Assessment of the inhibitory potential of anabolic steroids towards human AKR1D1 by computational methods and in vitro evaluation.

Exposure to xenobiotics can adversely affect biochemical reactions, including hepatic bile acid synthesis. Bile acids are essential for dissolving lipophilic compounds in the hydrophilic environment of the gastrointestinal tract. The critical micellar concentration of bile acids depends on the Δ4-reduction stereochemistry, with the 3-oxo-5ß-steroid-Δ4-dehydrogenase (AKR1D1) introducing the cis ring A/B conformation. Loss-of-function mutations in AKR1D1 cause hepatic cholestasis, which, if left untreated can progress into steatosis and liver cirrhosis. Furthermore, AKR1D1 is involved in clearing steroids with an A-ring Δ4-double bond. Here, we tested whether anabolic-androgenic steroids (AAS), often taken off-label at high doses, might inhibit AKR1D1, thereby potentially causing hepatotoxicity. A computational molecular model was established and used for virtual screening of the DrugBank database consisting of 2740 molecules, yielding mainly steroidal hits. Fourteen AAS were selected for in vitro evaluation, as such compounds can reach high hepatic concentrations in an abuse situation. Nandrolone, clostebol, methasterone, drostanolone, and methenolone inhibited to various extent the AKR1D1-mediated reduction of testosterone. Molecular modeling suggests that 9 out of 14 investigated AAS are competitive inhibitors. Moreover quantum mechanical calculations show that nadrolone and clostebol are substrates of AKR1D1 with different activation energy barriers for the hydrogen transfer from cofactor to the C5 position affecting their turnover. In this multidisciplinary approach, we established a molecular model of AKR1D1, identified several AAS as inhibitors, and described their binding mode. This approach may be applied to study other classes of inhibitors including non-steroidal compounds.

A qualitative assessment of anabolic-androgenic steroid use among gym users in Jordan: motives, perception, and safety.

BACKGROUND: Over the years, the use of anabolic-androgenic steroids (AAS) has become widespread among athletes and bodybuilders. The prevalence of their use has been estimated at around 20 to 50% globally. Unfortunately, many athletes do not have the proper knowledge about the effects of these banned substances Thus, this study aims to qualitatively assess Jordanian gym users' AAS intentions, perceptions, and safety. METHODS: Twenty male Jordanian anabolic steroid users were interviewed using in-depth interviews as part of a qualitative study evaluating the motivations, perceptions, and safety of AAS among gym users. RESULTS: The findings of this study indicate that the desire to compete in bodybuilding contests was the primary motivation for participants to use AAS. The study participants mentioned using a combination of oral and injectable medications. Gym coaches and trainers were also identified as an essential source of information for AAS use. A very limited number of AAS users were getting their information from healthcare providers, and most of them have experienced some of these medications side effects but are still willing to continue the use of AAS to get what they need in terms of their physical appearance or for winning competitions. CONCLUSION: There is an urgent need for structured awareness campaigns targeting gyms and fitness clubs' members to increase their knowledge about the side effects and health risks associated with the use of AAS. In addition, sports governing bodies should have stricter measures to tackle this problem and discourage athletes from using such products.

Performance assessment of an equine metabolomics model for screening a range of anabolic agents.

INTRODUCTION: Despite their ban, Anabolic Androgenic Steroids (AAS) are considered as the most important threat for equine doping purposes. In the context of controlling such practices in horse racing, metabolomics has emerged as a promising alternative strategy to study the effect of a substance on metabolism and to discover new relevant biomarkers of effect. Based on the monitoring of 4 metabolomics derived candidate biomarkers in urine, a prediction model to screen for testosterone esters abuse was previously developed. The present work focuses on assessing the robustness of the associated method and define its scope of application. MATERIALS AND METHODS: Several hundred urine samples were selected from 14 different horses of ethically approved administration studies involving various doping agents' (AAS, SARMS, ß-agonists, SAID, NSAID) (328 urine samples). In addition, 553 urine samples from untreated horses of doping control population were included in the study. Samples were characterized with the previously described LC-HRMS/MS method, with the objective of assessing both its biological and analytical robustness. RESULTS: The study concluded that the measurement of the 4 biomarkers involved in the model was fit for purpose. Further, the classification model confirmed its effectiveness in screening for testosterone esters use; and it demonstrated its ability to screen for the misuse of other anabolic agents, allowing the development of a global screening tool dedicated to this class of substances. Finally, the results were compared to a direct screening method targeting anabolic agents demonstrating complementary performances of traditional and omics approaches in the screening of anabolic agents in horses.

