PLASMA NEPRILYSIN LEVELS IN PATIENTS WITH POLYCYSTIC OVARY SYNDROME.

Context: Insulin resistance has been detected in a majority of patients with polycystic ovary syndrome (PCOS). Elevated neprilysin levels are associated with insulin resistance. Objective: The present study aims to investigate plasma neprilysin and its relationship with endocrine and metabolic characteristics in patients with PCOS. Subjects and Methods: Thirty-five premenopausal PCOS patients and 35 healthy volunteers of similar age were included in the study. Demographic characteristics, biochemical and hormonal findings and also plasma neprilysin levels were determined in these patients and healthy controls. Results: In our study, HOMA-IR values were significantly higher in PCOS patients (3.3 ± 1.8) compared with the controls [(1.6 ± 1), p<0.01]. Plasma neprilysin levels were significantly higher in the PCOS group compared to the control group (1502.1 ± 1641.2 vs. 764.6 ± 562.6 pg/mL). There was no difference in plasma neprilysin levels when PCOS patients were classified as overweight-obesity (BMI≥25kg/m2) or non-obesity (BMI<25kg/m2). Conclusion: Our findings revealed significantly higher levels for plasma neprilysin and HOMA-IR values in PCOS patients when compared to controls. No significant differences were noted between obese PCOS patients and non-obese PCOS patients in terms of plasma neprilysin levels.

Effects of thiamine treatment on oxidative stress in experimental diabetes.

AIM: Hyperglycemia, oxidative stress and hyperlipidemia are features of diabetes mellitus. Thiamine has beneficial effects on carbohydrate metabolism and it was proposed that this vitamin has antihyperlipidemic and antioxidant effects. Our aim was to investigate the effects of thiamine on oxidative stress and metabolic changes in streptozotocin (STZ) induced diabetic rats. METHOD: Diabetes was induced by a single intraperitoneal injection of STZ. Thiamine (6 mg/kg) was added to drinking water for five weeks. The rats were divided into four groups: control rats; thiamine treated control rats; diabetic rats; thiamine treated diabetic rats. Plasma and tissue malondialdehyde (MDA) levels were measured by high-performance liquid chromatography and spectrophotometry, respectively. Paraoxonase (PON) and arylesterase (AE) activities were measured with spectrophotometric methods, and erythrocyte superoxide dismutase (SOD) and blood glutathione peroxidase (GSH-Px) activities were determined using commercial kits. RESULTS: Thiamine treatment reduced plasma and tissue MDA levels, serum glucose, total cholesterol and triglyceride levels, and increased serum high density lipoprotein- cholesterol and insulin levels, serum PON and AE, erythrocyte SOD and blood GSH-Px activities. CONCLUSION: Thiamine significantly improves oxidative stress and has hyperinsulinemic and antihyperlipidemic effects so we suggest that thiamine might be used as a supportive therapeutic agent in diabetes (Tab. 2, Fig. 3, Ref. 53).

Total and acylated ghrelin levels in type 2 diabetic patients: similar levels observed after treatment with metformin, pioglitazone or diet therapy.

Ghrelin, a potent gut-brain orexigenic peptide, has a role in stimulation of food intake and long-term regulation of body weight. Metformin and pioglitazone treatment have different effects on body weight. This discrepancy might be related with the effect of these two drugs on plasma ghrelin levels. We investigated the effect of these two drugs on post-prandial acylated and total ghrelin levels in patients with type 2 diabetes. Eleven patients treated with diet, 12 patients treated with 850 mg/day metformin monotherapy and 12 patients treated with 30 mg/day pioglitazone monotherapy for at least 6 months were enrolled in the study. Plasma acylated and total ghrelin levels were investigated at baseline and at the 60 (th), 120 (th), 180 (th), 240 (th) minutes after a mixed meal test. There were no differences between groups in any of baseline metabolic and anthropometric parameters, including acylated and total ghrelin levels. Acylated and total ghrelin concentrations were suppressed similarly after food consumption, and we could not determine any significant difference between the groups at any time interval. A prolonged postprandial suppression of acylated ghrelin concentrations was observed in the pioglitazone treatment group compared with baseline values. In conclusion, total and acylated ghrelin levels after a mixed meal test were similar in type 2 diabetic patients treated with metformin, pioglitazone or diet therapy alone. These results suggest that changes in body weight during metformin and pioglitazone treatment are not associated with plasma ghrelin levels.

Effects of Origanum onites on endothelial function and serum biochemical markers in hyperlipidaemic patients.

