Ahmet Var

Oxidative stress but not endothelial dysfunction exists in non‐obese, young group of patients with polycystic ovary syndrome

Objective. To determine if oxidative stress and endothelial dysfunction exist at the same time in a young, non‐obese group of patients with polycystic ovary syndrome (PCOS). Design. Cross‐sectional study. Setting. Celal Bayar University, School of Medicine, Manisa, Turkey. Sample. Thirty‐one young, non‐obese patients with PCOS and 23 age‐ and body mass index‐matched controls. Methods. Following clinical and biochemical diagnosis, malonyldialdehyde (MDA), superoxide dismutase (SOD), von Willebrand Factor (vWF), and nitric oxide (NO) levels of patients and controls were measured and compared. Main outcome measures. To find out oxidative stress and endothelial dysfunction parameters. Results. MDA (0.12±0.03 vs 0.10±0.03, p = 0.01) and SOD (8.0±0.7 vs 7.28±0.8, p = 0.001) levels were significantly higher in PCOS group while there was no difference in vWF (527.2±280.1 vs 568.1±276.8, p>0.05) and NO levels (169.9±47.4 vs 168.9±80, p>0.05). When the results of the PCOS patients were divided into two subgroups in terms of insulin resistance (IR– and IR +), the IR– subgroup had significantly higher MDA levels compared to the control (0.125±0.03 vs 0.101±0.03, p = 0.03). Though IR+ group also had higher MDA than the control group, it did not reach to a significant level (0.117±0.05 vs 0.101±0.03, p>0.05). Both IR– and IR+ groups had significantly higher SOD levels compared with control group (7.99±0.7 vs 7.28±0.8, p = 0.009 and 8.22±0.8 vs 7.28±0.8, p = 0.03, respectively). vWF and NO levels were not different among these three groups (p>0.05). Conclusions. Oxidative stress is prominent while endothelial dysfunction does not exist in young, non‐obese patients with PCOS.

Endothelial Dysfunction in Preeclampsia

Endothelial dysfunction underlies the pathogenesis of preeclampsia, but its mechanism has not yet been completely understood. Elevated oxygen free radicals may partially explain the endothelial cell damage. In this study, we have aimed to measure homocysteine (Hcy) and nitric oxide (NO) levels as endothelial dysfunction markers in preeclamptic women. Nineteen preeclamptic (33.9 ± 1.4 weeks) and 15 gestational-age-matched normal pregnant women (35.5 ± 0.7 weeks) were included in the study. Mean NO level was significantly lower (p < 0.001) and mean Hcy level was significantly higher (p < 0.001) in the preeclamptic group. Elevated Hcy and oxygen free radical levels could decrease NO levels due to the reaction with each other and reduced NO may increase blood pressure and ischemia in preeclamptic patients. We have concluded that increased Hcy and oxygen free radical levels, and decreased NO levels are closely associated with preeclampsia-related endothelial dysfunction.

Atherogenic profile in preeclampsia.

Abstract. Atherosis is accepted to underlie the pathogenesis of preeclampsia, therefore we aimed to determine malonyldialdehyde (MDA) levels as a marker of lipid peroxidation, and lipoprotein(a) (Lp(a)), apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B) levels as a marker of atherogenic profile in preeclamptic and normal pregnant women. Twenty preeclamptic and 20 gestational-age matched normal pregnant patients were enrolled in the study, mean gestational ages for the preeclamptic and the control group were 33.9±1.4 and 35.5±0.7 weeks, respectively. Blood was withdrawn from the patients soon after diagnosis, and from the controls at their routine prenatal visits. MDA levels was significantly higher in preeclamptic patients (P=0.0003), but no difference was observed in Apo A-1 and Apo B and Lp(a) levels between the 2 groups. We consider that higher MDA was due to oxidative stress seen in preeclampsia, and similar Apo A-1 and Apo B and Lp(a) levels were due to lack of systemic atherosis.

