The Heavy Metals in Agrosystems and Impact on Health and Quality of Life.
The metal is a chemical element that conducts electricity well and heat, and the nonferrous metals builds cations and ionic bonds. Heavy metals include metals whose density is higher than 5 g/cm(3). The whole range of the metal is in the form of essential trace elements, essential for a number of functions in the human body, and its deficiency results in a lack of occurrence of a serious symptom. The best examples are anemia lack of iron, lack of chromium in diabetes, growth problems in lack of nickel. Other elements such as lead, cadmium, mercury, arsenic and molybdenum have been shown to exhibit large quantities of toxic effects. The paper examines the problem of heavy metals originating from agriculture on agroecosystems. This group of pollutants is considered the most important cause of degradation of soil quality, surface and groundwater and direct causal adverse effects on human and animal health. In order to complete the environmental monitoring of pollutants, these main categories, origins, and possible negative impacts of the basic principles of preventing their toxic effects were examined.


Ensuring success: research by committee.
The Nursing Research Committee at a community teaching hospital conducted a research study on alternatives to restraints in a confused population. The authors describe the process this committee used to successfully conduct the study, from starting a research focus group and setting goals to choosing a research topic, designing the study, and collecting data. Critical success factors for completing research by committee are described.


The CcmFH complex is the system I holocytochrome c synthetase: engineering cytochrome c maturation independent of CcmABCDE.
Cytochrome c maturation (ccm) in many bacteria, archaea and plant mitochondria requires eight membrane proteins, CcmABCDEFGH, called system I. This pathway delivers and attaches haem covalently to two cysteines (of Cys-Xxx-Xxx-Cys-His) in the cytochrome c. All models propose that CcmFH facilitates covalent attachment of haem to the apocytochrome; namely, that it is the synthetase. However, holocytochrome c synthetase activity has not been directly demonstrated for CcmFH. We report formation of holocytochromes c by CcmFH and CcmG, a periplasmic thioredoxin, independent of CcmABCDE (we term this activity CcmFGH-only). Cytochrome c produced in the absence of CcmABCDE is indistinguishable from cytochrome c produced by the full system I, with a cleaved signal sequence and two covalent bonds to haem. We engineered increased cytochrome c production by CcmFGH-only, with yields approaching those from the full system I. Three conserved histidines in CcmF (TM-His1, TM-His2 and P-His1) are required for activity, as are the conserved cysteine pairs in CcmG and CcmH. Our findings establish that CcmFH is the system I holocytochrome c synthetase. Although we discuss why this engineering would likely not replace the need for CcmABCDE in nature, these results provide unique mechanistic and evolutionary insights into cytochrome c biosynthesis.


The SRC family of protein tyrosine kinases: a new and promising target for colorectal cancer therapy.
Aberrant activation of the Src family of tyrosine kinases has been implicated in the development and progression of colorectal cancer (CRC). As a result, Src inhibitors are now being studied as possible therapeutic agents to treat metastatic disease. In this review, we discuss the effects of aberrant Src activation in CRC, Src as a target of single-agent drug therapy, and Src as a target of combination therapy with epidermal growth factor receptor inhibition and cytotoxic chemotherapy. The greatest potential for clinically relevant benefit most likely lies in combination regimens. Further evaluation with biomarkers will continue to define the molecular phenotype of patients with CRC who will benefit the most from Src-based therapy.


Innovation under federal health care reform.
Health care reform, which seeks to expand coverage and control spending, contains mixed messages for innovators. Policies that advance reform goals are likely to shift resources away from hospitals, specialists, and expensive procedures and toward areas such as prevention and primary care where innovation may yield greater health improvements per dollar spent. The size of these effects depends critically on the extent of cost containment achieved. Constraining spending will be politically difficult because it requires that consumers forego some possible health benefits in return for lower costs. In a climate of cost containment, systematic evaluation of new technology is vital to identify and expand coverage to worthwhile innovations and to assure a fair hearing for innovators.


