue Tissucol Kit was used. Tissucol rapidly and firmly joined the wound areas, its direct contact with uveal tissue did not produce an inflammatory reaction and the exudate from the anterior chamber and vitreous body was absorbed rapidly and completely. PMID:1913913
Solvent constituents in paint, glue and thinner for plastic miniature hobby.
Saito, J; Ikeda, M
Solvent-containing products (8 paint, 29 glue and 4 thinner preparations) for plastic miniature hobby were analyzed for solvent constituents by capillary gas-chromatography. Acetone and methyl isobutyl ketone were two most extensively used solvents both in terms of frequency and concentration. Other popular solvents included ethyl alcohol and two esters of ethyl acetate and butyl acetate. In contrast, aromatics, chlorinated hydrocarbons and ethylene glycol derivatives were seldomly detected. The present findings were discussed in comparison with the observation on the materials abused for sniffing in the past, as well as constituents in the products for industrial application. PMID:3176022
GlueX a new facility to search for gluonic degrees of freedom in mesons
Zihlmann, Benedikt
The GlueX detector facility in Hall-D at Jefferson lab in Newport News is part of the 12 GeV upgrade and dedicated to the search for gluonic degrees of freedom in mesons by scattering high energy linearly polarized real photons of up to 9 GeV from nucleon targets. Civil construction of the Hall-D complex has started as well as the construction of the various detector components. The current status of the project is outlined here.
The pattern of fatal fibrinous pneumonia (shipping fever) affecting calves in a large feedlot in Alberta (1985-1988).
Ribble, C S; Meek, A H; Jim, G K; Guichon, P T
Data from a retrospective field study were used to describe the epidemiology of fatal fibrinous pneumonia as it affected beef calves entering a large commercial feedlot in southwestern Alberta during the fall months of y 1985 to 1988. A chute-side computer system was used to record processing and health data on 58885 calves during this period. The large annual variation (10%-57%) in the proportion of total mortality due to fibrinous pneumonia indicated that crude mortality cannot be used in epidemiological studies as a surrogate measure of fibrinous pneumonia mortality. Yearly epidemic curves for fatal fibrinous pneumonia were very similar, with a short time interval (median, 19-22 d) between arrival and fatal disease. Fully 75% of the calves that died of fibrinous pneumonia already were sick within 2 weeks of arrival. Studies of the biological, environmental, and population factors that are present before and shortly after arrival at the feedlot are needed to identify strategies for reducing the incidence of fatal fibrinous pneumonia. PMID:8748443
[BMP-2 gene carried by biodegradable scaffold and fibrinous gel for repairing segmental radial defect in rabbit].
Li, Jianjun; Wang, Enbo; Sun, Hongbin; Han, Dong; Wang, Huan; Bai, Lunhao; Li, Lei; Liu, Xueyong; Xu, Xinxiang
Adenovirus carrying BMP-2 gene, after being mixed with fibrinous gel, was siphoned off on biodegradable scaffolds (PLA/PCL). The composite was used to repair 1.5 cm long radius defect in rabbits. Four methods were in use in the experiments: Ad-BMP-2 plus fibrinous gel and PLA/PCL (Group A), reconstructed hBMP-2 plus fibrinous gel and PLA/PCL (Group B), Ad-Lacz plus fibrinous gel and PLA/PCL (Group C), and fibrinous gel and PLA/PCL (Group D). Results showed that the defects treated in Group A were repaired with much more new bone regenerated, bridged earlier and stronger than those in Group B 12 weeks after operation. The defects treated in the other two groups could not attain osseous tissue healing. BMP-2 gene carried by biodegradable scaffold and fibrinous gel is easy to conduct and has very strong osteoinduction ability. It is really a good method to repair segmental bone defects. PMID:17591257
Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture.
Lee, Yeong-Bae; Polio, Samuel; Lee, Wonhye; Dai, Guohao; Menon, Lata; Carroll, Rona S; Yoo, Seung-Schik
Time-released delivery of soluble growth factors (GFs) in engineered hydrogel tissue constructs promotes the migration and proliferation of embedded cells, which is an important factor for designing scaffolds that ultimately aim for neural tissue regeneration. We report a tissue engineering technique to print murine neural stem cells (C17.2), collagen hydrogel, and GF (vascular endothelial growth factor: VEGF)-releasing fibrin gel to construct an artificial neural tissue. We examined the morphological changes of the printed C17.2 cells embedded in the collagen and its migration toward the fibrin gel. The cells showed high viability (92.89+/-2.32%) after printing, which was equivalent to that of manually-plated cells. C17.2 cells printed within 1mm from the border of VEGF-releasing fibrin gel showed GF-induced changes in their morphology. The cells printed in this range also migrated toward the fibrin gel, with the total migration distance of 102.4+/-76.1microm over 3days. The cells in the control samples (fibrin without the VEGF or VEGF printed directly in collagen) neither proliferated nor migrated. The results demonstrated that bio-printing of VEGF-containing fibrin gel supported sustained release of the GF in the collagen scaffold. The presented method can be gainfully used in the development of three-dimensional (3D) artificial tissue assays and neural tissue regeneration applications. PMID:20211178
"Fibrinogen Tokyo II". An abnormal fibrinogen with an impaired polymerization site on the aligned DD domain of fibrin molecules.
