The role of metformin response in lipid metabolism in patients with recent-onset type 2 diabetes: HbA1c level as a criterion for designating patients as responders or nonresponders to metformin

Background: In this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods: A total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000mg twice daily): responders (patients showing >1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily. Principal Findings: HbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036). Conclusions: Metformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders. © 2016 Kashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Analysis of Receptor’s Distribution in Entorhinal Cortex after Induction of Spreading Depression in Juvenile Rats

Spreading depression (SD), discovered by Leao in 1944, is a pathophysiological wave which propagates slowly in the brain (3 mm/min) and cause dramatic ionic and hemodynamic changes. SD appears to act through several mechanisms and receptors which have not completely understood. Here, we studied the effect of inhibitory system in animal model of SD using immunohistochemistry technique. After implanting recording electrodes and cannula over the brain, repetitive SD was induced by KCl injection (2 M) in juvenile rats for four consecutive weeks. Then all rats were decapitated and the brains removed. Mean number of dark neurons in entorhinal cortex were determined using Toluidine blue staining. To identify the prevalence and distribution of γ-aminobutyric acid A (GABA-A) subunit receptors and glutamic acid decarboxylase (GAD), immunohistochemistry technique was performed. The mean number of SD induced by KCl injection was statistically increased during four weeks of experiments (P=0.036). The mean number of dark neurons in entorhinal cortex was significantly increased in SD group compared to sham rats (P≤0.001). Also, expression of GAD 65 receptor in the Entorhinal cortex significantly increased in SD group compare to control group (P<0.05). GABA-Aα and GABA-Aβ receptors didn’t show significant change in that region. These data suggest that SD is able to damage neural cells and also it could lead to enhancement of GAD, the enzyme which is responsible for synthesizing an important inhibitory neurotransmitter, GABA receptor, in the central nervous system. Keywords: Cortical Spreading Depression, Entorhinal Cortex, Gamma-Aminobutyric Acid

Stress among medical students of Gorgan (South East of Caspian Sea), Iran

Objective: This study aims to estimate the prevalence of psychological stress and association between the levels of stress and study variables among Gorgan medical students. Materials and methods: All three year medical students (129 basic sciences students) in Gorgan Faculty of Medicine, Golestan University of medical Sciences, were asked to complete the Kessler 10 questionnaire. Results: The findings showed mild, moderate and severe stress among 26.22%, 20.50% and 14.75% study subjects. 39.35% of medical students had no stress. There was statistically significant association between year of study and stress levels (p= 0.040). Conclusion: The results indicate that there is a decrease in the psychological health of first year medical students. Provided that stress management courses are organised by medical schools, when the students arrive, they will cope up with the stress in coming years. These courses may reduce the negative effects of stress on medical students. By providing such courses and reducing stress level, medical students may improve their medical education

Rate-dependent and antiarrhythmic reentrant tachycardia (AVNRT) effects of simvastatin in isolated rabbit atrioventricular nodal model

Background and purpose: Several previous studies have shown the direct and indirect effects of statins on supraventricular and ventricular arrhythmia. The purpose of the present study is to determine (1) whether Simvastatin modifies the rate-dependent properties of the AV node, (2) to what extent such changes are related to effect of Simvastatin on the basic properties of AV nodal conduction and refractoriness. Materials and methods: AV nodal refractoriness (AVERP & AVFRP) and rate dependency protocols Fatigue and Facilitation were used to assesse the electrophysiological properties of AV node. We used an isolated perfussed rabbit with AV nodal preparation in one group (N=8). The stimulation protocols were carried out during control phase and in the presence of various concentrations of Simvastatin (0.5 , 0.8 , 1, 3 ,10 μm). Results: Simvastatin in concentration-dependent manner successfully prolonged effective and functional nodal refractory period (AVERP & AVFRP). Also an increase in Wenckebach cycle length was observed. Simvastatin in high concentration (3,10 μm) increases the arrhythmia threshold. Various concentrations of simvastatin increased fatigue, but it reached to significant level only at 30 μM. Conclusion: Simvastatin has potential anti-AVNRT effects by elevating arrhythmia threshold and prolongation of nodal refractoriness

Alleviation of experimental allergic encephalomyelitis in C57BL/6 mice by Soy Daidzein