Predictors of vertigo in patients with untreated vestibular schwannoma.
Previous studies have shown that vertigo is the most powerful negative predictor of quality of life in patients with vestibular schwannomas, but the variability in vertigo symptom severity is still poorly understood. We wanted to find out whether vertigo could be related to objective parameters such as tumor size, location, vestibular nerve function, hearing, and postural stability in patients with untreated vestibular schwannomas. Baseline data from prospective cohort study. Tertiary referral center. Four hundred thirty-four consecutive patients with unilateral VS diagnosed on MRI. Mean age 56 years (range 16-84 yr). Fifty-three percent women. Diagnostic, with a medical history, otolaryngological examination, pure-tone and speech audiometry, MRI, posturography, and videonystagmography with bithermal caloric tests. Dizziness measured on a 100-mm visual analog scale (VAS). Secondary outcome measures were canal paresis and postural imbalance (static and dynamic posturography). Three hundred three patients (70%) completed the VAS. Severe dizziness, defined as VAS 75 or greater, was reported by 9% of the patients. Larger tumors were associated with higher risk of postural instability and canal paresis. Moderate to severe dizziness was associated with postural imbalance and canal paresis, and possibly with small to medium-sized tumors. Postural instability was related to tumor size and canal paresis when measured by dynamic, but not with static, posturography. A minority of VS patients experience severe vestibular symptoms related to canal paresis and postural instability. A curvilinear relationship is hypothesized between tumor size and dizziness.


Importins: Diverse roles in male fertility.
Regulated nucleocytoplasmic transport is central to the changes in gene expression that underpin cellular development and homeostasis, including in the testis, and proteins in the importin family are the predominant facilitators of cargo transport through the nuclear envelope. Reports documenting cell-specific profiles of importin transcripts and proteins during spermatogenesis led us to hypothesize that importins facilitate developmental switches in the testis. More recently, importins have been shown to serve additional functions, both inside and outside the nucleus; these include acting as subcellular scaffolding, mediating cellular stress responses, and controlling transcription. This paper seeks to provide an overview and update on the functions of importin proteins, with a focus on testis development and spermatogenesis. We present an extended survey of importins by combining published single cell RNAseq data with immunohistochemistry on developing and adult mouse testes. This approach reinforces and broadens knowledge of importins in biological processes, including in spermatogenesis and during testis development, revealing additional avenues for impactful investigations.


The emergence of Kawasaki disease in India and China.
Kawasaki disease (KD) is recognized as a leading cause of acquired heart disease in children in developed countries. Although global in distribution, Japan records the highest incidence of KD in the world. Epidemiological reports from the two most populous countries in the world, namely China and India, indicate that KD is now being increasingly recognized. Whether this increased reporting is due to increased ascertainment, or is due to a true increase in incidence, remains a matter of conjecture. The diagnosis and management of KD in developing countries is a challenging proposition. In this review we highlight some of the difficulties faced by physicians in managing children with KD in resource-constrained settings.


Properdin inhibition ameliorates hepatic ischemia/reperfusion injury without interfering with liver regeneration in mice.
Hepatic ischemia/reperfusion injury (IRI) often causes serious complications in liver surgeries, including transplantation. Complement activation seems to be involved in hepatic IRI; however, no complement-targeted intervention has been clinically applied. We investigated the therapeutic potential of Properdin-targeted complement regulation in hepatic IRI. Male wild-type mice (B10D2/nSn) were exposed to 90-minute partial hepatic IRI to the left and median lobes with either monoclonal anti-Properdin-antibody (Ab) or control-immunoglobulin (IgG) administration. Since the complement system is closely involved in liver regeneration, the influence of anti-Properdin-Ab on liver regeneration was also evaluated in a mouse model of 70% partial hepatectomy. Anti-Properdin-Ab significantly reduced serum transaminases and histopathological damages at 2 and 6 hours after reperfusion (P <0.001, respectively). These improvements at 2 hours was accompanied by significant reductions in CD41+ platelet aggregation (P =0.010) and ssDNA+ cells (P <0.001), indicating significant amelioration in hepatic microcirculation and apoptosis, respectively. Characteristically, F4/80+ cells representing macrophages, mainly Kupffer cells, were maintained by anti-Properdin-Ab (P <0.001). Western blot showed decreased phosphorylation of only Erk1/2 among MAPKs (P =0.004). After 6 hours of reperfusion, anti-Properdin-Ab significantly attenuated the release of HMGB-1, which provokes the release of proinflammatory cytokines/chemokines (P =0.002). Infiltration of CD11b+ and Ly6-G+ cells, representing infiltrating macrophages and neutrophils, respectively, were significantly alleviated by anti-Properdin-Ab (both P <0.001). Notably, anti-Properdin-Ab did not affect remnant liver weight and BrdU+ cells at 48 hours after 70% partial hepatectomy (P =0.13 and 0.31, respectively). In conclusion, Properdin inhibition significantly ameliorates hepatic IRI without interfering with liver regeneration.