The beneficial effects of physical exercise on antioxidant status in asthmatic children

BACKGROUND The pathogenesis of asthma involves both airway inflammation and an oxidant/antioxidant imbalance. It is demonstrated in asthmatic adults that exercise programmes improve lung function, a mechanism yet to be elucidated. The purpose of this study was to investigate the possible beneficial effects of physical exercise on antioxidant status in asthmatic children which may lead to ameliorated lung function. METHODS The study enrolled thirteen control and thirty asthmatic children. The asthmatic group was subdivided into two: the first group receiving only pharmacological treatment (n=15) and the second receiving pharmacological treatment with exercise programme (n=15) for 8 weeks. Blood samples were drawn from the subjects before and after treatment periods. As oxidant stress markers blood levels of malondialdehyde (MDA) and total nitric oxide (NO), and as antioxidant status, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activities were assessed. RESULTS Before any treatment was initiated, MDA and NO levels in the asthmatic group were significantly higher than the controls (3.40±0.96 nmol/ml vs 2.46±0.58 nmol/ml, and 12.53±2.10 vs 9.40±1.39 micromol/L, respectively). Both SOD (p=0.0001) and GSH-Px (p=0.023) activities were significantly lower in the asthmatic group. Pharmacological treatment and exercise programme together significantly improved lung performance and decreased the levels of oxidant stress markers, in concordance with a significantly increase in antioxidant enzyme activity measures when compared to the pharmacological treatment. CONCLUSION Structured exercise programme in asthmatic children resulted in better lung function, which may be attributed to its effect on antioxidant status.

Abdominal insufflation-deflation injury in small intestine in rabbits.

OBJECTIVE To investigate the effect of increased intra-abdominal pressure followed by abdominal deflation on small intestine with or without previous intestinal ischaemia. DESIGN Randomised experimental study. SETTING University hospital, Turkey. ANIMALS 78 male New Zealand white rabbits. INTERVENTIONS Experiment 1: 30 rabbits (10 in each group) were subjected to intra-abdominal pressure of 0 mmHg (controls), 15 mmHg or 25 mmHg for 60 minutes. Experiment 2: 48 rabbits were divided into four groups (n = 12 in each). The first comprised sham-operated controls. In the other 3, the superior mesenteric artery was occluded for 60 minutes. Reperfusion was started and maintained under intra-abdominal pressure of 0 mmHg, 15 mmHg, or 25 mmHg for one hour. Intestinal specimens were obtained five and 60 minutes after abdominal deflation in the pressure groups and at identical times in the other groups in both experiments. MAIN OUTCOME MEASURES Intestinal malondialdehyde concentration, wet:dry intestinal weight ratio, and mucosal injury score under light microscopy. RESULTS In experiment I the malondialdehyde concentration, wet:dry weight ratio, and mucosal injury scores were higher in the 25 mmHg group than in the other groups in both specimens. There was a significant increase in malondialdehyde concentration in the 15 mmHg group in only the 5-minute specimen. In experiment 2, except for the wet:dry weight ratio in the 5-minute specimen in the 15 mmHg group, there were significant increases in malondialdehyde concentration, wet:dry weight ratio, and mucosal injury score in all groups except controls in both specimens. Malondialdehyde concentration and wet:dry weight ratio were higher in the 25 mmHg group than in the 0 mmHg group in the 60-minute specimen, and higher than the 15 mmHg group in both specimens. Wet:dry weight ratio was less in the 15 mmHg group than the 0 mmHg group in both specimens. Mucosal injury score was higher in the 25 mmHg group than the other groups in both specimens. CONCLUSION Increased intra-abdominal pressure for 60 minutes followed by abdominal deflation led to an ischaemia-reperfusion-like injury in normal small intestine in rabbits, and added to reperfusion injury in the ischaemic small intestine at an intra-abdominal pressure of 25 mmHg.

Oxidative stress impairs endothelial nitric oxide levels in Behçets’ disease

Background: Behçet’s disease (BD) is an inflammatory vasculitis. Endogenous nitric oxide (NO), produced by endothelial cells, has pleiotropic effects such as vasodilatator, antiplatelet, antiproliferative. Reactive oxygen species (ROS) are produced at sites of endothelial inflammation. ROS target polyunsaturated lipids, which results in malondialdehyde (MDA) production. Objective: The aim was to investigate the oxidative stress in BD patients by measuring MDA and total antioxidant status (TAS) levels and to establish a possible relationship with respect to NO levels regarding disease activity. Materials and methods: 55 BD patients (30 active/25 inactive) and 20 healthy volunteers were included in the study. Blood samples were drawn following an overnight fasting. TAS and MDA levels were determined spectrophotometrically. Serum nitrite (NO2−) and nitrate (NO3−) levels were measured to estimate NO production. Data were expressed as mean ± SD. Results: TAS levels were significantly lower in BD patients than the controls (1.19 ± 0.34 vs. 3.29 ± 0.89 mmol/L). In the active BD group, MDA levels (0.36 ± 0.19 nmol/mL) were significantly higher than both the inactive BD group (0.25 ± 0.18 nmol/mL) and controls (0.18 ± 0.41 nmol/mL). NO levels were significantly lower in the active group compared to the inactive group (18.0 ± 2.80 vs. 19.40 ± 2.70 µmol/L). MDA levels correlated negatively with NO levels in the active group. Conclusion: Decreased NO levels mediated by increased oxidative stress significantly contribute to endothelial dysfunction observed in BD.

