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pubmed_38_14527
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In this study, we investigated the anti-tumor effects and possible mechanisms of fucoxanthin, which has been reported to inhibit tumor proliferation and induce apoptosis in vitro or in vivo. Human gastric adenocarcinoma MGC-803 cells were treated with fucoxanthin (25μM, 50μM or 75μM). Data of flow cytometry revealed that fucoxanthin (50μM or 75μM) increased the ratio of cell in G2/M phase and apoptotic MGC-803 cells varying on a dose-dependent manner. Results from reverse transcriptase-polymerase chain reaction and Western blot showed that treatment with fucoxanthin (50μM or 75μM) significantly decreased the expressions of CyclinB1, survivin and STAT3 in MGC-803 cells in a dose-dependent manner both at the time of 24h and 48h. In addition, immunofluorescence microscopy analysis also revealed the suppressed expressions of CyclinB1 and survivin by fucoxanthin. After pretreatment with AG490 (the inhibitor for JAK/STAT signal pathway), the expressions of p-STAT3 and survivin remained also slightly lower than the vehicle control group. Co-treated with fucoxanthin (75μM) and AG490, the reduction on the expressions of STAT3, p-STAT3 and CyclinB1 by fucoxanthin were attenuated while that of survivin was enhanced. Taken together, fucoxanthin can down-regulate the expressions of CyclinB1 and survivin, inducing cell cycle arrest in G2/M phase, and apoptosis in MGC-803 cells. The reduction of CyclinB1 by fucoxanthin was associated with JAK/STAT signal pathway.
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10.1016/j.ejphar.2010.12.006
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pubmed_664_11312
|
We consider the contact between elastically soft solids with randomly rough surfaces in sliding contact in a fluid, which is assumed to be Newtonian with constant (pressure-independent) viscosity. We discuss the nature of the transition from boundary lubrication at low sliding velocity, where direct solid-solid contact occurs, to hydrodynamic lubrication at high sliding velocity, where the solids are separated by a thin fluid film. We consider both hydrophilic and hydrophobic systems, and cylinder-on-flat and sphere-on-flat sliding configurations. We show that, for elastically soft solids such as rubber, including cavitation or not results in nearly the same friction.
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10.1088/0953-8984/21/18/185002
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pubmed_970_15827
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It has been reported that pantothenic acid (vitamin B5) and panthenol, an alcohol derivative of pantothenic acid, have beneficial moisturizing effects on the skin. However, few studies have investigated the mechanism of action of pantothenic acid on skin tissues. We tried to clarify the role of pantothenic acid on skin function by using keratinocytes and fibroblasts. The depletion of pantothenic acid from the culture medium suppressed keratinocyte proliferation and promoted differentiation. Moreover, pantothenic acid depletion decreased the synthesis of keratinocyte growth factor and procollagen 4a2 in fibroblasts. These results suggest that pantothenic acid is essential for maintaining keratinocyte proliferation and differentiation.
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10.1254/jphs.10224SC
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pubmed_978_21079
|
We have determined the mutation in a child with partial adenosine deaminase (ADA) deficiency who is phenotypically homozygous for a mutant ADA gene encoding a heat-labile enzyme (Am. J. Hum. Genet. 38: 13-25). Sequencing of cDNA demonstrated a C to A transversion that results in the replacement of a proline by a glutamine residue at codon 297. As this mutation generated a new recognition site in exon 10 of genomic DNA for the enzyme Alu I, Southern blot analysis was used to establish that this child was indeed homozygous for the mutation. The abnormal restriction fragment generated by this mutation was also found in a second partially ADA-deficient patient who phenotypically is a genetic compound and also expresses a heat-labile ADA (in addition to a more acidic than normal ADA) (Am. J. Hum. Genet. 38: 13-25). Sequencing of cDNA clones from the second patient established the identical codon 297 mutation. Transfection of the mutant cDNA into heterologous cells resulted in expression of a heat-labile ADA of normal electrophoretic mobility and isoelectric point, properties exhibited by the ADA in the patients' cells.
|
10.1172/JCI113909
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pubmed_841_15050
|
Providing education and development to patient care personnel with minimal disruption to patient care activities is a daily challenge to staff educators. This article describes how a small nursing development department planned and coordinated the orientation to a new facility and the education and training on new equipment to over 1,000 nurses over a period of several months. The strategies used at this large, urban, academic medical center can be applied to other healthcare facilities.
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pubmed_841_15050
|
pubmed_1084_13509
|
Environmental exposures impose a disproportionate health burden on low-income populations and communities of color. One contributing factor may be the obstacles such communities face to full participation in making policy decisions about environmental health. This study described and analyzed the characteristics that contributed to communities' capacity to participate in making environmental decisions and suggested steps public agencies could take to achieve more meaningful participation. By strengthening community capacity, advancing authentic participation, and building democratic power, it might be possible to alter current patterns of health inequities. Strengthening participation by working with communities to develop the capacities needed to be effective in such processes is a key role for local, state, and national environmental agencies.
|
10.2105/AJPH.2011.300265
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pubmed_122_12104
|
AIMS
To seek new conservative treatments for young women with early-stage endometrial carcinoma (EC) who desire to retain fertility, we investigated the effects and the underlying mechanism of silibinin in EC, which exhibits promising anti-cancer and tumour-suppressing properties in many malignant tumours.
MAIN METHODS
Through relevant experiments such as MTT assay, cell colony formation assay and subcutaneous xenograft experiment, we showed that silibinin inhibited the proliferation of EC cells and tumours. Silibinin significantly induced cell cycle arrest and promoted apoptosis in vitro. In vivo TUNEL assay confirmed the apoptotic effect caused by silibinin. STAT3 is activated in the development of tumours. Silibinin notably inhibited the expression of STAT3 phosphorylation and regulated the expression of downstream genes involved in cell cycle and apoptosis at protein and mRNA levels in EC cells. Furthermore, silibinin decreased the expression of intranuclear SREBP1, which is a key regulator of lipid metabolism in the nucleus, and reduced the lipid accumulation in EC cells. Downregulation of the expression levels of SREBP1 and its downstream genes associated with lipid metabolism was also observed in silibinin-treated EC cells.
KEY FINDINGS
The results revealed that a novel anticancer drug, silibinin, markedly suppressed cell proliferation, cell cycle progression, apoptosis inhibition and lipid accumulation by blocking STAT3 and SERBP1 signalling pathways in EC cells.
SIGNIFICANCE
Silibinin has anti-tumour characteristics and inhibits abnormal lipid metabolism in EC. This compound is expected to contribute to the conservative and adjuvant treatment of EC and should therefore be investigated further.
|
10.1016/j.lfs.2018.11.037
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pubmed_897_11983
|
Extensor tendons in the finger are flat and not amenable to repair by core and epitendinous sutures. Mattress sutures and Kessler repairs without epitendinous stitching are often used for extensor tendon divisions in the fingers. Except when in full extension, the finger presents a series of curved surfaces (at each joint) to the tendon. It was hypothesized that extensor tendons are subject to the 'tension band' principle and that they might be amenable to repair by dorsal-only epitendinous sutures. A Silfverskiöld dorsal-only repair was compared with mattress and Kessler repairs in vitro on a curvilinear testing apparatus. The epitendinous technique was found to be significantly more resistant to gapping and rupture, as well as more resistant to deformation (i.e. stiffer) than the conventional techniques.
|
10.1177/1753193410396637
|
pubmed_340_17462
|
The coordination chemistry of solvated Ag(I) and Au(I) ions has been studied in some of the most strong electron-pair donor solvents, liquid and aqueous ammonia, and the P donor solvents triethyl, tri-n-butyl, and triphenyl phosphite and tri-n-butylphosphine. The solvated Ag(I) ions have been characterized in solution by means of extended X-ray absorption fine structure (EXAFS), Raman, and (107)Ag NMR spectroscopy and the solid solvates by means of thermogravimetry and EXAFS and Raman spectroscopy. The Ag(I) ion is two- and three-coordinated in aqueous and liquid ammonia solutions with mean Ag-N bond distances of 2.15(1) and 2.26(1) A, respectively. The crystal structure of [Ag(NH3)3]ClO4.0.47 NH3 (1) reveals a regular trigonal-coplanar coordination around the Ag(I) ion with Ag-N bond distances of 2.263(6) A and a Ag...Ag distance of 3.278(2) A separating the complexes. The decomposition products of 1 have been analyzed, and one of them, [Ag(NH3)2]ClO4, has been structurally characterized by means of EXAFS, showing [Ag(NH3)2] units connected into chains by double O bridges from perchlorate ions; the Ag...Ag distance is 3.01(1) A. The linear bisamminegold(I) complex, [Au(NH3)2]+, is predominant in both liquid and aqueous ammonia solutions, as well as in solid [Au(NH3)2]BF4, with Au-N bond distances of 2.022(5), 2.025(5), and 2.026(7) A, respectively. The solvated Ag(I) ions are three-coordinated, most probably in triangular fashion, in the P donor solvents with mean Ag-P bond distances of 2.48-2.53 A. The Au(I) ions are three-coordinated in triethyl phosphite and tri-n-butylphosphine solutions with mean Au-P bond distances of 2.37(1) and 2.40(1) A, respectively.
|
10.1021/ic060175v
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pubmed_1111_18772
|
Integrated biomechanical and engineering assessments were used to determine how humans responded to variations in turf during running and turning. Ground reaction force (AMTI, 960 Hz) and kinematic data (Vicon Peak Motus, 120 Hz) were collected from eight participants during running (3.83 m/s) and turning (10 trials per condition) on three natural turf surfaces in the laboratory. Surface hardness (Clegg hammer) and shear strength (cruciform shear vane) were measured before and after participant testing. Peak loading rate during running was significantly higher (p < .05) on the least hard surface (sandy; 101.48 BW/s ± 23.3) compared with clay (84.67 BW/s ± 22.9). There were no significant differences in running kinematics. Compared with the "medium" condition, fifth MTP impact velocities during turning were significantly (RM-ANOVA, p < .05) lower on clay (resultant: 2.30 m/s [± 0.68] compared with 2.64 m/s [± 0.70]), which was significantly (p < .05) harder "after" and had the greatest shear strength both "before" and "after" participant testing. This unique finding suggests that further study of foot impact velocities are important to increase understanding of overuse injury mechanisms.
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10.1123/jab.27.1.54
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pubmed_531_4210
|
Soviet anion-exchangers were comparatively studied to specify an optimal carrier useful for isolation of factor ix of the blood coagulation system from donor's blood cryosupernatant. The main criteria of gel selection were the yield and purification degree of factor IX, as well as its specific activity and concentration in eluates. It has been shown that DEAE-agarose 6B-CL, possessing pronounced activity with respect to specific sorption of factor IX, meets these requirements to the greatest degree.
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pubmed_531_4210
|
pubmed_399_2945
|
This study examined the effects of a smoking prevention program on the acquisition of refusal skills among junior high school students. Two conditions were compared: one in which the subjects participated in a videotaped training program on resisting pressures to smoke, and the other an untreated control group. As predicted, the results showed significant improvement in the skill training group, while the untreated controls showed no change relative to their pretest performance. These findings suggest that smoking prevention programs which focus on resisting social pressures can enhance the young person's ability to say "no" to smoking.
|
10.1016/0306-4603(89)90049-x
|
pubmed_592_19943
|
Attention Deficit Hyperactivity Disorder (ADHD) has, historically, been viewed as a childhood disorder which would be outgrown by adulthood. More recent findings have established that the disorder often persists into adult-hood in a significant number of those diagnosed as children. Due to increased awareness and media attention being focused on ADHD in adults, greater numbers of adults are seeking evaluation and treatment for this disorder. The symptoms of ADHD are common to a variety of other psychiatric disorders including learning disabilities, so clinicians need to update their knowledge of assessment, treatment, and differential diagnosis issues regarding this often misunderstood disorder. This article discusses some current methods used in the assessment and treatment of adults with ADHD.
|
10.1055/s-2008-1064102
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pubmed_36_20750
|
BACKGROUND
Chronic thromboembolic pulmonary hypertension (CTEPH) results from inadequate recanalization of the pulmonary circulation after pulmonary thromboembolism. Its 2-year prevalence is 1-4% . If untreated, patients with CTEPH have a mean life expectancy of less than three years. Fortunately, a number of effective treatments are now available.
METHODS
This review is based on a selective search of PubMed for pertinent articles published from 1980 to 2014.
RESULTS
The gold-standard test for the exclusion of CTEPH is perfusion scintigraphy: the predictive value of a negative test is nearly 100% . On the other hand, confirmation of a positive diagnosis for treatment planning requires right-heart catheterization and pulmonary angiography. The treatment of first choice for CTEPH is surgical pulmonary endarterectomy (PEA), with which about 70% of patients can be cured. The perioperative mortality of this procedure in experienced centers is now 2-4% . Thirty to 50% of all patients with CTEPH are considered inoperable; for these patients, and for patients with persistent pulmonary hypertension after PEA, the drug riociguat was introduced in Germany in 2014 (the first drug specifically introduced for the treatment of CTEPH). There is also a new interventional treatment option for inoperable patients-pulmonary balloon angioplasty, which is currently being performed in a small number of centers.
CONCLUSION
The timely diagnosis of CTEPH, followed by referral to a specialized center, is now more important than ever, because treatment options are now available for nearly all of the forms in which this disease can manifest itself.