Health service engagement, side effects and concerns among men with anabolic-androgenic steroid use: a cross-sectional Norwegian study.

BACKGROUND: Recreational use of anabolic-androgenic steroids (AAS) is a public health concern world-wide associated with a range of physical and psychological side effects. Still, people who use AAS tend to be reluctant to seek treatment. This study aims to explore use characteristics, treatment-seeking behaviour, side effects and associated health concerns among men with AAS use. METHODS: The study includes cross-sectional self-report data from 90 men with a current or previous use of AAS exceeding 12 months, where 41 (45.6%) had sought treatment at least once during their lifetime, and 49 (54.4%) had not. Health service engagement was examined with descriptive statistics on reasons for contacting health services, transparency about AAS use, satisfaction with health services and reasons for not seeking treatment. Furthermore, experienced side effects and health concerns were compared between the treatment seeking and the non-treatment seeking group, using two-sample t-tests and Chi2 or Fisher exact tests for numerical and categorical variables, respectively. RESULTS: All 90 AAS-using men reported side effects from AAS use. Treatment seekers were significantly younger, experienced more side effects including gynecomastia, excessive sweating, fatigue, depression and anxiety, and expressed more concern for testosterone deficiency. Preventive health check-up was the most common reason for seeking treatment (n = 22, 53.7%), and 38 men (93%) were transparent about AAS use during consultations with health professionals. The main reported reasons for not seeking healthcare services were that the experienced side effects were not considered to be of treatment demanding nature (n = 39, 79.6%) and the belief that healthcare providers had scarce knowledge about AAS use and its health impacts (n = 12, 24.5%). CONCLUSIONS: Reluctance to seek treatment among people who use AAS, despite having associated side effects and health concerns, may contribute to continued health risks. It is important to fill the knowledge gap on how to reach and treat this new patient group, and policy makers and treatment providers need to be educated on how to meet their treatment needs.

Assessment of the excretion of oxidative stress biomarkers and anabolic steroids based on sewage: A case study of college students and the general population.

The use of wastewater-based epidemiology to evaluate the health and lifestyle of the population is a novel research interest. However, studies concerning the excretion of endogenous metabolites due to oxidative stress and the consumption of anabolic steroids have rarely been involved. In this study, we compared the effects of events such as final examination and sports meeting on the levels of four oxidative stress biomarkers (8-isoPGF2α, HNE-MA, 8-OHdG, and HCY) and four prohibited anabolic steroids (Testosterone, Androstenedione, Boldenone, and Metandienone) in sewage, using university students and urban populations as studying target. It was found that the per capita mass load of the four oxidative stress biomarkers 8-isoPGF2α, HNE-MA, 8-OHdG, and HCY in the sewage of Guangzhou urban area and university town were 256.6 ± 76.1, 9.4 ± 3.8, 1.1 ± 0.5, and 0.9 ± 0.4 mg/d/1000, respectively. The mean mass load of 8-isoPGF2α was significantly higher than that before the COVID-19 pandemic (74.9 ± 29.6 mg/d/1000 people, P < 0.05). The per capita load levels of oxidative stress biomarkers were significantly higher (P < 0.05) during the 2022 exam week relative to the pre-exam period, indicating that the exams caused transient stress to students. The per capita mass load of androgenic steroids was 77.7 mg/d/1000 people. There was an increase in the per capita load level of androgenic steroids during the provincial sports meeting. In this study, we quantified the concentration of oxidative stress biomarkers and androgenic steroids in the sewage and better realized the application of WBE on the health level and lifestyle of the population during special events.

Adenosine receptors participate in anabolic-androgenic steroid-induced changes on risk assessment/anxiety-like behaviors in male and female rats.