The effects of Origanum onites on endothelial function and antioxidative status were investigated in 48 patients with mild hyperlipidaemia who required no drug therapy. All participants were given lifestyle and low-fat dietary advice, however 32 of the patients (study group) were also prescribed 25 ml of aqueous distillate of Origanum onites to be taken after each meal for 3 months. The remaining 16 patients were the control group. Various biochemical markers and endothelial function parameters were measured at baseline and after 3 months. A significantly greater increase in high density lipoprotein-cholesterol and significantly greater decreases in low density lipoprotein-cholesterol, apolipoprotein B, lipoprotein(a) and high sensitivity C-reactive protein occurred in the study group compared with the control group over the 3-month study period. Paraoxonase and arylesterase activities, and flow- and nitroglycerine-mediated dilatation of the brachial artery showed significantly greater increases in the study group compared with the changes in the control group. In conclusion, consumption of Origanum onites distillate had beneficial effects on lipid profiles, antioxidant status and endothelial function in patients with mild hyperlipidaemia.

Oxidative status and prevalent cardiovascular disease in patients with chronic renal failure treated by hemodialysis.

BACKGROUND: Hemodialysis (HD) patients are exposed to oxidative stress which contributes to cardiovascular disease (CVD). The purpose of this study was to investigate the oxidative and antioxidative status in HD patients with (CVD+, n = 38) and without (CVD-, n = 67) prevalent CVD. PATIENTS AND METHODS: A total of 105 HD patients and 21 healthy controls were assessed for lipid peroxidation indices (plasma malondialdehyde (MDA)), oxidizability of apolipoprotein B-containing lipoproteins (apo B-deltaMDA) and red blood cells (RBC-MDA) together with various components of the antioxidant system in plasma (paraoxonase/arylesterase activities, total carotenoids, vitamins C and E) and RBC (superoxide dismutase and glutathione peroxidase activities). RESULTS: Plasma MDA and RBC-MDA were significantly higher, vitamin C and total carotenoid levels were significantly lower in both CVD+ and CVD- HD groups than in the control group. Plasma MDA levels were significantly higher and serum paraoxonase activity, uric acid and albumin levels were significantly lower in patients with CVD+ HD patients compared to those of the CVD- patients. CONCLUSION: This study suggests that the elevated level of plasma MDA and the lower activity of paraoxonase could contribute to the increased incidence of cardiovascular disease in hemodialysis patients.

The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study.

Classical antipsychotics like haloperidol are suggested to increase oxidative stress and oxidative cell injury in the brain. Pro-oxidant effect of haloperidol may influence the course and treatment outcomes of schizophrenia. Dietary supplementation of either antioxidants or omega-3 fatty acids was found to improve symptoms of schizophrenia. Thus we decided to assess the impact of combining omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol. Ongoing haloperidol treatment of 17 schizophrenia patients was supplemented with 1000 mg capsule of omega-3 fatty acids (180 mg EPA+120 mg DHA) bid, vitamin E 400 IU bid and vitamin C 1000 mg/day. Patients were assessed with Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS) over a 4 month period. Gluthatione peroxidase, superoxide dismutase, malondialdehyde, vitamin E and C levels were also evaluated at baseline and at the end of study. BPRS, SANS, SAS and BARS scores obtained at follow-up visits were significantly lower compared to baseline. Superoxide dismutase level was significantly lower at the end of study. No significant differences were detected in other laboratory parameters. Our results support the beneficial effect of the supplementation on positive and negative symptoms of schizophrenia as well as the severity of side effects induced by haloperidol. The effect of supplementation on akathisia is especially noteworthy and it has not been investigated in previous studies.

Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol.

The purpose of this study was to investigate the individual and combined antioxidant effects of menstrual cycle phase-related alterations in blood serum oestradiol concentrations and of dietary vitamin E supplementation on exercise-induced oxidative stress and muscle performance. A group of 18 sedentary women, aged 19-35 years, were given supplements of 300 mg alpha-tocopherol (n = 10) or placebo (n = 8) daily during the course of two menstrual cycles. The subjects exercised the knee isokinetically to exhaustion after cycling submaximally at 50% maximal oxygen uptake during the menstrual and preovulatory phases of their menstrual cycles. Blood samples were taken before and after the exercise, to evaluate haematocrit, plasma lactic acid and malondialdehyde concentrations, erythrocyte antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and apolipoprotein B containing lipoprotein (non-high density lipoprotein, HDL, fraction) oxidation. Serum vitamin E, follicle stimulating hormone, luteinizing hormone and oestradiol concentrations were measured in pre-exercise blood samples. Neither vitamin E supplementation nor oestradiol concentrations influenced SOD and GPx activities or the susceptibility of the non-HDL fraction to oxidation while at rest. Plasma malondialdehyde concentration was unaffected by exercise, however significant reductions in erythrocyte SOD and GPx activities and increased susceptibility of the non-HDL fraction to oxidation were noted after exercise. Exercise-induced changes were reduced when oestradiol concentration was high in the preovulatory phase, independent of the serum vitamin E concentrations. In addition, both pre- (r = 0.58, P < 0.05) and post-exercise (r = 0.73, P < 0.001) GPx activities in placebo administered subjects were positively correlated with oestradiol concentrations. In conclusion, these findings suggest a better protective role of oestradiol against oxidative injury, compared to vitamin E. Exhausting muscle performance was, however, not influenced by vitamin E supplementation and/or cycle-phase related changes in oestradiol concentrations.