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pubmed_36_20750
|
pubmed_223_16221
|
Osmolyte interactions with ligands can affect their affinity for proteins and are dependent upon the cosolute and the functional groups of the ligand. Here, we explored ligand binding to Bacillus anthracis dihydropteroate synthase (BaDHPS) under osmotic stress conditions. Osmolyte effects were specific to the cosolute and ligand, suggesting interaction of the osmolytes with the free ligands in solution. The association rates of pterin pyrophosphate were mostly unaffected by the osmolytes, except for a 2-fold decrease in the presence of 1 M trehalose, while the dissociation rates decreased in most osmolyte solutions. The viscosity and dielectric constant of the solution did not correlate with the effects of the osmolytes. Experimental results were compared with predicted preferential interaction coefficients (Δμ23/RT) between the osmolytes and ligands. The Δμ23/RT were able to predict the experimental data for most of the osmolytes. Trehalose and proline effects did not correlate with the predicted values, indicating that these two osmolytes may affect binding in more complex ways than simple preferential interactions. Additionally, osmolytes weakly interacted with the sulfa drug sulfathiazole, which altered its affinity for BaDHPS, suggesting that these types of weak interactions can also impact drug binding. As osmolytes affect ligands binding to two different folate cycle enzymes (DHFRs and DHPS), we predicted how ligand binding to other folate cycle enzymes will be altered by the presence of osmolytes.
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10.1021/acs.jpcb.0c03311
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pubmed_97_8822
|
Sleep-related breathing disorders can strain the cardiovascular system. Link-ups with arterial hypertension have been confirmed in obstructive or mixed sleep apnoea which is characterised by discontinuous nocturnal snoring. On the other hand, it is known that arterial hypertension is very frequently seen in snorers. The present study deals with short-term, breathing-related blood pressure patterns and blood pressure changes during the snoring phase. 18 obstructive snoring phases were identified in 4 male patients aged 50 years (42-65), Broca index 136 (119-171). Polysomnographic measurements were carried out in the sleep laboratory and the blood pressure was continuously recorded via the a. brachialis. The short-term breathing-dependent blood pressure changes were systolic 10.8 (10-30) mmHg at the beginning and 17.5 (10-30) mmHg at the end of the snoring phase (P less than 0.01). Diastolically there was a difference of 9.4 (5-15) mmHg versus 13.9 (5-25) mmHg (P less than 0.01). During the snoring phases the systolic blood pressure increased from 140.3 (120-190) mmHg to 170.0 (145-235) mmHg and the diastolic pressure from 69.7 (50-110) mmHg to 93.1 (70-120) mmHg. The study proves that blood pressure increases occur not only in apnoeic snoring but also in continuous obstructive snoring. It is suspected that these changes are responsible for the high frequency of arterial hypertension among continuous snorers.
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pubmed_97_8822
|
pubmed_1018_1745
|
The analgesic effect and adverse events of the weak opioid codeine is assumed to be mediated by its metabolite morphine. The cytochrome P-450 enzyme CYP2D6 catalysing the formation of morphine exhibits a genetic polymorphism. Two distinct phenotypes, the extensive (EMs) and poor metabolisers (PMs), are present in the population. The prevalence of PMs in the Caucasian population is 7% to 10%. Since PMs do not express functional CYP2D6, they have a severely impaired capacity to metabolise drugs which are substrates of this enzyme. Provided the analgesic effect and the adverse events of codeine are mediated by its metabolite morphine, large phenotype-related differences are to be expected and PMs, as they form only trace amounts of morphine, can serve as a model to test the hypothesis whether the analgesia and adverse events of codeine are mediated by the parent drug or its metabolite morphine. Therefore we have studied in a randomised placebo-controlled double-blind trial the analgesic effect of 170 mg codeine (p.o.) compared to 20 mg morphine (p.o.) and placebo in 9 EMs and 9 PMs using the cold pressor test. The duration and intensity of the side effects were assessed using visual analogue scales (VAS). Codeine and morphine concentrations were measured in serum and urine. Compared to placebo, 20 mg morphine caused a significant increase in pain tolerance in both phenotypes, EMs and PMs (16.2+/-27.4 vs. -0.66+/-27.4 s x h, n=18). However, following administration of codeine, analgesia was only observed in EMs but not in PMs (EMs: 54.9+/-42.2 vs. 1.7+/-4.2 s x h, P < 0.01; PMs: 9.6+/-10.9 vs. 3.3+/-23.7 s x h, not significant). Adverse events were significantly more pronounced after morphine and codeine compared to placebo in both EMs and PMs. In contrast to the phenotype-related differences in the analgesic effect of codeine, however, no difference in adverse events between the phenotypes could be observed. In the pharmacokinetic studies, significant differences between the two phenotypes in the formation of morphine after codeine administration could be observed. Whereas morphine plasma concentrations were similar in PMs (Cmax: 44+/-13 nmol/l: AUC: 199+/-45 nmol x h/l) and EMs (Cmax: 48+/-17 nmol/l); AUC: 210+/-65 nmol x h/l) after morphine administration, following 170 mg codeine, morphine plasma concentrations comparable to those after morphine application were only observed in EMs (Cmax: 38+/-16 nmol/l; AUC: 173+/-90 nmol x h/l). In PMs only traces of morphine could be detected in plasma (Cmax: 2+/-1 nmol/l; AUC: 10+/-7 nmol x h/l). The percentage of the codeine dose converted to morphine and its metabolites was 3.9% in EMs and 0.17% in PMs. The interindividual variability in analgesia of codeine which is related to genetically determined differences in the formation of morphine clearly indicate that this metabolite is responsible for the analgesic effect of codeine. In contrast to the analgesic effect, frequency and intensity of the adverse events did not present significant differences between the two phenotypes. These findings have implications for the clinical use of codeine. Since side effects occurred in both EM and PM subjects, the use of codeine as an analgesic will expose 7% to 10% of patients who are PMs to the side effects of the drug without providing any beneficial analgesic effects.
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10.1016/s0304-3959(98)00021-9
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pubmed_249_15537
|
Photodynamic therapy (PDT) is a noninvasive modality used topically for several skin cancers. We evaluated the effects of PDT on basal cell carcinoma (BCC) of the nose, using aminolevulinic acid (ALA) as a photosensitizer and a non-laser light source (Versa-Light). The advantages of this light source are synergistic, hyperthermia and fewer side effects. A paste of 20% ALA was applied topically to biopsy-proven BCC of the nose. Lesions were covered with occlusive light-shielding dressing and after 18 hours they were submitted to 10 minutes of exposure to the light. Initial evaluation was made after 21 days and every 3 months thereafter. Patients who did not respond after 2 treatments were referred for surgery. Mean follow-up in 31 patients was 19 months (range 6-36). There were no significant side-effects. There was complete response in 24/27 (88.9%), in whom there was recurrence in 2/27 (7.4%).
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pubmed_249_15537
|
pubmed_928_20536
|
Lyso-GM3 and -GM1 gangliosides were prepared from the corresponding N,N'-dideacylated gangliosides using N-trifluoroacetylation at the sphingosine moiety, followed by N-acetylation and mild saponification. The blocking reaction was performed using a water-ether bilayer system at alkaline medium, in which the N-trifluoroacetylation occurred predominantly at the lipid moiety. Through the procedure, lysoGM3 and lysoGM1 were obtained with higher yields from the corresponding dideacylated gangliosides than through the previous method using 9-fluorenylmethoxycarbonyl chloride as a blocking group or of direct N-acetylation of it on liposomes containing starting ganglioside and other lipid. Chemical structures of the lysogangliosides and the synthetic intermediates were confirmed by the proton nuclear magnetic resonance spectrometry and negative fast atom bombardment-mass spectrometry.
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pubmed_928_20536
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pubmed_1138_21265
|
We investigated the effects of arterial carbon dioxide tension on myocardial blood flow, tissue oxygen tension and metabolism in the anesthetized dogs. Eighteen adult mongrel dogs weighing 13.4 +/- 3.6 kg were anesthetized with 0.5% isoflurane, intubated and ventilated mechanically with 50% oxygen to maintain normocapnia. Endtidal CO2 fraction (FECO2) was monitored continuously by capnograph. Regional myocardial tissue PO2 was measured using a monopolar polarographic needle electrode inserted to the myocardium. Electromagnetic blood flow probes were applied on the left anterior descending artery and circumflex artery. For cardiac venous blood sampling, a 23G intravenous catheter was inserted into the cardiac veins (great coronary veins) carefully. After normocapnic ventilation, hypocapnia was induced by increasing the respiratory rate, and hypercapnia was induced by adding 10% carbon dioxide to the inspired gas. The coronary blood flow and myocardial tissue oxygen tension increased during hypercapnia and the myocardial lactate extraction decreased, while excess lactate and cardiac venous L/P ratio increased during hypercapnia. These results indicate that hypercapnia increase coronary flow and myocardial tissue oxygen tension but myocardial aerobic metabolism is impaired during hypercapnia.
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pubmed_1138_21265
|
pubmed_855_15328
|
Rest and exercise first pass radionuclide ventriculograms were obtained in 62 morbidly obese subjects (56 women, six men, mean age 38 years, mean weight 269.2 +/- 46.0 lb, mean height 65.2 +/- 3.1 in., mean Body Mass Index 44.5 +/- 6.2 kg/m(2), mean excess body weight 134.1 +/- 41.1 lb) scheduled for vertical banded gastroplasty. Fifty-six percent demonstrated exercise-induced wall motion abnormalities mimicking coronary disease, compared to 12% of controls (p = 0.03). No subject with exercise-induced abnormalities had coronary disease at cardiac catheterization although only those with an anginal chest pain history underwent angiography. Twenty-six percent demonstrated resting left ventricular systolic dysfunction as manifested by a reduced resting left ventricular ejection fraction ( <0.50). Thirty-one percent of these patients demonstrated exercise-induced abnormalities, versus 65% of morbidly obese subjects with normal resting ejection fractions (p = 0.04). Obesity-induced left ventricular hypertrophy with associated reduced coronary vasodilator reserve could explain the abnormalities. Six month post-gastroplasty follow-up radionuclide ventriculograms show group normalization of the resting left ventricular ejection fraction in those with preoperative dysfunction, possibly due to left ventricular unloading with some regression of hypertrophy.
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10.1381/096089291765561448
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pubmed_1064_6963
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The SET domain, first identified within and named after proteins encoded by three Drosophila genes [Su(var)3-9, E(z), and Trithorax], is recognized as a signature motif for histone methyltransferases that are involved in epigenetic processes. The SUV39H family of SET domain proteins methylate specifically the residue lysine 9 of histone H3, creating a code for gene silencing. This family of proteins contain at their C termini a unique catalytic domain consisting of pre-SET, SET, and post-SET domains. Sequence homology-based searches identified 15 Arabidopsis, 14 maize, and 12 rice proteins that can be assigned to the SUV39H family. These high numbers in plants are in marked contrast to the situation in animals, in which each species appears to contain only two to three proteins of this family. Our phylogenetic analyses revealed that plant proteins can be classified into seven orthology groups. Representative members of each group can be found in single plant species, suggesting that different group members are evolutionarily conserved to perform specific functions.
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10.1196/annals.1329.077
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pubmed_106_3469
|
AIM
To test the hypothesis that MG-63 osteosarcoma cells and primary osteoblasts react differently to ProRoot trade mark MTA (mineral trioxide aggregate) and White MTA by: (i) investigating the attachment of primary osteoblasts and MG-63 osteosarcoma cells to ProRoot trade mark MTA and White MTA; and (ii) comparing the osteogenic behaviour of both cell lines in contact with these endodontic materials.
METHODOLOGY
Primary osteoblasts were harvested from foetal rat calvaria by sequential digestion and MG-63 osteosarcoma cells were purchased. Cells were exposed to ProRoot trade mark MTA and White MTA prepared according to the manufacturer's instructions. All samples and controls were prepared in quadruplicate. After 6, 9 and 13 days exposure to MTA, the cells were fixed and prepared for SEM examination. In addition, both the cell types were grown to confluence and exposed to beta-glycerophosphate and dexamethasone to assess mineralized nodule formation as a function of osteogenic behaviour.
RESULTS
The number of cells on the surface of the culture dish and on top of the materials increased in all samples throughout the 3 time periods, except for White MTA where no primary osteoblasts were visible on top of the material by the end of 13 days. After exposing cells to differentiation medium nodules were observed in cultures of primary osteoblasts, but not of MG-63 osteosarcoma cells.
CONCLUSIONS
Under the conditions of this study, whilst primary osteoblasts initially bound to White MTA, they did not survive on the surface by the end of 13 days. Primary osteoblasts formed mineralized nodules when exposed to differentiation medium, whilst MG-63 cells did not form nodules. As MG-63 cells do not behave osteogenically by forming mineralized nodules, and primary osteoblasts are more sensitive than MG-63 osteosarcoma cells to White MTA in cell culture, primary osteoblasts are more appropriate than MG-63 cells for testing endodontic materials in cell culture.
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10.1046/j.1365-2591.2003.00691.x
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pubmed_757_16694
|
Background
Nesfatin-1 is an 82-amino acid polypeptide, cleaved from the 396-amino acid precursor protein nucleobindin-2 (NUCB2) and discovered in 2006 in the rat hypothalamus. In contrast to the growing body of evidence for the pleiotropic effects of the peptide, the receptor mediating these effects and the exact signaling cascades remain still unknown.
Methods
This systematic review was conducted using a search in the Embase, PubMed, and Web of Science databases. The keywords "nesfatin-1" combined with "receptor", "signaling", "distribution", "pathway", g- protein coupled receptor", and "binding" were used to identify all relevant articles reporting about potential nesfatin-1 signaling and the assumed mediation via a Gi protein-coupled receptor.
Results
Finally, 1,147 articles were found, of which 1,077 were excluded in several steps of screening, 70 articles were included in this systematic review. Inclusion criteria were studies investigating nesfatin-1's putative receptor or signaling cascade, observational preclinical and clinical studies, experimental studies, registry-based studies, cohort studies, population-based studies, and studies in English language. After screening for eligibility, the studies were assigned to the following subtopics and discussed regarding intracellular signaling of nesfatin-1 including the potential receptor mediating these effects and downstream signaling of the peptide.
Conclusion
The present review sheds light on the various effects of nesfatin-1 by influencing several intracellular signaling pathways and downstream cascades, including the peptide's influence on various hormones and their receptors. These data point towards mediation via a Gi protein-coupled receptor. Nonetheless, the identification of the nesfatin-1 receptor will enable us to better investigate the exact mediating mechanisms underlying the different effects of the peptide along with the development of agonists and antagonists.
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10.3389/fendo.2021.740174
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pubmed_110_13538
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To study the incidence of upper respiratory and digestive tract cancer in Denmark in relation to changes in tobacco and alcohol consumption, the incidence trends are compared to the figures for average annual consumption during the period 1943-1982. The comparison is made using relative risk estimates available from previous investigations. From the available data on alcohol and tobacco consumption, an attempt is also made to predict the future incidence trends of these cancers. Since no data on the distribution of smoking versus drinking by sex and age are available from Denmark over the study period, two hypotheses are used. It is shown that the predicted incidence is strongly dependent on the distribution of smoking and drinking, and that the existence of a group with heavy consumption of tobacco and alcohol could be responsible for very high incidences of these cancers in the near future in Denmark.
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10.1177/140349488801600413
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pubmed_751_3557
|
Lysine is a major constituent of amino acid parenteral nutrition solutions which have recently been shown to increase the severity of various types of acute renal failure in the rat. In previous studies the authors have shown that high-dose lysine alone is capable of causing acute renal failure. However, it has remained unclear what the morphologic expression of this type of acute renal failure is in the maintenance phase of the syndrome, whether other amino acids produce a similar lesion, and whether lysine in lower doses also produces acute renal failure. In the present study the authors show that lysine, when given in a dose of 600 mg/rat over 4 hours, produced persisting acute renal failure which at 48 hours was characterized morphologically by a picture similar to that in human "acute tubular necrosis"--little overt tubular necrosis, but a focal loss of individual tubular cells with regenerative changes and mitotic figures. Extensive hyaline cast formation was seen, particularly in the thin limbs of the loops of Henle, and these thin limb casts were shown to contain Tamm-Horsfall protein. Equivalent doses of glycine, arginine, and glutamic acid and lower doses of lysine produced no significant renal morphologic or functional changes.
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pubmed_751_3557
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pubmed_5_13342
|
RATIONALE
Previous drug discrimination studies with clozapine have not reliably distinguished between atypical and typical antipsychotics.
OBJECTIVES
The present study was conducted to determine whether low-dose clozapine drug discrimination could distinguish atypical from typical antipsychotics.
METHODS
Rats were trained to discriminate 1.25 mg/kg clozapine from vehicle in a two-lever drug discrimination procedure.
RESULTS
Generalization testing revealed full substitution with the atypical antipsychotics olanzapine (90.3% maximum generalization), sertindole (99.8%), and risperidone (87.1%) and partial substitution for quetiapine (seroquel, 66.4%) and the typical antipsychotics haloperidol (56.8%) and thioridazine (74.3%). Remoxipride (23.1%) and the typical antipsychotics chlorpromazine (27.9%) and fluphenazine (29.5%) did not reliably substitute for clozapine.
CONCLUSIONS
In contrast to previous clozapine drug discrimination studies with higher training doses, the atypical antipsychotics olanzapine, sertindole, and risperidone reliably substituted for clozapine while typical antipsychotics did not. These results suggest that low-dose clozapine drug discrimination may be a more sensitive assay for distinguishing atypical from typical antipsychotic drugs.
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10.1007/s002139900366
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pubmed_391_12737
|
The poliovirus capsid (160S) is modified during eclipse in HeLa cells, which results in at least three types of particles having sedimentation coefficients of 135, 110, and 80S. The lysosomotropic agent chloroquine redirected the production of eclipse products from 135 and 110S particles (containing RNA) to 80S particles (without RNA). The effect started at 5 microM and was fully developed with 20 microM chloroquine. Viral protein synthesis and virion production remained unaffected. The results show that chloroquine can redirect the processing of input virions without interfering with productive uncoating.
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10.1128/JVI.65.12.7008-7011.1991
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pubmed_469_12048
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AIMS
Naringin is a flavonoid with a polyphenolic structure which induces formation of reactive oxygen species (ROS). Although the antibacterial effect of naringin has been demonstrated, the mechanism underlying this effect has not yet been elucidated. We focused on investigating the antibacterial mode of action of naringin in Escherichia coli following ROS generation. The contributions of ROS, hydroxy radicals (OH-), super oxide (O2-), and hydrogen peroxide (H2O2) were investigated.
MAIN METHODS
ROS accumulation was detected using fluorescence dyes, and all experiments were conducted using the scavenger including tiron, sodium pyruvate, and thiourea to assess the contribution of each ROS. Western blotting assays were used to observe the activation of the SOS response for DNA repair. DNA fragmentation, membrane depolarization, and phosphatidylserine exposure were estimated using TUNEL, DiBAC4(3), and Annexin V/PI.
KEY FINDINGS
Accumulation of ROS was observed in Escherichia coli after treatment with naringin. Oxidative stress induced cellular dysfunction including DNA damage, which results in SOS response activation. Eventually, apoptosis-like death occurred in cells treated with naringin. The cells had different contributions of each ROS and accompanying apoptotic factors. The ROS most destructive to E. coli was OH-, followed by H2O2 and O2-.
SIGNIFICANCE
Due to its efficacy, naringin is a useful antimicrobial agent. An initial investigation into the antibacterial mode of action of naringin is presented in this paper. The contribution of each ROS to apoptosis-like cell death (ALD) was investigated, and the results enhanced our understanding of the correlation between the SOS response and oxidative stress in bacteria.
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10.1016/j.lfs.2022.120700
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pubmed_1095_15596
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Low dose of D-cycloserine (DCS), a partial agonist of glycine binding site on N-methyl-D-aspartate (NMDA) receptors, can facilitate extracellular signal-regulated kinase1/2 (ERK1/2) activity in the amygdala and modulate emotional behavior. However, the relationship between ERK1/2 activation, individual anxiety levels, and DCS is unknown. Therefore, based on open arm time in the elevated plus-maze, male Wistar rats were divided into subgroups with either low (LOA) or high open arm (HOA) time. Open arm time is usually accepted as a critical index of unconditioned anxiety-like/avoidance behavior. On the following day, DCS (30 mg/kg, i.p.) was administered 30 min before the second elevated plus-maze test. On day 8 and 9, the rats were subjected to a 2-day session of the forced swim test, receiving the DCS treatment again 30 min before the 2nd day. On the 16th day, 30 min after the administration of DCS, the rats were sacrificed in order to detect the phosphorylation of ERK1/2 (p-ERK1/2) in the amygdala by Western blots. The results showed that: (1) DCS decreased the open arm time in HOA but not LOA rats. (2) DCS suppressed the immobility in the day-2 trial of the forced swim test and increased the p-ERK1/2 level in the amygdala in LOA but not HOA rats. This is the first instance data has been found indicating different sensitivities of p-ERK1/2 and behavioral responses to the treatment of DCS between HOA and LOA rats. The results suggest that the activity of NMDA receptor-mediated ERK1/2 signaling is mediated by individual behavioral differences which are related to the antidepressant-like activity of DCS. This study provides first insight into the pathophysiological role of ERK signaling with regard to individual differences in emotional behavior.
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10.1016/j.bbr.2007.09.013
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pubmed_241_12533
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Accumulating evidence suggests that antipsychotics affect dopamine release from dopaminergic neurons, but the precise mechanisms are not fully understood. Besides, there are few studies on the effects of antipsychotics on intracellular dopamine content. In this study, the effects of 8 antipsychotics on dopamine release and intracellular dopamine content in PC12 cells were investigated. Pretreatment with haloperidol, spiperone, pimozide, aripiprazole and risperidone markedly inhibited high potassium-evoked dopamine release. By contrast, pretreatment with chlorpromazine slightly increased high potassium-evoked dopamine release, while pretreatment with sulpiride and olanzapine had no effect. Haloperidol, spiperone, pimozide, chlorpromazine, aripiprazole and olanzapine evoked dopamine release, while sulpiride and risperidone had no effect. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced intracellular dopamine content in a concentration-dependent manner. These results suggest that the reduction in high potassium-evoked dopamine release by pretreatment with antipsychotics results from the reduction in vesicular dopamine content. Treatment with the 8 antipsychotics did not affect the expression of total or phosphorylated tyrosine hydroxylase. Instead, haloperidol, spiperone, pimozide and aripiprazole as well as reserpine transiently increased extracellular levels of dopamine metabolites. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced vesicular [3H]dopamine transport. These results suggest that the inhibition of vesicular dopamine transport by haloperidol, spiperone, pimozide and aripiprazole results in a reduction in vesicular dopamine content.
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10.1016/j.ejphar.2010.04.043
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pubmed_100_9383
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While the distribution of RNA polymerase II (PolII) in a variety of complex genomes is correlated with gene expression, the presence of PolII at a gene does not necessarily indicate active expression. Various patterns of PolII binding have been described genome wide; however, whether or not PolII binds at transcriptionally inactive sites remains uncertain. The two X chromosomes in female cells in mammals present an opportunity to examine each of the two alleles of a given locus in both active and inactive states, depending on which X chromosome is silenced by X chromosome inactivation. Here, we investigated PolII occupancy and expression of the associated genes across the active (Xa) and inactive (Xi) X chromosomes in human female cells to elucidate the relationship of gene expression and PolII binding. We find that, while PolII in the pseudoautosomal region occupies both chromosomes at similar levels, it is significantly biased toward the Xa throughout the rest of the chromosome. The general paucity of PolII on the Xi notwithstanding, detectable (albeit significantly reduced) binding can be observed, especially on the evolutionarily younger short arm of the X. PolII levels at genes that escape inactivation correlate with the levels of their expression; however, additional PolII sites can be found at apparently silenced regions, suggesting the possibility of a subset of genes on the Xi that are poised for expression. Consistent with this hypothesis, we show that a high proportion of genes associated with PolII-accessible sites, while silenced in GM12878, are expressed in other female cell lines.
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10.1093/hmg/ddr315
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pubmed_644_1830
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The experience of developing, preclinical examinations and results of introduction to clinical practice of a new fixating device, owing original construction, of the "METOST" system was summarized.
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pubmed_644_1830
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pubmed_26_13130
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Manganese (Mn) and iron (Fe) are both paramagnetic species that can affect magnetic resonance relaxation rates. They also share common transport systems in vivo and thus in experimental models of metal exposure their effects on relaxation rates may interact in a complex fashion. Here we present a novel model to interpret the combined effects of Mn and Fe on MRI relaxation rates. To achieve varying levels of both metals, adult rats were separated into four groups; a control group and three groups treated with weekly intravenous injections of 3 mg Mn/kg body for 14 weeks. The three treated groups were fed either a normal diet, Fe deficient or Fe enriched diet. All rats were scanned using MRI at the 14th week to measure regional water relaxation rates. Rat brains were removed at the end of the study (14th week) and dissected into regions for measurement of Mn and Fe by atomic absorption spectroscopy. For the normal diet groups, R(1) was strongly correlated with tissue Mn concentrations. However, the slopes of the linear regression fits varied significantly among different brain regions, and a simple linear model failed to explain the changes in relaxation rate when both Mn and Fe contents changed. We propose a competition model, which is based on the ability of Mn and Fe to compete in vivo for common binding sites. The combined effect of Mn and Fe on the relaxation rates is complicated and additional studies will be necessary to explain how MRI signals are affected when the levels of both metals are varied.
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10.1002/nbm.1348
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pubmed_661_3583
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We addressed questions pertaining to the immunogenetics of an in vitro alloinduced suppressor T cell (Ts) previously shown to inhibit cytotoxic T-lymphocyte (CTL) development by suppressing CTL precursor proliferation. Using intra-MHC recombinant strains of B10 congenic mice, the requirements for H-2 differences to induce Ts activity, the antigen specificity of the Ts, and the genetic restriction of Ts function were studied. It was found that differences at the K, D, or I regions alone can induce strong suppressor activity. Suppression of CTL development does not appear to be genetically restricted since the Ts inhibit CTL from responder cells disparate at K, K and D, I, or K and I. The alloinduced Ts is specific for the antigen stimulating its induction, but also inhibits CTL responses against immunologically unrelated determinants, even between class I and class II antigens, provided those determinants are carried on cells expressing the original inducing antigen. Ts can be triggered by antigens present on the responder cells but absent on the stimulator cells, indicating that the suppressive signal may be exerted directly on the responder population without specific interaction with stimulator cells.
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10.1016/0008-8749(86)90163-2
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pubmed_362_5757
|
Petroleum refinery wastewater (PRW) is a complex mixture of hydrocarbons, sulphides, ammonia, oils, suspended and dissolved solids, and heavy metals. As these pollutants are toxic and recalcitrant, it is essential to address the above issue with efficient, economical, and eco-friendly technologies. In this review, initially, an overview of the characteristics of wastewater discharged from different petroleum refinery units is discussed. Further, various pre-treatment and post-treatment strategies for complex PRW are introduced. A segregated approach has been proposed to treat the crude desalting, sour, spent caustic, and oily wastewater of petroleum refineries. The combined systems (e.g., ozonation + moving bed biofilm reactor and photocatalysis + packed bed biofilm reactor) for the treatment of low biodegradability index wastewater (BOD5/COD < 0.2) were discussed to construct a perspective map and implement the proposed system efficiently. The economic, toxicity, and biodegradability aspects are also introduced, along with research gaps and future scope.
