Effects of natto extract on endothelial injury in a rat model

Vascular endothelial damage has been found to be associated with thrombus formation, which is considered to be a risk factor for cardiovascular disease. A diet of natto leads to a low prevalence of cardiovascular disease. The aim of the present study was to investigate the effects of natto extract on vascular endothelia damage with exposure to laser irradiation. Endothelial damage both in vitro and in vivo was induced by irradiation of rose bengal using a DPSS green laser. Cell viability was determined by MTS assay, and the intimal thickening was verified by a histological approach. The antioxidant content of natto extract was determined for the free radical scavenging activity. Endothelial cells were injured in the presence of rose bengal irradiated in a dose-dependent manner. Natto extract exhibits high levels of antioxidant activity compared with purified natto kinase. Apoptosis of laser-injured endothelial cells was significantly reduced in the presence of natto extract. Both the natto extract and natto kinase suppressed intimal thickening in rats with endothelial injury. The present findings suggest that natto extract suppresses vessel thickening as a synergic effect attributed to its antioxidant and anti-apoptosis properties

Timeframe for return to driving for patients with minimally invasive knee arthroplasty is associated with knee performance on functional tests

BACKGROUND: This study hopes to establish the timeframe for a safe return to driving under different speed conditions for patients after minimally invasive total knee arthroplasty and further explores how well various kinds of functional tests on knee performance can predict the patients’ braking ability. METHODS: 14 patients with right knee osteoarthritis were included in the present study and instructed to perform three simulated driving tasks at preoperative, 2 weeks postoperative and 4 weeks postoperative. RESULTS: The results showed that the total braking time at 4 week postoperative has attained the preoperative level at the driving speed 50 and 70 km/hr but not at the driving speed 90 km/hr. It had significantly improving in knee reaction time and maximum isometric force at 4 weeks postoperative. Besides, there was a moderate to high correlation between the scores of the step counts and the total braking time. CONCLUSIONS: Summary, it is recommended that driving may be resumed 4 weeks after a right knee replacement but had to drive at low or moderate speed and the best predictor of safety driving is step counts

Diaqua­bis­(3-nitro­benzoato-κO 1)bis­[1H-5-(3-pyrid­yl)-3-(4-pyrid­yl)-1H-1,2,4-triazole-κN 5]cobalt(II) dihydrate

In the centrosymmetric title compound, [Co(C7H4NO4)2(C12H9N5)2(H2O)2]·2H2O, the CoII atom, located on an inversion center, is coordinated by two N atoms [Co—N = 2.155 (3) Å] and four O atoms [Co—O = 2.099 (2)–2.117 (3) Å] in a distorted octa­hedral geometry. Inter­molecular N—H⋯O, O—H⋯N and O—H⋯O hydrogen bonds link the components into a three-dimensional supramolecular framework

Prognostic factors and monomicrobial necrotizing fasciitis: gram-positive versus gram-negative pathogens

<p>Abstract</p> <p>Background</p> <p>Monomicrobial necrotizing fasciitis is rapidly progressive and life-threatening. This study was undertaken to ascertain whether the clinical presentation and outcome for patients with this disease differ for those infected with a gram-positive as compared to gram-negative pathogen.</p> <p>Methods</p> <p>Forty-six patients with monomicrobial necrotizing fasciitis were examined retrospectively from November 2002 to January 2008. All patients received adequate broad-spectrum antibiotic therapy, aggressive resuscitation, prompt radical debridement and adjuvant hyperbaric oxygen therapy. Eleven patients were infected with a gram-positive pathogen (Group 1) and 35 patients with a gram-negative pathogen (Group 2).</p> <p>Results</p> <p>Group 2 was characterized by a higher incidence of hemorrhagic bullae and septic shock, higher APACHE II scores at 24 h post-admission, a higher rate of thrombocytopenia, and a higher prevalence of chronic liver dysfunction. Gouty arthritis was more prevalent in Group 1. For non-survivors, the incidences of chronic liver dysfunction, chronic renal failure and thrombocytopenia were higher in comparison with those for survivors. Lower level of serum albumin was also demonstrated in the non-survivors as compared to those in survivors.</p> <p>Conclusions</p> <p>Pre-existing chronic liver dysfunction, chronic renal failure, thrombocytopenia and hypoalbuminemia, and post-operative dependence on mechanical ventilation represent poor prognostic factors in monomicrobial necrotizing fasciitis. Patients with gram-negative monobacterial necrotizing fasciitis present with more fulminant sepsis.</p

The Association Between the Sedative Loads and Clinical Severity Indicators in the First-Onset Major Depressive Disorder