Matsuda, M; Baba, M; Morimoto, K; Nakamikawa, C
A hereditary dysfibrinogenemia associated with defective aggregation of fibrin monomers was found in a 39-yr-old female and in the members of her immediate family, who had all been asymptomatic. The abnormality was probably due to an impaired polymerization site exposed in the DD domain of two adjacent fibrin molecules, because plasmic fragment DD derived from the propositus' cross-linked fibrin bound far less tightly to insolubilized normal fragment E than that from the normal one. Its complementary polymerization site in the E domain of fibrin, which was exposed by thrombin cleavage, and the polymerization site in the D domain of fibrinogen, which was available without activation by thrombin, were both found to be normal. More anodal migration of the abnormal fragment DD than the normal one, as shown by immunoelectrophoresis, seemed to support our concept that the mutation most likely resides in the D domain of the abnormal fibrinogen molecule at or near a region closely related to the polymerization site that is exposed when two fibrin molecules are linearly aligned. The work of others on the polymerization of normal fibrin with different techniques yielded results consistent with our conclusions. We tentatively designate this type of abnormal fibrinogen "fibrinogen Tokyo II," but its possible identity with other abnormalities of fibrinogen reported heretofore is not excluded. Images FIGURE 1 FIGURE 5 FIGURE 7 PMID:6886002
Addressing subjective decision-making inherent in GLUE-based multi-criteria rainfall-runoff model calibration
NASA Astrophysics Data System (ADS)
Shafii, Mahyar; Tolson, Bryan; Shawn Matott, L.
GLUE is one of the most commonly used informal methodologies for uncertainty estimation in hydrological modelling. Despite the ease-of-use of GLUE, it involves a number of subjective decisions such as the strategy for identifying the behavioural solutions. This study evaluates the impact of behavioural solution identification strategies in GLUE on the quality of model output uncertainty. Moreover, two new strategies are developed to objectively identify behavioural solutions. The first strategy considers Pareto-based ranking of parameter sets, while the second one is based on ranking the parameter sets based on an aggregated criterion. The proposed strategies, as well as the traditional strategies in the literature, are evaluated with respect to reliability (coverage of observations by the envelope of model outcomes) and sharpness (width of the envelope of model outcomes) in different numerical experiments. These experiments include multi-criteria calibration and uncertainty estimation of three rainfall-runoff models with different number of parameters. To demonstrate the importance of behavioural solution identification strategy more appropriately, GLUE is also compared with two other informal multi-criteria calibration and uncertainty estimation methods (Pareto optimization and DDS-AU). The results show that the model output uncertainty varies with the behavioural solution identification strategy, and furthermore, a robust GLUE implementation would require considering multiple behavioural solution identification strategies and choosing the one that generates the desired balance between sharpness and reliability. The proposed objective strategies prove to be the best options in most of the case studies investigated in this research. Implementing such an approach for a high-dimensional calibration problem enables GLUE to generate robust results in comparison with Pareto optimization and DDS-AU.
Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.
Hurd, D D
Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445
Defective autologous mixed lymphocyte reactivity in multiple sclerosis.
Hirsch, R L
T cells from patients with multiple sclerosis (MS) and normal controls were assessed for their ability to respond in the autologous mixed lymphocyte reaction (AMLR). Cells from stable MS patients demonstrated a significant defect in their proliferative response to non-T cells in comparison to normal controls. Despite the defective AMLR response, T cells from MS patients reacted as well as T cells from normal controls to allogeneic stimuli. Furthermore, MS non-T-cells were fully capable of stimulating allogeneic MLR responses by normal and MS T cells. Since the T4+ cell is the major subpopulation which proliferates in the AMLR, these studies suggest a functional defect in a subpopulation of T4+ cells in MS patients. Since the AMLR may represent an important mechanism by which immune responses are regulated, a defect in the ability of MS T cells to respond to autologous cells could account for several of the autoimmune features of the disease. PMID:2942317
Correction of deep gluteal depression by autologous fat grafting.
Lewis, C M
In the past, the traditional method of contouring the iliac crest and lateral femoral areas has been liposuction or the surgical removal of the bulges. Unfortunately, this method fails to correct the deep gluteal depression juxtaposed at these two sites. Since we use autologous fat grafts to correct contouring deficiencies elsewhere, it seems logical to investigate whether this technique is applicable to correcting this deformity. We have performed autologous fat grafting to the gluteal depression on 12 patients who underwent lipoplasty of the iliac crest and lateral femoral sites. The longest followup was one year. We have found that this method corrects the deep gluteal depression and yields an improved aesthetic contour. This article describes the technique, addresses the problems encountered, and shows postoperative results. PMID:1626462
Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma without Cryopreservation
Al-Anazi, Khalid Ahmed
High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is considered the standard of care for multiple myeloma patients who are eligible for transplantation. The process of autografting comprises the following steps: control of the primary disease by using a certain induction therapeutic protocol, mobilization of stem cells, collection of mobilized stem cells by apheresis, cryopreservation of the apheresis product, administration of high-dose pretransplant conditioning therapy, and finally infusion of the cryopreserved stem cells after thawing. However, in cancer centers that treat patients with multiple myeloma and have transplantation capabilities but lack or are in the process of acquiring cryopreservation facilities, alternatively noncryopreserved autologous stem cell therapy has been performed with remarkable success as the pretransplant conditioning therapy is usually brief. PMID:22693672
Computer-assisted selection of donor sites for autologous grafts
NASA Astrophysics Data System (ADS)
Krol, Zdzislaw; Zeilhofer, Hans-Florian U.; Sader, Robert; Hoffmann, Karl-Heinz; Gerhardt, Paul; Horch, Hans-Henning
A new method is proposed for a precise planning of autologous bone grafts in cranio- and maxillofacial surgery. In patients with defects of the facial skeleton, autologous bone transplants can be harvested from various donor sites in the body. The preselection of a donor site depends i.a. on the morphological fit of the available bone mass and the shape of the part that is to be transplanted. A thorough planning and simulation of the surgical intervention based on 3D CT studies leads to a geometrical description and the volumetric characterization of the bone part to be resected and transplanted. Both, an optimal fit and a minimal lesion of the donor site are guidelines in this process. We use surface similarity and voxel similarity measures in order to select the optimal donor region for an individually designed transplant.