Relation between lipoprotein (a) and in vitro oxidation of apolipoprotein B-containing lipoproteins.

OBJECTIVES: To assess the relationship between lipoprotein (a) [Lp (a)] and lipoprotein oxidation in patients with coronary artery disease (CAD). DESIGN AND METHODS: Oxidation of apolipoprotein (apo)B-containing lipoproteins, vitamin E, carotenoids, lipid-lipoprotein levels were determined in 171 CAD and 70 non-CAD subjects. RESULTS: In CAD patients with Lp (a) concentrations >/= 30 mg/dL; total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and apo B levels were significantly higher and lag-time and age were significantly lower than those of CAD patients with Lp (a) concentrations < 30 mg/dL. In non-CAD subjects with Lp (a) concentrations >/= 30 mg/dL; TC, LDL-C, and vitamin E levels were significantly higher and lag-time was significantly lower than those of non-CAD subjects with Lp (a) concentrations < 30 mg/dL. In CAD patients, Lp (a) correlated negatively with lag-time and positively with MDA levels. Lp (a) correlated negatively with lag-time and vitamin E levels in non-CAD subjects. CONCLUSIONS: We have shown that plasma apo B-containing lipoproteins of both CAD and non-CAD subjects with Lp (a) levels >/= 30 mg/dL are more susceptible to in vitro oxidative modification than those of subjects with Lp (a) levels < 30 mg/dL. The relationship between Lp (a) and enhanced susceptibility of apo B-containing lipoproteins to oxidation, appears to support routine investigation of Lp (a).

Effects of smoking on serum lipid and lipoprotein concentrations and lecithin: cholesterol acyltransferase activity.

Cigarette smoking is one of the major risk factors for cardiovascular disease. The mechanism responsible for this association is still unknown. We measured the activity of lecithin: cholesterol acyltransferase (LCAT), a key factor in the esterification of plasma cholesterol and reverse cholesterol transport, and the levels of lipids and apolipoproteins in the serum of 27 cigarette smoking and 31 non-smoking (control) men. We could not find any significant difference among these parameters between the groups. Serum LCAT activity was lower in smokers, but the difference was statistically nonsignificant. We also classified the two groups in respect to their serum lipid levels as hyper- and normolipidemic, we observed that normolipidemic-smokers had lower (p < 0.05) high density lipoprotein-cholesterol (HDL-C) and HDL-ester cholesterol levels compared to the normolipidemic-nonsmokers. While there were no any significant differences between hyperlipidemic-smokers and nonsmokers with respect to any of the parameters. In the end we have got the idea that smoking seems to affect HDL-C and HDL-ester cholesterol levels in the normolipidemic-smokers group, only, Also, LCAT activity tended to be lower in smokers compared to nonsmokers.

Susceptibility of non-HDL fraction to oxidation in experimental nephrotic syndrome.

Hyperlipidemia is a striking feature of nephrotic syndrome (NS) and the lipid profile seen in NS is accepted as atherogenic. Both low density lipoprotein (LDL) and very low density lipoprotein (VLDL) are apolipoprotein B-containing lipoproteins which are accepted as atherogenic. Oxidized-LDL (ox-LDL) has been suggested to play a fundamental role in atherogenesis. In this study, male Sprague-Dawley rats were made nephrotic by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight). We found significant elevation in serum triglycerides, total cholesterol, malondialdehyde, vitamin E levels and total cholesterol/vitamin E ratio and decrease in total protein and albumin levels in the NS group (n:8) compared with the control group (n:9). High density lipoprotein (HDL)-cholesterol and free fatty acid levels were not significantly different between these two groups. Apolipoprotein B-containing lipoproteins (non-HDL fraction) were separated by precipitation and amount of thiobarbituric acid-reactive substances (TBARS) of non-HDL fraction were measured after 60, 90, 120, 180 minutes of incubation with copper sulphate. TBARS levels of non-HDL fraction were significantly higher in the NS group compared with the control group at all of the time periods above. In nephrotic animals, the increased lipid peroxidation was influenced by serum lipids.