Shorter telomeres in patients with cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL).

CADASIL is a hereditary systemic vasculopathy which affects mainly small cerebral arteries and is caused by mutations in the Notch3 gene. Misfolding of Notch3 is linked to endoplasmic reticulum stress and increased reactive oxygen species, which may result in dysfunction of endothelial cells, inflammation and ischemia. Oxidative stress and inflammation may induce a rapid telomere shortening in peripheral blood leukocytes (PBLs). The aim of this study was to assess the telomere length in PBLs from 29 patients with a genetic diagnosis of CADASIL by using a modified quantitative real-time polymerase chain reaction based assay. PBL telomere length was significantly shorter in CADASIL patients (T/S ratio = 0.17, 95% CI, 0.14-0.20) than in the controls (T/S ratio = 0.31, 95% CI, 0.27-0.35, t-test p < 0.001). Moreover, patients with functional dependence displayed shorter telomeres than those with functional independence (p = 0.039). Our data provide the first evidence that PBL telomere length is shortened in CADASIL disease, and this may be a systemic oxidative stress indicator in CADASIL patients, providing a possible biomarker of disease progression and for future therapeutic strategies.

Semen quality and hormonal levels in infertile patients with varicocele.

OBJECTIVE: Aim of this study was to evaluate the semen quality and the serum concentration of follicle-stimulating hormone (FSH) and Testosterone (T) in infertile patients with and without varicocele. MATERIAL AND METHODS: 365 infertile patients undergoing Assisted Reproduction Tecnique (ART) were retrospectively included in the study. All subject were evaluated by history, physical examination, semen analysis, semen culture, mixed anti-immunoglobulin reaction test (MAR) for demonstration of sperm agglutination antibodies IgG and IgA, serum FSH and T determination. RESULTS: We observed 97 (26.6%) patients affected by varicocele compared to 268 (73.4%) without varicocele. A significant reduced percentage of motile spermatozoa (24.58 +/- 21.68 vs 21.01 +/- 12.62, p < 0.001) and lower sperm concentration (15.50 +/- 23.30 vs 16.50 +/- 15.22, p < 0.001) were observed in patients with varicocele compared to patients without varicocele. No significant differences were observed in sperm vitality between the two population of men with and without varicocele. Serum FSH (10.42 +/- 10.84 vs 9.11 +/- 18.81, p < 0.001) and Testosterone (5.73 +/- 5.97 vs 5.21 +/- 2.43, p < 0.001) levels were significantly higher in patients with varicocele compared to patients without varicocele. Detection of IgG and IgA sperm antibodies were negative in both man with and without varicocele. CONCLUSION: The direct connection between varicocele and infertility is not clear. The data of the present study suggest that the presence of a clinical varicocele rule out fertility in men affecting the hypothalamic pituitary-gonadal axis.