Smith, Sonali M.; van Besien, Koen; Carreras, Jeanette; Bashey, Asad; Cairo, Mitchell S.; Freytes, Cesar O.; Gale, Robert Peter; Hale, Gregory A.; Hayes-Lattin, Brandon; Holmberg, Leona A.; Keating, Armand; Maziarz, Richard T.; McCarthy, Philip L.; Navarro, Willis H.; Pavlovsky, Santiago; Schouten, Harry C.; Seftel, Matthew; Wiernik, Peter H.; Vose, Julie M.; Lazarus, Hillard M.; Hari, Parameswaran
We determined treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n=21) or non-Hodgkin lymphoma (NHL, n=19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range, 16–61) and 22 (58%) patients had a Karnofsky performance score less than 90. HCT2 was performed >1 year after HCT1 in 82%. The probability of TRM at day 100 was 15% (95% CI, 3–22%). The 1, 3 and 5 yr probabilities of PFS were 50% (95% CI, 34–66%), 36% (95% CI, 21–52%) and 30% (95% CI, 16–46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50–79%), 36% (95% CI, 22–52%) and 30% (95% CI, 17–46%), respectively. At a median follow up of 72 months (range, 12–124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower TRM than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options. PMID:18640574
Proton NMR study of the state of water in fibrin gels, plasma, and blood clots
Blinc, A.; Lahajnar, G.; Blinc, R.; Zidansek, A.; Sepe, A. )
A proton NMR relaxation and pulsed field gradient self-diffusion study of water in fibrin gels, plasma, and blood clots has been performed with special emphasis on the effect of the sol-gel and shrinkage transitions. Deuteron NMR in fibrin gels was also studied to supplement the proton data. It is shown that a measurement of the water proton or deuteron T1/T2 ratio allows for a determination of the bound water fraction in all these systems. The change in the T1/T2 ratio at the shrinkage transition further allows for a determination of the surface fractal dimension of the gel if the change in the volume of the gel is known. The self-diffusion coefficient of water in these systems, which determines the transport properties of the gel, is found to be proportional to the free water fraction in both the nonshrunken and shrunken state.
Acute fibrinous and organising pneumonia: a rare histopathological variant of chemotherapy-induced lung injury.
Gupta, Arjun; Sen, Shiraj; Naina, Harris
Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury. PMID:27053543
Localization of the binding site of tissue-type plasminogen activator to fibrin.
Ichinose, A; Takio, K; Fujikawa, K
Functionally active A and B chains were separated from a two-chain form of recombinant tissue-type plasminogen activator after mild reduction and alkylation. The A chain was found to be responsible for the binding to lysine-Sepharose or fibrin and the B chain contained the catalytic activity of tissue-type plasminogen activator. An extensive reduction of two-chain tissue-type plasminogen activator, however, destroyed both the binding and catalytic activities. A thermolytic fragment, Fr. 1, of tissue-type plasminogen activator that contained a growth factor and two kringle segments retained its lysine binding activity. Additional thermolytic cleavages in the kringle-2 segment of Fr. 1 caused a total loss of the binding activity. These results indicated that the binding site of tissue-type plasminogen activator to fibrin was located in the kringle-2 segment. Images PMID:3088041
Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids
Nguyen, Lam-Phuong; Ahdoot, Stella; Sriratanaviriyakul, Narin; Zhang, Yanhong; Stollenwerk, Nicholas; Schivo, Michael; Harper, Richart
Acute fibrinous and organizing pneumonia (AFOP) is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids. PMID:27152316
Spirulan from blue-green algae inhibits fibrin and blood clots: its potent antithrombotic effects.
Choi, Jun-Hui; Kim, Seung; Kim, Sung-Jun
We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins. In vitro assays using human fibrin and mouse blood clots showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3 )-induced carotid arterial thrombus model and collagen and epinephrine-induced pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for thrombosis-related diseases. PMID:25651404
Canine intracranial meningiomas: Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers.
Font, Cristina; de la Fuente, Cristian; Pumarola, Martí; Blasco, Ester; Fernández, Francisco; Viu, Judit; Añor, Sònia
The haemostatic system influences angiogenesis, cell growth and metastasis in solid tumours. The aim of this study was to investigate tissue factor (TF) expression, fibrin/fibrinogen and D-dimer deposition, as well as the occurrence of intravascular thrombosis (IVT) in canine intracranial meningiomas using immunohistochemistry. All but three (26/29) meningiomas expressed TF. TF immunolabelling was significantly higher in high-grade (grades II and III) than in low-grade (grade I) meningiomas. Fibrin/fibrinogen and D-dimer deposits were detected in all meningiomas and staining scores were statistically different between different meningioma grades. IVT was detected in 19/29 specimens, but no statistical differences were observed between different malignancy grades. In conclusion, the haemostatic system may be involved in meningioma pathobiology and may be a potential therapeutic target for canine meningiomas, as also suggested for human meningiomas. PMID:26526524
Enhancing Interfacial Bonding between Anisotropically Oriented Grains Using a Glue-Nanofiller for Advanced Li-Ion Battery Cathode.
Kim, Hyejung; Lee, Sanghan; Cho, Hyeon; Kim, Junhyeok; Lee, Jieun; Park, Suhyeon; Joo, Se Hun; Kim, Su Hwan; Cho, Yoon-Gyo; Song, Hyun-Kon; Kwak, Sang Kyu; Cho, Jaephil
Formation of a glue-nanofiller layer between grains, consisting of a middle-temperature spinel-like Lix CoO2 phase, reinforces the strength of the incoherent interfacial binding between anisotropically oriented grains by enhancing the face-to-face adhesion strength. The cathode treated with the glue-layer exhibits steady cycling performance at both room-temperature and 60 °C. These results represent a step forward in advanced lithium-ion batteries via simple cathode coating. PMID:27074141
Incomplete defect filling after third generation autologous chondrocyte implantation
Pietschmann, Matthias F.; Ficklscherer, Andreas; Gülecyüz, Mehmet F.; Hammerschmid, Florian; Müller, Peter E.