Anabolic-androgenic steroids (AAS) and caffeine can induce several behavioral alterations in humans and rodents. Administration of nandrolone decanoate is known to affect defensive responses to aversive stimuli, generally decreasing inhibitory control and increasing aggressivity but whether caffeine intake influences behavioral changes induced by AAS is unknown. The present study aimed to investigate behavioral effects of caffeine (a non-selective antagonist of adenosine receptors) alone or combined with nandrolone decanoate (one of the most commonly AAS abused) in female and male Lister Hooded rats. Our results indicated that chronic administration of nandrolone decanoate (10 mg/kg, i.m., once a week for 8 weeks) decreased risk assessment/anxiety-like behaviors (in the elevated plus maze test), regardless of sex. These effects were prevented by combined caffeine intake (0.1 g/L, p.o., ad libitum). Overall, the present study heralds a key role for caffeine intake in the modulation of nandrolone decanoate-induced behavioral changes in rats, suggesting adenosine receptors as candidate targets to manage impact of AAS on brain function and behavior.

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO).

Several drugs are available for the treatment of osteoporosis in postmenopausal women. Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, while anabolic agents were considered a last resource for those with therapeutic failure. However, recent randomized trials in patients with severe osteoporosis have shown that anabolic agents reduce fractures to a greater extent than antiresorptive medications. Additionally, evidence indicates that increases in bone mineral density (BMD) are maximized when patients are treated with anabolic agents first, followed by antiresorptive therapy. This evidence is key, considering that greater increases in BMD during osteoporosis treatment are associated with a more pronounced reduction in fracture risk. Thus, international guidelines have recently proposed an individualized approach to osteoporosis treatment based on fracture risk stratification, in which the stratification risk has been refined to include a category of patients at very high risk of fracture who should be managed with anabolic agents as first-line therapy. In this document, the Brazilian Society of Endocrinology and Metabolism and the Brazilian Association of Bone Assessment and Metabolism propose the definition of very high risk of osteoporotic fracture in postmenopausal women, for whom anabolic agents should be considered as first-line therapy. This document also reviews the factors associated with increased fracture risk, trials comparing anabolic versus antiresorptive agents, efficacy of anabolic agents in patients who are treatment naïve versus those previously treated with antiresorptive agents, and safety of anabolic agents.

Psychiatric morbidity among men using anabolic steroids.

OBJECTIVE: The purpose of this study was to investigate the psychiatric morbidity among men with abuse of anabolic steroids. METHODS: The design is a retrospectively matched cohort study. Five hundred and fourty-five males, who tested positive for anabolic steroids in Danish fitness centers during the period January 3, 2006 to March 1, 2018, were matched with 5450 randomly chosen male controls. Data was cross-referenced with seven national registers pertaining to information about education, employment status, and psychiatric comorbidity. Main outcomes and measures were prescription of psychopharmacological treatment. RESULTS: The incidence of treatment with anxiolytics (HR: 2.34, 95% CI: 1.62-3.38) and antipsychotics (HR: 2.69, 95% CI: 1.99-3.63) displayed a remarkable increase in the years following doping sanction, compared to the control group. The prevalence of antidepressant use was already markedly elevated several years before doping sanction, but also displayed a higher incidence in the years following sanction (HR: 1.65, 95% CI: 1.28-2.13). The associations remained highly significant after controlling for socioeconomic factors. CONCLUSION: Anabolic steroids use is strongly associated with psychiatric morbidity.

The economic burden of HIV-associated wasting in the era of modern antiretroviral therapy.