3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair.
Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.


A monoclonal antibody, GR7A4, reacting with the T10 antigen.
The monoclonal antibody GR7A4 was produced against a human lymphoblastic leukemia (ALL-B). Biochemical characterization of GR7A4 was carried out with Raji cells in SDS-PAGE studies. GR7A4 precipitated a 43 kd molecule. The tissue distribution and molecular weight were similar to the T10 antigen. Modulation and capping of GR7A4 antigen reduced its binding ability to cells with either GR7A4 or OKT10. However, the cell surface distribution pattern observed was somewhat different from other similar monoclonal antibodies. Thus GR7A4 reacted greatly with pre-B-cell lines, Burkitt cell lines, EBV cell lines and activated PHA, ConA and PWM lymphocytes, however reactivity with leukemic cells was very limited. The kinetics of appearance of GR7A4 antigen on PWM blasts show that this molecule seems to represent an intermediate stage in lymphocytic activation. The differences in comparison with other similar MAbs are discussed and correlated with the peculiar discontinous pattern of appearance of this antigen.


Spleen Tyrosine Kinase: A Crucial Player and Potential Therapeutic Target in Renal Disease.
Spleen tyrosine kinase (Syk), a 72 kDa cytoplasmic non-receptor protein-tyrosine kinase, plays an important role in signal transduction in a variety of cell types. Ever since its discovery in the early 1990s, there has been accumulating evidence to suggest a pathogenic role of Syk in various allergic disorders, autoimmune diseases and malignancies. Additionally, there is emerging data from both pre-clinical and clinical studies that Syk is implicated in the pathogenesis of proliferative glomerulonephritis (GN), including anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated GN, lupus nephritis and immunoglobulin A nephropathy (IgAN). Moreover, recent animal studies have shed light on the importance of Syk in mediating acute renal allograft rejection, Epstein Barr virus-associated post-transplant lymphoproliferative disease and kidney fibrosis. Fostamatinib, an oral Syk inhibitor, has undergone clinical testing in rheumatoid arthritis, refractory immune thrombocytopenic purpura, leukemia and lymphoma. The recent STOP-IgAN trial showed that the addition of non-selective immunosuppressive therapy to intensive supportive care did not improve clinical outcomes in high-risk IgAN patients. A Syk-targeted approach may be beneficial and is currently being evaluated in a phase II randomized controlled trial. In this review, we will discuss the pathogenic role of Syk and potential use of Syk inhibitor in a variety of renal diseases.


Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone.
Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known "agonist analogs" of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. We have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and we found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: [His5,Trp7,Gln8]LHRH; [His5,Trp7,Leu8]LHRH; [His5,Trp7]LHRH; [Trp7]LHRH; [His5]LHRH. Two of these five agonists variably released relatively more FSH than LH. One or more of these five agonists may occur in nature and one may be follicle-stimulating hormone-releasing hormone. The two peptides with Gln8 and Leu8, if occurring in nature, may have different receptors according to radioreceptor assays and to the ratio of LH/FSH release in vivo. These structures are a basis for the design of antagonists without Arg8 toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of Arg8 and Gln8 or Leu8 antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas.


Functional interaction of PkcA and PldB regulate aggregation and development in Dictyostelium discoideum.
Multicellular development in Dictyostelium discoideum involves tightly regulated signaling events controlling the entry into development, initiation of aggregation and chemotaxis, and cellular differentiation. Here we show that PkcA, a Dictyostelium discoideum Protein Kinase C-orthologue, is involved in quorum sensing and the initiation of development, as well as cAMP sensing during chemotaxis. Additionally, by epistasis analysis we provide evidence that PkcA and PldB (a Phospholipase D-orthologue) functionally interact to regulate aggregation, differentiation, and cell-cell adhesion during development. Finally, we show that PkcA acts as a positive regulator of intracellular PLD-activity during development. Taken together, our results suggest that PkcA act through PldB, by regulating PLD-activity, in order to control events during development.