Introduction Third generation autologous chondrocyte implantation (ACI) is a suitable method for the treatment of cartilage defects in the knee joint. However, knowledge about the development of graft thickness and the clinical relevance of incomplete defect filling in the postoperative course is low. This prospective study analyses the graft integration into the surrounding cartilage, with special consideration of the graft thickness. Material and methods A total of 71 consecutive patients with 79 cartilage defects were treated with third generation autologous chondrocyte implantation (NOVOCART 3D) in the knee. Follow-up magnetic resonance imaging (MRI) was performed at 0.25, 0.5, 1 and 2 years. Graft thickness was measured compared to the surrounding healthy cartilage. The International Knee Documentation Committee (IKDC) scoring system and the visual analogue scale (VAS) were used for clinical evaluation. Cartilage defect filling was classified as the percentage of the surrounding cartilage. Results The average graft thickness showed a significant increase between 3 and 6 months after autologous chondrocyte implantation. Incomplete defect filling occurred in 44 (55.7%) cases. Of these, 33 cases showed incomplete defect filling grade I (> 75%), 10 cases were grade II (> 50%) and one case grade III (> 25%). Incomplete defect filling grade IV (< 25%) was not observed. Incomplete defect filling occurred significantly more often in women (p = 0.021), without worse clinical results. Conclusions Graft thickness after third generation autologous chondrocyte implantation shows increasing graft thickness over the period of 2 years postoperatively. A high rate of incomplete defect filling in the surrounding cartilage was observed, without worse clinical results. PMID:27478460
Autologous Rib Grafts in the Management of the Crooked Nose.
Porter, Paul; Kriet, J David; Humphrey, Clinton D
Rhinoplasty is arguably one of the most challenging procedures a facial plastic surgeon performs. Numerous techniques have been developed since the inception of rhinoplasty to aid in correction of aesthetic and functional issues. Congenital, iatrogenic, and traumatic etiologies can all lead to a crooked nose. Autologous rib or costal cartilage grafting is a powerful tool that can aid the surgeon in successful correction of the crooked nose. PMID:26126219
Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction
Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana
Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665
Delayed Cranioplasty: Outcomes Using Frozen Autologous Bone Flaps.
Hng, Daniel; Bhaskar, Ivan; Khan, Mumtaz; Budgeon, Charley; Damodaran, Omprakash; Knuckey, Neville; Lee, Gabriel
Reconstruction of skull defects following decompressive craniectomy is associated with a high rate of complications. Implantation of autologous cryopreserved bone has been associated with infection rates of up to 33%, resulting in considerable patient morbidity. Predisposing factors for infection and other complications are poorly understood. Patients undergoing cranioplasty between 1999 and 2009 were identified from a prospectively maintained database. Records and imaging were reviewed retrospectively. Demographics, the initial craniectomy and subsequent cranioplasty surgeries, complications, and outcomes were recorded. A total of 187 patients underwent delayed cranioplasty using autologous bone flaps cryopreserved at -30°C following decompressive craniectomy. Indications for craniectomy were trauma (77.0%), stroke (16.0%), subarachnoid hemorrhage (2.67%), tumor (2.14%), and infection (2.14%). There were 64 complications overall (34.2%), the most common being infection (11.2%) and bone resorption (5.35%). After multivariate analysis, intraoperative cerebrospinal fluid (CSF) leak was significantly associated with infection, whereas longer duration of surgery and unilateral site were associated with resorption. Cranioplasty using frozen autologous bone is associated with a high rate of infective complications. Intraoperative CSF leak is a potentially modifiable risk factor. Meticulous dissection during cranioplasty surgery to minimize the chance of breaching the dural or pseudodural plane may reduce the chance of bone flap. PMID:26269726
Anatomic and physiological fundamentals for autologous breast reconstruction
Mohan, Anita T.
The success of autologous tissue transfer is reliant on adequate blood supply and as we endeavour to tailor our reconstructive options through our flap choices and design. Autologous breast reconstruction has made substantial progress over the years and the evolution of refinements over the last 30 years has allowed flaps to be based on specific perforators. The ultimate goal of breast reconstruction following mastectomy is to match optimal tissue replacement with minimal donor-site expenditure. In parallel surgeons will seek ways to ensure safe flap design and harvest while maintaining predictability and reliable tissue perfusion. Better understanding of the vascular anatomy and physiology of the cutaneous circulation of soft tissues, and that of patterns of blood flow from individual perforator has provided insight to advance perforator flap harvest and modifications in flap design. The aim of this article is to review the principles of blood supply and flap design exemplified through common flaps used in autologous breast reconstructive surgery, to better understand approaches for safe flap harvest and transfer of well perfused tissue. PMID:26005644
Autologous Matrix-Induced Chondrogenesis in the Knee
Suzer, Ferzan; Thermann, Hajo
Objective: Autologous matrix-induced chondrogenesis (AMIC) is a 1-step cartilage restoration technique that combines microfracture with the use of an exogenous scaffold. This matrix covers and mechanically stabilizes the clot. There have been an increasing number of studies performed related to the AMIC technique and an update of its use and results is warranted. Design and methods: Using the PubMed database, a literature search was performed using the terms "AMIC" or "Autologous Matrix Induced Chondrogenesis." A total of 19 basic science and clinical articles were identified. Results: Ten studies that were published on the use of AMIC for knee chondral defects were identified and the results of 219 patients were analyzed. The improvements in Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee Subjective, Lysholm and Tegner scores at 2 years were comparable to the published results from autologous chondrocyte implantation (ACI) and matrix ACI techniques for cartilage repair. Conclusions: Our systematic review of the current state of the AMIC technique suggests that it is a promising 1-stage cartilage repair technique. The short-term clinical outcomes and magnetic resonance imaging results are comparable to other cell-based methods. Further studies with AMIC in randomized studies versus other repair techniques such as ACI are needed in the future. PMID:26069694
Tissue-engineered autologous grafts for facial bone reconstruction.
Bhumiratana, Sarindr; Bernhard, Jonathan C; Alfi, David M; Yeager, Keith; Eton, Ryan E; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M; Lopez, Mandi J; Eisig, Sidney B; Vunjak-Novakovic, Gordana
Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care-the use of bone harvested from another region in the body-has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665
The Fibrin slide assay for detecting urokinase activity in human fetal kidney cells
NASA Technical Reports Server (NTRS)
Sedor, K.
