Simvastatin reverses cyclosporin A-induced endothelial damage in rats: lipid-lowering-dependent and -independent effects

Cydosporin A [CyA] is the immunosuppressant most frequently used in transplant surgery and in the management of autoimmune diseases. CyA-induced oxidative stress together with dyslipidemia have been implicated in the pathogenesis of vascular dysfunction associating CyA therapy. The present study investigated the possible protective effect of simvastatin, a lipid-lowering drug with potent antioxidant properties, against CyA-induced endothelial damage in male rats. Eighteen male Wistar rats were used. They were divided into 3 groups: control, CyA and CyA + simvastatin. In the control group, rats were administered the vehicle, olive oil; in the CyA group, rats were administered CyA [20 mg/kg/day, s.c. for 14 days] and in the CyA+simvastatin group, rats were co-administered simvastatin [2.5 mg/kg/day, s.c. for 14 days] and CyA. Administration of CyA [20 mg/kg/day, s.c. for 14 days] in male rats resulted in a significant increase in the lipid peroxidation product, malondialdehyde [MDA], and a significant decrease in superoxide dismutase [SOD] activity in plasma. CyA treatment was also associated with a significant increase in plasma nitrite level as well as an elevation in plasma cholesterol, triglycerides [TGs], low density lipoproteins [LDL] and a reduction in high density lipoproteins [HDL] levels. CyA-induced vascular dysfunction was further confirmed by the attenuation of endothelium-dependent relaxations produced by carbachol in rat isolated aortic rings. Co-administration of simvastatin [2.5 mg/kg/day, s.c. for 14 days] with CyA significantly reversed the deleterious biochemical and functional vascular effects that accompanied CyA treatment. The present study provides good evidence that both oxidative stress and dyslipidemia underlie the CyA-induced vascular damage, an effect that could be reversed by simvastatin co-administration

Role of cytogenetic study in diagnosis and management of primary gonadal failure

The present study investigates the clinical, cytogenetic and hormonal features of patients with primary gonadal failure aiming to define the role of cytogenetic study in their diagnosis and management. 30 patients were included in this study. They all had hypogonadism, elevated gonadotropin levels and streak or hypoplastic gonads by sonography. From the results obtained it was concluded that karyotyping is most useful in any patient with delayed sexual development, elevated serum gonadotropins and streak gonads