Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.
Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.
Objective: Several studies have assessed the effect of allopurinol on endothelial function, but these studies were relatively small in size and used different methods of evaluating endothelial function. We conducted a meta-analysis to investigate the effect of allopurinol on both endothelial-dependent and -independent vasodilatation. Methods: Electronic databases, Medline, PubMed, EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical Trials were searched from January 1985 to July 2013 on clinical trials (randomized and non-randomized) which assessed the effect of allopurinol on endothelial function. We conducted a sensitivity analysis to assess the contribution of each study to the pooled treatment effect by excluding each study one at a time and recalculating the pooled treatment effect for the remaining studies. Treatment effect was significant if p < 0.05. We assessed for heterogeneity in treatment estimates using the Cochran Q test and the χ2 statistic (with substantial heterogeneity defined as values >50%). Results: The final analysis consisted of 11 studies (2 observational and 9 randomized). For the endothelial-dependent vasodilatation there were 6 studies, including 257 patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients that reported data on forearm blood flow response to acetylcholine or flow-dependent vasodilatation. Overall, there was a significant increase in the endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI 2.49, 2.89%, p < 0.001; heterogeneity χ2 = 319.1, I2 = 96%, p < 0.001). There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4 studies (73 patients) evaluating forearm blood flow response to sodium nitroprusside as measures of endothelial-independent vasodilatation. The overall analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity χ2 = 9.0, I2 = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium-independent vasodilatation. Conclusions: We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.
OBJECTIVE:The aim of this study is to evaluate the demographic characteristics of critically ill patients and to determine intensive care unit (ICU) mortality and its predictors.METHODS:This study was undertaken in the Istanbul Medeniyet University Göztepe Training and Research Hospital Medical ICU. Between May 2012 and January 2013, 111 patients (53 female, 58 male; mean age, 73.79±14.73, mean length of ICU length stay, 9.1±10.7; prevalence of geriatric patients, 77.5%) were admitted to the ICU. The common indications for ICU admission, prevalence of mechanical ventilation support, hematological and biochemical parameters and their effects on mortality were assessed.RESULTS:The common indications for ICU admission were hemodynamic instability (48.6%), respiratory failure (27.9%) and sepsis (15.3%). Hypertension (46.8%) was the most common comorbidity. Prevalance rates of heart failure and diabetes mellitus were 32.4% and 25.2% respectively. Mortality rate was 52.3% in all patients. Approximately 80% of all deaths was observed within the first fifteen-day. In additon, mortality rate (85.7%) was prominent within patients in need of the mechanical ventilation support. Mechanical ventilation requirement, increased ferritin and vitamin B12 levels were independent risk factors for mortality in critically ill patients (p<0.01, for all).CONCLUSION:Mortality rate was higher in medical ICU. Herein, increased prevalence of geriatric population, concomitant comorbidities and mechanical ventilation requirements may play role.
Although impaired LV diastolic function was detected using conventional parameters, only novel advanced echocardiographic modalities demonstrated impaired bi-ventricular and atrial mechanical functions in patients with sarcoidosis.
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