The Fibrin Slide Technique of Hau C. Kwaan and Tage Astrup is discussed. This relatively simple assay involves two steps: the formation of an artificial clot and then the addition of an enzyme (UKOKINASE) to dissolve the clot. The actual dissolving away of the clot is detected by the appearance of holes (lysis zones) in the stained clot. The procedure of Kwaan and Astrup is repeated, along with modifications and suggestions for improvements based on experience with the technique.
Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves.
Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J; Jockenhoevel, Stefan; Mela, Petra
Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels. PMID:25654448
Adhesins of Leptospira interrogans Mediate the Interaction to Fibrinogen and Inhibit Fibrin Clot Formation In Vitro
Oliveira, Rosane; Domingos, Renan F.; Siqueira, Gabriela H.; Fernandes, Luis G.; Souza, Natalie M.; Vieira, Monica L.; de Morais, Zenaide M.; Vasconcellos, Silvio A.; Nascimento, Ana L. T. O.
We report in this work that Leptospira strains, virulent L. interrogans serovar Copenhageni, attenuated L. interrogans serovar Copenhageni and saprophytic L. biflexa serovar Patoc are capable of binding fibrinogen (Fg). The interaction of leptospires with Fg inhibits thrombin- induced fibrin clot formation that may affect the haemostatic equilibrium. Additionally, we show that plasminogen (PLG)/plasmin (PLA) generation on the surface of Leptospira causes degradation of human Fg. The data suggest that PLA-coated leptospires were capable to employ their proteolytic activity to decrease one substrate of the coagulation cascade. We also present six leptospiral adhesins and PLG- interacting proteins, rLIC12238, Lsa33, Lsa30, OmpL1, rLIC11360 and rLIC11975, as novel Fg-binding proteins. The recombinant proteins interact with Fg in a dose-dependent and saturable fashion when increasing protein concentration was set to react to a fix human Fg concentration. The calculated dissociation equilibrium constants (KD) of these reactions ranged from 733.3±276.8 to 128±89.9 nM for rLIC12238 and Lsa33, respectively. The interaction of recombinant proteins with human Fg resulted in inhibition of fibrin clot by thrombin-catalyzed reaction, suggesting that these versatile proteins could mediate Fg interaction in Leptospira. Our data reveal for the first time the inhibition of fibrin clot by Leptospira spp. and presents adhesins that could mediate these interactions. Decreasing fibrin clot would cause an imbalance of the coagulation cascade that may facilitate bleeding and help bacteria dissemination PMID:24009788
Internal Iliac Artery Aneurysm Embolization with Fibrin Sealant: A Simple and Effective Solution
Brountzos, Elias N.; Malagari, Katerina; Papathanasiou, Mathildi A.; Gougoulakis, Alexandros; Kelekis, Dimitrios A.
Endovascular treatment of internal iliac artery (IIA) aneurysms is an attractive alternative to surgical management, because the former is associated with less morbidity and mortality.Embolization with coils or exclusion of the IIA orifice with stent -grafts are the preferred techniques. Although uncommon, technical failures occur with reported aneurysm rupture. Two patients with IIA aneurysms are reported here, where we describe successful occlusion of their IIA aneurysms with the use of fibrin sealant, after initial failure of coil embolization.
Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves
Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J.
Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels. PMID:25654448
Our experience of fibrin sealant-assisted implantation of Ahmed glaucoma valve
Choudhari, Nikhil S; Neog, Aditya; Sharma, Anuj; Iyer, Geetha K; Srinivasan, Bhaskar
Aim: To report our experience with the fibrin sealant as a suture substitute for securing the human scleral patch graft during implantation of Ahmed glaucoma valve (AGV). Materials and Methods: A retrospective, non-comparative study of 12 eyes of 12 patients who underwent an AGV implantation with fibrin sealant for part of the procedure during June 2009 to September 2010. Results: The mean patient age was 21.5 ± 20.6 years. Male: Female ratio was 2 : 1. Seven (58.3%) patients were monocular. The indications for AGV were varied. The mean number of intra-ocular surgeries prior to an implantation of AGV was 1.8. The mean follow-up duration was 24.5 ± 17.9 weeks. There was a statistically significant reduction in the mean IOP and in the mean number of anti-glaucoma medications at the final visit compared to the pre-operative values (P < 0.01, paired t test). Conjunctival retraction was seen in 1 (8.3%) case. The scleral patch graft was retracted posteriorly in another (8.3%) case. There was no case of AGV tube exposure, tube-cornea touch, or conjunctival erosion. Vision threatening complication viz. late post-operative rhegmatogenous retinal detachment, unlikely to be related to the use of the fibrin sealant, occurred in 2 (16.6%) eyes. Conclusion: The fibrin sealant offers the advantages of safety and convenience to the placement of a scleral patch graft during an AGV implantation. PMID:23275217
[Fibrin-collagen substance as a vehicle for local application of antibacterial agents].
Gorskiĭ, V A; Gertsog, A A; Leonenko, I V; Shamanek, T P; Sokov, B N
Inhibitory activity of fibrin-collagen substance (FCS) impregnated by various antibacterial agents against various microorganisms was investigated. It was demonstrated that antibacterials bind well with FCS, providing its sufficient antibacterial activity. Determination of growth-inhibition zones showed that antibacterial agents diffuse into medium well and demonstrated the same activity as discs with antibiotics. For clinical practice it is recommended to use for impregnation the following drugs: gentamycin, meropenem, cefriaxone and ciprofloxacin. PMID:12422648
Pathological findings of saccular cerebral aneurysms-impact of subintimal fibrin deposition on aneurysm rupture.