Experimental allergic encephalomyelitis (EAE) is considered as the murine model of multiple sclerosis. Daidzein a phytostrogenic compound of soy is known to impose immunomodulatory and antioxidative effects. We conducted this study to assess the potential protective and therapeutic effects of daidzein on allergic encephalomyelitis. C57BL/6 mice were induced with allergic encephalomyelitis using myelin oligodendrocyte glycoprotein (35-55) and received daidzein or dimethyl sulfoxide as the vehicle control. To assess the protective effect of daidzein, the mice were administered with 20 mg/kg of daidzein from 21 days prior to 21 days post EAE induction on a daily basis. To evaluate the therapeutic effect of daidzein, mice were fed with 300 mg/kg daidzein after the appearance of the first clinical signs for 10 days. One day after the last gavage, the mice were sacrificed. Spleen and brain were removed for further histological and immunological analysis. Feeding mice with low dose of daidzein prior to disease induction did not affect disease severity. However, treating with high dose of daidzein after the onset of the disease reduced interferon-3 and interleukin-12 secretion, enhanced interleukin-10 production, suppressed lymphocyte proliferation, and decreased cytotoxicity as judged by lactate dehydrogenase release. In conclusion, daidzein reduced the extent of demyelination and disease severity. Chronic oral therapy with low dose of daidzein did not prevent experimental autoimmune encephalomyelitis. However, high doses of daidzein could prohibit disease exacerbation. © Summer 2014, Iran J Allergy Asthma Immunol. All rights reserved

Effects of intermittent fasting on experimental autoimune encephalomyelitis in C57BL/6 mice

Several religions recommend periods of fasting. One of the most frequently asked questions of MS patients before the holy month of Ramadan is weather fasting might have an unfavorable effect on their disease course. This debate became more challenging after the publication of experimental studies suggesting that calorie restriction prior to disease induction attenuates disease severity. We conducted this study to assess early and late effects of fasting on the animal model of MS, known as autoimmune encephalomyelitis. EAE was induced in the C57BL/6 mice, using Myelin Oligodendrocyte Glycopeptide (MOG) 35-55 and they fasted every other day either after the appearance of the first clinical sign or 30 days after disease induction for ten days. Thereafter, the mice were sacrificed for further histological and immunological evaluations. Intermittent fasting after the establishment of EAE did not have any unfavorable effect on the course of disease. Moreover, fasting at the early phase of disease alleviated EAE severity by ameliorating spinal cord demyelination. Fasting suppressed the secretion of IFN-γ, TNF-α and raised IL-10 production in splenocytes. Fasting was also associated with a lower percent of cytotoxicity. Intermittent fasting not only had no unfavorable effect on EAE but also reduced EAE severity if started at early phase of disease. © Summer 2016, Iran J Allergy Asthma Immunol. All rights reserved

Studies of Seed Characteristics of Ecotypes of Lucerne, \u3cem\u3eBromus\u3c/em\u3e and \u3cem\u3eAgropyron\u3c/em\u3e in Response to \u3cem\u3eFusarium Oxysporum\u3c/em\u3e and \u3cem\u3eF. Solani\u3c/em\u3e

Vigorous seeds and seedlings are more resistant to pathogens than non-vigorous seeds and seedlings (Kim, 1994). Therefore, it is necessary to assess seed and seedling performance in response to seed borne fungi

Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer

Background: Genistein (GEN), a naturally occurring flavonoid present in soy bean, has attracted scientific interest for its possible benefits in cancer. Objective: The potential immunomodulatory effects of genistein on the immune system and against TC-1 tumor cell line were evaluated in adult female C57BL/6 mice. Methods: Mice were treated with GEN 10 days before to 10 days after the tumor induction. Thirty days after the last GEN treatment, lymphocyte proliferation, Lactase Dehydrogenase (LDH) cytolytic activity and cytokine secretion were analyzed in GEN and control groups. Results: The results showed that ingestion of genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment with genistein also caused a significant increment in interferon gamma (IFN-γ). In addition, the treatment achieved significant therapeutic effect in tumor models compared to the control group. These results indicated that the effect of GEN on tumor growth may be attributed to its effect on lymphocyte proliferation, cytolytic activity and IFN-γ production. Conclusion: These results demonstrate that GEN exerts an immunomodulatory effect in a mouse model of Human Papillomavirus (HPV) associated-cervical cancer

Studies of Seed Characteristics of Ecotypes of Lucerne, \u3cem\u3eBromus\u3c/em\u3e and \u3cem\u3eAgropyron\u3c/em\u3e in Response to \u3cem\u3eFusarium Oxysporum\u3c/em\u3e and \u3cem\u3eF. Solani\u3c/em\u3e

Vigorous seeds and seedlings are more resistant to pathogens than non-vigorous seeds and seedlings (Kim, 1994). Therefore, it is necessary to assess seed and seedling performance in response to seed borne fungi