BACKGROUND: HIV-associated wasting (HIVAW) is associated with increased morbidity and mortality in people living with HIV (PWH). Evaluating health care resource utilization and cost predictors of HIVAW is important in understanding the overall economic burden of the disease. OBJECTIVE: To evaluate the economic burden and cost predictors associated with HIVAW. METHODS: This analysis of the IBM MarketScan Commercial, Medicare Supplemental, and Medicaid databases included members with a claim for HIV (using International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification codes) between July 2012 and September 2018, with the HIV index date defined as the first HIV diagnosis claim in the dataset. PWH were excluded if they were aged less than 18 years, had any malignancy claim, or had less than 6 months of enrollment data pre-HIV or post-HIV index date. Members were defined as having HIVAW using an algorithm of claims for weight loss-related diagnoses, appetite stimulant or nontestosterone anabolic agents, or enteral/parenteral nutrition at any time post-HIV index. Taking antiretroviral therapy (ART) was defined as having at least 1 pharmacy claim of any ART 12 months post-HIV index. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department visits, outpatient visits, and pharmacy use. A multivariate generalized linear model with log-link and γ distribution was used to estimate the impact of HIVAW predictors of total all-cause costs. RESULTS: Among 42,587 members with HIV included in the study (64.6% male; mean age: 44 years; 67.5% insured with Medicaid; and 63.9% taking ART), the overall prevalence of HIVAW was 18.3% during the study period. HIVAW prevalence was 17.9% for those taking ART and 19.1% for those not taking ART. Prevalence by payer type was 7.5% for Commercial ± Medicare Supplemental and 23.5% for Medicaid. Members with HIVAW had more comorbidities and opportunistic infections compared with members without HIVAW. Members with HIVAW were also more than twice as likely to be hospitalized (71.1% vs 32.1%) and had 5 times the number of hospitalizations (1.0 vs 0.2) and twice the number of emergency department visits (3.0 vs 1.3) per year post-index compared with members without HIVAW (P < 0.01). HIVAW was associated with 1.3-times-higher mean annualized total all-cause costs per member (95% CI = 1.26-1.36). CONCLUSIONS: HIVAW remains prevalent despite advances in ART and is associated with additional health care resource utilization and costs. Further research is needed to better understand the relationship between HIVAW and comorbidity burden and ART utilization and payer types. DISCLOSURES: This study was sponsored by EMD Serono, Inc., Rockland, MA, USA (CrossRef Funder ID: 10.13039/100004755). Dr Siddiqui has received consulting and speaking fees from AbbVie, BioFire, Cumberland, EMD Serono, Inc., Rockland, MA, USA, and Merck. Dr Samuel, Ms Hayward, Ms Wirka, Dr Phillips, and Dr Harbour are employees of EMD Serono, Inc., Rockland, MA, USA. Drs Deering and Harshaw are employees of EPI-Q, Inc., which received payment from EMD Serono, Inc., Rockland, MA, USA, for the development and execution of this study.

In-Sewer Stability Assessment of Anabolic Steroids and Selective Androgen Receptor Modulators.

Wastewater-based epidemiology is a potential complementary technique for monitoring the use of performance- and image-enhancing drugs (PIEDs), such as anabolic steroids and selective androgen receptor modulators (SARMs), within the general population. Assessing in-sewer transformation and degradation is critical for understanding uncertainties associated with wastewater analysis. An electrospray ionization liquid chromatography mass spectrometry method for the quantification of 59 anabolic agents in wastewater influent was developed. Limits of detection and limits of quantification ranged from 0.004 to 1.56 µg/L and 0.01 to 4.75 µg/L, respectively. Method performance was acceptable for linearity (R2 > 0.995, few exceptions), accuracy (68-119%), and precision (1-21%RSD), and applicability was successfully demonstrated. To assess the stability of the selected biomarkers in wastewater, we used laboratory-scale sewer reactors to subject the anabolic agents to simulated realistic sewer environments for 12 h. Anabolic agents, including parent compounds and metabolites, were spiked into freshly collected wastewater that was then fed into three sewer reactor types: control sewer (no biofilm), gravity sewer (aerobic conditions), and rising main sewer (anaerobic conditions). Our results revealed that while most glucuronide conjugates were completely transformed following 12 h in the sewer reactors, 50% of the investigated biomarkers had half-lives longer than 4 h (mean residence time) under gravity sewer conditions. Most anabolic agents were likely subject to biofilm sorption and desorption. These novel results lay the groundwork for any future wastewater-based epidemiology research involving anabolic steroids and SARMs.

Ion mobility-high resolution mass spectrometry in anti-doping analysis. Part I: Implementation of a screening method with the assessment of a library of substances prohibited in sports.

In this series of two papers, 192 doping agents belonging to the classes of stimulants, narcotics, cannabinoids, diuretics, ß2-agonists, ß-blockers, anabolic agents, and hormone and metabolic modulators were investigated, with the aim to assess the benefits and limitations of ion mobility spectrometry (IMS) in combination with ultra-high performance liquid chromatography (UHPLC) and high resolution mass spectrometry (HRMS) in anti-doping analysis. In this first part, a generic UHPLC-IM-HRMS method was successfully developed to analyze these 192 doping agents in standard solutions and urine samples, and an exhaustive database including retention times, TWCCSN2 values, and m/z ratios was constructed. Urine samples were analyzed using either a simple "dilute and shoot" procedure or a supported liquid-liquid extraction (SLE) procedure, depending on the physicochemical properties of the compounds and sensitivity criteria established by the World Anti-Doping Agency (WADA) as the minimum required performance levels (MRPL). Then, the precision of the generic UHPLC-IM-HRMS method was assessed as intraday, interday as well as interweek variation of UHPLC retention times and TWCCSN2 values, for which RSD the values were always lower than 2% in urine samples. The possibility to filter MS data using IMS dimension was also investigated, and in average, the application of IMS filtration provided low energy MS spectra with 86% less interfering peaks in both standard and urine samples. Therefore, the filtered MS spectra allowed for an easier interpretation and a lower risk of false positive result interpretations. Finally, IMS also offers additional selectivity to the UHPLC-HRMS enabling to separate isobaric and isomeric substances. Among the selected set of 192 doping agents, there were 30 pairs of isobaric or isomeric compounds, and only two pairs could not be resolved under the developed conditions. This illustrates the potential of adding ion mobility to UHPLC-HRMS in anti-doping analyses.

