Bladder Dysfunction in Diabetes Mellitus

Diabetic cystopathy is a well-recognized complication of diabetes mellitus, which usually develops in middle-aged or elderly patients with long-standing and poorly controlled disease. It may have broad spectrum clinical presentations. Patients may be asymptomatic, or have a wide variety of voiding complaints from overactive bladder and urge incontinence to decreased bladder sensation and overflow incontinence. This review focuses on pathophysiological mechanisms responsible for urologic complications of diabetes and emphasizing on recent developments in our understanding of this condition. We also tried to shed some light on therapeutic modalities like behavioral, pharmacological, and surgical approaches

Exercise and the Cardiovascular System

There are alarming increases in the incidence of obesity, insulin resistance, type II diabetes, and cardiovascular disease. The risk of these diseases is significantly reduced by appropriate lifestyle modifications such as increased physical activity. However, the exact mechanisms by which exercise influences the development and progression of cardiovascular disease are unclear. In this paper we review some important exercise-induced changes in cardiac, vascular, and blood tissues and discuss recent clinical trials related to the benefits of exercise. We also discuss the roles of boosting antioxidant levels, consequences of epicardial fat reduction, increases in expression of heat shock proteins and endoplasmic reticulum stress proteins, mitochondrial adaptation, and the role of sarcolemmal and mitochondrial potassium channels in the contributing to the cardioprotection offered by exercise. In terms of vascular benefits, the main effects discussed are changes in exercise-induced vascular remodeling and endothelial function. Exercise-induced fibrinolytic and rheological changes also underlie the hematological benefits of exercise

Molecular Mechanisms in Exercise-Induced Cardioprotection

Physical inactivity is increasingly recognized as modifiable behavioral risk factor for cardiovascular diseases. A partial list of proposed mechanisms for exercise-induced cardioprotection include induction of heat shock proteins, increase in cardiac antioxidant capacity, expression of endoplasmic reticulum stress proteins, anatomical and physiological changes in the coronary arteries, changes in nitric oxide production, adaptational changes in cardiac mitochondria, increased autophagy, and improved function of sarcolemmal and/or mitochondrial ATP-sensitive potassium channels. It is currently unclear which of these protective mechanisms are essential for exercise-induced cardioprotection. However, most investigations focus on sarcolemmal KATP channels, NO production, and mitochondrial changes although it is very likely that other mechanisms may also exist. This paper discusses current information about these aforementioned topics and does not consider potentially important adaptations within blood or the autonomic nervous system. A better understanding of the molecular basis of exercise-induced cardioprotection will help to develop better therapeutic strategies

Diabetes and Alpha Lipoic Acid

Diabetes mellitus is a multi-faceted metabolic disorder where there is increased oxidative stress that contributes to the pathogenesis of this debilitating disease. This has prompted several investigations into the use of antioxidants as a complementary therapeutic approach. Alpha lipoic acid, a naturally occurring dithiol compound which plays an essential role in mitochondrial bioenergetic reactions, has gained considerable attention as an antioxidant for use in managing diabetic complications. Lipoic acid quenches reactive oxygen species, chelates metal ions, and reduces the oxidized forms of other antioxidants such as vitamin C, vitamin E, and glutathione. It also boosts antioxidant defense system through Nrf-2-mediated antioxidant gene expression and by modulation of peroxisome proliferator activated receptors-regulated genes. ALA inhibits nuclear factor kappa B and activates AMPK in skeletal muscles, which in turn have a plethora of metabolic consequences. These diverse actions suggest that lipoic acid acts by multiple mechanisms, many of which have only been uncovered recently. In this review we briefly summarize the known biochemical properties of lipoic acid and then discussed the oxidative mechanisms implicated in diabetic complications and the mechanisms by which lipoic acid may ameliorate these reactions. The findings of some of the clinical trials in which lipoic acid administration has been tested in diabetic patients during the last 10 years are summarized. It appears that the clearest benefit of lipoic acid supplementation is in patients with diabetic neuropathy

Antioxidant and Anti-Inflammatory Effects of Exercise in Diabetic Patients

Diabetes is a chronic metabolic disease which is characterized by absolute or relative deficiencies in insulin secretion and/or insulin action. The key roles of oxidative stress and inflammation in the progression of vascular complications of this disease are well recognized. Accumulating epidemiologic evidence confirms that physical inactivity is an independent risk factor for insulin resistance and type II diabetes. This paper briefly reviews the pathophysiological pathways associated with oxidative stress and inflammation in diabetes mellitus and then discusses the impact of exercise on these systems. In this regard, we discuss exercise induced activation of cellular antioxidant systems through “nuclear factor erythroid 2-related factor.” We also discuss anti-inflammatory myokines, which are produced and released by contracting muscle fibers. Antiapoptotic, anti-inflammatory and chaperon effects of exercise-induced heat shock proteins are also reviewed

The role of Calmodulin inhibition in intrathecal Trifluoperazine-induced analgesia