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10.1016/j.biortech.2022.127263
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pubmed_313_11576
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The use of in vitro assays is important for the biodetection of endocrine active substances (EAS), reducing and replacing the in vivo studies required for regulatory assessment. However, this approach often fails to take into account the role of biotransformation on the activity of the test substances. A method incorporating an S9 metabolic system into the CALUX-reporter gene assays for estrogen receptor α- and anti-androgen receptor -mediated activities has been developed. Methoxychlor, which is known to exhibit increased estrogenic and anti-androgenic activities after biotransformation, was used to set up the method in ERa and anti-AR CALUX. For the anti-androgenic assay, stanozolol was used as a competing agonist not metabolized by S9. The method was first applied in both agonist and antagonist modes to methoxychlor and bisphenol A, as positive and negative controls, respectively. Then, benzo(a)pyrene and flutamide were also tested for their potential of bioactivation. Co-treatment with S9 successfully increased the ERα agonist and AR antagonist potency of methoxychlor; no change was observed for bisphenol A. Incubation with S9 also enhanced the anti-androgenic activity of flutamide. Interestingly, the metabolism of benzo(a)pyrene by the S9 resulted in an increased estrogen receptor-mediated transcriptional activation; any increase in the potency was only minor. It is likely that both enzyme kinetics and metabolite stability have influenced these effects, which would affect the composition of the final metabolite mixture. Together these results demonstrate the relevance of including biotransformation in in vitro bioassays for the detection of EAS.
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10.14573/altex.1611021
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pubmed_1033_8658
|
BACKGROUND AND OBJECTIVES
Cytotoxic T-lymphocytes (CTL) have been generated in vitro against chronic myeloid leukemia (CML)-associated BCR/ABL-specific peptides. We analyzed the existence of high-avidity T cells recognizing endogenously processed BCR/ABL-specific proteins.
DESIGN AND METHODS
We performed binding studies of BCR/ABL-specific peptides, proteosomal digestion of BCR/ABL breakpoint overlapping protein, mass spectrometry of eluates from HLA-*0301-transduced K562 cells, and tried to isolate peptide-specific T-cells using tetramers.
RESULTS
We confirmed the binding of the BCR/ABL-specific peptides KQSSKALQR to HLA-A*0301 and GFKQSSKAL to HLA-B*0801. Proteasomal digestion showed cleavage sites leading to KQSSKALQR but not to GFKQSSKAL. Using mass spectrometry KQSSKALQR could not be detected in the eluates from HLA-A*0301-transduced K562 cells. We attempted to induce BCR/ABL-specific CTL lines from 4 healthy donors using dendritic cells pulsed with KQSSKALQR and performed single cell sorting to isolate tetramer-positive T cells. None of 31 generated clones showed BCR/ABL-specific cytotoxicity. Isolation of tetramer-positive cells from peripheral blood of relapsed CML patients after allogeneic transplantation treated with donor lymphocyte infusion resulted in 38 T-cell clones which did not show peptide-specific cytotoxicity.
INTERPRETATION AND CONCLUSIONS
We provide evidence that BCR/ABL protein processing can lead to KQSSKALQR peptide binding to HLA-A*0301. However, KQSSKALQR could not be detected in HLA-A*0301-transduced K562 cells, and KQSSKALQR could not be demonstrated to induce high-avidity BCR/ABL-specific CTL.
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pubmed_1033_8658
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pubmed_351_4184
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Antibody microprobes bearing antibodies to the C-terminus of substance P (SP) were used to measure release of immunoreactive (ir) SP in the dorsal horn of barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated primary afferents of the ipsilateral tibial nerve produced a relatively localised release of ir SP in the superficial dorsal horn. Prior microinjection of the peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in ir SP being detected over the whole of the dorsal horn and the overlying dorsal column. This pattern had previously been observed with evoked release of ir neurokinin A and supports the proposal that a slow degradation results in a neuropeptide accessing many sites remote from sites of release.
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10.1016/0006-8993(92)90059-i
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pubmed_454_18209
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An important iatrogenic cause of anaemia in the intensive care unit is loss of the discarded blood during phlebotomy via indwelling vascular catheters. A closed system blood conservation device has previously been shown to reduce the need for blood transfusion and to blunt the decrease of haemoglobin in intensive care unit patients. However such a device may not benefit patients who are admitted with a relatively preserved haemoglobin. In this sub-group analysis of a before-and-after study, 128 patients had admission haemoglobin > or =115 g/l and did not receive any blood transfusions while in the intensive care unit. In the control group of 50 patients a blood conservation device was not used, while in the active group of 78 patients the device was used. Use of the blood conservation device did not affect the haemoglobin trends when both groups were compared using the general linear model. For patients with admission haemoglobin > or = 115 g/l, use of a blood conservation device does not affect the subsequent rate of haemoglobin decline in the intensive care unit. These patients are unlikely to benefit from the use of such devices.
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10.1177/0310057X1103900313
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pubmed_359_14118
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When chronically elevated, insulin increases hepatic lipogenesis and VLDL synthesis. However, the hormone reduces liver lipids when acutely elevated. Work in this issue of Cell Metabolism (Najjar at al., 2005) suggests a new mechanism for the inhibition of the rate-limiting enzyme in liver, fatty acid synthase.
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10.1016/j.cmet.2005.06.010
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pubmed_605_4977
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Endometriosis has clearly three distinct clinical presentations and deep endometriosis, especially compromising the rectosigmoid is probably the most concerning one for both patients and surgeons. Currently, with the available tools, it is mandatory to have a precise diagnostic of this type of disease prior to indication of treatment. Strategies to manage this form of endometriosis will take into account several involved aspects, such as age of the patient, reproductive desire or infertility, clinical symptoms, as well as the extension and localization of the disease. Treatment could vary from more conservative to more radical depending on those aspects. As we pointed out in this article, the key to manage colorectal endometriosis is to start with a good diagnosis. Knowing exactly what is the extension and localization of the disease and knowing the patient's wishes as well as the clinical complaints, surgeons are able to define the best option for each patient. Critical points should always be discussed; for example, patients chosen to have clinical treatment should be aware of important issues regarding the follow-up, while patients undergoing surgery must be advised about all surgical possibilities and related complications.
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10.1055/s-0036-1597307
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pubmed_834_17732
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We have examined the expression of SRY mRNA in individual in vitro fertilized preimplantation human embryos; because of ethical constraints, these studies were confined to embryos with one and three pronuclei. Using a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we observed SRY mRNA at the one-cell through the blastula stages but not in spermatozoa. These results indicate that the de novo transcription of this sex-specific gene occurs at a developmental time considerably earlier than that of gonadal differentiation. Our results also indicate that in vitro fertilized embryos with one pronucleus are likely to be diploid.
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10.1002/ajmg.1320550121
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pubmed_1066_7860
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We aimed to evaluate the efficacy and safety of endoanal ultrasound (EAUS)-guided botulinum toxin (BT) in the treatment of chronic anal fissure (CAF). All patients were classified into 2 groups: conventional and EAUS groups. In total, 90 units of BT were injected into the internal anal sphincter at the 3, 6, and 9 o'clock positions in the EAUS group. An injection was performed into the intersphincteric space at the 3, 6, and 9 o'clock positions in the conventional group. Adverse effects and efficacy were analyzed. There were 44 patients: 26 in the conventional group and 18 in the EAUS group. Pain and incontinence rates were similar between groups (P > .05). The efficacy rate was higher in the EAUS group (69.23%) than in the conventional group (81.82%), but this difference was not significant (P = .466). EAUS-guided BT injection is safe and effective in patients with CAFs.
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10.1177/00031348211034750
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pubmed_215_15890
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The Rho GTPase-activating proteins (RhoGAPs) are a family of multifunctional molecules that transduce diverse intracellular signals by regulating Rho GTPase activities. A novel RhoGAP family member, p200RhoGAP, is cloned in human and mouse. The murine p200RhoGAP shares 86% sequence identity with the human homolog. In addition to a conserved RhoGAP domain at the N terminus, multiple proline-rich motifs are found in the C-terminal region of the molecules. Northern blot analysis revealed a brain-specific expression pattern of p200RhoGAP. The RhoGAP domain of p200RhoGAP stimulated the GTPase activities of Rac1 and RhoA in vitro and in vivo, and the conserved catalytic arginine residue (Arg-58) contributed to the GAP activity. Expression of the RhoGAP domain of p200RhoGAP in Swiss 3T3 fibroblasts inhibited actin stress fiber formation stimulated by lysophosphatidic acid and platelet-derived growth factor-induced membrane ruffling but not Bradykinin-induced filopodia formation. Endogenous p200RhoGAP was localized to cortical actin in naive N1E-115 neuroblastoma cells and to the edges of extended neurites of differentiated N1E-115 cells. Transient expression of the RhoGAP domain and the full-length molecule, but not the catalytic arginine mutants, readily induced a differentiation phenotype in N1E-115 cells. Finally, p200RhoGAP was capable of binding to the Src homology 3 domains of Src, Crk, and phospholipase Cgamma in vitro and became tyrosine-phosphorylated upon association with activated Src in cells. These results suggest that p200RhoGAP is involved in the regulation of neurite outgrowth by exerting its RhoGAP activity and that its cellular activity may be regulated through interaction with Src-like tyrosine kinases.
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10.1074/jbc.M207789200
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pubmed_374_21068
|
In their article "Integrated Care Improves Mental Health in a Medically Underserved U.S. Mexico Border Population," Flynn, Gonzalez, Mata, Salinas, and Atkins (see record 2020-40858-002) report on an integrated care model using promotoras to address diabetes in a Latino population. Overall, they found that participants had improved quality of life (QoL) and depression measures; however, physical health outcomes did not improve significantly compared to the comparison group. In this commentary, we draw on our expertise working with the Latino population in mental health settings, most recently with refugees at the U.S.-Mexico border, as well as our experience working on integrated care teams and our deep understanding of the impact of trauma on health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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10.1037/fsh0000487
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pubmed_345_25162
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The human vitamin D receptor mRNA expression in preconfluent human cultured keratinocytes was upregulated by treatment of these cells with 10(-8) M 1,25(OH)2D3 for 24 hours. Additionally, human c-myc mRNA expression was decreased in a dose dependent manner by 1,25(OH)2D3 in both preconfluent and confluent cultured human keratinocytes.
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10.1007/BF02631442
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pubmed_437_10842
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A 24-year-old man presented to the emergency department with fever, maculopapular rash, myalgia and polyarthralgia, thoracic pain and dry cough, which had been present for 24 h. At the time of observation he had high fever (39°C), maculopapular rash on the torso, arms and legs proximally, axillary adenopathies and pharyngitis. Laboratorial data showed elevated inflammation markers (leukocytosis, C reactive protein of 44 mg/dL, erythrocyte sedimentation rate of 120 mm), elevated transaminases, lactate dehydrogenase, ferritin levels (>2000 ng/mL) and rising troponin. ECG had sinus rhythm and ST elevation in leads V1-V5. Thoracic radiography revealed bilateral interstitial infiltrate confirmed by CT scan. Echocardiographic findings included diffuse hypokinesia of the left ventricle and impaired systolic function. After the investigation of an infectious or autoimmune aetiology was negative, the diagnosis of adult-onset Still's disease was considered. The patient was put on a 60 mg/day prednisolone regimen with remission of symptoms and normalisation of systolic function and ECG.
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pubmed_437_10842
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pubmed_674_22522
|
Neurogenic tumours of the paraspinal space can occur in all age groups. It is common in adult population and relatively rare in elderly group. Usually they are benign, but in children, arising from the autonomic system, tends to be malignant in nature. Usually in adults, they arise from peripheral nerve sheath and are labelled as schwannomas. For a given tumour, determination of a correct surgical approach is mandatory to achieve a successful surgical outcome. Several factors like tumour size, histology, involvement of the bony spinal canal, etc. are some of the deciding factors for a correct surgical approach. Since many such tumours are benign, total excision is possible with a correct surgical approach. If the tumour involves the integrity of the spine then additionally a stabilization procedure may have to be carried out. Unfortunately, there are still no guidelines regarding the choice of surgical approach for the excision of such tumors. Presented here is a series of five patients managed by us over a period of 10 years. Four patients were adults and one female child was three years old. Four patients were operated upon successfully and the fifth one is waiting for surgery.
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10.1080/01616412.2017.1297556
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pubmed_624_15452
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Respiratory viral infections which occur in patients with spontaneous or therapeutic immunodepression are frequent and serious. Apart from these acute situations, viruses are responsible for some chronic respiratory pathologies which affect the functional prognosis, as illustrated by the relationship between the respiratory pathologies demands an accurate diagnosis. Two methods can be used routinely to demonstrate the presence of a virus in bronchoalveolar lavage fluid or in transbronchial biopsy: (1) direct immunofluorescence or immunoenzymatic technique; the concomitant finding of a cytopathogenic effect on the cells that constitute the sample makes this method more sensitive and confirms the pathogenic character of viruses demonstrated by immunological techniques; (2) isolation of the virus from cell cultures; the sensitivity of this method can be increased by an immunological search for the virus (fast culture). Hybridization in situ is a new and promising method where a DNA probe complementary to viral nucleic acids is used to evidence the viral genome in the infected cells. Serum IgM assays, which provide proof of an active infection, should be preferred to conventional serology, although seroconversion is inconstant in immunodepressed patients. Improvements in virological diagnostic methods should result in the future use of new antiviral treatments.
