Current pharmaceutical design
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Methamphetamine (METH) is one of the most widely distributed psychostimulants worldwide. Despite active counter measures taken by different countries, neither overall usage of METH nor the frequency of repeat users has reduced over the past decade. METH induces abuse and dependence as it acts on the central nervous system and temporarily stimulates the brain. The recidivism rate for abuse of stimulants in Japan is very high and therefore prevention of repeated usage is paramount. However, we lack information about the relationship between METH users and genomic changes in humans in Japan, which would provide important information to aid such efforts. ⋯ These results suggest that the DNA methylation rate of SHATI/NAT8L promotor regions offers a new diagnostic method for METH usage.
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Anticoagulation therapy is the cornerstone of treatment in acute vein thrombosis (DVT) and it aims to reduce symptoms, thrombus extension, DVT recurrences, and mortality. The treatment for DVT depends on its anatomical extent, among other factors. Anticoagulation therapy for proximal DVT is clearly recommended (at least for 3 months), while AT for isolated distal DVT should be considered, especially in the presence of high thromboembolic risk factors. ⋯ NOACs offer a simple route of administration (oral agents), a rapid onset-offset of their action along with a good efficacy and safety profile in comparison with Vitamin K Antagonists (VKAs). However, there are issues about their efficacy and safety profile in specific populations with high thromboembolic and bleeding risks, such as renal failure patients, active-cancer patients, and pregnant women, in which VKAs and heparins were the standard care of treatment. Since the available data are promising for the use of NOACs in end-stage chronic kidney disease and cancer patients, several ongoing randomized trials are currently trying to solve that issues and give evidence about the safety and efficacy of NOACs in these populations.
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Insulin resistance, dyslipidemia and chronic inflammation are important risk factors for cardiovascular diseases (CVD). Hence, vitamin D supplementation might be an appropriate approach to decrease the complications of CVD. This systematic review and meta-analysis aimed to determine the effects of vitamin D supplementation on glycemic control, lipid profiles, and C-reactive protein among patients with coronary artery disease. ⋯ This meta-analysis demonstrated the beneficial effects of vitamin D supplementation on improving glycemic control, HDL-cholesterol and CRP levels among patients with CVD, though it did not affect triglycerides, total- and LDL-cholesterol levels.
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The findings of trials investigating the effects of L-carnitine administration on serum lipids are inconsistent. This meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effects of L-carnitine intake on serum lipids in patients and healthy individuals. ⋯ This meta-analysis demonstrated that L-carnitine administration significantly reduced triglycerides, total cholesterol and LDL-cholesterol levels, and significantly increased HDL-cholesterol levels in the pooled analyses, but did not affect VLDL-cholesterol levels; however, these findings were not confirmed in our subgroup analyses by participant's health conditions, age, dosage of L-carnitine, duration of study, sample size, and study location.
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Sepsis and septic shock are known to prompt multiple organ failure including cardiac contractile dysfunction, which is typically referred to as septic cardiomyopathy. Among various theories postulated for the etiology of septic cardiomyopathy, mitochondrial injury (both morphology and function) in the heart is perceived as the main culprit for reduced myocardial performance and ultimately heart failure in the face of sepsis. ⋯ Here we will briefly summarize the recent experimental and clinical progress on myocardial mitochondrial morphology and function in sepsis, and discuss possible underlying mechanisms, as well as the contemporary interventional options.