Background: High sedative use in a major depressive episode may imply specific clinical features. This study aims to examine the correlation between sedative use and clinical severity indicators in the initial treatment phase of first-onset major depressive disorder.Methods: A study cohort in the first episode of major depressive disorder was used to conduct pharmacological dissection. All participants had at least a 2-year follow-up period with a complete treatment record. The defined daily dose of antidepressants and augmentation agents were calculated as the antidepressant load and augmentation load, respectively. Sedative use, which was calculated as the equivalent dosage of lorazepam, were defined as the sedative load. These psychotropic loads were measured monthly and the averaged psychotropic loads for each day were obtained.Results: A total of 106 individuals (75.5% female) were included. The mean duration of disease course in participants was 5.5 ± 3.5 years. In the multiple regression analysis, after controlling for other classes of psychotropics and comorbid anxiety disorders, the sedative load independently correlated with higher number of antidepressants used, higher number of antidepressant used with an adequate dose and duration, more psychiatric emergency and outpatient visits within 2 years of disease onset.Conclusion: High loading of sedatives correlated with several indicators of clinical severity in major depressive disorder. The sedative load may be used as a specifier to identify subgroups in patients with major depressive disorder

A Randomised Placebo-Controlled Trial of a Traditional Chinese Herbal Formula in the Treatment of Primary Dysmenorrhoea

BACKGROUND: Most traditional Chinese herbal formulas consist of at least four herbs. Four-Agents-Decoction (Si Wu Tang) is a documented eight hundred year old formula containing four herbs and has been widely used to relieve menstrual discomfort in Taiwan. However, no specific effect had been systematically evaluated. We applied Western methodology to assess its effectiveness and safety for primary dysmenorrhoea and to evaluate the compliance and feasibility for a future trial. METHODOLOGY/PRINCIPAL FINDINGS: A randomised, double-blind, placebo-controlled, pilot clinical trial was conducted in an ad hoc clinic setting at a teaching hospital in Taipei, Taiwan. Seventy-eight primary dysmenorrheic young women were enrolled after 326 women with self-reported menstrual discomfort in the Taipei metropolitan area of Taiwan were screened by a questionnaire and subsequently diagnosed by two gynaecologists concurrently with pelvic ultrasonography. A dosage of 15 odorless capsules daily for five days starting from the onset of bleeding or pain was administered. Participants were followed with two to four cycles for an initial washout interval, one to two baseline cycles, three to four treatment cycles, and three follow-up cycles. Study outcome was pain intensity measured by using unmarked horizontal visual analog pain scale in an online daily diary submitted directly by the participants for 5 days starting from the onset of bleeding or pain of each menstrual cycle. Overall-pain was the average pain intensity among days in pain and peak-pain was the maximal single-day pain intensity. At the end of treatment, both the overall-pain and peak-pain decreased in the Four-Agents-Decoction (Si Wu Tang) group and increased in the placebo group; however, the differences between the two groups were not statistically significant. The trends persisted to follow-up phase. Statistically significant differences in both peak-pain and overall-pain appeared in the first follow-up cycle, at which the reduced peak-pain in the Four-Agents-Decoction (Si Wu Tang) group did not differ significantly by treatment length. However, the reduced peak-pain did differ profoundly among women treated for four menstrual cycles (2.69 (2.06) cm, mean (standard deviation), for the 20 women with Four-Agents-Decoction and 4.68 (3.16) for the 22 women with placebo, p = .020.) There was no difference in adverse symptoms between the Four-Agents-Decoction (Si Wu Tang) and placebo groups. CONCLUSION/SIGNIFICANCE: Four-Agents-Decoction (Si Wu Tang) therapy in this pilot post-market clinical trial, while meeting the standards of conventional medicine, showed no statistically significant difference in reducing menstrual pain intensity of primary dysmenorrhoea at the end of treatment. Its use, with our dosage regimen and treatment length, was not associated with adverse reactions. The finding of statistically significant pain-reducing effect in the first follow-up cycle was unexpected and warrants further study. A larger similar trial among primary dysmenorrheic young women with longer treatment phase and multiple batched study products can determine the definitive efficacy of this historically documented formula. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN23374750

Cardiac Myosin Binding Protein C and MAP-Kinase Activating Death Domain-Containing Gene Polymorphisms and Diastolic Heart Failure

OBJECTIVE: Myosin binding protein C (MYBPC3) plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3) gene polymorphisms and diastolic heart failure (DHF) in a human case-control study. METHODS: A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs) according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≥ 5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD) structure of the MYBPC3 gene. RESULTS: In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031). The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25-3.66; p = 0.004) for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17-3.63; p = 0.013), corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C) was also significantly associated with DHF (odds ratio 2.10 (1.53-2.89); permuted p = 0.029). CONCLUSIONS: We identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population

Structure and dynamics of the active Gs-coupled human secretin receptor

The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is important for its therapeutic exploitation. We combined cryo-electron microscopy, molecular dynamics, and biochemical cross-linking to determine a 2.3 Å structure, and interrogate dynamics, of secretin bound to the SecR:Gs complex. SecR exhibited a unique organization of its extracellular domain (ECD) relative to its 7-transmembrane (TM) core, forming more extended interactions than other family members. Numerous polar interactions formed between secretin and the receptor extracellular loops (ECLs) and TM helices. Cysteine-cross-linking, cryo-electron microscopy multivariate analysis and molecular dynamics simulations revealed that interactions between peptide and receptor were dynamic, and suggested a model for initial peptide engagement where early interactions between the far N-terminus of the peptide and SecR ECL2 likely occur following initial binding of the peptide C-terminus to the ECD