A sentinel population: The public health benefits of monitoring enhanced body builders.

There is heightened recognition of the public health implications of anabolic androgenic steroids (AAS) for the use of image and performance enhancement; with increasing evidence of their long-term negative health impacts, the hazards associated with their administration (often via injection), and the variability and unpredictability of their contents. In order to optimise the effects of these drugs, together with strict dietary and training regimes, AAS users typically supplement their use with an expansive and continually evolving range of ancillary drugs. The discovery and subsequent adoption of these drugs by the broader AAS user population is largely dependent upon a minority of social influencers within the bodybuilding community. Pioneering enhanced bodybuilders who self-experiment with a diverse range of image and performance enhancing drugs (IPEDs) and ancillary drugs have been the forerunners in the development of an underground user-led literature, online discussion forums, and were early adopters of internet-facilitated drug markets. Yet the impact of their self-experimentations extends well beyond the enhanced bodybuilding community, particularly in their use of ancillary drugs. Most significantly has been their role in the diffusion of various enhancement and psychoactive drugs to the wider population. Using the theoretical framework of the 'diffusion of innovation' we consider the role that pioneering enhanced bodybuilders have played in the diffusion of various enhancement and psychoactive drugs to the wider population through a focus on three substances: dinitrophenol (DNP), melanotan II and gamma-hydroxybtyrate (GHB). With an increasing range of drugs used by bodybuilders, coupled with an expansion in the use of online forums and online platforms to purchase pharmacological and new psychoactive drugs, we anticipate this trend of diffusion amongst the wider population will continue to flourish. Therefore, we highlight the need for policy makers to monitor emergent trends, not only in the general AAS population but particularly amongst enhanced bodybuilders.

Development of a multi-residue high-throughput UHPLC-MS/MS method for routine monitoring of SARM compounds in equine and bovine blood.

Selective androgen receptor modulators (SARMs) are a group of anabolic enhancer drugs posing threats to the integrity of animal sports and the safety of animal-derived foods. The current research describes for the first time the development of a semi-quantitative assay for the monitoring of SARM family compounds in blood and establishes the relative stability of these analytes under various storage conditions prior to analysis. The presented screening method validation was performed in line with current EU legislation for the inspection of livestock and produce of animal origin, with detection capability (CCß) values determined at 0.5 ng/mL (Ly2452473), 1 ng/mL (AC-262536 and PF-06260414), 2 ng/mL (bicalutamide, GLPG0492, LGD-2226, ostarine, S-1, S-6, and S-23), and 5 ng/mL (andarine, BMS-564929, LGD-4033, RAD140, and S-9), respectively. The applicability of the developed assay was demonstrated through the analysis of blood samples from racehorses and cattle. The developed method presents a high-throughput cost-effective tool for the routine screening for a range of SARM compounds in sport and livestock animals.

Investigations into the analysis of intact drug conjugates in animal sport doping control - Development and assessment of a rapid and economical approach for screening greyhound urine.