[Stenting of symptomatic stenosis of the internal carotid artery is not preferred over endarterectomy at this time].
Carotid endarterectomy reduces the risk of stroke in patients with symptomatic internal carotid-artery stenosis of 50% or greater. Carotid-artery stenting may be an attractive alternative. Two randomised trials comparing carotid endarterectomy with stenting have recently been terminated prematurely. Reasons for termination included an excess in stroke and death after stenting, compared with carotid endarterectomy (the EVA-3S trial) and futility reasons and the absence of funding (the SPACE trial). Given that both trials failed to prove the non-inferiority of stenting compared with carotid endarterectomy in the first 30 days, the use of stenting should be restricted to patients with contraindications to surgery and those participating in randomised clinical trials.


The role of the 3' external transcribed spacer in yeast pre-rRNA processing.
We have undertaken a deletion analysis of the 3' external transcribed spacer (3' ETS) in the pre-rRNA of Saccharomyces cerevisiae. A stem loop structure immediately 3' to the 25 S rRNA region is necessary and sufficient for processing of the 3' ETS. This is believed to be by cotranscriptional cleavage by Rnt1p, the yeast homologue of RNase III. In addition, this stem-loop is required for cleavage of site A3 by RNase MRP and for processing at site B1L, in the 3' region of ITS1. Processing at an upstream site in ITS1, site A2, and at sites in the 5' external transcribed spacer are not affected, even by complete deletion of the 3' ETS. We conclude that processing in the 3' ETS and in ITS1 is coupled. This would constitute a quality control that prevents synthesis of the 5. 8 S rRNA and 5' end maturation of the 25 S rRNA in transcripts which are incomplete due to premature transcription termination.


A novel strategy to design sustained-release poorly water-soluble drug mesoporous silica microparticles based on supercritical fluid technique.
The organic solvent solution immersion method was often used to achieve the loading of the drugs into mesoporous silica, but the drugs that have loaded into the pores of the mesoporous silica would inevitable migrate from the inside to the external surface or near the outside surface during the process of drying. Hence, it often leads to the pores of mesoporous materials not be fully utilized, and results in a low drug loading efficiency and a fast releasing rate. The purpose of this study was to develop a novel drug loading strategy to avoid soluble component migration during the process of drying, then, to prepare poorly water-soluble drug mesoporous silica microparticles with higher drug loading efficiency and longer sustained-release time. Ibuprofen was used as model drug. The microparticles were prepared by a novel method based on mesoporous silica and supercritical fluid (SCF) technique. The drug-loaded mesoporous silica microparticles prepared by SCF technique were analyzed by thermogravimetric analysis (TGA), N2 adsorption/desorption, scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC). In vitro releasing study was used to evaluate the sustained-release effect of the drug-loaded microparticles. By virtue of the high diffusibility and the high dissolving capacity of the supercritical carbon dioxide (SCF-CO2), the poorly water-soluble drugs, ibuprofen, entered the pores of the mesoporous silica. The amount and the depth of ibuprofen entered the pores of the mesoporous silica by SCF technique were both larger than those by the solution immersion method. It was found that ibuprofen loaded into the mesoporous silica by SCF technique was amorphous and the largest amount of the ibuprofen loaded into the mesoporous silica by SCF technique could reach 386 mg/g (w/w, ibuprofen/SiO2), it was more than that by the solution immersion method. In vitro releasing study showed that the sustained-release effect of ibuprofen in the samples prepared by SCF technique was 50% in 15 min and 90% in 60 min. It was longer than that prepared by the solution immersion method. Present study showed that sustained-release poorly water-soluble drug mesoporous silica microparticle based on SCF technique has twofold advantages. One is the larger drug loading amount in internal pores of the mesoporous silica, the other is the longer drug releasing time.