Interleukin-6 levels in hyperemesis gravidarum.

Introduction.Hyperemesis gravidarum (HG) is associated with higher levels of serum β-hCG levels and hyperthyroidism. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is reported to enhance secretion of β-hCG from trophoblastic cell line.Methods.We measured serum levels of IL-6, thyroid hormones and β-hCG of hyperemetic patients and gestational age-matched controls to search for a difference between the two groups.Results.There was a significant difference in β-hCG (p=0.028), though IL-6 levels were higher in the hyperemetic group, it did not reach a significant level. Interleukin-6 positively correlated with β-hCG (r=0.38 and p=0.13).

The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-α and anabolic bone parameters

In this prospective study, we aimed to evaluate the effect of simvastatin on bone metabolism and the correlation between changes in bone turnover parameters and serum cytokine levels. For this purpose, 38 postmenopausal subjects with hypercholesterolemia (>240 mg/dl), not on osteoporosis treatment, were studied. Simvastatin was started at a dose of 20 mg daily and continued for 3 months. Six patients were excluded from the study during the follow-up period. Pre- and post-treatment samples were analyzed for bone alkaline phosphatase (BAP) and osteocalcin (OCL), as markers of bone formation; for carboxyterminal telopeptide of collagen I (CTX), as a marker of bone resorption; and for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) cytokine levels. Total cholesterol level was decreased from 262.1 ± 30.9 to 210.2 ± 35.6 mg/dl after simvastatin treatment (P < 0.0001). While no significant change was observed in serum CTX level, BAP and OCL levels were significantly increased (from 120.8 ± 56.6 to 149.5 ± 57.6 IU/l [P = 0.008], and from 20.8 ± 12.6 to 34.7 ± 18.4 µg/l [P = 0.015], respectively). In the analysis of cytokines, while no significant change was observed in IL-6 levels, the TNF-α level was found to be significantly decreased after simvastatin treatment (from 77.9 ± 31.6 pg/ml to 23.5 ± 12.6 pg/ml [P = 0.021]). Individual changes in TNF-α levels showed a moderate negative correlation with the individual changes in BAP and OCL levels (r = −0.550 [P = 0.001], and r = −0.497 [P = 0.004], respectively). In conclusion; 20-mg daily simvastatin treatment for 3 months significantly increased BAP and OCL levels (markers of bone formation) in hypercholesterolemic postmenopausal subjects, without affecting bone resorption. These findings support the idea that simvastatin has an anabolic effect on bone formation. Additionally, the presence of a negative correlation between TNF-α levels and the anabolic bone parameters suggests that a cytokine-lowering effect of simvastatin may also be involved in the remodeling process and could exert some additive beneficial effect on bone metabolism.

Are Human Adenovirus-5 and 36 Associated With Obesity in Children?

Objectives The aims of this study were to determine the association between adenovirus-5– and adenovirus-36–specific antibodies and obesity in children and to investigate their relationship with serum lipid and leptin levels. Methods A cross-sectional study was performed on a total of 120 children who were divided into subgroups according to body mass index percentile as obese (≥95th percentile) or nonobese (<95th percentile). The presence of adenovirus-36 and adenovirus-5–neutralizing antibodies was investigated by using the serum neutralization assay. Serum leptin levels were determined by microenzyme immonoassay; high-density lipoprotein, low-density lipoprotein, triglyceride, and cholesterol levels were measured by chemiluminescence method. Results The presence of adenovirus-5–specific antibodies was 28.3% and 6.6% in the obese children and in non–obese children, respectively (P = 0.02). The frequency of adenovirus-36–specific antibodies was significantly greater (P = 0.018) in the obese children (26.6%) than in the non–obese children (10.0%). Serum leptin level of the obese group were significantly higher than that of the non–obese group (P = 0.000). Conclusions Our data support the association between obesity and the presence of specific antibodies to adenovirus-36 and adenovirus-5 in children. Our research has the feature of being the first national study to indicate the relationship between adenovirus-36 and human obesity as well as the first international study to indicate the relationship between adenovirus-5 and human obesity.

Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats

Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30 mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10 mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6 g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5 mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes.