Objective Accumulating evidence connects polycystic ovary syndrome (PCOS) withincreased risk of cardiovascular disease. Endothelial dysfunction is present in PCOS and represents an early, reversible marker of cardiovascular damage. As androgens and renin-angiotensin-aldosterone system are implicated in the atherogenesis process of PCOS, we tested the hypothesis that treatment with spironolactone, an androgen and mineralocorticoid receptor blocking drug,might reverse endothelial dysfunction in PCOS. Patients A total of 30 non-obese PCOS patients, compared with 20 body mass index matched control subjects, were evaluated. PCOS patients were given spironolactone 100 mg dailyin 21-day long intervals followed by a 7-day pause, for 6 months. Measurements Flow-mediated dilatation (FMD), glyceryl trinitrate-induced dilatation, free testosterone, androstenedione, DHEA-sulfate, total, low-density lipoprotein (LDL)-, high-density lipoprotein-cholesterol, and triglycerides were determined at baseline and after 6 months. Results Results are expressed as median (25-75th percentile). At baseline, FMD was significantly lower in PCOS patients than in controls: 6.0 (0.0-11.7) vs 10.2 (6.8-15.9) %, P=0.018. This difference disappeared after 6 months of spironolactone treatment, as FMD in PCOS patients significantly increased to 8.3 (5.7-10.3) %, P=0.034, and was no longer different from controls. In PCOS patients, serum androgen levels did not change during treatment, while total and LDL-cholesterol decreased significantly from 4.8 (4.1-5.1) mmol/l to 4.4 (3.9-4.8) mmol/l and from 2.5 (2.1-3.1) to 2.2. (2.1-2.5) mmol/l, P(0.05 and P(0.05 respectively. Conclusion Treatment with spironolactone normalized endothelial function and improved cholesterol levels in non-obese PCOS patients.
COBISS.SI-ID: 28112345
Objective: Oxidative stress participates in decreasing bone formation and stimulating bone resorption. Furthermore, antioxidant enzymes have been observed to have low protective activity in women with osteoporosis. The aim of the present study was to examine any association of selected gene polymorphisms of the glutathione S-reductase (GSR), superoxide dismutase (SOD1and SOD2), and catalase (CAT) genes, alone or in combination, with the bone mineral density (BMD) values of femoral neck (fn), lumbar spine (ls), andtotal hip (th) in Slovenian postmenopausal women. Methods: The gene polymorphisms of CAT, GSR, SOD1, and SOD2 genes in 468 postmenopausal women were analyzed using restriction fragment length polymorphism and a fluorescent5'-exonuclease genotyping method. BMD_fn, BMD_ls, and BMD_th were measured using dual-energy x-ray absorptiometry. Moreover, univariate statistic analysis and two-way analysis of variance for interaction testing were performed. Results: A significant association of BMD_th values (P = 0.027) was found in genotype subgroups of 423-287G)A GSR polymorphism located in the third intron among postmenopausal women. Furthermore, women with at least one G allele showed significantly higher levels of BMD_fn (P = 0.044), BMD_th (P = 0.009), and BMD_ls (P = 0.043) than those that are AA homozygotes.Interestingly, the 423-287G)A_GSR*1154-393T)A_GSR combination was significantly associated with BMD_fn (P = 0.013) and BMD_th (P = 0.002) in postmenopausal women. Conclusions: The results of our study demonstrate for the first time that antioxidant enzyme GSR gene polymorphisms are significantly associated with BMD, suggesting that the A allele of 423-287G)A GSR polymorphism could contribute to decreased BMD values in postmenopausal women.
COBISS.SI-ID: 3156593
To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria (200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range [IQR]) was 0.32 mL/min per 1.73 m(2) (IQR: 0.16-0.50 mL/min per 1.73 m(2)) on combined therapy, 0.36 mL/min per 1.73 m(2) (IQR: 0.18-0.53 mL/min per 1.73 m(2)) on delapril, and 0.30 mL/min per 1.73 m(2) (IQR: 0.12-0.50 mL/min per 1.73 m(2)) on placebo (P=0.87 and P=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04-0.78; P=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07-0.99; P=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24-0.87; P=0.017) and 0.52 (0.27-0.99; P=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (P=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.
COBISS.SI-ID: še ni v Co