Hokari, Masaaki; Nakayama, Naoki; Nishihara, Hiroshi; Houkin, Kiyohiro
Although several studies have suggested that aneurysmal wall inflammation and laminar thrombus are associated with the rupture of saccular aneurysms, the mechanisms leading to the rupture remain obscure. We performed full exposure of aneurysms before clip application and attempted to keep the fibrin cap on the rupture point. Using these specimens in a nearly original state before surgery, we conducted a pathological analysis and studied the differences between ruptured and unruptured aneurysms to clarify the mechanism of aneurysmal wall degeneration. This study included ruptured (n = 28) and unruptured (n = 12) saccular aneurysms resected after clipping. All of the ruptured aneurysms were obtained within 24 h of onset. Immunostainings for markers of inflammatory cells (CD68) and classical histological staining techniques were performed. Clinical variables and pathological findings from ruptured and unruptured aneurysms were compared. Patients with ruptured or unruptured aneurysms did not differ by age, gender, size, location, and risk factors, such as hypertension, smoking, and hyperlipidemia. The absence or fragmentation of the internal elastica lamina, the myointimal hyperplasia, and the thinning of the aneurysmal wall were generally observed in both aneurysms. The existence of subintimal fibrin deposition, organized laminar thrombus, intramural hemorrhage, neovascularization, and monocyte infiltration are more frequently observed in ruptured aneurysms. Multivariate logistic regression analysis showed that ruptured aneurysm was associated with presence of subintimal fibrin deposition and monocyte infiltration. These findings suggest that subintimal fibrin deposition and chronic inflammation have a strong impact on degeneration of the aneurysmal wall leading to their rupture, and this finding may be caused by endothelial dysfunction. PMID:25860660
N-butyl Cyanoacrylate Glue Embolization of Arterial Networks to Facilitate Hepatic Arterial Skeletonization before Radioembolization
Samuelson, Shaun D.; Louie, John D.; Sze, Daniel Y.
Purpose. Avoidance of nontarget microsphere deposition via hepatoenteric anastomoses is essential to the safety of yttrium-90 radioembolization (RE). The hepatic hilar arterial network may remain partially patent after coil embolization of major arteries, resulting in persistent risk. We retrospectively reviewed cases where n-butyl cyanoacrylate (n-BCA) glue embolization was used to facilitate endovascular hepatic arterial skeletonization before RE. Methods. A total of 543 RE procedures performed between June 2004 and March 2012 were reviewed, and 10 were identified where n-BCA was used to embolize hepatoenteric anastomoses. Arterial anatomy, prior coil embolization, and technical details were recorded. Outcomes were reviewed to identify subsequent complications of n-BCA embolization or nontarget RE. Results. The rate of complete technical success was 80 % and partial success 20 %, with one nontarget embolization complication resulting in a minor change in treatment plan. No evidence of gastrointestinal or biliary ischemia or infarction was identified, and no microsphere-related gastroduodenal ulcerations or other evidence of nontarget RE were seen. Median volume of n-BCA used was <0.1 ml. Conclusion. n-BCA glue embolization is useful to eliminate hepatoenteric networks that may result in nontarget RE, especially in those that persist after coil embolization of major vessels such as the gastroduodenal and right gastric arteries.
Study of the nature of the confinement in the GlueX experiment
Somov, S.; Berdnikov, Vladmir; Tolstukhin, Ivan; Somov, Alexander S.
Confinement is a fundamental property of quantum chromodynamics (QCD) associated with the unique role of the gluonic field responsible for binding quarks in hadrons. Understanding the role of gluons in the confinement of quarks is one of the most tantalizing topics in modern particle physics to be explored. The new experiment GlueX has been recently constructed at Jefferson Lab. The experiment was designed to search for hybrid mesons with exotic quantum numbers using a beam of linearly polarized photons incident on a liquid hydrogen target. The spectrum of these states and their mass splitting from normal mesons may yield information on confinement. In addition, these observations in combination with detailed chromodynamics calculations such as on the Lattice can provide important tests for our understanding of the role of gluons. The production of exotic mesons is expected to be enhanced in p interactions, where the experimental data is very limited. We present the description of the GlueX detector, beam line, and first results of the commissioning with photon beam.
Characteristics of S12045(X) photon sensors for GlueX
NASA Astrophysics Data System (ADS)
Smith, E. S.; Qiang, Y.; Tolstukhin, I.; Brooks, W. K.; Hakobyan, H.; Kuleshov, S.; Soto, O.; Toro, A.
The barrel calorimeter of the GlueX detector in Hall D at Jefferson Lab will be instrumented with 4000 large-area (1.2x1.2 cm^2) silicon photomultipliers (SiPMs) [1]. These photon sensors have properties similar to vacuum photomultipliers, but are unaffected by high magnetic fields. In our experiment, they will operate in magnetic fields exceeding 1,. After extensive tests with a variety of sensors, we chose the S12045(X) custom SiPM arrays manufactured by Hamamatsu Corporation, also known as multi-pixel photon counters (MPPCs) [2]. All production units have been delivered and we have measured the photon detection efficiency (PDE), gain, dark rate, cross talk and after pulsing at three different temperatures (5, 7 and 20^oC). We will present a summary of these measurements and the plan for use of these sensors in the GlueX experiment.[4pt] [1] F. Barbosa et al., NIM A695 (2012) 100.[0pt] [2] Y. Qiang et al., NIM A698 (2013) 234.
Equifinality of formal (DREAM) and informal (GLUE) bayesian approaches in hydrologic modeling?
