Purification and bioactivity of exendin-4, a peptide analogue of GLP-1, expressed in Pichia pastoris

Exendin-4, a peptide analogue of glucagon-like peptide-1 (GLP-1), has been developed for treatment of type 2 diabetes. Herein, the secretive exendin-4 fusion protein, expressed by methanol induction in Pichia pastoris system, was purified to homogeneity by chromatography followed by enterokinase cleavage of the fusion protein and subsequent purification of the recombinant exendin-4. Purity of the recombinant exendin-4 was 95.6%. Bioactivity assay revealed that it had glucose-lowering and insulin-releasing action in vivo

Women's Status and Violence against Young Married Women in Rural Nepal

<p>Abstract</p> <p>Background</p> <p>Studies conducted around the world consistently show the existence of violence against women. Despite the increasing number of studies being conducted on violence against young married women elsewhere, this subject has received little attention from researchers and policy makers in Nepal. This paper assesses the prevalence of violence among young married women in rural Nepal. Specifically, it examines [factors related to] women's status in order to better understand the risk of violence.</p> <p>Methods</p> <p>A cross-sectional study was conducted in 2009 among 1,296 young married women aged 15-24 years in four major ethnic groups. Bivariate analysis and multivariate logistic regression were used to examine the association between selected risk factors and violence.</p> <p>Results</p> <p>More than half the women (51.9%) reported having experienced some form of violence in their lifetime. One-fourth (25.3%) reported physical violence and nearly half (46.2%) reported sexual violence. Likewise, one-third (35.8%) of women reported experiencing some form of violence in the past 12 months. No or little inter-spousal communication and low autonomy of women significantly increases the odds of experiencing violence among married women.</p> <p>Conclusions</p> <p>The violence against women is quite common among young married women in rural Nepal. Although the Domestic Violence and Punishment Act 2066 has been enacted, equal attention needs to be given to increasing women's autonomy and activities that encourage inter-spousal communication. Furthermore, more research is required in Nepal that examines dynamics of violence perpetrated by husbands.</p

A study of soft tissue sarcomas after childhood cancer in Britain

Among 16 541 3-year survivors of childhood cancer in Britain, 39 soft tissue sarcomas (STSs) occurred and 1.1 sarcomas were expected, yielding a standardised incidence ratio (SIR) of 16.1. When retinoblastomas were excluded from the cohort, the SIR for STSs was 15.9, and the cumulative risk of developing a soft tissue tumour after childhood cancer within 20 years of 3-year survival was 0.23%. In the case–control study, there was a significant excess of STSs in those patients exposed to both radiotherapy (RT) and chemotherapy, which was five times that observed among those not exposed (P=0.02). On the basis of individual radiation dosimetry, there was evidence of a strong dose–response effect with a significant increase in the risk of STS with increasing dose of RT (P<0.001). This effect remained significant in a multivariate model. The adjusted risk in patients exposed to RT doses of over 3000 cGy was over 50 times the risk in the unexposed. There was evidence of a dose–response effect with exposure to alkylating agents, the risk increasing substantially with increasing cumulative dose (P=0.05). This effect remained after adjusting for the effect of radiation exposure

How does one become spiritual? The Spiritual Modeling Inventory of Life Environments (SMILE)

We report psychometric properties, correlates and underlying theory of the Spiritual Modeling Index of Life Environments (SMILE), a measure of perceptions of spiritual models, defined as everyday and prominent people who have functioned for respondents as exemplars of spiritual qualities, such as compassion, self-control, or faith. Demographic, spiritual, and personality correlates were examined in an ethnically diverse sample of college students from California, Connecticut, and Tennessee (N=1010). A summary measure of model influence was constructed from perceived models within family, school, religious organization, and among prominent individuals from both tradition and media. The SMILE, based on concepts from Bandura\u27s (1986) Social Cognitive Theory, was well-received by respondents. The summary measure demonstrated good 7-week test/retest reliability (r=.83); patterns of correlation supporting convergent, divergent, and criterion-related validity; demographic differences in expected directions; and substantial individual heterogeneity. Implications are discussed for further research and for pastoral, educational, and health-focused interventions

A Simple, Inexpensive Device for Nucleic Acid Amplification without Electricity—Toward Instrument-Free Molecular Diagnostics in Low-Resource Settings

Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation).In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented.We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes

Effects of Hydrogen Peroxide on Wound Healing in Mice in Relation to Oxidative Damage

10.1371/journal.pone.0049215PLoS ONE711

Exendin-4 Improves Blood Glucose Control in Both Young and Aging Normal Non-Diabetic Mice, Possible Contribution of Beta Cell Independent Effects

Type 2 diabetes is highly prevalent in the elderly population. Glucagon like Peptide-1 mimetic such as exendin-4 augments post-prandial insulin secretion. However, the potential influence of aging on the therapeutic effects of this peptide has not been well studied. In this study, we examined the glucose regulatory effects of exendin-4 in mice with different ages.We treated 3-month and 20 to 22-month old C57/DBA mice with 10 nM/kg exendin-4 for 10 days with measurements of blood glucose and body weight. We performed OGTT and ITT to evaluate the glucose response and insulin sensitivity. Islet morphology and beta cell mass were measured by immuno-staining and beta cell proliferation was evaluated by BrdU incorporation and PCNA staining. Real-time PCR and western blot were used to measure protein changes in the liver tissue after exendin-4 treatment.Exendin-4 treatment improved glycemic control in both 3-month and 20 to 22-month old mice. In both groups of mice, the blood glucose lowering effect was independent of beta cell function as indicated by unchanged beta cell proliferation, insulin secretion or beta cell mass. Moreover, we found that exendin-4 treatment increased hepatic AKT and FOXO1 phosphorylation and inhibited glucose-6-phosphotase (G6P) and Phosphoenolpyruvate carboxykinase (PEPCK) expression in young mice, but this effect was attenuated in aging mice while the insulin sensitivity showed no change in the young group but significantly improved in aging mice.Based on these data, we conclude that the glucose lowering effect of exendin-4 in normal non-diabetic mice was not blunted by aging. We further showed that although there was slight difference in the glucose modulating mechanism of exendin-4 therapy in young and aged mice, the improved glucose control seemed uncorrelated with increased beta cell mass or insulin secretion

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion

<p>Abstract</p> <p>Background</p> <p>Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion.</p> <p>Methods</p> <p>Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode.</p> <p>Results</p> <p>In group 1 the Pw/Pa ratio decreased by 10 ± 22% from 0.20 ± 0.09 to 0.19 ± 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 ± 15% from 0.22 ± 0.09 to 0.24 ± 0.10 (p = 0.001) when electrical neurostimulation was activated.</p> <p>Conclusion</p> <p>Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.</p