OBJECTIVE -Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of L-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation. RESEARCH DESIGN AND METHODS-A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC ϩ ARG for 6 months.RESULTS -The NAC ϩ ARG treatment caused a reduction of both systolic (P Ͻ 0.05) and diastolic (P Ͻ 0.05) mean arterial blood pressure, total cholesterol (P Ͻ 0.01), LDL cholesterol (P Ͻ 0.005), oxidized LDL (P Ͻ 0.05), high-sensitive C-reactive protein (P Ͻ 0.05), intracellular adhesion molecule (P Ͻ 0.05), vascular cell adhesion molecule (P Ͻ 0.01), nitrotyrosine (P Ͻ 0.01), fibrinogen (P Ͻ 0.01), and plasminogen activator inhibitor-1 (P Ͻ 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P Ͻ 0.02). HDL cholesterol increased (P Ͻ 0.05). No changes in other parameters studied were observed.CONCLUSIONS -NAC ϩ ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients. Diabetes Care 31:940-944, 2008

A high-glucose meal produces an increase in oxidation parameters in patients with DMT2. The administration of NAC reduces the oxidative stress and, by doing so, reduces the endothelial activation. In conclusion, NAC could be efficacious in the slackening of the progression of vascular damage in DMT2.

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from l-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). The GSH red blood cell concentration was significantly lower in ED than in C (X +/- SD; 1782.12 +/- 518.02 vs. 2269.20 +/- 231.56 mumol/L, p < 0.001). In particular, GSH was significantly reduced in ED/DM vs. ED/wDM (1670.74 +/- 437.68 vs. 1930.63 +/- 581.01 micromol/L, p < 0.01). In DM, GSH was significantly lower than in C and significantly higher than in ED/DM (2084.20 +/- 118.14 vs. 2269.20 +/- 231.56 and vs. 1670.74 +/- 437.68 micromol/L, p < 0.002 and p < 0.001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r = -0.34, p < 0.01) and with the duration of DM (r = -0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.

Varicocele is a common cause of male infertility; it can be treated by percutaneous retrograde embolization of the internal spermatic vein in order to improve sperm parameters and male fertility. The aim of this study was to verify the improvement of semen parameters after varicocele retrograde sclerotherapy. We evaluated 223 patients with left (206) or bilateral (17) varicocele (mean age +/- SD, 27.3 +/- 4.7 yr, range 18-37) by clinical, Doppler and seminal examinations; all the patients underwent phlebography, using 5F Cobra catheter from the right femoral vein access to the internal spermatic vein and varicocele sclerosing with Hydroxy-polyaethoxydodecanol. Doppler and seminal examinations 6 months after sclerotherapy were requested for the follow-up. Sixty-seven patients with left or bilateral varicocele who did not undergo sclerotherapy were studied as controls. Six months after sclerotherapy, a complete resolution of left varicocele was present in 172 patients (77.1%), while a partial improvement was obtained in 34 patients (15.3%). In these 206 patients seminal examination showed a significant improvement of sperm concentration (mean +/- SEM, 52.1 +/- 4.1 vs 44.2 +/- 3.6 million/ml, p = 0.002) and progressive motility (40.5 +/- 2.2 vs 33.3 +/- 2.0%, p = 0.0001), but not of normal sperm morphology (38.9 +/- 2.3 vs 37.4 +/- 2.1%, ns). In the control group no significant variations of seminal parameters were observed 6 months after the basal examination. In conclusion, varicocele retrograde sclerotherapy is a well-tolerated technique with a low cost-benefit ratio, able to improve semen parameters.

The aim of this study was to verify the effect of goserelin, a GnRH agonist, in women with post-menopausal virilization. Six patients with post-menopausal virilization and increase in 17-hydroxyprogesterone (17-OHP), total (TT) and free testosterone (FT) levels underwent single subcutaneous administration of goserelin, 3.6 mg. Serum 17-OHP, TT, FT, LH, FSH, E2, delta4 and 3alpha-andro-stanediol glucuronide levels were measured before and 4, 8 and 18 days after goserelin administration. Goserelin administration was followed by progressive inhibition of FSH and LH, which fell to premenopausal levels on day 18, and progressive normalization of androgen parameters. The low E2 levels recorded at baseline were further reduced by goserelin administration. Four patients then underwent ovariectomy while in two patients, rejecting surgical treatment, goserelin treatment was protracted up to 6 and 12 months, respectively, with remission of hyperandrogenism. This study shows that in post-menopausal patients with virilization GnRH agonist allows to confirm the diagnosis of gonadotropin-dependent ovarian hyperandrogenism: its administration induces inhibition of gonadotropin levels, normalization of androgen parameters, and remission of virilization when the treatment is protracted in patients waiting for surgery.