Vrugt, Jasper A; Robinson, Bruce A; Ter Braak, Cajo J F; Gupta, Hoshin V
In recent years, a strong debate has emerged in the hydrologic literature regarding what constitutes an appropriate framework for uncertainty estimation. Particularly, there is strong disagreement whether an uncertainty framework should have its roots within a proper statistical (Bayesian) context, or whether such a framework should be based on a different philosophy and implement informal measures and weaker inference to summarize parameter and predictive distributions. In this paper, we compare a formal Bayesian approach using Markov Chain Monte Carlo (MCMC) with generalized likelihood uncertainty estimation (GLUE) for assessing uncertainty in conceptual watershed modeling. Our formal Bayesian approach is implemented using the recently developed differential evolution adaptive metropolis (DREAM) MCMC scheme with a likelihood function that explicitly considers model structural, input and parameter uncertainty. Our results demonstrate that DREAM and GLUE can generate very similar estimates of total streamflow uncertainty. This suggests that formal and informal Bayesian approaches have more common ground than the hydrologic literature and ongoing debate might suggest. The main advantage of formal approaches is, however, that they attempt to disentangle the effect of forcing, parameter and model structural error on total predictive uncertainty. This is key to improving hydrologic theory and to better understand and predict the flow of water through catchments.
A first look at reconstructed data from the GlueX detector
NASA Astrophysics Data System (ADS)
Taylor, Simon; GlueX Collaboration
Construction of the GlueX detector in Hall D at the Thomas Jefferson National Accelerator Facility has recently been completed as part of the 12 GeV Upgrade to the facility. The detector consists of a barrel region containing devices for tracking charged particles and a lead-scintillator calorimeter for detecting photons, and a forward region consisting of two layers of scintillator paddles for time-of-flight measurements and a lead-glass electromagnetic calorimeter. The electron beam from the accelerator is converted into a photon beam by inserting a diamond radiator, thereby producing a coherent bremsstrahlung spectrum of photons impinging on a 30 cm-long LH2 target. The energy of the photon beam is determined using a tagging spectrometer. A commissioning run took place in Spring of 2015 during which all of the detector components were read out. Preliminary calibrations have been determined to a level sufficient to allow reconstruction of final states with several charged tracks and neutral particles. A first look at results of reconstruction of events using the GlueX detector will be presented. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics under Contract DE-AC05-06OR23177.
Characteristics of SiPM Photo Sensors for GlueX
NASA Astrophysics Data System (ADS)
Qiang, Yi; Smith, Elton; Tolstukhin, Ivan; Brooks, Will; Hakobyan, Hayk; Kuleshov, Sergey; Soto, Orlando; Toro, Alam; Lolos, George; Papandreou, Zisis; Semenov, Andrey
The barrel calorimeter of the GlueX detector in Hall D at Jefferson Lab will be instrumented with 3840 large-area (1.2 ×1.2 cm2) custom silicon photomultiplier (SiPM) arrays manufactured by Hamamatsu Corporation. These photon sensors have properties similar to vacuum photomultipliers, but are unaffected by high magnetic fields. In our experiment, they will operate in magnetic fields exceeding 1 T. A series of measurements have been carried out by several groups to characterize these SiPMs including the photon detection efficiency (PDE), gain, dark rate, cross talk and after-pulsing at different bias voltages and temperatures. A special study was performed for the first time to separate the cross talk and after pulsing by analyzing ADC spectra with different gate widths. These measurements allow a unique extraction of after-pulsing parameters. We will present a summary of these measurements and the plan for use of these sensors in the GlueX experiment.
Flash ADC readout of the GlueX forward electromagnetic calorimeter
NASA Astrophysics Data System (ADS)
Kornicer, Mihajlo
The GlueX experiment at Jefferson Lab will use a 9 GeV high-rate (10^7 -10^8/s) photon beam, incident on a liquid hydrogen target, to search for hybrid-meson production in the mass range of 1.5-2.5 GeV/c^2. Abundant photon production from neutral meson decays is expected in the decay chains of hybrid mesons, which will result in several photons in the forward region. The forward electromagnetic calorimeter (FCAL) of the GlueX detector is designed to reconstruct final state photons using an array of 2800 lead-glass blocks. The FCAL will employ flash analog-to-digital converter (FADC) technology to measure both deposited energy and photon arrival time using pulses from FEU-84-3 photomultiplier tubes. A real-time sum of the total calorimeter energy will be used as an input to the trigger. Timing information from individual crystals will be used to suppress the expected high-level of electromagnetic background from the photon beam and forward-going charged particles. We present the performance characteristics of the calorimeter readout based on simulation and data taken with a prototype 12-bit, 250 MHz flash ADC.
Double-network gels and the toughness of terrestrial slug glue.
Wilks, Alex M; Rabice, Sarah R; Garbacz, Holland S; Harro, Cailin C; Smith, Andrew M
The terrestrial slug Arion subfuscus produces a defensive secretion that is sticky and tough, despite being a dilute gel. It is unusual in having high stiffness for a gel, yet retaining the high extensibility typical of mucus. In tensile tests, it sustains an average peak stress of 101 kPa, and fails at an average strain of 9.5. This gives the gel toughness; it requires much greater strain energy to fracture than most gels. This toughness may arise from a double-network type mechanism. In this mechanism, two separate, interpenetrating networks of polymers with different properties combine to give toughness that can be several orders of magnitude greater than either network individually. Native gel electrophoresis suggests that A. subfuscus glue consists of two networks: a network of negatively charged proteins ranging in Mr from 40×10(3) to 220×10(3) that can be dissociated by hydroxylamine and a network of heparan sulfate-like proteoglycans. The two networks are not tightly linked, though proteins of Mr 40×10(3) and 165×10(3) may associate with the carbohydrates. Targeted disruption of either network separately, using enzymatic hydrolysis, disulfide bond breakage or imine bond disruption completely disrupted the glue, resulting in no measurable toughness. Thus, the two networks separately provide little toughness, but together they work synergistically to create a tough material, as predicted in the double-network mechanism. PMID:26276864
Calibrations for Charged Particle Tracking with the GlueX Detector
NASA Astrophysics Data System (ADS)
Staib, Michael; GlueX Collaboration
Two gas detectors comprise the tracking system for the GlueX experiment, the Central Drift Chamber (CDC) and the Forward Drift Chamber (FDC). The CDC is a cylindrical straw-tube detector covering polar angles between 6° and 168°, delivering spatial resolution of ~150 μm. The FDC is a Cathode Strip Chamber consisting of four packages, each with six alternating layers of anode wires and cathode strips. The FDC is designed to track forward-going charged particles with polar angles between 1° and 20° with a spatial resolution of ~200 μm. Both tracking detectors record timing information and energy loss measurements useful for particle identification. During Fall 2014 and Spring 2015, the first photon beam was delivered on target for commissioning of the GlueX detector in Hall-D at Jefferson Lab. These data are currently being used in a large effort to calibrate the individual detector subsystems to achieve design performance. Methods and results for calibrations of each of the tracking detectors are presented. Techniques for alignment of the tracking system using a combination of cosmic rays and beam data is discussed. Finally, some early results of physics measurements including charged final-state particles are presented. This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Nuclear Physics under Contract DE-AC05-06OR23177.
