Postnatal exposure to finasteride causes different effects on the prostate of male and female gerbils

The development and maintenance of prostate function depend on a fine balance between oestrogen and androgen levels. Finasteride inhibits 5α‐reductase, which is responsible for the conversion of testosterone into its most active form, dihydrotestosterone. Enzymes that metabolize these hormones have a highly relevant role in both the normal prostate metabolism and in the occurrence of pathological conditions. There are few studies on the impact of finasteride on male prostate development and fewer studies on the female prostate and possible intersexual differences. Therefore, we treated male and female gerbils from 7 to 14 days in postnatal life with a high dose of finasteride (500 μg/kg/day); the prostate complexes were then removed and submitted to immunohistochemistry, immunofluorescence and three‐dimensional reconstruction. In addition, hormonal serum dosages were administered. Treatment with finasteride resulted in an increased thickness of the periductal smooth musculature in the prostate of both male and female gerbils, such as well as a reduction in the thickness of developing prostate alveoli in both sexes. In addition, intersexual differences were observed as increased epithelial proliferation and decreases in the number of developing alveoli in females. Together, the data indicate that postnatal exposure to finasteride causes greater changes in the female gerbil prostate than in the male.     

Prophylactic Application of MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Prevents or Slows the Progression of Obesity,Insulin Resistance,and Cognitive Impairment in a Mouse Model of Type 2 Diabetes Mellitus

International Journal of Peptide Research and Therapeutics - Oral delivery of MA-[d-Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic...     

Effect of lipopolysaccharides from Vibrio alginolyticus on the Mx gene expression and virus recovery from gilthead sea bream (Sparus aurata L.) experimentally infected with Nodavirus

Infections with nodavirus affect a wild and farmed fish species throughout the world, mostly from the marine environment. The aim of this work was to determine the immune status of gilthead sea bream that comes as a result of a Nodavirus infection, induced by activation of the interferon response pathway by lipopolysaccharides from Vibrio alginolyticus and the expression of interferoninduced Mx protein in liver samples. The enhancement of Mx protein gene expression was detected in liver samples of experimentally nodavirus infected fish and, furthermore, the immunostimulant LPS of V. alginolyticus decreased almost three times the virus titration with respect to no-immunized or infected with nodavirus group of fish.     

Renoprotection by α-mangostin is related to the attenuation in renal oxidative/nitrosative stress induced by cisplatin nephrotoxicity

Cisplatin (CDDP) is a chemotherapeutic agent that produces nephrotoxicity associated with oxidative/nitrosative stress. α-Mangostin (α-M) is a xanthone extracted from mangosteen with antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate the renoprotective effect of α-M on the CDDP-induced nephrotoxicity. α-M was administered (12.5 mg/kg/day, i.g.) for 10 days (7 days before and 3 days after CDDP injection). On day 7, rats were treated with a single injection of CDDP (7.5 mg/Kg, i.p.); 3 days after the rats were killed. α-M attenuated renal dysfunction, structural damage, oxidative/nitrosative stress, decrease in catalase expression and increase in mRNA levels of tumour necrosis factor alpha and transforming growth factor beta. In conclusion the renoprotective effect of α-M on CDDP-induced nephrotoxicity was associated with the attenuation in oxidative/nitrosative stress and inflammatory and fibrotic markers and preservation of catalase activity.     

Study protocol to examine the effects of spaceflight and a spaceflight analog on neurocognitive performance: extent,longevity, and neural bases

Background

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether spaceflight also affects other central nervous system functions such as cognition is yet largely unknown, but of importance in consideration of the health and performance of crewmembers both in- and post-flight. We are therefore conducting a controlled prospective longitudinal study to investigate the effects of spaceflight on the extent, longevity and neural bases of sensorimotor and cognitive performance changes. Here we present the protocol of our study.

Methods/design

This study includes three groups (astronauts, bed rest subjects, ground-based control subjects) for which each the design is single group with repeated measures. The effects of spaceflight on the brain will be investigated in astronauts who will be assessed at two time points pre-, at three time points during-, and at four time points following a spaceflight mission of six months. To parse out the effect of microgravity from the overall effects of spaceflight, we investigate the effects of seventy days head-down tilted bed rest. Bed rest subjects will be assessed at two time points before-, two time points during-, and three time points post-bed rest. A third group of ground based controls will be measured at four time points to assess reliability of our measures over time. For all participants and at all time points, except in flight, measures of neurocognitive performance, fine motor control, gait, balance, structural MRI (T1, DTI), task fMRI, and functional connectivity MRI will be obtained. In flight, astronauts will complete some of the tasks that they complete pre- and post flight, including tasks measuring spatial working memory, sensorimotor adaptation, and fine motor performance. Potential changes over time and associations between cognition, motor-behavior, and brain structure and function will be analyzed.

Discussion

This study explores how spaceflight induced brain changes impact functional performance. This understanding could aid in the design of targeted countermeasures to mitigate the negative effects of long-duration spaceflight.

     

Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists

Abstract

A series of nitrogen heterocycles containing α–ethoxyphenylpropionic acid derivatives were designed as dual PPARα/γ agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one was the most tolerant of the tested heterocycles in which incorporation of O-methyl oxime ether and trifluoroethoxy group followed by enantiomeric resolution led to the (S)-stereoisomer 44?b displaying the best in vitro pharmacological profile. Compound 44?b acted as a very potent full PPARγ agonist and a weak partial agonist on the PPARα receptor subtype. Compound 44?b showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain and could be considered as a selective PPARγ modulator (SPPARγM).