[Proton spin and computerized tomography in ligament injuries of the knee joint].
In a prospective study we evaluated the use of cat-scan an MRI in 106 patients with chronic complaints and acute injuries of the knee joint. All patients went to surgery afterwards. A total of 30 patients suffered from acute or chronic ligament ruptures. There were 20 ACL ruptures, 2 PCL ruptures, 3 MCL ruptures, and 2 LCL ruptures. In patients with ACL ruptures the MRI had a sensitivity of 80%, a specificity value of 80%, and a negative predictive value of 95%; whereas cat-scan had a sensitivity of 90%, a specificity of 95%, an accuracy of 94%, a positive predictive value of 82%, and a negative predictive value of 98%. All complete ACL ruptures we correctly diagnosed. However, 4 partial ACL ruptures were missed by MRI and 2 partial ruptures were missed by cat-scan. All other ligament ruptures (PCL, MCL, LCL) except one MCL rupture were correctly diagnosed by MRI as well as by cat-scan. In this study cat-scan and MRI proved to have a very high negative predictive value. Having a negative result in one of these imaging techniques means that a rupture of a ligament is highly unlikely. This may have influence on the number of unnecessary invasive arthroscopic procedures.


"No matter what, I will not give up": Community practice on the front lines of COVID-19.
The COVID-19 pandemic has required frontline health care workers to cope with an unexpected and almost unprecedented emergency situation. Community social workers had played a crucial role during the pandemic, working to alleviate its adverse effects on marginalized communities. The present study investigated community social workers' experiences and hardships in coping with the "age of COVID-19." Drawing on in-depth interviews with 30 frontline community social workers in Israel, the findings highlighted three main themes: (a) the hope for recognition and the reality of underutilization; (b) the impact of the dysfunctional state on community social workers; and (c) realizing the core values and activities of community social work practice during the pandemic. Findings pointed to community social workers' professionalism and integrity despite the hardships they endured at the local and national levels. Committing on an altruistic level seemed to be an adaptive coping style, alongside facing "the politics of pandemics." Implications for community practice are outlined. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Sunitinib does not impair natural killer cell function in patients with renal cell carcinoma.
Although the available treatment options have expanded, the survival of patients with metastatic renal cell carcinoma (RCC) remains poor. As patients with RCC lack responsiveness to chemotherapy or radiation, therapeutic options predominantly include surgical interventions and immunomodulatory approaches, including the administration of tyrosine kinase inhibitors (TKIs) such as sunitinib. Natural killer (NK) cells have been reported to be key players in TKI-mediated off-target effects on the immune system. However, only limited information is available regarding the possible impact of sunitinib on the function of NK cells of individual patients. The present study reports on the immunomonitoring results of three patients with metastatic RCC who underwent sunitinib treatment. These results were compared with age-matched, healthy controls in terms of the immune status of T, B and NK cells, focusing on functional in vitro analyses of NK cells. In all three patients, NK cell number, subset distribution and function, as measured by cluster of differentiation 107a degranulation, did not exhibit any significant alterations as a result of sunitinib treatment. These results indicate that sunitinib does not negatively affect NK cell function, which supports the pursuit of therapeutic modalities that combine immunomodulation and NK cell-stimulating approaches.


Advances in Drug Discovery of New Antitubercular Multidrug-Resistant Compounds.
Tuberculosis (TB), a disease caused mainly by the Mycobacterium tuberculosis (Mtb), is according to the World Health Organization (WHO) the infectious disease responsible for the highest number of deaths worldwide. The increased number of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains, and the ineffectiveness of the current treatment against latent tuberculosis are challenges to be overcome in the coming years. The scenario of drug discovery becomes alarming when it is considered that the number of new drugs does not increase proportionally to the emergence of drug resistance. In this review, we will demonstrate the current advances in antitubercular drug discovery, focusing on the research of compounds with potent antituberculosis activity against MDR-TB strains. Herein, active compounds against MDR-TB with minimum inhibitory concentrations (MICs) less than 11 µM and low toxicity published in the last 4 years in the databases PubMed, Web of Science and Scopus will be presented and discussed.


A comparison of the effects of altered thyroid and parathyroid function on reproduction in the rat.
Mild maternal hypothyroidism produced by surgical thyroidectomy resulted in significantly reduced food intake along with retarded reproductive performance in rats. Hyperthyroidism increased food consumption above the control level along with an increase in fetal resorptions which was the only parameter of reproductive performance altered by the twenty-second day of gestation. In animals which underwent pregnancies, reproductive performance suffered a further decline in the second gestation due to increasing duration of the hypothyroidism. Food restriction alone failed to duplicate these adverse effects on fetal development. Serum gonadotropins (LH and FSH) were not significantly altered by mild maternal hypothyroidism of hypoparathyroidism. The hematocrit and total blood volume of hypothyroid but not hypoparathyroid rats was significantly reduced from normal. Maternal hypoparathyroidism alone did not affect fetal development grossly.


