Valproate is an anti-androgen and anti-progestin

Anti-convulsant treatment is associated with a high prevalence of reproductive dysfunction compared with age-matched non-epileptics. We examined the widely used anti-convulsants valproate (VPA) and carbamazepine (CBZ) for steroidal bioactivity using a yeast-based steroid receptor-β-galactosidase reporter assay for the androgen receptor (AR), progesterone receptor (PR) or estrogen receptor (ER). Bioassays were performed (a) to detect agonist activity by exposing yeast to 100 μM CBZ or VPA or (b) to detect antagonist activity by exposing yeast stimulated with testosterone (5 × 10-9 M, AR), progesterone (1.6 × 10-9 M, PR) or estradiol (2.6 × 10-11 M, ER) together with either VPA or CBZ for 4 (PR) or 16 (AR, ER) hours. VPA showed dose-dependent (1-800 μM) inhibition of progesterone-induced PR- and testosterone-induced AR activity but had no ER antagonist bioactivity and no significant PR, AR or ER agonist bioactivity. VPA also showed a dose-dependent (1-200 μM) blockade of DHT's suppression of AR-mediated NF-κB activation in human mammalian cells. By contrast, CBZ had no significant PR, AR or ER agonist or AR and ER antagonist bioactivity but at the highest concentration tested (800 μM) it did antagonize PR activity. We conclude that VPA is a non-steroidal antagonist for human AR and PR but not ER. VPA's androgen and progesterone antagonism at concentrations within therapeutic blood levels (350-700 μM) seems likely to contribute to the frequency of reproductive endocrine disturbances among patients treated with VPA. © 2005 Elsevier Inc. All rights reserved

Frequency and type of adverse analytical findings in athletics: Differences among disciplines.

Athletics is a highly diverse sport that contains a set of disciplines grouped into jumps, throws, races of varying distances, and combined events. From a physiological standpoint, the physical capabilities linked to success are quite different among disciplines, with varying involvements of muscle strength, muscle power, and endurance. Thus, the use of banned substances in athletics might be dictated by physical dimensions of each discipline. Thus, the aim of this investigation was to analyse the number and distribution of adverse analytical findings per drug class in athletic disciplines. The data included in this investigation were gathered from the Anti-Doping Testing Figure Report made available by the World Anti-Doping Agency (from 2016 to 2018). Interestingly, there were no differences in the frequency of adverse findings (overall, 0.95%, range from 0.77 to 1.70%) among disciplines despite long distance runners having the highest number of samples analysed per year ( 9812 samples/year). Sprinters and throwers presented abnormally high proportions of adverse analytical findings within the group of anabolic agents (p < 0.01); middle- and long-distance runners presented atypically high proportions of findings related to peptide hormones and growth factors (p < 0.01); racewalkers presented atypically high proportions of banned diuretics and masking agents (p = 0.05). These results suggest that the proportion of athletes that are using banned substances is similar among the different disciplines of athletics. However, there are substantial differences in the class of drugs more commonly used in each discipline. This information can be used to effectively enhance anti-doping testing protocols in athletics.post-print1.911 K

Brain mapping in cognitive disorders: a multidisciplinary approach to learning the tools and applications of functional neuroimaging

<p>Abstract</p> <p>Background</p> <p>With rapid advances in functional imaging methods, human studies that feature functional neuroimaging techniques are increasing exponentially and have opened a vast arena of new possibilities for understanding brain function and improving the care of patients with cognitive disorders in the clinical setting. There is a growing need for medical centers to offer clinically relevant functional neuroimaging courses that emphasize the multifaceted and multidisciplinary nature of this field. In this paper, we describe the implementation of a functional neuroimaging course focusing on cognitive disorders that might serve as a model for other medical centers. We identify key components of an active learning course design that impact student learning gains in methods and issues pertaining to functional neuroimaging that deserve consideration when optimizing the medical neuroimaging curriculum.</p> <p>Methods</p> <p>Learning gains associated with the course were assessed using polychoric correlation analysis of responses to the SALG (Student Assessment of Learning Gains) instrument.</p> <p>Results</p> <p>Student gains in the functional neuroimaging of cognition as assessed by the SALG instrument were strongly associated with several aspects of the course design.</p> <p>Conclusion</p> <p>Our implementation of a multidisciplinary and active learning functional neuroimaging course produced positive learning outcomes. Inquiry-based learning activities and an online learning environment contributed positively to reported gains. This functional neuroimaging course design may serve as a useful model for other medical centers.</p

