Osman Kostek

Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia

Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Methods Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months. Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed. Conclusions 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.

Increased morning blood pressure surge and coronary microvascular dysfunction in patient with early stage hypertension

Morning blood pressure surge (MBPS) is defined as an excessive increase in blood pressure (BP) in the morning from the lowest systolic BP during sleep, and it has been reported as a risk factor for cardiovascular events in current clinical studies. In this study, we evaluated the association between the rate of BP variation derived from ambulatory BP monitoring data analysis and coronary microvascular function in patients with early stage hypertension. One hundred seventy patients with prehypertension and Stage 1 hypertension who fulfilled the inclusion and exclusion criteria were included in the study. We divided our study population into two subgroups according to the median value of coronary flow reserve (CFR). Patients with CFR values <2.5 were defined as the impaired CFR group, and patients with CFR values ≥2.5 were defined as the preserved CFR group, and we compared the MBPS measurements of these two subgroups. CFR was measured using transthoracic Doppler echocardiography (TTDE). Ambulatory 24-hour systolic and diastolic BP, uric acid, systolic MBPS amplitude, diastolic MBPS amplitude, high-sensitivity C-reactive protein, and mitral flow E/A ratio were statistically significant. These predictors were included in age- and gender-adjusted multivariate analysis; ambulatory 24-hour systolic BP (ß = 0.077, P < .001; odds ratio [OR] = 1.080; 95% confidence interval [CI] [1.037-1.124]) and systolic MBPS amplitude (ß = 0.043, P = .022; OR = 1.044; 95% CI [1.006-1.084]) were determined to be independent predictors of impaired CFR (Hosmer-Lemeshow test, P = .165, Nagelkerkes R(2) = 0.320). We found that increased changes in MBPS values in patients with prehypertension and Stage 1 hypertension seemed to cause microvascular dysfunction in the absence of obstructive coronary artery disease.

Endocan: A New Molecule Playing a Role in the Development of Hypertension and Chronic Kidney Disease?

Recently, endocan—formerly known as endothelial cell‐specific molecule 1 (ESM‐1)—was found to be associated with entities such as cancer, hypertension, renal transplant rejection, and chronic renal failure. Endothelial cells of many organs secrete endocan, but the exact functions of this relatively new molecule have not been elucidated completely. Emerging evidence suggests, however, that endocan plays an important role in inflammation, upregulation of cell adhesion molecules, lymphocyte functions, and endothelial cytoskeleton rearrangement. As suggested above, endocan has a prognostic impact in hypertension, transplant rejection, and chronic renal failure. In the current review, the evidence regarding endocan, hypertension, and chronic renal failure are summarized.

Endocan: A Novel Predıctor of Endothelıal Dysfunctıon ın Obstructıve Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSA) is an independent risk factor for endothelial dysfunction and cardiometabolic diseases. Plasma endocan levels are elevated in a large number of diseases, and is a novel surrogate endothelial cell dysfunction marker. We aimed to assess the role of serum endocan level as a potential mechanism of endothelial dysfunction in OSA patients.

Effects of Low Intensity Exercise Against Apoptosis and Oxidative Stress in Streptozotocin-induced Diabetic Rat Heart.

Background The aim of this study was to investigate the effects of low intensity exercise on heart of streptozotocin (STZ)-induced diabetic rats. Materials and Methods The rats were randomly divided into 3 experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with low intensity exercise); each group contains 8 animals. B and C groups received STZ. Diabetes was induced in 2 groups by a single intraperitoneal (i.p) injection of STZ (40 mg/kg, freshly dissolved in 0,1 M citrate buffer, pH 4.2). 2 days after STZ treatment, diabetes in 2 experimental groups was confirmed by measuring blood glucose levels. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. Animals in the exercise group were made to run the treadmill once a day for 4 consecutive weeks. Exercise started 3 days prior to STZ administration. Results After induction of diabetes, histological abnormalities were observed, including myofibrillar loss, vacuolization of cytoplasm and irregularity of myofibrils. These alterations were attenuated by low intensity exercise. Our data indicates a significant reduction of oxidative stress and apoptosis in cardiomyocytes after exercise. Treatment of diabetic animals with low intensity exercise, decreased the elevated tissue malondialdehyde (MDA) levels and increased the reduced activities of the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in cardiac tissue. Conclusion These findings suggest that low intensity exercise has a therapeutic protective effect in diabetes by decreasing oxidative stress and apoptosis, and by preservation of myocardial integrity.

The effect of CPAP therapy on insulin-like growth factor and cognitive functions in obstructive sleep apnea patients

Cognitive impairment is common among patients with obstructive sleep apnea syndrome (OSAS). In this study, we aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy on serum insulin‐like growth factor‐1 (IGF‐1) levels and cognitive functions in patients with OSAS.

Is serum Klotho protective against atherosclerosis in patients with type 1 diabetes mellitus

OBJECTIVE Klotho deficiency is associated with several metabolic disorders. Two dimensional (2D) longitudinal strain (LS) of left ventricle (LV), carotid artery intima-media thickness (CIMT), flow-mediated dilation (FMD) of brachial artery and epicardial fat thickness (EFT) have been reported to be early predictors of atherosclerosis. We aimed to investigate the relationship between serum Klotho levels and these early predictors of atherosclerosis in patients with type 1 diabetes mellitus (DM). METHODS The study included 45 type 1 diabetic patients and 35 controls. Serum Klotho levels were determined by ELISA method. The patient group was also divided into two subgroups according to serum Klotho levels: high (HK) and low Klotho (LK) groups. EFT, CIMT and FMD were measured according to appropriate recommendations. Speckle tracking analysis was performed using the Echopac software. RESULTS The patient group had significantly lower serum Klotho (p=0.001), FMD (p<0.001) and LS of LV (p<0.001) values, but larger EFT (p<0.001) and CIMT (p<0.001) values than controls. LK subgroup had also significantly lower FMD (p<0.001) and LS of LV (p<0.001) but larger EFT (p=0.002) and CIMT (p<0.001) values than HK subgroup. CONCLUSION Serum Klotho may have a protective effect against atherosclerosis and endothelial dysfunction in type 1 DM.

Morning blood pressure surge is associated with carotid intima-media thickness in prehypertensive patients

Objective Morning blood pressure (BP) surge (MBPS) is defined as an excessive increase in the morning BP from the lowest systolic BP during sleep and is reported as a risk factor for cardiovascular events in current clinical studies. In this study, we aimed to investigate the relationship between MBPS and carotid intima-media thickness (C-IMT) in prehypertensive patients. Patients and methods We evaluated the association between the rate of BP variation derived from ambulatory BP monitoring and C-IMT in patients with prehypertension. Results One hundred and seventy patients with prehypertension were included in the study. All office BP measurements and ambulatory 24-h, day-time, and night-time measurements were similar between each group. C-IMT [0.60 (range: 0.57–0.65) vs. 0.55 (range: 0.50–0.60) cm; P<0.001] and the mean platelet volume [8.7 (range: 7.9–9.1) vs. 7.9 (range: 7.3–8.8)  fl; P=0.002] were significantly higher in the greater MBPS group than the lower group. In multivariate analysis, male sex [odds ratio (OR): 2.271, confidence interval (CI): 1.011–5.100, P=0.047], greater MBPS (OR: 8.474, CI: 3.623–19.608, P<0.001), and elevated mean platelet volume levels (OR: 3.359, CI: 1.978–5.705, P<0.001) were found to be independent predictors of greater C-IMT in prehypertensive patients. Conclusion Our study suggests that greater MBPS is associated independently with C-IMT in prehypertensive patients.

Protective Effects of Curcumin on Intestinal Damage in Cholestatic Rats

ABSTRACT Background: The aim of this study was to evaluate the possible protective effects of curcumin on oxidative stress, cell proliferation, and apoptosis in the rat intestinal mucosa after bile duct ligation (BDL). Methods: A total of 18 male Sprague Dawley rats were divided into three groups: sham control, BDL and BDL+curcumin; each group contain six animals. The rats in the curcumin-treated group were given curcumin (100 mg/kg) once a day orally for 14 days, starting 3 days prior to BDL operation. Following 14 days of treatment, all the animals were decapitated and intestinal tissues samples obtained for biochemical and histopathological investigation. Results: Curcumin treatment was found to significantly lower elevated tissue malondialdehyde levels and myeloperoxidase activity, and to raise reduced glutathione levels in intestinal tissues samples. BDL caused severe histopathological injury, including shortening of the villi, loss of villous epithelium, multiple erosions, inflammatory cell infiltration, necrosis, and hemorrhage into the intestinal wall. Curcumin treatment significantly attenuated the severity of intestinal injury, with inhibition of BDL-induced apoptosis and cell proliferation. Conclusion: Curcumin treatment has a protective effect against intestinal damage induced by BDL. The ability of curcumin treatment is to inhibit BDL-induced oxidative stress, apoptosis, and cell proliferation.

Chronic rhinosinusitis, endothelial dysfunction, and atherosclerosis.

Background Chronic inflammation is associated with accelerated atherosclerosis, endothelial dysfunction (ED), and cardiovascular diseases. Because chronic rhinosinusitis (CRS) is an inflammatory disease, it may be associated with the development of ED and accelerated atherosclerosis. Objective To investigate the relationship between CRS and carotid intima-media thickness (CIMT), flow-mediated dilation (FMD) of the brachial artery, and microalbuminuria. Materials and Methods This cross-sectional study included 38 patients with CRS and 29 healthy controls. In addition to measuring spot urine albumin-creatinine ratios, FMD of the brachial artery and CIMT were assessed noninvasively. Results Patients with CRS had lower FMD scores (p = 0.031), higher CIMT scores (p = 0.005), and a higher urinary albumin-creatinine ratio (p = 0.036) compared with healthy controls. In a multivariate analysis, CIMT and FMD were independently associated with the presence of CRS. However, the relationship between urinary albumin and creatinine, and the presence of CRS was no longer observed. Conclusions CRS is associated with ED and atherosclerosis, as indicated by decreased FMD and increased CIMT in patients with CRS. Further studies are necessary to identify the exact pathophysiologic mechanisms responsible for our findings.