Animal sport doping control laboratories are constantly reviewing ways in which they can improve their service offering whilst ensuring that they remain economically viable. This paper describes the development and assessment of a rapid and economical method for the detection of intact glucuronide conjugates of three anabolic steroids and their metabolites along with three corticosteroids in canine urine. The analysis of intact drug conjugates for animal sport doping control is generally not performed routinely as it presents a number of analytical challenges, not least of which is the lack of availability of appropriate reference standards. Here, we report the development of a UHPLC-MS/MS method using APCI in the negative ion mode for the detection of intact phase II conjugates, including the importance of in vitro incubations in order to provide appropriate reference materials. Cross-validation of the developed method demonstrated that the detection capability of the intact phase II conjugates of stanozolol, boldenone, nandrolone, and their metabolites along with the corticosteroids dexamethasone and methylprednisolone was equivalent to that achieved in routine race-day screens. The new process has been in operation for approximately 2 years and has been used to analyze in excess of 13500 canine urine samples, resulting in a number of positive screening findings. To the best of our knowledge, this is the first reported use of a routine screen for intact drug conjugates within animal sport doping control.

The impact of nandrolone decanoate abuse on experimental animal model: Hormonal and biochemical assessment.

Nandrolone decanoate (ND) is one of the most commonly abused anabolic androgenic steroids compounds in the world owing to its ability to improve physical performance but its abuse is associated with several adverse effects. The current study was performed to evaluate the effect of recommended and overdose of nandrolone decanoate (ND) for short and long term on the alterations of biochemical markers related to kidney, liver, adrenal, thyroid gland functions and oxidant and antioxidant activities. Sixty male rats were randomly assigned into two major groups. The first was treated with ND for 6 weeks and the second was treated with same drug for 12 weeks. Each of these groups was further subdivided into three sub groups: 1-Control (untreated rats), 2- Rats intraperitoneally injected with ND 3 mg/kg weekly, 3- Rats intraperitoneally injected with ND 15 mg/kg weekly. Administration of high ND dose for either short or long term significantly elevated kidney function biomarkers, liver enzymes both in serum, cytosol and mitochondria, insignificantly increased thyroid function, significantly increased adrenal function while, decreased ACTH. Moreover, oxidative stress biomarkers were significantly upregulated associated with depression in antioxidants activities. Administration of high ND dose for either short or long term as well as the repeated use of recommended ND dose for long term proved to have harmful effects manifested in impairing the functions of kidneys, liver, thyroid and adrenal glands as well as oxidant antioxidant balance.

Anabolic-androgenic steroids and the risk of imprisonment.

BACKGROUND: The use of Anabolic-Androgenic Steroids (AAS) has been associated with increased aggressiveness and violent behavior. We therefore investigated the proposed correlation between the use of AAS and criminality while controlling for important socio-economics covariates and for psychiatric comorbidity. METHODS: The primary endpoints were prison sentences, and time to first prison sentence. A retrospective matched cohort study design consisting of 545 males, who tested positive for AAS in Danish gyms during the period January 3, 2006 to January 31, 2017. They were matched with 5450 randomly chosen male controls. Data were cross-referenced with national register information on education, employment status, substance abuse and psychiatric comorbidity. In addition, 638 males sanctioned because they rejected to participate in the doping control and 6380 controls were used as a replication cohort. RESULTS: Already at baseline, 20.6% of the AAS users had a previous prison sentence whereas the rate was 3.7% in the control cohort (p < 0.0001). During the follow-up period the cumulative prevalence increased to 29.5% and 4.9%, respectively (unadjusted HR 9.15, 95% CI 6.33-13.20). The associations remained highly significant after controlling for socio-economic factors, drug abuse and psychiatric comorbidity. The results could be replicated in a similar cohort. CONCLUSION: Our study shows that AAS users have a 9-fold increased risk of being convicted of a crime compared to matched controls, randomly chosen from the general population. This association could not be explained by common socioeconomic factors or by psychiatric comorbidity.

Anabolic competence: Assessment and integration of the multimodality interventional approach in disease-related malnutrition.

Disease-related malnutrition (DRM) is a frequent clinical problem, characterized by loss of lean body mass and decreased function, including muscle function and immunocompetence. In DRM, nutritional intervention is necessary, but it has not consistently been shown to be sufficient. Other factors, for example, physical activity and hormonal or metabolic influencers of the internal milieu, are also important in the treatment of DRM. A prerequisite for successful treatment of DRM is the positive balance between anabolism and catabolism. The aim of this review was to approach DRM using this paradigm of anabolic competence, for conceptual and practical reasons. Anabolic competence is defined as "that state which optimally supports protein synthesis and lean body mass, global aspects of muscle and organ function, and immune response." Anabolic competence and interdisciplinary, multimodality interventions create a practical foundation to approach DRM in a proactive comprehensive way. Here, we describe the paradigm of anabolic competence, and its operationalization by measuring factors related to anabolic competence and suited for clinical management of patients with DRM.

A pilot wastewater-based epidemiology assessment of anabolic steroid use in Queensland, Australia.

Anabolic-androgenic steroids are synthetic compounds prohibited due to their performance-enhancing characteristics. The use of these substances is known to cause health-related issues, which highlights the importance of being able to evaluate the scale of consumption by the general population. However, most available research on the analysis of anabolic steroids is focused on animals and athletes in connection with doping. The potential of wastewater-based epidemiology as an intelligence tool for the assessment of community level use of anabolic steroids is presented herein. A liquid chromatography tandem mass spectrometry method was developed for the analysis of 10 anabolic-androgenic steroids and 14 endogenous hormones in influent wastewater. The validated method was applied to sixteen 24-hour composite wastewater influent samples that were collected over a period of five years from two wastewater treatment plants in Queensland, Australia. Nine investigated compounds were found to be present at concentrations between 14 and 611 ng L-1 which translated into 3-104 mg excreted per 1000 individuals per day. It was concluded that the developed analytical method is suitable for the analysis of AAS in wastewater matrix. Additionally, both the inclusion of metabolites and further investigation into deconjugation by enzymatic hydrolysis would aid in understanding and evaluating community anabolic steroid use. For the first time, this study presents the application of wastewater-based epidemiology on anabolic-androgenic steroids in Australia.

Assessment of the impact of oxandrolone on outcomes in burn injured patients.

The purpose of this study is to use a retrospective cohort of burn patients to evaluate the contribution of oxandrolone on burn care outcomes. Longitudinal clinical data is used to analyze outcomes from a new perspective. Our random-effects longitudinal regression analysis model used temporal clinical data to evaluate oxandrolone's impact on outcomes (oxandrolone/non-oxandrolone n=50/11, median length of stay [LOS]=42.2/39.3, mean weight (kg)=192.2/207.6, mean initial prealbumin (mg/dL) 10.1/7.5). The resultant predictive models (p<0.001) described how certain factors influence clinically significant outcomes via a robust data analysis method. LOS was predicted and extended by a greater magnitude of 3rd-degree versus 2nd-degree burns (1.01 versus 0.85 additional days for each %TBSA, p<0.001). Weight was decreased by LOS (145.2g lost per day, p<0.001). Oxandrolone improved prealbumin (3.503mg/dL increase, p<0.001) but instead did not influence patient weight (p>0.05) nor LOS (5.27days shortening, p=0.361). Prealbumin over time was also influenced by initial value (0.293mg/dL, p=0.003), LOS (0.072mg/dL increase per additional day, p<0.001), and the presence of inhalation injury (2.652mg/dL decrease if present, p=0.009). Oxandrolone appears to benefit anabolic protein production. It is difficult to isolate the role of oxandrolone on major outcomes due to the concomitant influence of other variables.

Computational Assessment of Pharmacokinetics and Biological Effects of Some Anabolic and Androgen Steroids.

PURPOSE: The aim of this study is to use computational approaches to predict the ADME-Tox profiles, pharmacokinetics, molecular targets, biological activity spectra and side/toxic effects of 31 anabolic and androgen steroids in humans. METHODS: The following computational tools are used: (i) FAFDrugs4, SwissADME and admetSARfor obtaining the ADME-Tox profiles and for predicting pharmacokinetics;(ii) SwissTargetPrediction and PASS online for predicting the molecular targets and biological activities; (iii) PASS online, Toxtree, admetSAR and Endocrine Disruptomefor envisaging the specific toxicities; (iv) SwissDock to assess the interactions of investigated steroids with cytochromes involved in drugs metabolism. RESULTS: Investigated steroids usually reveal a high gastrointestinal absorption and a good oral bioavailability, may inhibit someof the human cytochromes involved in the metabolism of xenobiotics (CYP2C9 being the most affected) and reflect a good capacity for skin penetration. There are predicted numerous side effects of investigated steroids in humans: genotoxic carcinogenicity, hepatotoxicity, cardiovascular, hematotoxic and genitourinary effects, dermal irritations, endocrine disruption and reproductive dysfunction. CONCLUSIONS: These results are important to be known as an occupational exposure to anabolic and androgenic steroids at workplaces may occur and because there also is a deliberate human exposure to steroids for their performance enhancement and anti-aging properties.