Transcriptional networks associated with 5-alpha-dihydrotestosterone in the fathead minnow (Pimephales promelas) ovary.

Androgens play a significant role in regulating oogenesis in teleost fishes. The androgen dihydrotestosterone (DHT) is a potent non-aromatizable androgen involved in sexual differentiation in mammals; however, its actions are not well understood in teleost fish. To better characterize the physiological role of DHT in the fathead minnow (FHM) ovary on a temporal scale, in vitro assays for 17ß-estradiol (E2) production were conducted in parallel with microarray analysis. Ovarian explants were incubated at different concentrations of DHT (10(-6), 10(-7), and 10(-8)M DHT) in three separate experiments conducted at 6, 9, and 12h. DHT treatment resulted in a rapid and consistent increase in E2 production from the ovary at all three time points. Therefore, DHT may act to shift the balance of metabolites in the steroidogenic pathway within the ovary. Major biological themes affected by DHT in the ovary in one or more of the time points included those related to blood (e.g. vasodilation, blood vessel contraction, clotting), lipids (e.g. lipid storage, cholesterol metabolism, lipid degradation) and reproduction (e.g. hormone and steroid metabolism). Gene networks related to immune responses and calcium signaling were also affected by DHT, suggesting that this androgen may play a role in regulating these processes in the ovary. This study detected no change in mRNA levels of steroidogenic enzymes (cyp19a1, star, 11ßhsd, 17ßhsd, srd5a isoforms), suggesting that the observed increase in E2 production is likely more dependent on the pre-existing gene or protein complement in the ovary rather than the de novo expression of transcripts. This study increases knowledge regarding the roles of DHT and androgens in general in the teleost ovary and identifies molecular signaling pathways that may be associated with increased E2 production.

Ezetimibe in combination with a statin does not reduce all-cause mortality.

BACKGROUND: Although the ezetimibe-statin combination has been shown to reduce LDL cholesterol by 12% compared to a statin alone, its effect on hard clinical endpoints such as mortality is less certain. Prior trials evaluated this combination in highly select population groups, but impact on all- cause mortality in the general population has not been reported. METHODS: A total of 3,827 subjects who were prescribed either a statin (group 1) or the combination of statin with ezetimibe (group 2) between January 1st, 2005 and January 1st, 2008 were studied. Socio-demographic and clinical variables and mortality records were analyzed. Univariate and stepwise multivariate logistic regression analysis was performed to identify the impact of ezetimibe on all-cause mortality, controlling for patient characteristics, selected cardiovascular diseases and risk factors, and medications. RESULTS: Group 1 (n = 2,909), and group 2 (n = 918) were similar in regards to most demographic variables, 152 patients died from any cause during the study period. There was no difference in all cause mortality between the groups. Hypertension, higher HDL-C and omega-3 fatty acid use were associated with ezetimibe use in this cohort of patients and were considered as covariates in the analysis. Patients on the drug combination did not experience lower mortality after controlling for covariates and other significant risk factors. CONCLUSIONS: No significant mortality benefit was found with the use of ezetimibe in combination with a statin over use of a statin alone. Omega-3 fatty acid use and higher HDL-C demonstrated a substantial survival benefit.

Comparative outcomes of laparoscopic adjustable gastric banding in adolescents and adults.

BACKGROUND: Obesity is a major health problem in all age groups. Morbidly obese adolescents often fail to lose weight with diet and exercise and, as adults, become candidates for surgical intervention. METHODS: We matched adolescents (14-19 yr) and adults (19-73 yr) retrospectively from university medical center-based adolescent and adult obesity surgery programs who had undergone laparoscopic adjustable gastric banding by gender and body mass index (n = 115). RESULTS: The most common co-morbid condition in adolescents was menstrual irregularity/polycystic ovary syndrome. Hypertension was the most common co-morbid condition in adults. The adults were nearly 9 times as likely to be diabetic as the adolescents. We analyzed patients with ≥6 months of follow-up for the percentage of excess weight loss at 6-month intervals for ≤24 months. Both groups demonstrated progressive weight loss that did not differ significantly in the initial 12 months; however, the data beyond 12 months were limited by the small numbers. CONCLUSION: The presence of more serious co-morbidities in obese adults, coupled with the successful weight loss after laparoscopic adjustable gastric banding, in adolescents suggests that weight loss surgery might be indicated at a younger age for severely obese individuals.