“
“We recently demonstrated

that female mice are resistant to the development of obesity-induced hypertension through a sex hormone-dependent mechanism that involved adipose angiotensin-converting enzyme 2 (ACE2). In this study, we hypothesized that provision of 17 beta-estradiol (E-2) to ovariectomized (OVX) high-fat (HF)-fed female hypertensive mice would reverse obesity-hypertension through an ACE2-dependent mechanism. Pilot studies defined dose-dependent effects of E-2 in OVX female mice selleckchem on serum E-2 concentrations and uterine weights. An E-2 dose of 36 mu g/ml restored normal serum E-2 concentrations and uterine weights. Therefore, HF-fed OVX female Ace2(+/+) and Ace2(-/-) mice were administered vehicle or E-2 (36 mu g/ml) for 16 wk. E-2 administration significantly decreased body weights of HF-fed OVX female Ace2(+/+) and Ace2(-/-) mice of either genotype. At 15 wk, E-2 administration decreased systolic blood pressure (SBP) of OVX HF-fed Ace2(+/+) but not Ace2(-/-) females during the light but not the dark cycle. E-2-mediated reductions in SBP in Ace2(+/+) females were associated with significant elevations in adipose ACE2 mRNA abundance and activity and reduced plasma ANG II concentrations. In contrast to females, E-2 administration had no effect on any parameter quantified in HF-fed male hypertensive mice. In 3T3-L1 adipocytes, E-2 promoted ACE2 mRNA abundance through effects at estrogen receptor-alpha (ER alpha) and resulted

in ER alpha-mediated binding at the ACE2 promoter. These results demonstrate that E-2 administration to OVX females reduces obesity-induced elevations in SBP (light cycle) through an ACE2-dependent mechanism. Beneficial PF-4708671 inhibitor Protein Tyrosine Kinase inhibitor effects of E-2 to decrease blood pressure in OVX obese females may result from stimulation of adipose ACE2.”
“Background: Establishing a safe prophylactic antimicrobial protocol in bone grafting may enhance osseous volume outcomes. The purpose of this in vitro study is to

assess human osteoblast response and safety after explant antimicrobial exposure.\n\nMethods: Fresh human bone explants were exposed to three antimicrobials: povidone-iodine (Povl; 0.05%, 1%, and 5%), chlorhexidine (CHX; 0.2% and 1%), and sodium hypochlorite (NaOCl; 2.5%, 4.5%, and 5.25%) at different times (15, 30, 45, and 60 seconds) and concentrations to assess cellular toxicity. Explants were washed three times with saline after exposure. Controls, explants cultured in the absence of antimicrobials, were performed for all experimental situations tested. Trials were conducted in triplicate. Particle size influence on osteoblast growth was determined between bone fragments with a diameter <2 and >= 2 to 5 mm. Test and control groups were monitored by light microscopy to evaluate cellular growth. Osteoblast differentiation and morphology was assessed by alkaline phosphatase activity and scanning electron microscopy (SEM).\n\nResults: Osteoblast growth was similar for particles <2 and to 5 mm.