Early Improvements in insulin sensitivity and inflammatory markers are induced by pravastatin in nondiabetic subjects with hypercholesterolemia

Background: Statins may improve lipid profiles and inflammation-associated biomarkers, but the effect on insulin sensitivity is controversial. We investigated the effects of 2 doses of pravastatin (40 and 10 mg/day) on insulin sensitivity and serum inflammatory markers in nondiabetic hypercholesterolemic patients. Methods: This was a randomized, parallel, comparative design study. A total of 40 nondiabetic subjects with elevated low-density lipoprotein (LDL) cholesterol were randomized to either the 40 mg pravastatin/day group (n =21) or the 10 mg pravastatin/day group (n=19) for 8 weeks. The fasting serum lipid profile, homeostasis model assessment (HOMA), glucose and insulin response of the two-hour glucose tolerance test (2 h-OGTT), and several inflammatory markers were determined. Results: Eight weeks of pravastatin treatment in both dose groups led to a significant reduction in serum LDL cholesterol, total cholesterol, triglycerides, and total cholesterol/high-density lipoprotein (HDL) cholesterol ratios (all p<0.01 in 40 mg group and all p<0.05 in 10 mg group), though the 40 mg group had greater effects. Although the fasting HOMA insulin resistance did not change significantly in either group, glucose and insulin areas under the curve of 2 h-OGTT were significantly decreased, suggesting improvement in insulin sensitivity post glucose challenge. Serum CD-40 ligand concentration was significantly reduced in the 40 mg pravastatin/day group and soluble P-selectin significantly reduced in both groups. Conclusions: Pravastatin treatment, at 10 mg or 40 mg daily for 8 weeks, reduced serum lipids and some inflammatory markers in nondiabetic hypercholesterolemic subjects. Furthermore, insulin resistance was improved even in short-teen treatment by pravastatin. (C) 2008 Elsevier B.V. All rights reserved

Association of heat shock protein 70 with semen quality in boars

This study attempted to clarify the relationship between the levels of 70 kDa heat shock protein (HSP70) and semen quality in boars. Semen samples from 29 (13 Duroc, 9 Landrace, and 7 Yorkshire) boars (mean age=25.2+/-2.2 months) were examined. Three to four ejaculates per boar, collected during cool and hot seasons, were evaluated in terms of the sperm concentration, sperm motility, percentage of normal and abnormal sperm, as well as percentage of sperm with proximal and distal plasma droplets. Significant seasonal and breed differences in semen quality were observed. Experimental results indicate that the semen quality of Landrace boars was better than those of Yorkshire and Duroc boars (P<0.05) and semen quality declined significantly during the hot season (P<0.05). One-dimensional SDS-PAGE analysis of spermatozoa proteins indicated that protein profiles did not significantly differ between seasons and among breeds. Both constitutive and stress-inducible form of HSP70 were detected in boar spermatozoa by Western blot analysis. The level of HSP70, which revealed no difference among breeds within a season, was significantly lower during the hot season in all the three breeds (P<0.05). although there appeared to be low correlation coefficients between the level of HSP70 and semen quality traits, the semen quality tended to decline significantly in samples with a lower level of HSP70. Results in this study suggest that the levels of HSP70 in boar spermatozoa are significantly lower during the hot season and might be associated with semen quality. (C) 2000 Elsevier Science B.V. All rights reserved

The decline of porcine sperm motility by geldanamycin, a specific inhibitor of heat-shock protein 90 (HSP90)

Sperm motility is an important parameter for fertility. The molecular mechanisms of mammalian sperm motility are still largely undefined. Our previous observations suggested that heat shock protein 90 (HSP90) may be associated with porcine sperm motility. The aim of the present study was to further characterize the plausible novel function of HSP90 on sperm motility. Semen from normal, sexually mature boars with sperm motility higher than 80% was used. An HSP90-specific inhibitor, geldanamycin (GA), was added to diluted semen at 0.5, 1.0, 2.5 or 5.0 mu g/mL, and the semen was then incubated at 37 degrees C for 15, 30, 45 or 60 min. Sperm motility was determined by using computer-assisted semen analyzer at the end of incubation. The results indicated that GA significantly reduced sperm motility in a dose and time dependent manner. Moreover, incubation of semen with 5.0 mu g/mL GA for 15 min completely stopped sperm motility. To test the reversibility of the GA effect on sperm motility, GA was removed after 30 min incubation and was replaced with fresh extender alone or with extender plus 5 mM caffeine, then incubated for another 15, 30, 45 or 60 min. The results showed that simply removing GA did not reverse the inhibitory effect on sperm motility, while adding caffeine partially reversed this inhibitory effect. However, the effect of 2.5 or 5.0 mu g/mL GA was not reversed by caffeine. Considering the specificity of GA targeting to HSP90, the above observations suggested that HSP90 may play a crucial role in regulating porcine sperm motility. (C) 2000 by Elsevier Science

Substantial decrease of heat-shock protein 90 precedes the decline of sperm motility during cooling of boar spermatozoa

The decline in boar semen quality after cryopreservation may be attributed to changes in intracellular proteins. Thus, the aim of the present study was to evaluate the change of protein profiles in boar spermatozoa during the process of cooling and after cryopreservation. A total of 9 sexually mature boars (mean age=25.5+/-12.3 mo) was used. Samples for protein analysis were collected before chilling, after cooling to 15 degrees C, after cooling to 5 degrees C, following thawing after freezing to -100 degrees C, and following thawing after 1 wk of cryopreservation at -196 degrees C. Semen characteristics evaluated included progressive motility and the percentage of morphologically normal spermatozoa. Total proteins from 5x10(6) spermatozoa were separated and analyzed by SDS-PAGE. The results revealed that there was a substantial decrease of a 90 kDa protein in the frozen-thawed spermatozoa. Western blot analysis demonstrated that this protein was 90 kDa heat-shock protein (HSP90). Time course study showed that the decrease of HSP90 in spermatozoa initially occurred in the first hour during cooling to 5 degrees C. When compared with the fresh spermatozoa before chilling, there was a 64% decrease of HSP90 in spermatozoa after cooling to 5 degrees C. However, the motility and percentage of normal spermatozoa did not significantly decrease during this period of treatment. Both declined substantially as the semen was thawed after freezing from -100 degrees C. The results indicated that the decrease of HSP90 precedes the decline of semen characteristics. The length of time between a decrease of HSP90 and the decline in sperm motility was estimated to be 2 to 3 h. Taken together, the above results suggested that a substantial decrease of HSP90 might be associated with a decline in sperm motility during cooling of boar spermatozoa. (C) 1999 by Elsevier Science Inc