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pubmed_624_15452
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pubmed_1015_8174
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Two cases with expressive speech disorders were studied neuropsychologically and neurologically; anatomical and histopathological examinations were performed in both cases. In case 1, a small infarction in the foot of the left third frontal gyrus (F3) produced only transient word-finding difficulties that did not recur after a second stroke with lesion of the symmetrical zone in the right hemisphere. A transient, predominantly articulatory difficulty was observed in case 2; this was thought to be associated with a small infarction in the lower motor strip, including the Rolandic operculum. On the basis of the literature and our two cases, it may be concluded that overlapping lesions of these two areas play an important role in the development of persistent Broca's aphasia and that each of these two areas may be responsible for different components of the speech production: work-finding difficulties being associated with lesions of posterior F3 and articulatory disorders with lesions of the Rolandic operculum.
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10.1001/archneur.1981.00510080048005
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pubmed_914_24522
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The aim of this study was to investigate how the different excipients influenced the chemical stability of betamethasone dipropionate in creams. The chemical stability was evaluated by analyzing betamethasone related substance content. Transcutol is the excipient ensuring maximum stability to betamethasone. Incompatibilities between betamethasone dipropionate and hexylene glycol were observed. The pH values in the weak acid range confer chemical stability to betamethasone.
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pubmed_914_24522
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pubmed_412_17242
|
The delineation of the molecular basis of cancer in general, and of ovarian carcinoma in particular, allows for the possibility of specific intervention at the molecular level for therapeutic purposes. To this end, three main approaches have been developed: mutation compensation, molecular chemotherapy, and genetic immunopotentiation. For each of these conceptual approaches, human clinical protocols, including those specific for ovarian carcinoma, have entered phase I clinical trials to assess dose escalation, safety, and toxicity issues. However, major problems remain to be solved before these approaches can become effective and commonplace strategies for the treatment of cancer. In this regard, an examination of the applications of gene therapy for ovarian carcinoma can exemplify the rationality and the problems observed in the development of gene therapy, and may illustrate prospects for their solution that are being refined, including current efforts in our laboratory. An overriding obstacle is the basic ability to deliver therapeutic genes quantitatively, and specifically, into tumor cells. As vector technology fulfills these requirements, it is anticipated that promising results already observed in preclinical studies will translate quickly into the clinical setting for amelioration of this life-threatening disease in women.
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10.1093/ajcp/109.4.444
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pubmed_891_1066
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In vitro determination of the hemoglobin oxygen dissociation curve (ODC) requires highly elaborate, specialized, and costly technical equipment. In addition, there is a lack of methods that combine reliable ODC recordings with high throughput in small blood samples for routine analysis. We here introduce a modified, commercial 96-well plate with an integrated unidirectional gas flow system specifically adapted for use in fluorescence microplate readers. Up to 92 samples of whole or hemolyzed, buffered or unbuffered blood, including appropriate controls or internal standard hemoglobin solutions, can be analyzed within ~25 min. Oxygen saturation is measured in each well with dual wavelength spectroscopy, and oxygen partial pressure using fluorescence lifetime of commercial oxygen sensors at the in- and outlet ports of the gas-flow system. Precision and accuracy of this method have been determined and were compared with those of a standard method. We further present two applications that exemplarily highlight the usefulness and impact of this novel approach for clinical diagnostics or basic research.
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10.14814/phy2.14995
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pubmed_742_7947
|
West Nile virus (WNV) is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%-40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002) found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS), and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis.
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10.3390/v5112856
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pubmed_122_1660
|
During locomotion, energy flow through the legs is governed by the mechanical impedance of each joint. These mechanical properties, including stiffness and damping, have recently been quantified at the ankle joint. However, the relevance of these properties in human sensorimotor control is unclear. An important aspect of sensorimotor control is the ability to sense small changes in stimuli. Thus, we investigated the human ability to detect small changes in the stiffness and damping components of leg joint impedance when interacting with a mechanical system coupled to the ankle or knee. The perception threshold was determined via a psychophysical paradigm that required subjects to compare the mechanical impedance of virtual spring-mass-damper systems. Subjects reliably detected impedance changes of 11% and 12% at the ankle and knee, respectively. Additionally, the perception of stiffness and damping were comparable, indicating that the biomechanical relevance of the stiffness and damping components of impedance may be similar. Finally, these results offer novel insight into the design and control of impedance-based technologies, such as prostheses and exoskeletons.
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10.1109/EMBC.2018.8513022
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pubmed_17_12380
|
Asymmetric mRNA expression was found in preoptic anterior and hypothalamic anterior areas of the two estrogen receptor isoforms and the gonadotropin-releasing hormone. On the right side of these areas, estrogen receptor alpha mRNA expression reached its peak on estrus day, while on the left side the peak was reached on proestrus day. Estrogen receptor beta mRNA expression peaked on both sides on the same day, diestrous-2 day, but at different hours, showing a sustained expression for the next measured hour on the left side, while peaking and dropping abruptly on the right side. Gonadotropin-releasing hormone also peaked on both sides on diestrous-2 day, being the left side peak expression significantly lower than the peak expression at the right side. The side expression differences suggest that different sides of the before mentioned areas may play different roles of endocrine reproductive functions, while differences of expression at different times may suggest interaction between sides for the same functions.
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10.1385/ENDO:21:3:251
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pubmed_528_15367
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Recurrent major depressive disorder with regular seasonal patterns, commonly known as seasonal affective disorder (SAD), has evoked substantial research in the last two decades. It is now recognised that SAD is a common condition with prevalence rates between 0.4% and 2.9% of the general population, and that patients with SAD experience significant morbidity and impairment in psychosocial function. There is good evidence that bright light therapy and antidepressant medications are effective for the short-term treatment of SAD; however, given that SAD is characterised by recurrent major depressive episodes, long-term and maintenance treatment must be considered. Unfortunately, there are few studies of longer term (>8 weeks) and maintenance (preventative) treatments for SAD. The weight of evidence suggests that light therapy usually needs to be continued daily throughout the winter season because of rapid relapse when light is stopped too early in the treatment period. However, some studies support the use of antidepressants to continue the response from a brief (1-2 weeks) course of light therapy early in the depressive episode, as soon as the first symptoms emerge in autumn. Only small studies have examined preventative treatment (before onset of symptoms) with light therapy, all of which have methodological limitations. The best evidence for preventative treatment in SAD comes from antidepressant studies. Three large, randomised, placebo-controlled studies have shown that preventative treatment with bupropion XL reduces the recurrence rate of depressive episodes in patients with SAD. Given the limitations in the evidence base and the inconsistent recurrence rate of winter depressive episodes, clinical recommendations for long-term and preventative treatment must individualise treatment choices and weigh potential benefits against possible adverse effects.
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10.2165/00023210-200721110-00003
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pubmed_68_10597
|
PURPOSE
The authors describe the properties of a new retrievable nitinol vena cava filter and report experimental and initial clinical results.
MATERIALS AND METHODS
The filters, made of nitinol monofilament wire that forms a spiral cone and retrieval wire, were introduced through an indwelling 5.5-F transfemoral sheath into the infrarenal portion of the inferior vena cava in 10 sheep. In seven animals, four 4 x 30-mm radiopaque clots were injected below the filter to test its thrombus-trapping efficacy. Aspiration thrombectomy was then attempted, and the filter was removed. Follow-up venography was performed 1 week after placement in three other animals. After successful preclinical testing, the filter was implanted and retrieved in two patients.
RESULTS
All 10 filters were successfully and easily placed in sheep. All filters were thrombus-free at follow-up venography. All clots injected in the iliac veins were trapped by the filter and successfully removed by means of aspiration thrombectomy. All 10 filters were retrieved without difficulty. Temporary filter implantation and retrieval were accomplished in two patients for 5 and 7 days. In one patient, infrafilter thrombus was aspirated. Perisheath thrombosis occurred in both patients. One patient subsequently underwent permanent filter placement.
CONCLUSION
Temporary vena cava filtration is feasible. Potential advantages include easy placement, surveillance, and retrieval. One current limitation is pericatheter thrombosis, which may be eliminated by a less thrombogenic sheath.
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10.1016/s1051-0443(94)71539-6
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pubmed_996_17788
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Integration of retroviral genomes is a site-specific process with respect to the virus but not the host genome. Numerous chromosomal sites and various sequences can be used as targets. Nevertheless, preferential regions and integration patterns have been observed. Using a functional assay, we investigated if host structural DNA elements could be associated with retroviral integration sites. The results were that 9 of 10 distinct retroviral integration events occurred in close proximity of structural elements behaving like intrinsically bent DNA.
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10.1006/viro.1994.1310
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pubmed_126_10067
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Unique protein domains, concentration gradients, and asymmetric protein distributions or polarities are principle forces establishing the identity and fate of individual cells during early development in lower vertebrates and invertebrates. Here, we present evidence that these same forces exist during mammalian development in the form of two representative regulatory proteins, leptin and STAT3. Leptin, the 16 kDa cytokine product of the obese gene (ob) is involved in the activation of STAT3, a member of the signal transducer and activation of transcription family of proteins. We examined the temporal and spatial aspects of leptin and STAT3 immunofluorescence in mouse and human oocytes and preimplantation stage embryos. The findings demonstrate that both leptin and STAT3 are polarized in the oocyte and, as a consequence of their location and the position of the cleavage planes with respect to these protein domains: (i) differences in allocation of these proteins between blastomeres occur at the first cell division such that by the 8-cell stage; (ii) unique cellular domains consisting of leptin/STAT3 rich and leptin/STAT3 poor populations of cells are generated. By the morula stage, a cell-borne concentration gradient of these proteins extending along the surface of the embryo is observed. A potential role of these proteins in early development is indicated at the morula stage where the 'inner' cells consist of blastomeres that contain little, if any, leptin/STAT3 while 'outer' cells contain both leptin/STAT3 rich and poor cells. This pattern persists through the hatched blastocyst stage with little, if any, leptin/STAT3 detected in the inner cell mass and populations of leptin/STAT3 rich and poor cells forming the trophoblast. We have examined oocytes from mutant C57BL/6J ob/ob mice which are both obese and infertile (although fertility can be restored by the exogenous provision of leptin) and have found STAT3 and the mutant (truncated) leptin protein to be present and polarized, suggesting the possibility that the truncated leptin protein may still contain operational domains which are functional during oocyte development and early embryogenesis. Furthermore, analysis of leptin and STAT3 in intact ovarian follicles suggests that these proteins may be maternally derived and in particular, that a subpopulation of follicle cells may be partly responsible for the establishment of their polarized distribution in the oocyte. The results are discussed with respect to the proposition that leptin and STAT3 have critical roles in early mammalian development, and may be involved in the determination of the animal pole of the oocyte and in the establishment of the inner cell mass and trophoblast in the preimplantation stage embryo.
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10.1093/molehr/3.12.1067
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pubmed_653_18451
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Because the aging process varies among individuals, elderly people of the same age, especially those over 80 years, do not necessarily have similar organ function. After consideration of lower organ function and concomitant disease, less invasive treatment should be selected for elderly patients. Therefore, it is important to limit preventive lymph node dissection, and when determining the dose of anticancer drugs, major organ function should be taken into consideration.
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pubmed_653_18451
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pubmed_954_17136
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This work analyses the distribution of living benthic foraminiferal assemblages of surface sediments in different intertidal areas of Ria de Aveiro (Portugal), a polihaline and anthropized coastal lagoon. The relationships among foraminiferal assemblages in association with environmental parameters (temperature, salinity, Eh and pH), grain size, the quantity and quality of organic matter (enrichment in carbohydrates, proteins and lipids), pollution caused by metals, and mineralogical data are studied in an attempt to identify indicators of adaptability to environmental stress. In particular, concentrations of selected metals in the surficial sediment are investigated to assess environmental pollution levels that are further synthetically parameterised by the Pollution Load Index (PLI). The PLI variations allowed the identification of five main polluted areas. Concentrations of metals were also analysed in three extracted phases to evaluate their possible mobility, bioavailability and toxicity in the surficial sediment. Polluted sediment in the form of both organic matter and metals can be found in the most confined zones. Whereas enrichment in organic matter and related biopolymers causes an increase in foraminifera density, pollution by metals leads to a decline in foraminiferal abundance and diversity in those zones. The first situation may be justified by the existence of opportunistic species (with high reproduction rate) that can live in low oxic conditions. The second is explained by the sensitivity of some species to pressure caused by metals. The quality of the organic matter found in these places and the option of a different food source should also explain the tolerance of several species to pollution caused by metals, despite their low reproductive rate in the most polluted areas. In this study, species that are sensitive and tolerant to organic matter and metal enrichment are identified, as is the differential sensitivity/tolerance of some species to metals enrichment.
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10.1371/journal.pone.0118077
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pubmed_257_8961
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Many youth wishing to refuse drugs or alcohol offered to them are deficient in the interpersonal abilities which constitute such refusal skills. This article describes Skillstreaming, an interpersonal skill training approach of apparent effectiveness when used for such behavioral enhancement purposes. Presented are its constituent training procedures, specific skills content, and methods for promoting the transfer and maintenance of skill competence in real-world, refusal-relevant situations.
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10.2190/GDD6-U6BF-6NKN-B9W6
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pubmed_156_2806
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Thirty-two subjects (16 women, 16 men) performed two tasks that were the result of adapting the heartbeat perception tasks produced by Whitehead et al. [Biofeedback Self-Regul. 2 (1977) 371] and Katkin et al. [Psychophysiology 19 (1982) 568], respectively. In the Whitehead task, the delay values were the standard 128 ms for the S+ stimulus and 384 ms for the S- stimulus after the R-wave in one case; in the other case, the delay values were individually adjusted according to the median of the distribution of interval choices in an adaptation of the Brener and Kluvitse [Psychophysiology 25 (1988a) 554; Psychophysiology 25 (1988b) 436] task carried out previously. In the Katkin procedure, in one case S+ always occurred at a fixed interval (100 ms), whereas S- occurred at uniformly increasing intervals in relation to the R-wave. In the other case, the S+ and S- intervals were also individually modified according to the performance in the Brener and Kluvitse task. The results indicate that when the S+ values are individually adjusted, the sensitivity of subjects, as reflected in the 2(arcsin(p(A)(1/2))) values, significantly improves in the Whitehead task. Additionally, it was seen that the performance deteriorated from the first to the last 50 trials, especially when the S+ values were adjusted.