Chewing function, general health and the dentition of older Australian men: The Concord Health and Ageing in Men Project

Objectives To describe the associations between chewing function with oral health and certain general health characteristics, in a population of community‐dwelling older Australian men. Methods Analysis of data obtained from a cross‐sectional analysis of the 4th wave of the Concord Health and Ageing in Men Project cohort of 614 participants, 524 whom were dentate, aged 78 years and over. Their chewing capacity was assessed using three main indicators: capacity to chew eleven food items ranging from boiled eggs through to fresh carrots and nuts; discomfort when eating; and interruption of meals. Associations with chewing were tested for dentate vs edentate participants, numbers of teeth present, active dental disease and key general health conditions such as disabilities, comorbidities and cognitive status. Log binomial regression models adjusted for age, country of birth, income, education and marital status. Prevalence ratios and 95% confidence intervals were estimated. Results Twenty‐one per cent of participants could not eat hard foods, while 23.1% reported discomfort when eating, and 8.8% reported interrupted meals when eating. There was a threefold difference in the capacity of dentate men to chew firm meat over that of edentulous men (95% CI, 2.0‐4.9); a 2.5 times greater likelihood of edentate men reporting discomfort when eating (95% CI: 1.5‐4.3); and 1.9 times greater likelihood of edentate participants reporting having meals interrupted (95% CI: 1.4‐2.6). Chewing/eating difficulties were associated with both dental status (number of teeth, active dental caries) and self‐rated dental health. Fewer than 20 teeth and the presence of active coronal or root decay were associated with more discomfort when eating. General health conditions associated with chewing function included disability, physical activity, comorbidities, cognitive status and depression. Older men's self‐rated oral health and general health perceptions were also associated with aspects of chewing function. Poorer self‐reported oral health was associated with inability to eat hard foods (95% CI: 1.3‐2.7) and with discomfort when eating (95% CI: 2.6‐5.1), while poorer self‐reported general health was associated with discomfort when eating (95% CI: 1.2‐2.2). Conclusions Falling rates of edentulism may lead to improved chewing and eating function in older men. Maintaining 20 or more natural teeth, and preventing active coronal and root caries should enhance chewing function and promote self‐reported health and oral health. Lower capacity to chew hard foods and a higher reporting of discomfort when eating is associated with co‐morbidity in older Australian men

Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function

Purpose: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Methods: Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. Results: In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 ± 16 to 25 ± 4 ng/l, p 550 nmol/l, n = 18). Five patients developed elevated HbA1clevels (> 6.5%). Conclusion: In men177Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA1c. Therefore, PRRT with177Lu-octreotate can be regarded as a safe treatment modality with respect to short-and long-term endocrine function

Proposal for a method to estimate nutrient shock effects in bacteria

Plating methods are still the golden standard in microbiology; however, some studies have shown that these techniques can underestimate the microbial concentrations and diversity. A nutrient shock is one of the mechanisms proposed to explain this phenomenon. In this study, a tentative method to assess nutrient shock effects was tested. Findings To estimate the extent of nutrient shock effects, two strains isolated from tap water (Sphingomonas capsulata and Methylobacterium sp.) and two culture collection strains (E. coli CECT 434 and Pseudomonas fluorescens ATCC 13525) were exposed both to low and high nutrient conditions for different times and then placed in low nutrient medium (R2A) and rich nutrient medium (TSA). The average improvement (A.I.) of recovery between R2A and TSA for the different times was calculated to more simply assess the difference obtained in culturability between each medium. As expected, A.I. was higher when cells were plated after the exposition to water than when they were recovered from high-nutrient medium showing the existence of a nutrient shock for the diverse bacteria used. S. capsulata was the species most affected by this phenomenon. This work provides a method to consistently determine the extent of nutrient shock effects on different microorganisms and hence quantify the ability of each species to deal with sudden increases in substrate concentration. <br/

Determinants of male reproductive health disorders: the Men in Australia Telephone Survey (MATeS)

Background: The relationship between reproductive health disorders and lifestyle factors in middle-aged and older men is not clear. The aim of this study is to describe lifestyle and biomedical associations as possible causes of erectile dysfunction (ED), prostate disease (PD), lower urinary tract symptoms (LUTS) and perceived symptoms of androgen deficiency (pAD) in a representative population of middle-aged and older men, using the Men in Australia Telephone Survey (MATeS). Methods: A representative sample (n = 5990) of men aged 40+ years, stratified by age and State, was contacted by random selection of households, with an individual response rate of 78%. All men participated in a 20-minute computer-assisted telephone interview exploring general and reproductive health. Associations between male reproductive health disorders and lifestyle and biomedical factors were analysed using multivariate logistic regression (odds ratio [95% confidence interval]). Variables studied included age, body mass index, waist circumference, smoking, alcohol consumption, physical activity, co-morbid disease and medication use for hypertension, high cholesterol and symptoms of depression. Results: Controlling for age and a range of lifestyle and co-morbid exposures, sedentary lifestyle and being underweight was associated with an increased likelihood of ED (1.4 [1.1-1.8]; 2.9 [1.5-5.8], respectively) and pAD (1.3 [1.1-1.7]; 2.7 [1.4-5.0], respectively. Diabetes and cardiovascular disease were both associated with ED, with hypertension strongly associated with LUTS and pAD. Current smoking (inverse association) and depressive symptomatology were the only variables independently associated with PD. All reproductive disorders showed consistent associations with depression (measured either by depressive symptomatology or medication use) in both age-adjusted and multivariate analyses. Conclusion: A range of lifestyle factors, more often associated with chronic disease, were significantly associated with male reproductive health disorders. Education strategies directed to improving general health may also confer benefits to male reproductive health.Carol A. Holden, Robert I. McLachlan, Marian Pitts, Robert Cumming, Gary Wittert, Johnathon P. Ehsani, David M. de Kretser, David J. Handelsma

Troubled social background of male anabolic-androgenic steroid abusers in treatment

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the social background and current social situation of male abusers of anabolic-androgenic steroids (AAS).</p> <p>Methods</p> <p>We compared thirty-four AAS-abusing patients from an Addiction Centre (AC) with two groups, 18 users and 259 non-users of AAS from a public gym in Orebro, Sweden. The study is based on semi-structured interviews and questionnaires.</p> <p>Results</p> <p>Histories of a troubled childhood as well as current social disadvantage were both more frequent among the AAS users. Users also reported poor relationships with their parents and almost half of them had experienced physical or mental abuse. The AC group's experiences from school were mostly negative, and included concentration problems, boredom and learning difficulties. Their current circumstance included abuse of other drugs, battering of spouses and other criminality such as assault, illegal possession of weapons and theft.</p> <p>Conclusion</p> <p>In conclusion, this study shows that abusers of AAS often have a troubled social background. This underlines the importance of making a thorough social assessment as a part of the treatment programme. The results of the study may help in directing appropriate questions relevant to the abuse of AAS.</p

Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification

Vascular calcification powerfully predicts mortality and morbidity from cardiovascular disease. Men have a greater risk of cardiovascular disease, compared to women of a similar age. These gender disparities suggest an influence of sex hormones. Testosterone is the primary and most well-recognised androgen in men. Therefore, we addressed the hypothesis that exogenous androgen treatment induces vascular calcification. Immunohistochemical analysis revealed expression of androgen receptor (AR) in the calcified media of human femoral artery tissue and calcified human valves. Furthermore, in vitro studies revealed increased phosphate (Pi)-induced mouse vascular smooth muscle cell (VSMC) calcification following either testosterone or dihydrotestosterone (DHT) treatment for 9 days. Testosterone and DHT treatment increased tissue non-specific alkaline phosphatase (Alpl) mRNA expression. Testosterone-induced calcification was blunted in VSMC-specific AR-ablated (SM-ARKO) VSMCs compared to WT. Consistent with these data, SM-ARKO VSMCs showed a reduction in Osterix mRNA expression. However, intriguingly, a counter-intuitive increase in Alpl was observed. These novel data demonstrate that androgens play a role in inducing vascular calcification through the AR. Androgen signalling may represent a novel potential therapeutic target for clinical intervention