Synthesis and characterization of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton

A series of new aromatic esters based on 4,16-pregnadiene-6,20-dione skeleton, namely 3β-benzoyloxy-4,16-pregnadiene-6,20-dione and 3β-furoyloxy-4,16-pregnadiene- 6,20-dione, which may be good inhibitors for the 5α-reductase enzyme and show high antiandrogenic activity, were synthesized starting from diosgenin. The structures of the steroids were characterized by elemental analysis, 1H NMR, 13C NMR, IR and mass spectrum. Single crystal X-ray diffraction measurement on one of the new compounds, 3β-(p-methoxybenzoyloxy)-4,16-pregnadiene-6,20-dione revealed that the A, B, C, and D ring adopted half chair, distorted chair, distorted chair, and distorted envelope conformation, respectively. The molecules in the crystal were packed face-to-face at the normal van der Waals distances

Strengthening self-regulation and reducing poverty to prevent adolescent depression and anxiety: Rationale, approach and methods of the ALIVE interdisciplinary research collaboration in Colombia, Nepal and South Africa.

This is the final version. Available from Cambridge University Press via the DOI in this record. Availability of data and materials: Data and materials from this study are not yet available for sharing as the study is still in the data collection phase.AIMS: Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the 'Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)' study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa. METHODS: This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites. RESULTS: The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach. CONCLUSIONS: By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice.Wellcome TrustUK Research and InnovationNational Institute for Health Researc

Validation of the OECD reproduction test guideline with the New Zealand mudsnail Potamopyrgus antipodarum using trenbolone and prochloraz

The Organisation for Economic Cooperation and Development (OECD) provides several standard test methods for the environmental hazard assessment of chemicals, mainly based on primary producers, arthropods, and fish. In April 2016, two new test guidelines with two mollusc species representing different reproductive strategies were approved by OECD member countries. One test guideline describes a 28-day reproduction test with the parthenogenetic New Zealand mudsnail Potamopyrgus antipodarum. The main endpoint of the test is reproduction, reflected by the embryo number in the brood pouch per female. The development of a new OECD test guideline involves several phases including inter-laboratory validation studies to demonstrate the robustness of the proposed test design and the reproducibility of the test results. Therefore, a ring test of the reproduction test with P. antipodarum was conducted including eight laboratories with the test substances trenbolone and prochloraz and results are presented here. Most laboratories could meet test validity criteria, thus demonstrating the robustness of the proposed test protocol. Trenbolone did not have an effect on the reproduction of the snails at the tested concentration range (nominal: 10-1000 ng/L). For prochloraz, laboratories produced similar EC10 and NOEC values, showing the inter-laboratory reproducibility of results. The average EC10 and NOEC values for reproduction (with coefficient of variation) were 26.2 µg/L (61.7%) and 29.7 µg/L (32.9%), respectively. This ring test shows that the mudsnail reproduction test is a well-suited tool for use in the chronic aquatic hazard and risk assessment of chemicals

Cognitive effects of testosterone and finasteride administration in older hypogonadal men

Stephen E Borst,1 Joshua F Yarrow,2 Carmen Fernandez,1 Christine F Conover,2 Fan Ye,2 John R Meuleman,1 Matthew Morrow,3 Baiming Zou,4 Jonathan J Shuster5 1Geriatric Research, Education and Clinical Center, 2Research Service, 3Pharmacy Service, Malcom Randall VA Medical Center, Gainesville Florida; 4Department of Biostatistics, 5Department of Health Outcomes and Policy, University of Florida, Gainesville, FL, USA Abstract: Serum concentrations of neuroactive androgens decline in older men and, in some ­studies, low testosterone is associated with decreased cognitive function and incidence of depression. Existing studies evaluating the effect of testosterone administration on cognition in older men have been largely inconclusive, with some studies reporting minor to moderate cognitive benefit, while others indicate no cognitive effect. Our objective was to assess the cognitive effects of treating older hypogonadal men for 1 year with a supraphysiological dose of testosterone, either alone or in combination with finasteride (a type II 5α-reductase inhibitor), in order to determine whether testosterone produces cognitive benefit and whether suppressed dihydrotestosterone influences cognition. Sixty men aged ≥60 years with a serum testosterone concentration of ≤300 ng/dL or bioavailable testosterone ≤70 ng/dL and no evidence of cognitive impairment received testosterone-enanthate (125 mg/week) versus vehicle, paired with finasteride (5 mg/day) versus placebo using a 2×2 factorial design. Testosterone caused a small decrease in depressive symptoms as assessed by the Geriatric Depression Scale and a moderate increase in visuospatial memory as assessed by performance on a recall trial of the Rey-Osterrieth Complex Figure Test. Finasteride caused a small increase in performance on the Benton Judgment of Line Orientation test. In total, major improvements in cognition were not observed either with testosterone or finasteride. Further studies are warranted to determine if testosterone replacement may improve cognition in other domains. Keywords: cognition, depression, 5 alpha reductase, testosterone enanthat

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle

Dalbo, VJ ORCiD: 0000-0002-5944-7558The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week−1) or ORX + trenbolone (TREN; 1.0 mg week−1). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p <.001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p <.01), with no differences between conditions for myonuclear number per muscle fibre (p =.948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p <.01). pan-SMAD2/3 protein was ~30–50% greater in ORX compared to SHAM (p =.006), ORX + TEST (p =.037) and ORX + TREN (p =.043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p <.05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy. © 2016 Blackwell Verlag GmbHAssociated Grant:This study was also supported in part by work supported from the Office of Research and Development, Rehabilitation Research and Development (RR&D) Service, Department of Veterans Affairs Merit Award to S.E.B., Veteran’s Health Administration Advanced Geriatrics Fellowship to D.T.B., and RR&D CDA-2 to J.F.Y