Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus.

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean ± SD age: 58.7 ± 9.2 years, body mass index: 28.2 ± 4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

The importance of paraoxonase 1 activity, nitric oxide and lipid peroxidation in hepatosteatosis.

This study evaluated the changes in oxidative status in hepatosteatosis patients in terms of lipid peroxidation, nitric oxide (NO) and paraoxonase 1 (PON1) activity. A total of 49 patients with hepatosteatosis (29 males and 20 females, mean age 47.2 +/- 3.6 years) and 25 healthy subjects (15 males and 10 females, mean age 46.1 +/- 3.2 years) were enrolled in the study. Serum PON1 was measured spectrophotometrically, malondialdehyde (MDA), an end-product of lipid peroxidation, was determined using the thiobarbituric acid method, and NO was assessed using the Griess reaction. Lipid and other biochemical parameters were determined by routine laboratory methods. PON1 activity and NO levels were significantly decreased and MDA levels significantly increased in hepatosteatosis patients compared with healthy subjects. PON1 activity was correlated with MDA level and NO level. In conclusion, oxidative stress seems significantly to suppress PON1 synthesis in hepatosteatosis patients. In addition, oxidative stress and oxidant-antioxidant imbalance may be part of the cytotoxic mechanisms leading to liver cell injury.

Nitric oxide, lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet's disease.

BACKGROUND: One of the prominent features of Behçet's disease (BD) is vasculitis and thrombosis as a result of endothelial dysfunction. Nitric oxide (NO) is responsible for endothelial vasorelaxation and inhibition of platelet adhesion. OBJECTIVES: To assess serum total NO, erythrocyte superoxide dismutase (SOD), whole blood glutathione peroxidase (GSH-Px), plasma total antioxidant status (TAS) and plasma malondialdehyde (MDA) in patients with BD and to correlate their levels with disease activity. METHODS: The study group consisted of 49 patients with BD and 26 healthy control subjects. None of the subjects was given a standardized diet. Patients with any systemic disease were excluded. Patients with BD were randomized to two groups according to their disease activity (active/inactive, 26/23). We measured serum total NO levels using the enzyme-linked immunosorbent assay method, and SOD, GSH-Px, TAS and MDA levels by spectrophotometric methods. RESULTS: In patients with active disease (n = 26), serum total NO levels were found to be significantly decreased when compared with the inactive (n = 23) and control (n = 26) groups. Levels were also significantly lower in patients with inactive disease and in total BD patients (n = 49) than in the controls. GSH-Px activities and TAS levels were significantly lower in total BD patients than those in the controls. Patients with active disease and total BD patients exhibited markedly higher MDA levels than the control subjects. MDA levels in the patients with active disease were also found to be elevated compared with the patients with inactive disease. CONCLUSIONS: We conclude that changes in parameters associated with oxidative stress such as NO-related processes, activities of antioxidant enzymes in the bloodstream and erythrocytes and total plasma antioxidant capacity are involved in the aetiopathogenesis of the vasculitis seen in BD.

Transfusional transmitted virus seroprevalence in asymptomatic HBsAg (+) hepatitis B carriers.

BACKGROUND: The aim of this study was to evaluate the transfusional transmitted virus (TTV) seroprevalence in asymptomatic HBsAg (+) patients and to assess the influence of TTV on the course of these patients. METHODS: Sixty asymptomatic HBV carriers were included and 31 healthy volunteers served as controls. Cases were followed at 6-month intervals for a total duration of 4 years. RESULTS: In the asymptomatic carrier group, 31 patients (51.7%) had a history of surgery and 10 (16.7%) had a history of blood transfusions. TTV-DNA was detected in 45 of these patients (75%). In the control group, 12 patients (38.7%) had a history of surgery and 2 had (6.5%) a history of blood transfusions. TTV-DNA was found in 20 (64.5%) of these subjects. The incidence of TTV-DNA positivity was not significantly different between the two groups (P > 0.05). CONCLUSION: In spite of the common occurrence of HBV and TTV, TTV-DNA was also detected in 64.5% of healthy controls. Furthermore, during 4 years of follow up, TTV had no detrimental effects on the course of asymptomatic HBV carriers. These results suggest that the hepatic injury due to TTV is insignificant in this group of patients.

Lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet's disease.

To evaluate plasma lipid peroxidation and enzymatic and non-enzymatic antioxidant systems in patients with Behçet's disease, plasma malondialdehyde levels and total antioxidant status, erythrocyte superoxide dismutase and whole blood glutathione peroxidase activities were studied in 15 patients with active disease and in 30 with inactive disease, and compared with 20 age-matched healthy control subjects. Plasma malondialdehyde levels were significantly higher in patients with active Behçet's disease than in patients with inactive disease, who had significantly higher levels than control subjects. The plasma total antioxidant status of both groups of patients was significantly lower than that of controls. Furthermore, whole blood glutathione peroxidase activity was significantly lower in patients with active versus inactive Behçet's disease. There were no significant differences in erythrocyte superoxide dismutase levels between the groups. In conclusion, there is an increase in oxidative stress in Behçet's disease. Despite this stress, the antioxidant system is deficient and inadequate, especially in patients who are in an active phase of the disease.