گزارشاتی مبنی بر اثر ضد درد داروهای ضد جنون وجود دارد ولی مکانیسم آن کاملا شناخته شده نیست. از سوی دیگر مقالاتی نیز در مورد اثر ضد درد مهار کننده های کالمودولین در سال های اخیر انتشار یافته است. در بین داروهای ضد جنون تری فلوپرازین یکی از قویترین مهار کننده های کالمودولین می باشد. در این تحقیق بررسی اثر ضد درد تری فلوپرازین مدنظر قرار گرفته و از آنجایی که این دارو اثرات آنتی دوپامینرژیک، آنتی کلینرژیک، آنتی ادرنرژیک و آنتی هیستامینیک نیز دارد سعی شده رابطه اثر ضد درد با تاثیر این دارو بر گیرنده های فوق نیز مورد مطالعه قرار گیرد. بدین منظور بعد از کاتتریزاسیون فضای ساب آراکنوئید موش صحرایی داروهای مختلف بصورت داخل نخاعی تزریق و بعد از 15 دقیقه، حیوانات با تست فرمالین مورد ارزیابی قرار گرفتند. ضمنا باتوجه به اینکه اندازه گیری شدت درد در تست فرمالین وابسته به فعالیتهای حرکتی است، جهت تشخیص عوارض حرکتی داروهای مورد استفاده از تست روتارود استفاده گردید. نتایج حاصل را می توان به شرح زیر خلاصه نمود: دزهای پایین تری فلوپرازین (10µg/rat و 1) اثر ضد درد نشان داد و دز (100µg/rat) بالا منجر به هیپرالژزی (Hyperalgesia) شد. هیچگونه اثر ضد دردی بعد از تزریق داخل نخاعی سولپیراید، آتروپین، فنتول آمین و برموفنیرامین مشاهده نشد. کالمیدازولیوم به عنوان آنتاگونیست کالمودولین به صورت وابسته به دز (250µg/rat و 50 و 10) دارای آثار ضد درد بود. در تزریق همزمان تری فلوپرازین با فیزوستیگمین، هیستامین، بروموکریپتین و نوراپی نفرین تغییری در اثر ضد درد مشاهده نگردید. کلسیم اثر ضد درد کالمیدازولیوم را مهار و اثر ضد درد تری فلوپرازین را کاهش داد. نالوکسان بصورت نسبی باعث کاهش اثر ضد درد تری فلوپرازین گردید درصورتی که بر اثر ضد درد کالمیدازولیوم تاثیر قابل توجه نداشت. باتوجه به آزمایشات فوق می توان نتیجه گرفت که احتمالا اثر ضد درد دزهای پایین تری فلوپرازین نخاعی ناشی از مهار کالمودولین بوده است. با افزایش دوز، آثار دیگر تری فلوپرازین تفوق یافته که منجر به هیپرالژزی شده است. همچنین می توان نتیجه گرفت سیستم اپیوئیدی اگرچه در اثر ضد درد تری فلوپرازین نقش دارد ولی اثر ضد درد مهار کالمودولین جدای از این سیستم می باش

Health Benefits of Fasting and Caloric Restriction

Purpose of Review: Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Recent Findings: Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. Summary: There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.Current Diabetes Reports (2017), 17(12): 12

Responses to oral glucose challenge differ by physical activity volume and intensity : a pilot study.

Background: One hour postprandial hyperglycaemia is associated with increased risk of type 2 diabetes and cardiovascular disease. Physical activity has short-term beneficial effects on post-meal glucose response. This study compared the oral glucose tolerance test results of 3 groups of people with habitually different levels of physical activity. Methods: Thirty-one adults without diabetes (age 25.9 ± 6.6 years; body mass index 23.8 ± 3.8 kg.m-2) were recruited into 3 groups based on self-reported physical activity volume and intensity: Low Activity = < 30 min.day-1 of 'moderate' intensity activity (n = 11), Moderately Active = ≥ 30 min.day-1 of 'moderate' intensity physical activity (n = 10), and Very Active = ≥ 60 min.day-1 of 'intense' physical activity (n = 10). Participants completed an oral glucose tolerance test (50 g glucose) with capillary blood samples obtained at baseline, 15, 30, 45, 60, 90 and 120 minutes post-ingestion. Results: There were no significant differences between groups for age or percentage body fat or glycated haemoglobin (p> 0.05). The groups were significantly different in terms of baseline glucose, gender and BMI and this was accounted for in the analysis. There was a statistically significant effect of physical activity on the one hour postprandial glucose results (p=0.029), with differences between Very Active and Low Activity (p=0.008) groups but not between the Moderately Active and Low Activity groups (p=0.360), even when baseline glucose and gender differences were accounted for. For iAUC there was no significant effect of activity group once gender and bodyfat % had been accounted for. Those in the Low Activity group took an average 13.2 (95% CI: 2.8 – 23.5) minutes longer to reach peak glucose level than those in the Very Active group and this was significant (p=0.015). Conclusion: The results suggest that high levels of physical activity have a beneficial effect on postprandial blood glucose profiles when compared to low and moderate levels of activity

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer