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      Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids

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          Abstract

          Background and objective

          With prolonged use of anabolic androgenic steroids (AAS), occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 ( UGT2B17) gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS.

          Presentation of the hypothesis

          The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate.

          Testing the hypothesis

          In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body.

          Implications of the hypothesis

          If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be exposed to an increased risk of developing renal disorders. In the current detecting - sanctioning anti-doping system, athletes motivated by the potential to evade detection owing to their unique genetic make-up could subject themselves to a serious health consequence. More research on AAS metabolism in the presence of UGT2B17 gene deletion is required. Benefit - harm evaluations in therapeutic use of anabolic steroids should also consider this potential link between UGT2B17 gene deletion polymorphism and renal disorders.

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          Most cited references54

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          The relative persuasiveness of gain-framed and loss-framed messages for encouraging disease prevention behaviors: a meta-analytic review.

          A meta-analytic review of 93 studies (N = 21,656) finds that in disease prevention messages, gain-framed appeals, which emphasize the advantages of compliance with the communicator's recommendation, are statistically significantly more persuasive than loss-framed appeals, which emphasize the disadvantages of noncompliance. This difference is quite small (corresponding to r = .03), however, and appears attributable to a relatively large (and statistically significant) effect for messages advocating dental hygiene behaviors. Despite very good statistical power, the analysis finds no statistically significant differences in persuasiveness between gain- and loss-framed messages concerning other preventive actions such as safer-sex behaviors, skin cancer prevention behaviors, or diet and nutrition behaviors.
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            Pharmacology of anabolic steroids.

            Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.
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              A meta-analysis of fear appeals: implications for effective public health campaigns.

              The fear appeal literature is examined in a comprehensive synthesis using meta-analytical techniques. The meta-analysis suggests that strong fear appeals produce high levels of perceived severity and susceptibility, and are more persuasive than low or weak fear appeals. The results also indicate that fear appeals motivate adaptive danger control actions such as message acceptance and maladaptive fear control actions such as defensive avoidance or reactance. It appears that strong fear appeals and high-efficacy messages produce the greatest behavior change, whereas strong fear appeals with low-efficacy messages produce the greatest levels of defensive responses. Future directions and practical implications are provided.
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                Author and article information

                Journal
                Subst Abuse Treat Prev Policy
                Substance Abuse Treatment, Prevention, and Policy
                BioMed Central
                1747-597X
                2010
                29 April 2010
                : 5
                : 7
                Affiliations
                [1 ]School of Pharmacy and Chemistry, Kingston University, London, UK
                [2 ]School of Life Sciences, Kingston University, London, UK
                [3 ]Department of Anatomy, Histology and Embryology, Semmelweis University of Medicine, Budapest IX, Tüzoltó utca 58, H-1450, Hungary
                Article
                1747-597X-5-7
                10.1186/1747-597X-5-7
                2877023
                20429943
                52183a52-9566-4406-a09c-509b03890768
                Copyright ©2010 Deshmukh et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 February 2010
                : 29 April 2010
                Categories
                Hypothesis

                Health & Social care
                Health & Social care

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