N-acetylcysteine is able to reduce the oxidation status and the endothelial activation after a high-glucose content meal in patients with Type 2 diabetes mellitus.

UNLABELLED: Post-prandial hyperglycemia seems to play a pivotal role in the pathogenesis of the cardiovascular complications of diabetes mellitus, as it leads to an oxidative stress which in turn causes a reduced NO bioavailability. These conditions produce an endothelial activation. AIM OF THE STUDY: The aim of this study was to assure that the administration of N-acetylcysteine (NAC), thiolic antioxidant, is able to decrease the oxidation status and endothelial activation after a high-glucose content meal. SUBJECTS AND METHODS: Ten patients with Type 2 diabetes mellitus (DMT2) (Group 1) and 10 normal subjects (Group 2) were studied. They assumed a high-glucose content meal without (phase A) or after (phase B) the administration of NAC. Glycemia, insulinemia, intercellular adhesion molecule 1, vascular adhesion molecule 1 (VCAM-1), E-selectin, malonaldehyde (MDA), and 4-hydroxynonenal (HNE) were assessed at -30, 0, +30, +60, +90, +120, and +180 min with respect to the meal consumption. RESULTS: During the phase A in Group 1, only HNE and MDA levels increased after the meal assumption; all parameters remained unchanged in Group 2. During the phase B, in Group 1, HNE, MDA, VCAM-1, and E-selectin levels after the meal were lower than those in phase A, while no change for all variables were observed in Group 2. CONCLUSIONS: 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.

Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus.

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.

Acute goserelin administration inhibits gonadotropin and androgen secretion in post-menopausal women with ovarian hyperandrogenism.

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.

Follow-up of varicocele treated with percutaneous retrograde sclerotherapy: technical, clinical and seminal aspects.

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.