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10.1016/s0301-0511(03)00079-6
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pubmed_1042_26058
|
OBJECTIVE
The current article is aimed at identifying the best practice for counseling around depression in community and outpatient pharmacies, resulting in a draft guideline, proposing key steps and an algorithm for integration of community pharmacists into care for patients with depression.
METHODS
A literature review was performed followed by a detailed analysis, for the purpose of creation a short draft document used as a basis for creation of a guideline for pharmaceutical care for patients with depression. The technological scheme PRISMA flow diagram was applied. The paper is based on current knowledge, taking into consideration already published articles, guidelines, and recommendations about pharmaceutical care for patients with depression, giving a basis for further studies.
RESULTS
This paper includes two main sections: 1) depression - a short description of the main symptoms, risk factors and pharmacotherapy guidelines available in Bulgaria important for the purposes of ensuring qualitative community-based pharmaceutical care; and 2) the pharmacists' role in providing high-quality care - the main aspects of pharmaceutical care for patients with depression with specific examples.
CONCLUSION
The involvement of pharmacists in supporting depressive patients is crucial taking into account the specific characteristics of the pharmacological treatment: delayed onset of clinical results, risks in case of sudden pharmacotherapy abruption without physician consultation, multiple adverse drug reactions and drug-drug, drug-food and drug-alcohol interactions, etc. The current article could also be used as an initial document for creating a methodological guideline for providing pharmaceutical care services for patients with depression.
|
10.2147/IPRP.S239672
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pubmed_879_14987
|
BACKGROUND
Studies conducted to date in Ethiopia did not explore the spatial distribution, individual-level, and community-level factors affecting women's nonautonomy on decision to use contraceptives. Hence, this study aimed to assess the spatial distribution of women's nonautonomy on decision regarding contraceptive utilization and its determinants in Ethiopia.
METHODS
Data were accessed from the Demographic Health Survey program official database website (https://dhsprogram.com). A weighted sample of 3,668 married reproductive-age women currently using contraceptives was included in this analysis. Bayesian multilevel logistic regression models were fitted to identify the determinants of women's nonautonomy on contraceptive utilization. Adjusted odds ratio with 95% credible interval was used to select variables that have a significant effect on nonautonomy on contraceptive utilization.
RESULTS
A high proportion of women with nonautonomy on decision regarding contraceptive utilization was found in northern parts of Southern Nations, Nationalities, and People's Region, Southern parts of Oromia, and Benishangul-Gumuz regions of the country. Overall, 2876 (78.40% (95% CI: 77.0%, 79.7%)) women were nonautonomous on decision regarding contraceptive utilization. In the final model, age from 35-49 (AOR (95% CI) = 0.63 (0.54, 0.72)), living in the richer households (AOR (95% CI) = 0.12 (0.03, 0.26)), being married at 18 years or above (AOR (95% CI) = 0.33 (0.19, 0.57)), and residing in an rural areas (AOR (95% CI) = 1.34 (1.01, 1.71)) and metropolitan regions (AOR (95% CI) = 0.71(0.54, 0.91)) were associated with women's nonautonomy on decision regarding contraceptive utilization.
CONCLUSIONS
In Ethiopia, the spatial distribution of women's nonautonomy on decision about contraceptive utilization was nonrandom. More than three-fourths of married reproductive-age women in Ethiopia are nonautonomous on decision regarding contraceptive utilization. Region, residence, current age, age at marriage, and wealth index were statistically associated with women's nonautonomy on decision regarding contraceptive utilization.
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10.1155/2021/2160922
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pubmed_680_5204
|
As a noninvasive treatment approach for cancer and other diseases, sonodynamic therapy (SDT) has attracted extensive attention due to the deep penetration of ultrasound, good focusing, and selective irradiation sites. However, intrinsic limitations of traditional sonosensitizers hinder the widespread application of SDT. With the development of nanotechnology, nanoparticles as sonosensitizers or as a vehicle to deliver sonosensitizers have been designed and used to target tissues or tumor cells with high specificity and accuracy. Autophagy is a common metabolic alteration in both normal cells and tumor cells. When autophagy happens, a double-membrane autophagosome with sequestrated intracellular components is delivered and fused with lysosomes for degradation. Recycling these cell materials can promote survival under a variety of stress conditions. Numerous studies have revealed that both apoptosis and autophagy occur after SDT. This review summarizes recent progress in autophagy activation by SDT through multiple mechanisms in tumor therapies, drug resistance, and lipid catabolism. A promising tumor therapy, which combines SDT with autophagy inhibition using a nanoparticle delivering system, is presented and investigated.
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10.3389/fphar.2022.961725
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pubmed_1014_11612
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A functional monomer was thermally polymerized inside the anodized aluminum oxide (AAO) channel into nanotubes, which were isolated and characterized to be semiconductive and blue fluorescent, and were utilized as nano-containers of Fe3O4 nanoparticles to form magnetic nanocomposites.
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10.1039/c4cc01877j
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pubmed_613_945
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The title compound, C(20)H(19)N(3)O(3)·C(3)H(7)NO, was synthesized by the reaction of 6-amino-pyrimidine-2,4(1H,3H)-dione and 4-methyl-benzaldehyde with 5,5-dimethyl-1,3-cyclo-hexa-nedione in 1-butyl-3-methyl-imidazolium bromide at 363 K. The pyrimidine ring adopts a half-chair conformation while the six-membered ring fused to the pyridine ring adopts a skew-boat conformation. The dihedral angle between the pyridine ring and the attached benzene ring is 2.38(8)°
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10.1107/S1600536808002924
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pubmed_830_8977
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Application of doxorubicin (Dox) for the treatment of cancer is restricted due to its severe side effects. We used combination strategy by combining doxorubicin (Dox) with withaferin A (WFA) to minimize the ill effects of Dox. Treatment of various epithelial ovarian cancer cell lines (A2780, A2780/CP70 and CaOV3) with combination of WFA and Dox (WFA/DOX) showed a time- and dose-dependent synergistic effect on inhibition of cell proliferation and induction of cell death, thus reducing the dosage requirement of Dox. Combination treatment resulted in a significant enhancement of ROS production resulting in immense DNA damage, induction of autophagy analyzed by transmission electron microscope and increase in expression of autophagy marker LC3B, and culminated in cell death analyzed by cleaved caspase 3. We validated combination therapy on tumor growth using an in vitro 3Dimension (3D) tumor model and the more classic in vivo xenograft model of ovarian cancer. Both tumor models showed a 70 to 80% reduction in tumor growth compared to control or animals treated with WFA or Dox alone. Immunohistochemical analysis of the tumor tissues from animals treated with WFA/Dox combination showed a significant reduction in cell proliferation and formation of microvessels accompanied by increased in LC3B level, cleaved caspase 3, and DNA damage. Taken together, our data suggest that combining WFA with Dox decreases the dosage requirement of Dox, therefore, minimizing/eliminating the severe side effects associated with high doses of DOX, suggesting the application of this combination strategy for the treatment of ovarian and other cancers with no or minimum side effects.
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10.1371/journal.pone.0042265
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pubmed_556_2665
|
BACKGROUND
Significant individual variation in bone loss associated with aromatase inhibitors (AIs) emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect. The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1) gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive breast cancer.
METHODS
The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046, extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at month 12 at the lumbar spine.
RESULTS
After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04).
CONCLUSION
Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single CYP19A1 gene variant in a genomic context.
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10.2174/1381612826666200908141858
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pubmed_31_5869
|
STUDY DESIGN
Cross-sectional cohort.
OBJECTIVE
To determine normative radiographic sagittal cervical alignment in asymptomatic volunteers based on Roussouly thoracolumbar sagittal alignment subtypes.
SUMMARY OF BACKGROUND DATA
Comprehension of differences in cervicothoracic alignment with respect to variations in thoracolumbar alignment is limited.
METHODS
Asymptomatic adults were recruited and the following parameters measured: PI, PT, SS, LL, orbital tilt, orbital slope, occipital slope and incidence, occiput-C2 lordosis, C2-7 lordosis, occiput-C7 lordosis, CBVA, T1 slope, cervicothoracic alignment, T2-5 kyphosis, and C2-C7 sagittal vertebral alignment (SVA). Each was classified into one of Roussouly's four thoracolumbar subtypes and cervical alignment parameters were compared between groups.
RESULTS
Eighty-seven individuals [male-23; female-64; average age 49 ± 16 yr (22-77 yr)] were included for analysis. The four groups were not different by age, sex, and body mass index (BMI). Lumbopelvic parameters (PI, SS, PT, LL) were different between Roussouly types. Average values for all patients included: CBVA (-1 ± 9°), occiput-C2 lordosis (28 ± 9°), occiput-C7 lordosis (39 ± 14°), C2-7 lordosis (11 ± 14°), C2-7 SVA (21 ± 9 mm), T1 slope (25 ± 9°), C6-T4 angle (5 ± 8°), T2-5 angle (16 ± 7°), thoracic kyphosis (47 ± 13°). No sagittal radiographic alignment measurements of the cervical spine and cervicothoracic junction were different between groups, except for the global cervical lordosis (occiput-C7 Cobb), which was found to be lowest for Roussouly type 2 (35 ± 14°) and highest for type 4 (48 ± 14°) (P = 0.01). Mean C2-C7 sagittal Cobb, T2-T5 sagittal Cobb, and T1 slope were not different between groups.
CONCLUSIONS
In asymptomatic volunteers, normative sagittal alignment parameters of the cervical spine, cervicothoracic junction, and thoracic spine based on variations in thoracolumbar sagittal alignment, as proposed by Roussouly, are established. These data may guide surgical correction of cervicothoracic deformities to ensure appropriate restoration of normal cervicothoracic parameters to maintain good horizontal gaze and overall sagittal plane alignment.
LEVEL OF EVIDENCE
3.
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10.1097/BRS.0000000000002941
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pubmed_105_10499
|
OBJECTIVE
To determine the pharmacokinetics of voriconazole after single IV or orally administered boluses in common ravens (Corvus corax).
ANIMALS
8 healthy common ravens.
PROCEDURES
Voriconazole (5 mg/mL, 10 mg/kg IV) was administered to 8 birds, and then plasma voriconazole concentrations were measured at various time points by high-pressure liquid chromatography with mass spectrometry. Starting 6 months later in a randomized 3-treatment 3-period regimen, birds received a single oral dose of voriconazole suspension (10 mg/mL; 6, 12, and 24 mg/kg PO). The study period was May 2015 to March 2016.
RESULTS
Voriconazole (10 mg/kg IV) achieved an initial plasma concentration of 6.31 µg/mL when measured over 21 hours. After oral administration of voriconazole at 6, 12, and 24 mg/kg, the relative bioavailability was 67.5%, 209%, and 183%, respectively. For the 6-mg/kg dose, the maximum plasma concentration was reached at 30 minutes after administration and remained in the therapeutic range of 0.5 to 1 µg/mL for approximately 15 hours. The 12- and 24-mg/kg doses resulted in concentrations in a potentially toxic range.
CLINICAL RELEVANCE
Voriconazole was well tolerated. All 4 doses resulted in plasma concentrations of voriconazole > 0.5 µg/mL, which is the minimum inhibitory concentration recommended for pathogenic species of Aspergillus fungi known to affect birds. A single dose of voriconazole administered as 10 mg/kg IV or 6 mg/kg PO resulted in recommended target plasma concentrations. Administration of voriconazole 6 mg/kg PO 2 to 3 times daily may be adequate for treatment without exceeding the toxic range.
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pubmed_105_10499
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pubmed_949_17311
|
Nonmethylotrophic (Candida maltosa and Saccharomyces cerevisiae) and methylotrophic (Hansenula polymorpha) yeast cells acidified their incubation media in the presence of formaldehyde. This was associated with the release of formate. We studied the formaldehyde-dependent production of formic acid and the enzymatic properties of these strains grown on media containing various carbon sources. The acidifying potential was considerably lower in formaldehyde dehydrogenase-deficient cells of mutant strains of H. polymorpha. The rates of acidification by C. maltosa and S. cerevisiae depended on the activity of their nonspecific aldehyde dehydrogenases. We suggest that accumulation of formate by yeast cells incubated in the presence of formaldehyde is caused by the total activity of formaldehyde dehydrogenase and nonspecific aldehyde dehydrogenase in methylotrophic yeasts or aldehyde dehydrogenase only in nonmethylotrophic yeasts. This is probably an additional mechanism for detoxification of formaldehyde.
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pubmed_949_17311
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pubmed_731_11633
|
Development and design of agents derived from natural sources with neuroprotective properties have received considerable attention. In the literature, it has been stated that these polyphenolic molecules have low adverse impacts and high efficacy when used in pathological conditions. Dietary flavonoids as a subgroup of polyphenols are bioactive products, extracted from several types of vegetables and fruits. Luteolin (3',4',5,7-tetrahydroxyflavone, LUT) is a widespread flavone known to have antioxidant and cytoprotective properties related to nuclear factor erythroid 2-related factor 2-(Nrf2) pathway. Extensive in vitro and in vivo investigations have indicated that LUT exhibits beneficial neuroprotective properties via different mechanisms. However, its psychopharmacological mechanisms are presently investigated in fewer studies. Therefore, we aimed to evaluate the neuroprotective impacts of LUT against central nervous system (CNS) disorders by reviewing available literature. Herein, we also reviewed the studies to understand the underlying mechanisms of LUT for curing CNS disorders.