Transcatheter aortic valve replacement in high risk patients with different anaesthetic techniques.
Percutaneous retrograde transfemoral or transsubclavian aortic valve replacement is a minimally invasive method of aortic valve replacement in elderly and high-risk patients with symptomatic aortic stenosis considered too fragile to go through conventional heart surgery. The purpose of this study was to compare two different anaesthetic techniques for percutaneous retrograde transfemoral or transsubclavian aortic valve replacement in terms of anaesthetic depth, hemodynamic stability and need for vasoactive drugs. Forty-eight elderly or high risk patients, two third of them in their eighties, were scheduled for percutaneous retrograde transfemoral or transsubclavian aortic valve replacement. Anaesthetic induction was standardized, but anaesthesia was afterwards maintained alternately with either propofol infusion or sevoflurane. Need for vasoactive drugs was recorded and anaesthetic depth was estimated from acoustic evoked potential measuring and clinical observation. Twenty-eight percent of the patients in the sevoflurane group and 30% of the patients in the propofol group required vasoactive therapy (P=0.84). Forty-four percent of the patients in the sevoflurane group and 57% of the patients in the propofol group had episodes of superficial anaesthesia recorded(P=0.38). We found no significant difference in the use of vasoactive drugs or in anaesthetic depth between propofol and sevoflurane anaesthesia. Both can be recommended for percutaneous aortic valve replacement.


Incorporation of stable isotope-labeled arachidonic acid into cellular phospholipid molecular species and analysis by fast atom bombardment tandem mass spectrometry.
The source of arachidonic acid metabolized to eicosanoids by 5-lipoxygenase was studied in a cultured neoplastic mast cell using a stable isotope tracer and tandem mass spectrometry strategy. Selected reaction monitoring and fast atom bombardment were used to analyze eight major arachidonate molecular species of glycerophosphocholine, nine major molecular species of glycerophosphoethanolamine, three major species of glycerophosphocholine, nine major molecular species of glycerophosphoethanolamine, three major species of glycerophosphoinositol, and three major glycerophosphoserine molecular species. Incubation of the mast cells with (2H8)arachidonic acid led to a time-dependent isotopic incorporation in each of these molecular species. Following stimulation with calcium ionophore A23187, the isotope incorporation of leukotriene B4 (LTB4) was found to be higher than that of the major arachidonate-containing glycerophospholipid molecular species. The isotope incorporation of LTB4 was similar to that found for free arachidonic acid present in the unstimulated cell. In order to prevent direct labeling of the intracellular, free arachidonic acid pool, (2H4)linoleic acid was added to the culture medium as a biochemical precursor of labeled arachidonic acid. There was a time-dependent increase of the specific incorporation of labeled arachidonic acid into each of the phospholipid molecular species of each lipid class after incubation with (2H4)linoleic acid. Importantly, (2H4)linoleic acid incubation also resulted in deuterium-labeled arachidonic acid in the free arachidonic acid, intracellular pool. The arachidonic acid isotopic incorporation in this pool very closely correlated with the isotopic incorporation of LTB4 (correlation coefficient 0.97) synthesized after A23187 stimulation, while the isotopic incorporation of the extracellularly released, not esterified arachidonic acid, after stimulation, did not.(ABSTRACT TRUNCATED AT 400 WORDS)


Gamma-seminoprotein--a new tumour marker in prostatic cancer? Results of a pilot study.
Serum levels of gamma-seminoprotein (GSM), prostate specific antigen (PSA) and prostate specific acid phosphatase (PAP) were examined, using enzyme immunoassay, in 250 patients with prostatic disease. The results indicated that the highest specificity was obtained with GSM (94%) and the lowest with PSA (60%). In contrast, the highest sensitivity in newly detected carcinomas (n = 41) was obtained with PSA (71%), whereas that of GSM (51%) was comparable to that of PAP (44%). Of 41 patients with newly detected prostatic cancer, 35 (85%) showed a significant increase in at least 1 of the tumour markers. Five of 6 patients whose markers were within normal limits had incidental carcinomas. During follow-up, PSA was raised in 88%, GSM in 66% and PAP in 55% within 12 months prior to clinical progression. Our results suggest that the determination of GSM may be of value in the serological detection and monitoring of prostatic cancer. These findings must be confirmed by further studies with larger numbers of patients and longer follow-up.