Novel sulfated xylogalactoarabinans from green seaweed Cladophora falklandica: Chemical structure and action on the fibrin network.
Arata, Paula X; Quintana, Irene; Raffo, María Paula; Ciancia, Marina
The water-soluble sulfated xylogalactoarabinans from green seaweed Cladophora falklandica are constituted by a backbone of 4-linked β-l-arabinopyranose units partially sulfated mainly on C3 and also on C2. Besides, partial glycosylation mostly on C2 with single stubs of β-d-xylopyranose, or single stubs of β-d-galactofuranose or short chains comprising (1→5)- and/or (1→6)-linkages, was also found. These compounds showed anticoagulant activity, although much lower than that of heparin. The effect of a purified fraction (F1) on the fibrin network was studied in detail. It modifies the kinetics of fibrin formation, suggesting an impaired polymerization process. Scanning electron microscopy showed a laxer conformation, with larger interstitial pores than the control. Accordingly, this network was lysed more easily. These fibrin properties would reduce the time of permanence of the clot in the blood vessel, inducing a lesser thrombogenic state. One of the possible mechanisms of its anticoagulant effect is direct thrombin inhibition. PMID:27577905
How to Assess Fibrinogen Levels and Fibrin Clot Properties in Clinical Practice?
Undas, Anetta
Fibrin formed from fibrinogen is the main component of thrombi. Clot structure is characterized by fiber thickness and pore size, which differs within a given clot and between individuals. Plasma clot architecture is largely determined by the quantity and quality of fibrinogen. Plasma fibrinogen concentrations are most commonly measured in citrated plasma using the Clauss method. However, several factors, including instrument type and reagent, may affect results. Other approaches to express the ability of fibrinogen to clot involve prothrombin time-derived or clottable protein assays, while fibrinogen antigen levels in clinical settings are measured using immunological or precipitation assays. Fibrin clot permeability (reflected by the Darcy constant, K s) being proportional to a buffer volume percolating through a clot under a given hydrostatic pressure is now the most commonly used measure of clot structure. Low K s values indicating tightly packed fibrin structure have been shown to be associated with venous and arterial thrombotic complications, while high K s might contribute to bleeding disorders. The measurement of K s, however, is not standardized and validated. This review summarizes the current knowledge on practical aspects of the measurement of fibrinogen levels and K s in patients. PMID:27071050
Clot contraction: compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin.
Cines, Douglas B; Lebedeva, Tatiana; Nagaswami, Chandrasekaran; Hayes, Vincent; Massefski, Walter; Litvinov, Rustem I; Rauova, Lubica; Lowery, Thomas J; Weisel, John W
Contraction of blood clots is necessary for hemostasis and wound healing and to restore flow past obstructive thrombi, but little is known about the structure of contracted clots or the role of erythrocytes in contraction. We found that contracted blood clots develop a remarkable structure, with a meshwork of fibrin and platelet aggregates on the exterior of the clot and a close-packed, tessellated array of compressed polyhedral erythrocytes within. The same results were obtained after initiation of clotting with various activators and also with clots from reconstituted human blood and mouse blood. Such close-packed arrays of polyhedral erythrocytes, or polyhedrocytes, were also observed in human arterial thrombi taken from patients. The mechanical nature of this shape change was confirmed by polyhedrocyte formation from the forces of centrifugation of blood without clotting. Platelets (with their cytoskeletal motility proteins) and fibrin(ogen) (as the substrate bridging platelets for contraction) are required to generate the forces necessary to segregate platelets/fibrin from erythrocytes and to compress erythrocytes into a tightly packed array. These results demonstrate how contracted clots form an impermeable barrier important for hemostasis and wound healing and help explain how fibrinolysis is greatly retarded as clots contract. PMID:24335500
Fibrin Encapsulation and Vascular Endothelial Growth Factor Delivery Promotes Ovarian Graft Survival in Mice
Shikanov, Ariella; Zhang, Zheng; Xu, Min; Smith, Rachel M.; Rajan, Aniruddha; Woodruff, Teresa K.
Ovarian cryopreservation before chemotherapy and autotransplantation post-treatment can restore fertility to women with premature ovarian failure. Although the majority of primordial follicles survive the cryopreservation cycle, the follicular pool is reduced after transplantation due to ischemic death. Therefore, we engineered a biomaterial-based system to promote angiogenesis in a mouse model of ovarian transplantation. To mimic the clinical situation of sterility, a bilateral ovariectomy was performed 2 weeks before transplantation, during which time serum levels of follicular stimulating hormone rose to menopausal levels. Before transplantation, vitrified/thawed ovarian tissue from 12-day-old C57Bl/6J pups was encapsulated in fibrin modified with heparin-binding peptide (HBP), heparin, and loaded with 0.5 μg vascular endothelial growth factor (VEGF). The group transplanted with fibrin-HBP-VEGF had twice as many surviving primordial follicles and an increased number of blood vessels relative to the no biomaterial control. Transplanted tissue was viable and supported natural conception that led to live and healthy offspring. The timeline of live births with VEGF delivery suggested that primary follicles survived transplantation, and provided the gametes for the first litter. Thus, VEGF delivery from fibrin supported integration of the transplant with the host, promoted angiogenesis, and enhanced engraftment and function of the tissue. PMID:21740332