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10.1007/s12031-018-1094-2
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pubmed_880_21005
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In the title compound {systematic name: methyl 1-[12-oxo-10-(3,4,5-trimethoxy-phen-yl)-4,6,13-trioxa-tetra-cyclo-[7.7.0.0(3,7).0(11,15)]hexa-deca-1,3(7),8-trien-16-yl]-1H-1,2,3-triazole-4-carboxyl-ate dichloro-methane solvate}, C(26)H(25)N(3)O(9)·CH(2)Cl(2), the tetra-hydro-furan ring and the six-membered ring fused to it both display envelope conformations.
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10.1107/S1600536809050612
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pubmed_271_1161
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The factors that limit the distribution of the highly diverse lemur fauna of Madagascar are still debated. We visited an understudied region of eastern Madagascar, a lowland rainforest site (Sahafina, 29-230 m a.s.l.) close to the Mantadia National Park, in order to conduct a survey and collect further distributional data on mouse lemurs. We captured, measured, photographed, and sampled mouse lemurs from the Sahafina forest, performed standard phylogenetic methods based on three mitochondrial DNA genes, and conducted morphometric comparisons in order to clarify their phylogenetic position and taxonomic status. The mouse lemurs from the Sahafina forest could not be assigned to any of the known mouse lemur species and were highly divergent in all molecular analyses from all previously described species. Since they also differed morphometrically from their sister species and from their geographic neighbors, we propose species status and include a species description at the end. This study suggests that M. lehilahytsara may be the first highland specialist among all mouse lemurs. The distribution of the newly described mouse lemur is not fully known, but seems to be rather restricted and highly fragmented, which raises serious conservation concerns.
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10.1007/s10329-011-0290-2
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pubmed_425_10686
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Free ranging ungulates, represented in Europe mostly by several deer species, are important hosts for ticks and reservoirs of tick-borne infections. A number of studies have focused on the prevalence of tick borne pathogens in deer chiefly with the aim to determine their potential role as reservoir hosts for important human and livestock pathogens. However, genetic similarity of Babesia spp. forming a group commonly termed as a clade VI that accommodates the deer piroplasms, complicates this task and has led to the description of a bewildering array of poorly characterised strains. This study aims to resolve this issue by using two independent genetic loci, nuclear 18S rRNA and mitochondrial cytochrome c oxidase subunit I genes, used in parallel to identify Babesia isolates in free-ranging red, sika, and roe deer in two areas of their co-occurrence in the Czech Republic. The COX1 loci, in contrast to 18S rRNA gene, shows a clear difference between interspecific and intraspecific variation at the nucleotide level. The findings confirm B. divergens, Babesia sp. EU1 and B. capreoli in studied deer species as well as common presence of another unnamed species that matches a taxon previously referred to as Babesia sp. or Babesia cf. odocoilei or Babesia CH1 group in several other sites throughout Europe. The invasive sika deers enter the life cycle of at least three piroplasmid species detected in native deer fauna. The presence of B. divergens in both sika and red deer in an area where bovine babesiosis is apparently absent raises important questions regarding the epidemiology, host specificity and taxonomic status of the parasite.
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10.1016/j.meegid.2019.104060
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pubmed_893_8238
|
BACKGROUND
Although fractional flow reserve (FFR) measurements during coronary angiography are performed in routine clinical practice, few studies have evaluated FFR measurements in dialysis patients.
METHODS
We retrospectively studied 42 hemodialysis patients with suspected or known coronary artery disease (CAD) who underwent stress myocardial perfusion imaging and coronary angiography with FFR measurements for 61 coronary lesions. The cut-off value for FFR to detect myocardial ischemia was determined by receiver operating characteristic (ROC) curve analysis.
RESULTS
There were 61 coronary vessels measured by FFR. The FFR range was 0.34-0.93 with a mean of 0.74±0.13. The ROC curve analysis revealed that the best cut-off value of FFR for detecting myocardial ischemia was 0.76 (p<0.0001), with 70% sensitivity, 86% specificity, and 76% accuracy for myocardial ischemia. Compared with patients who had positive myocardial ischemia and an FFR≤0.76, those who had negative myocardial ischemia despite an FFR≤0.76 had less left ventricular (LV) mass index, whereas patients who had positive myocardial ischemia despite an FFR>0.76 had greater LV mass indexor serum calcium-phosphorus product.
CONCLUSIONS
The cut-off value of FFR for myocardial ischemia in chronic hemodialysis patients is similar to that in other CAD patients. However, caution is necessary when FFR measurements are applied to dialysis patients with significantly increased LV mass index or serum calcium-phosphorus product.
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10.1016/j.jjcc.2017.05.007
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pubmed_622_6387
|
OBJECTIVE
To evaluate routine oral calcium and vitamin D administration for preventing symptoms of hypocalcemia after total thyroidectomy.
SUBJECTS AND METHODS
A total of 487 consecutive patients were prospectively randomized into two groups in terms of routine oral calcium and vitamin D supplementation: In the control group (244 patients) the treatment was not routinely started after surgery, whereas the treated group (243 patients) received routine supplementation that started on postoperative day 1.
RESULTS
Patients of treated group had only minor hypocalcemia symptoms, whereas 7 patients of control group experienced carpopedal spasm as a major symptom (p<0.001). None of the patients in the treated group required intravenous calcium administration. Average hospital stay of the treated group patients was significantly shorter than that of control group (p<0.001).
CONCLUSIONS
Routine postoperative calcium and vitamin D supplementation therapy may be useful for the prevention of symptomatic hypocalcemia after total thyroidectomy and may allow for a safe and early discharge from the hospital.
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pubmed_622_6387
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pubmed_980_22212
|
Starting in a new hospital can be an overwhelming experience for any grade of doctor. There is a vast amount of information that needs to be learnt immediately to function in the new environment. There is an annual changeover of doctors between hospitals in August nationwide and most junior doctors rotate specialties every 4-6 months. Evidence shows that doctors feel this transition has a negative impact on patient care and indicates that inpatient mortality rises during the August changeover. In our hospital, we noted problems with access to guidelines, referral information and investigations by junior doctors, especially at changeover. In an initial questionnaire, 100% of doctors had experienced difficulties with referring to a specialty and 96% felt time was wasted doing so. Furthermore, 87.5% of doctors had difficulties with ordering laboratory investigations and 100% of survey participates expressed difficulty accessing guidelines.To tackle this issue, we created guidelines on how to refer to different specialties, order investigations and general running of the hospital. We then used a free app platform called induction and uploaded the guidelines as well as formal hospital guidelines to the app. After use of the app, we assessed these problems via further questionnaires. Doctors reporting problems with finding how to refer to specialties reduced from 100% to 0% in the final survey. Problems finding how to request investigations fell from 100% to 14.3% after 1 month to 7.7% after 3 months. Finally, problems finding guidelines fell from 100% to 15.4%. Further, 100% of doctors felt the app saved time.Use of the induction app to access guidelines saves time and reduces problems accessing information needed to carry out tasks. This an easily replicated project with low running costs which proved to help with the universal problems around induction to a new hospital environment.
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10.1136/bmjoq-2020-000970
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pubmed_521_5886
|
A study was conducted over a 12 month period to assess the specificity and sensitivity of the 'slap test', using endoscopic evaluation, in the detection of cervical spinal cord and caudal brainstem lesions in horses. Fifteen ataxic horses were subjected to the 'slap test' and subsequently examined post mortem. Twelve out of the 15 had histopathological lesions consistent with their clinical signs. Thirteen horses with no history of neurological dysfunction and no histopathological evidence of cervical spinal cord or brainstem disease were used as controls. The laryngeal adductory responses exhibited by all horses were filmed and later scored independently by 3 assessors. The proportion of animals diagnosed with cervical spinal cord and/or brainstem disease, defined by histopathological criteria, was found to be statistically similar to the proportion with abnormal 'slap test' responses, using the McNemar chi-Square test. Despite statistical significance between proportions, sensitivity of the 'slap test' was low, 50% for the left side on both days and 58% for the right side. Specificity was higher, 69% (Day 1) and 75% (Day 2) for the left side and 75% (Day 1) and 69% (Day 2) for the right side. In contrast to this, conventional neurological examination was found to be 100% sensitive and 81% specific in the detection of lesions of histopathological significance in the cervical spinal cord/caudal brainstem. Agreement between scores for the 'slap test' from the same assessor on different days was good, with values for kappa of 0.59 to 0.85. In contrast, agreement between assessors on the 'slap test' score was poor, with kappa 0.35.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1111/j.2042-3306.1994.tb04403.x
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pubmed_992_5341
|
We describe an efficient Bayesian parallel GPU implementation of two classic statistical models-the Lasso and multinomial logistic regression. We focus on parallelizing the key components: matrix multiplication, matrix inversion, and sampling from the full conditionals. Our GPU implementations of Bayesian Lasso and multinomial logistic regression achieve 100-fold speedups on mid-level and high-end GPUs. Substantial speedups of 25 fold can also be achieved on older and lower end GPUs. Samplers are implemented in OpenCL and can be used on any type of GPU and other types of computational units, thereby being convenient and advantageous in practice compared to related work.
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10.1371/journal.pone.0180343
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pubmed_840_23753
|
Conserved polypeptides of the chitin synthase genes UmCHS3 and UmCHS6 from the phytopathogenic fungus Ustilago maydis were utilized as immunogens to obtain polyclonal antibodies that were purified by affinity procedures. Because of their similarities at the regions encoded by either polypeptide, it was concluded that anti-Chs3 antibodies recognized both Chs3 and Chs4 chitin synthases, whereas anti-Chs6 antibodies recognized Chs6 and Chs8 polypeptides. These antibodies were used to analyze the localization of the corresponding chitin synthases in U. maydis cells, using both indirect immunofluorescence microscopy and immunoelectron microscopy with colloidal-gold-labeled secondary antibodies. It was observed that chitin synthase proteins were accumulated both in the surface and in the cytoplasm of the fungal cells. Electron microscopy images revealed the accumulation of clusters of gold particles in vesicles, providing evidence for the possible origin and destination of chitin synthases in the fungal cells.
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10.1111/j.1567-1364.2006.00133.x
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pubmed_632_10133
|
BACKGROUND
Recently, we have shown that mast cell mitochondrial STAT3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT3 inhibitors (Mitocur-1 and Mitocur-3) modulate the allergic response.
METHODS
Experiments were performed both in vitro in cultured human/mouse mast cells and with rat basophilic leukemia (RBL) cells and also in vivo in mice. The effect of mitochondrial STAT3 inhibition on mast cell function was determined via checking degranulation and several cytokines secretion levels.
RESULTS
Here, we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT3 inhibitors had no effect on STAT3 target gene expression. However, these inhibitors caused a significant reduction in mast cell exocytosis and cytokine release, due to a decrease in OXPHOS activity and STAT3 serine 727 phosphorylation. It was also observed in an OVA mouse model of allergic asthma that one of the inhibitors used significantly reduced eosinophilia and neutrophilia compared to the control mice group. Furthermore, it was observed that treatment with this inhibitor resulted in a significant reduction in blood histamine levels in mice after IgE-Ag challenge.
CONCLUSION
The present data strongly suggest that the development of mitochondrial STAT3 inhibitors could serve as a potential treatment for allergy-associated diseases.
|
10.1111/all.13467
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pubmed_571_7353
|
BACKGROUND
beta-Blockers are a cornerstone in the treatment of systolic heart failure treatment, but not all beta-blockers are effective or in this setting.
OBJECTIVE
To define the role of bisoprolol, a highly selective beta(1)-antagonist in congestive heart failure due to systolic dysfunction.
METHODS
Using the keywords 'bisoprolol' and 'heart failure' PubMed and BIOSIS databases were searched for information regarding pharmacology and relevant randomised clinical trials. Supplementary publications were acquired by scrutinising reference lists of relevant papers. Additional information was obtained from the FDA website.
CONCLUSION
Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials.
|
10.1517/14656566.9.2.293
|
pubmed_83_25866
|
Early detection of chronic diseases helps to minimize the disease impact on patient's health and reduce the economic burden. Continuous monitoring of such diseases helps in the evaluation of rehabilitation program effectiveness as well as in the detection of exacerbation. The use of everyday wearables i.e. chest band, smartwatch and smart band equipped with good quality sensor and light weight machine learning algorithm for the early detection of diseases is very promising and holds tremendous potential as they are widely used. In this study, we have investigated the use of acceleration, electrocardiogram, and respiration sensor data from a chest band for the evaluation of obstructive lung disease severity. Recursive feature elimination technique has been used to identity top 15 features from a set of 62 features including gait characteristics, respiration pattern and heart rate variability. A precision of 0.93, recall of 0.91 and F-1 score of 0.92 have been achieved with a support vector machine for the classification of severe patients from the non-severe patients in a data set of 60 patients. In addition, the selected features showed significant correlation with the percentage of predicted FEV1.Clinical Relevance- The study result indicates that wearable sensor data collected during natural walk can be used in the early evaluation of pulmonary patients thus enabling them to seek medical attention and avoid exacerbation. In addition, it may serve as a complementary tool for pulmonary patient evaluation during a 6-minute walk test.
|
10.1109/EMBC44109.2020.9176559
|
pubmed_578_11491
|
To activate naive T cells convincingly using Mycobacterium bovis bacillus Calmette-Guérin (BCG), recombinant BCG (BCG-D70M) that was deficient in urease, expressed with gene encoding the fusion of BCG-derived heat shock protein (HSP) 70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed. BCG-D70M was more potent in activation of both CD4(+) and CD8(+) subsets of naive T cells than recombinant BCGs including urease-deficient BCG and BCG-70M secreting HSP70-MMP-II fusion protein. BCG-D70M efficiently activated dendritic cells (DCs) to induce cytokine production and phenotypic changes and activated CD4(+) T cells even when macrophages were used as APCs. The activation of both subsets of T cells was MHC and CD86 dependent. Pretreatment of DCs with chloroquine inhibited both surface expression of MMP-II on DCs and the activation of T cells by BCG-D70M-infected APCs. The naive CD8(+) T cell activation was inhibited by treatment of DCs with brefeldin A and lactacystin so that the T cell was activated by TAP- and proteosome-dependent cytosolic cross-priming pathway. From naive CD8(+) T cells, effector T cells producing perforin and memory T cells having migration markers were produced by BCG-D70M stimulation. BCG-D70M primary infection in C57BL/6 mice produced T cells responsive to in vitro secondary stimulation with MMP-II and HSP70 and more efficiently inhibited the multiplication of subsequently challenged M. leprae than vector control BCG. These results indicate that the triple combination of HSP70, MMP-II, and urease depletion may provide a useful tool for inducing better activation of naive T cells.
|
10.4049/jimmunol.1000198
|
pubmed_625_21560
|
OBJECTIVES
We sought to determine the incidence and risk factors for de novo atrial fibrillation (>90 days after surgery) in patients without preoperative atrial fibrillation.