Human semen quality and sperm DNA damage in relation to urinary metabolites of pyrethroid insecticides.
Exposure to synthetic pyrethroid insecticides is widespread, and is expected to increase among the general population due to the need to replace other common insecticides following regulatory use restrictions. On the basis of limited studies, there is animal and human evidence for altered reproductive or endocrine function following pyrethroid exposure. The present study measured urinary pyrethroid metabolites [3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA and TDCCA)], semen quality, sperm motion parameters and sperm DNA damage with the neutral comet assay in 207 men recruited from an infertility clinic. In multivariate analysis, the highest 3PBA quartile was associated with a suggestive 20.2 million sperm/ml reduction (95% confidence interval -37.1 to + 2.6) in sperm concentration compared with men below the 3PBA median. There were significant inverse associations between TDCCA and sperm motility and sperm motion parameters when adjusting for CDCCA and other covariates. The highest TDCCA quartile was associated with a 15.5% decline (95% confidence interval -26.2 to -4.8) in sperm motility compared with men below the median. In multiple logistic analyses, there were dose-dependent increased odds for below reference sperm concentration, motility and morphology in relation to TDCCA. Among the comet assay measures, 3PBA and CDCCA were associated with increased sperm DNA damage, measured as percent DNA in the comet tail. We found evidence for reduced semen quality and increased sperm DNA damage in relation to urinary metabolites of pyrethroid insecticides. These findings may be of concern due to increased pyrethroid use and prevalent human exposure.


Valproate therapy does not deplete carnitine levels in otherwise healthy children.
To determine whether children with epilepsy undergoing valproate (VPA) antiepileptic therapy and who are otherwise healthy have a lower serum level of carnitine (CAR) and a higher plasma level of plasma ammonia than do normal children. A total of 45 children with epilepsy, 6.3 to 21.7 years of age, who were treated solely with VPA and were free of abnormal neurologic findings or nutritional problems were randomly selected (VPA-treated group). An age-matched control group (n = 45) was selected from subjects without epilepsy (control group). Total (T) and free (F) serum CAR, serum VPA concentration, and the plasma ammonia level were measured and analyzed. Serum VPA concentration exhibited a weak negative correlation with both T- (r = -0.34) and F-CAR (r = -0.41). The T-CAR levels were 55.7 +/- 12.4 and 57.6 +/- 12.1 mM, and the F-CAR levels 42.7 +/- 9.9 and 44.4 +/- 9.9 mM in the VPA-treated and control groups, respectively. Thus, there was no significant difference in T- or F-CAR levels between the VPA-treated and control groups. Plasma ammonia levels were the same in the two groups: 26 +/- 9.2 and 29.4 +/- 11.8 mM in the VPA-treated and control groups, respectively. There was no significant correlation between blood ammonia and either T- (r = +0.024) or F-CAR (r = -0. 026). Children on a regular diet ingest a sufficient amount of CAR that more than meets their daily CAR requirement. The level of neither T- nor F-CAR in patients with epilepsy and without severe neurologic or nutritional problems being treated with VPA appeared to be affected by VPA therapy. Because the blood CAR level depends on nutritional condition rather than on blood VPA concentration, CAR deficiency caused by VPA is not likely to occur in this population. The usefulness of supplementation of CAR for this type of patient with epilepsy, therefore, must be reevaluated carefully.


BrisSynBio: a BBSRC/EPSRC-funded Synthetic Biology Research Centre.
BrisSynBio is the Bristol-based Biotechnology and Biological Sciences Research Council (BBSRC)/Engineering and Physical Sciences Research Council (EPSRC)-funded Synthetic Biology Research Centre. It is one of six such Centres in the U.K. BrisSynBio's emphasis is on rational and predictive bimolecular modelling, design and engineering in the context of synthetic biology. It trains the next generation of synthetic biologists in these approaches, to facilitate translation of fundamental synthetic biology research to industry and the clinic, and to do this within an innovative and responsible research framework.


