High total acrosin activity in varicocele individuals.

Varicocele is a common cause of male infertility and reports indicate that varicocelectomy has a beneficial effect on male fertility. The aims of this study were to evaluate and compare the total acrosin activity along with DNA integrity in semen samples obtained from 70 varicocele individuals with male factors infertility presenting grades II and III varicocele before and after the surgery and 30 fertile individuals without any clinical presentation of varicocele. Total acrosin activity, protamine deficiency, DNA fragmentation, and semen parameters including sperm concentration, motility and sperm morphology were assessed by spectrophotometery, CMA3 staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and WHO criteria, respectively. Total acrosin activity (P = 0.03), percentage CMA3 positivity (P = 0.00) and TUNEL-positive spermatozoa (P = 0.04) were higher in the varicocele individuals before the surgery compared with the fertile individuals; yet, all the aforementioned criteria decreased significantly after surgery (P < 0.05). The results of this study reveal that DNA fragmentation and protamine deficiency, as negative parameters in fertility, improve post-surgery; however, total acrosin activity as a positive parameter in fertility is higher in the varicocele individuals compared with fertile and decreases to a value close to the fertile control post-surgery. High levels of total acrosin activity in varicocele individuals need more research in future.

Varicocelectomy: semen parameters and protamine deficiency.

Different methods have been used to evaluate the beneficial effect of varicocelectomy; these include semen parameters and pregnancy rate. Because of high biological variability of semen parameters, sperm functional tests have been considered as an efficient end point in assessment of fertility. Therefore, the aim of this study was to evaluate the effect of varicocelectomy on semen parameters and sperm protamine deficiency in 192 patients. The results of the present study show that all the three semen parameters and percentage of sperms with normal protamine content have improved post-surgery. The cumulative pregnancy rate was 34.6%. Comparing the results of the semen parameters and protamine content between patients whose partner became pregnant to those who did not benefit from varicocelectomy before and 6 months after surgery, show that patients may benefit from varicocelectomy that had higher initial semen density and better sperm morphology prior to surgery. Detailed analyses of sperm morphology, along with aforementioned results reveal that the factors which account for pregnancy difference are: (i) improvement in early events of spermatogenesis, possibly during spermatocytogenesis and reduction division; and (ii) late spermiogenesis events. Thus, it can be suggested that patients with low initial sperm count may benefit more from assisted reproductive techniques or varicocelectomy followed by assisted reproduction.

Regulation of ubiquitin-conjugating enzymes by glutathione following oxidative stress.

Upon oxidative stress cells show an increase in the oxidized glutathione (GSSG) to reduced glutathione (GSH) ratio with a concomitant decrease in activity of the ubiquitinylation pathway. Because most of the enzymes involved in the attachment of ubiquitin to substrate proteins contain active site sulfhydryls that might be covalently modified (thiolated) upon enhancement of GSSG levels (glutathiolation), it appeared plausible that glutathiolation might alter ubiquitinylation rates upon cellular oxidative stress. This hypothesis was explored using intact retina and retinal pigment epithelial (RPE) cell models. Exposure of intact bovine retina and RPE cells to H2O2 (0.1-1.7 micromol/mg) resulted in a dose-dependent increase in the GSSG:GSH ratio and coincident dose-dependent reductions in the levels of endogenous ubiquitin-activating enzyme (E1)-ubiquitin thiol esters and endogenous protein-ubiquitin conjugates and in the ability to form de novo retinal protein-125I-labeled ubiquitin conjugates. Oxidant-induced decrements in ubiquitin conjugates were associated with 60-80% reductions in E1 and ubiquitin-conjugating enzyme (E2) activities as measured by formation of ubiquitin thiol esters. When GSH levels in RPE cells recovered to preoxidation levels following H2O2 removal, endogenous E1 activity and protein-ubiquitin conjugates were restored. Evidence that S thiolation of E1 and E2 enzymes is the biochemical link between cellular redox state and E1/E2 activities includes: (i) 5-fold increases in levels of immunoprecipitable, dithiothreitol-labile 35S-E1 adducts in metabolically labeled, H2O2-treated, RPE cells; (ii) diminished formation of E1- and E2-125I-labeled ubiquitin thiol esters, oligomerization of E225K, and coincident reductions in protein-125I-labeled ubiquitin conjugates in supernatants from nonstressed retinas upon addition of levels of GSSG equivalent to levels measured in oxidatively stressed retinas; and (iii) partial restoration of E1 and E2 activities and levels of protein-125I-labeled ubiquitin conjugates in supernatants from H2O2-treated retinas when GSSG:GSH ratios were restored to preoxidation levels by the addition of physiological levels of GSH. These data suggest that the cellular redox status modulates protein ubiquitinylation via reversible S thiolation of E1 and E2 enzymes, presumably by glutathione.

Maternal knowledge, attitudes, and practices as predictors of diarrboeal disease in Saudi children < 3 years of age.

Diarrhoeal disease continues to be a leading cause of morbidity and mortality in many developing countries. This study demonstrates the importance of behavioral risk factors as determinants of diarrhoeal disease. The study design used is incidence-base, case-control design. The cases were obtained from Primary Health Care Centers (PHCC) in Makkah area, Saudi Arabia, during October 1994 to January 1995. The studied sample consisted of 319 cases and 312 controls < 3 years of age. The results showed that mothers of cases were significant inferior knowledge about aetiology and transmission of diarrhoeal disease than did mothers of controls. Poor hygiene was significantly high in households of cases for two items; disposal of faeces in latrine and presence of toilet papers (p < 0.05). Assuming causal association between the risk factors and diarrhoeal disease, up to 60% of diarrhoeal disease in the study population may be attributable to the studied behavioral factors.