METHODS
From 2004 to 2014, 2261 patients underwent mitral valve surgery; 1288 patients (57%) did not have a history of atrial fibrillation, and 930 patients had rhythm information more than 90 days after surgery. De novo atrial fibrillation and death probabilities were estimated using a semi-competing risks, multi-state model. Univariable and multivariable risk factors for developing atrial fibrillation were identified using the Fine-Gray model.
RESULTS
The 5- and 10-year incidences of de novo atrial fibrillation were 14% and 23%, respectively. Univariable risk factors were older age, more complex operations, more tricuspid regurgitation, and congestive heart failure (all P < .05). Patients with degenerative mitral regurgitation were less likely to develop atrial fibrillation (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.24-0.65; P < .001). Multivariable risk factors for de novo atrial fibrillation were tricuspid valve surgery (HR, 1.80; 95% CI, 1.22, 2.65; P = .003), aortic valve surgery (HR, 1.49; 95% CI, 1.03-2.17; P = .035), and older age (HR, 1.03; 95% CI, 1.02-1.05; P < .001). De novo atrial fibrillation did not affect overall survival (P = .41). Among patients who developed de novo atrial fibrillation, we observed increased use of warfarin (P < .001) and a strong trend toward an increased risk of stroke (P = .055).
CONCLUSIONS
De novo atrial fibrillation develops progressively after mitral surgery and is associated with a strong trend toward stroke. Patients at high risk could be studied in a trial to reduce atrial fibrillation.
|
10.1016/j.jtcvs.2018.04.050
|
pubmed_220_3546
|
We performed 2-dimensional finite element model analysis to estimate the mechanical environment of the supraspinatus tendon. The geometric shape of the finite element model was determined by magnetic resonance imaging of a normal human shoulder obtained at 0 degrees, 30 degrees, and 60 degrees of abduction, whereas the histologic location of noncalcified and calcified fibrocartilage was determined from a cadaveric specimen. The supraspinatus tendon was pulled proximally with the force of 10 N at 0 degrees, 53 N at 30 degrees, and 115 N at 60 degrees of abduction. The area of high principal stress maximum was observed on the articular side of the supraspinatus tendon, which shifted toward the insertion as the arm was abducted. High stress concentration on the articular side of the supraspinatus tendon near its insertion during arm elevation may explain the frequent occurrence of rotator cuff tears at this site.
|
10.1016/s1058-2746(03)00214-3
|
pubmed_748_17260
|
OBJECTIVE
To explore the outcome of hypopharynx reconstruction by using remaining laryngeal mucosa flap and pectoralis major myocutaneous flap in advanced pyriform sinus cancer.
METHODS
Twelve patients with pyriform sinus cancers underwent hemilaryngectomy and partial pharyngectomy, two patients underwent cervical esophagectomy at the same time. The defects were reconstructed by remaining laryngeal mucosa flap. Four cases were involved in the bilateral larynx, received total laryngectomy and were repaired by pectoralis major myocutaneous flap.
RESULTS
There was no operative fatal case and all flaps survived. Only one suffered from postoperative pharyngocutaneous fistulas, whose defect was reconstructed by remaining laryngeal mucosa flap and had radiotherapy. All patients could swallow ordinary food and had no benign esophagostenosis and pharyngostenosis after operation. Out of 16 patients, 1 case died of general metastasis; 3 cases died of local tumor relapse, tumor relapse of cervical lymphonode and lung metastasis respectively within 1 year after operation; the other 12 cases survived over 2 years.
CONCLUSION
The advantage of hypopharynx reconstruction with remaining laryngeal mucosa flap is simple and convenient with less trauma and complication. The reconstruction should be completed by using the pectoralis major myocutaneous flap when the bilateral larynx are involved in.
|
pubmed_748_17260
|
pubmed_232_19604
|
HYPOTHESIS
Transtympanic administration of the antioxidant N-acetylcysteine or lactated Ringer's solution onto the round window membrane will prevent cisplatin ototoxicity in the guinea pig model.
BACKGROUND
Cochlear ototoxicity is a well-known side effect of cisplatin administration, with the mechanism of injury thought to rest in oxidative damage to the outer hair cells. However, previous attempts at transtympanic antioxidant delivery have met with varied success. We present an effective method of counteracting cisplatin ototoxicity via the transtympanic application of lactated Ringer's solution or N-acetylcysteine.
METHODS
Baseline distortion product otoacoustic emission measurements were obtained. Intraperitoneal cisplatin was administered to a cumulative dose of 20 mg/kg. The middle ears were either untreated (control) or filled with normal saline (negative control), 2%N-acetylcysteine diluted in normal saline (treatment), or lactated Ringer's solution (treatment) via anterosuperior quadrant myringotomies. Posttreatment distortion product otoacoustic emissions were obtained.
RESULTS
Animals in the untreated control group and the negative control normal saline group demonstrated consistent obliteration of distortion product otoacoustic emissions. However, those receiving either lactated Ringer's solution or 2%N-acetylcysteine diluted in normal saline demonstrated significant preservation of distortion product otoacoustic emissions. The treatment regimen was well tolerated, with minimal animal loss.
CONCLUSION
We have demonstrated the efficacy of transtympanic lactated Ringer's solution and N-acetylcysteine in the prevention of cisplatin ototoxicity using a guinea pig model. The possible mechanisms for the high efficacy of lactated Ringer's solution are discussed in detail.
|
10.1097/00129492-200411000-00009
|
pubmed_777_499
|
Heart glycogen represents a store of glucosyl residues which are mobilized by the catalysis of glycogen phosphorylase (GP) and are mainly destined to serve as substrates for the generation of ATP. The brain isoform of GP (GP BB) was studied in rat heart in comparison with the muscle isoform (GP MM) to find functional analogies to the brain. Western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed that at the protein level, but not at the mRNA level, the content of GP BB is similar in heart and brain. In contrast, GP MM is more abundant in the heart than in the brain. Immunocytochemically GP BB was colocalized with GP MM in cardiomyocytes. GP MM was also detected in interstitial cells identified as fibroblasts. The physiological role of co-expression of GP BB and GP MM in cardiomyocytes and in brain astrocytes is discussed in a comparative way.
|
10.1007/s11064-008-9825-3
|
pubmed_242_1521
|
The diversity of parasite communities in the Chinese sleeper Perccottus glenii, at the level of single specimens and populations, is manifested through three components: the number of species, the evenness of their abundance, and the taxonomic diversity. Variations in the diversity depend on the local characteristics of water bodies, as well as the sexual and dimensional factors of the host. This study was performed in four water bodies of the Russian Far East (Primorskii krai and Sakhalin Island).
|
pubmed_242_1521
|
pubmed_445_15499
|
Four children who developed severe lung disease after measles are described. One child died and three have been left with severe impairment of lung function. It is suggested that secondary infection with an adenovirus was responsible for causing the lung disease in these patients. The immune response to measles was abnormal. Measles virus may have rendered the children more susceptible to serious complications from infection with the adenovirus. The many deaths from 'measles pneumonia' in developing countries and the occasional occurence of post-measles bronchiectasis in this country may be due to secondary adenovirus infections. Further viral and serological studies are required to confirm this hypothesis.
|
10.1016/0007-0971(76)90012-7
|
pubmed_319_4901
|
Parkinson's disease (PD) is one of the most common neurodegenerative disorders characterized by decreased levels of the neurotransmitter dopamine (DA) in the striatum of the brain, as a result of degeneration of DA neurons. Levodopa (L-Dopa) crosses the blood-brain barrier and its administration replenishes the loss of DA in dopaminergic neurons in PD patients. Despite the evident beneficial effects, L-Dopa use may cause side effects and its toxicity found in in vitro assays has been attributed to the generation of reactive oxygen species (ROS): L-Dopa is converted to DA and its metabolism and autoxidation gives rise to quinones, semiquinones, and hydrogen peroxide. Despite this evidence, L-Dopa in some in vivo and in vitro experiments showed no toxic effects, or even antioxidant effects. Two major peripheral L-Dopa metabolic pathways, driven by the enzymes Aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyl transferase (COMT), significantly deplete the amount of L-Dopa reaching the brain. The low bioavailability of L-Dopa may cause a wide variation in clinical response between patients. Strategies addressing to improve the bioavailability of L-Dopa include coadministering L-Dopa with carbidopa, a decarboxylase inhibitor, as multiple daily doses. We utilized catecholaminergic human neuroblastoma cells to study DNA damage and ROS production after L-Dopa and carbidopa treatments. Our data lead us to confirm that L-Dopa may have a protective effect on dopaminergic cells especially at certain concentrations, in particular, toward the production of ROS and their toxic effects on DNA. Furthermore in the combined treatment, with induction of ROS following administration of H(2)O(2), carbidopa is effective in reducing the damage caused by reactive oxygen intermediates both alone and in combination with L-Dopa.
|
10.1089/dna.2011.1546
|
pubmed_203_7502
|
OBJECTIVES
This study was done to review and describe the care of paediatric trauma patients with respect to pain assessment and medication administration.
METHODS
A retrospective review of paediatric trauma patients, age <16 with a long bone fracture and GCS=15, cared for by our paediatric trauma response team (January 1998-August 2002). A single trained abstractor reviewed all records. Data were descriptively analysed.
RESULTS
Fifty-six children were included. All but three received pain medication during resuscitation. The median time to first dose of pain medication after arrival was 20 min (95% CI: 14-29 min). The median pre- and post-treatment pain scores, on a 5-point scale, were 4 and 2, respectively. Vital signs were unaffected.
CONCLUSIONS
As a group, our paediatric trauma resuscitation team did a much better job managing pain, in this segment of the population, than the preponderance of existing literature would predict.
|
10.1016/j.injury.2005.05.040
|
pubmed_974_19970
|
OBJECTIVE
The purpose of our study was to compare the clinical utility of administering 2 recommended developmental screening instruments, the Infant Developmental Inventory (IDI) and the Ages and Stages Questionnaire (ASQ), at 9-month well-child visits in paper format.
METHODS
Outcomes of the 2 screens, including correct completion and interpretation by clinician, time of visit, and screen outcome were compared.
RESULTS
Out of 33 children administered the ASQ and with documented scores, 12 (36.4%) did not receive passing scores, while 5 (12.2%) of the 41 children administered the IDI did not receive passing scores (P = .014). Out of 41 IDI screens, 12 (29.3%) were completed incorrectly, while there were no ASQ screens completed incorrectly (P < .001) by caregivers.
CONCLUSION
In our pilot study, the ASQ is more often completed correctly by caregivers and identifies more children at risk for delay as compared with the IDI. Additional larger scale studies are needed to evaluate the usefulness of developmental screening tools when used within primary care practice.
|
10.1177/2150131914560228
|
pubmed_279_11066
|
Vasoactive intestinal peptide (VIP) has been localized within the suprachiasmatic nucleus of the hypothalamus (SCN) and appears to play an important role in the entrainment of circadian rhythms with the light-dark (LD) cycle. The spontaneously hypertensive rat (SHR), an inbred strain used extensively in research on primary hypertension, has significantly more VIP mRNA in its brain than normotensive Wistar-Kyoto control (WKY) rats. Because VIP levels are abnormally high in SHR rats the present study examined whether the mechanisms controlling circadian rhythms are also altered in SHR rats. When entrained to a 24 h LD cycle, SHR rats began their wheel-running rhythm approximately 1.5 h earlier than WKY controls. SHR rats re-entrained to a phase delay in the LD cycle more slowly than did WKY rats, but tended to re-entrain to a phase advance more rapidly. The free-running period of SHR rats in both constant light and constant dark was significantly shorter than that of WKY rats. In SHR rats, phase delays produced by 1-h pulses of light were less than one-half the magnitude of the delays seen in WKY rats; however, the phase advances were nearly twice that of WKY rats. Using in situ hybridization, the SCN levels of mRNA encoding VIP were found to be significantly greater in SHR rats, but the mRNA levels of another peptide important for entrainment, gastrin releasing peptide, did not differ between SHR and WKY rats. These data indicate that the mechanisms controlling circadian rhythms in SHR rats differ significantly from those controlling rhythms in WKY rats and that VIP mRNA is significantly elevated within the SCN of SHR rats. The role of VIP in the entrainment of circadian rhythms is discussed.
|
10.1016/0006-8993(94)91733-7
|
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