Rabbit IL-1. Cloning, expression, biologic properties, and transcription during endotoxemia.
The cloning, sequencing, expression, and biologic activities of rabbit IL-1 alpha and beta are described. A cDNA library was constructed in lambda gt10 by using polyadenylated RNA extracted from rabbit adherent splenic macrophages 4 h after stimulation with endotoxin. By using the cDNA for human IL-1 beta and IL-1 alpha as hybridization probes, cDNA for both forms of rabbit IL-1 were isolated. The cDNA for rabbit IL-1 beta encodes a precursor polypeptide of 268 amino acids with an overall homology to human IL-1 beta of 74% (81% in the mature region coding for a 17.5 kDa carboxyl-terminal protein). The similarity between the two rabbit IL-1 forms is 31% for the entire molecule and 34% for the mature protein. The mature polypeptides of both forms were expressed in Escherichia coli. The recombinant proteins were purified to homogeneity and tested in a variety of biologic assays. Both forms produced typical endogenous pyrogen fevers in rabbits and augmented murine thymocyte and Th cell proliferation. Rabbit IL-1 alpha and beta were more pyrogenic in rabbits than human rIL-1 beta, whereas human rIL-1 alpha and beta were slightly more potent lymphocyte-activating factors. The recombinant rabbit proteins induced PGE and IL-1 production from human PBMC in vitro. A RIA for human IL-1 alpha did not recognize rabbit IL-1 alpha or beta, but rabbit IL-1 beta cross-reacted (as much as 30%) in a RIA for human IL-1 beta. Rabbits were injected with endotoxin and mRNA for both forms of IL-1 were observed primarily in the spleen and liver. The mRNA reached maximal levels after 60 min, then declined rapidly over the next 3 h, but were still present after 24 h. Liver tissue removed 4 h after endotoxin infusion produced lymphocyte-activating factors which were neutralized by more than 90% with a combination of goat anti-rabbit IL-1 alpha and anti-IL-1 beta.


Contrast reduction by the atmosphere and retrieval of nonuniform surface reflectance.
A radiative transfer model is developed which gives the upward radiance at nadir for any 1-D Lambertian surface reflectance. This model is used to depict the atmospheric effect on the transmittance of contrast for any 1-D surface reflectance. Here by contrast we mean a general variation of the radiation field across the image. With the aid of this model an inversion algorithm is developed for retrieval of true surface reflectance from high resolution satellite data (e.g., Landsat). This inversion technique can be a useful tool for extraction of surface reflectance from satellite data in the case of a surface reflectance variable in one dimension only (e.g., seashore or near borders of big fields). A sensitivity study of the inversion procedure on the knowledge of atmospheric parameters and sensor calibration was performed. It is shown that this inversion technique is stable even in the presence of errors in the sensor calibration and the atmospheric parameters. The method was applied to Landsat data in two wavelengths. The results show reasonable dependence of the derived surface reflectance on the distance from the seashore.


A fluorescent probe composed of quantum dot labeled aptamer and graphene oxide for the determination of the lipopolysaccharide endotoxin.
Endotoxins are complex lipopolysaccharides (LPS) and key components of the outer cell membrane of Gram-negative bacteria. The authors report on a fluorescent aptamer-based probe for the determination of LPS of Gram-negative bacteria. An aptamer against LPS was fluorescently labeled with CdSe/ZnS quantum dots. Its emission is quenched on addition of graphene oxide (GO). On addition of LPS, the aptamer binds LPS and GO is released. This results in the recovery of fluorescence, typically measured at excitation/emission wavelengths of 495/543 nm. The probe responds to LPS in the 10-500 ng·mL-1 concentration range, and the detection limit is 8.7 ng·mL-1. It can be used for selective detection of LPS from different Gram-negative bacteria, in the presence of biological interferents. Graphical abstract Schematic presentation of a green fluorescent probe comprised of an aptamer labelled with CdSe/ZnS quantum dots and of graphene oxide. Lipopolysaccharides bind to the aptamer and release graphene oxide to result in fluorescence recovery, which is measured at an emission wavelength 543 nm.