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1.
Bone-Targeting Systems to Systemically Deliver Therapeutics to Bone Fractures for Accelerated Healing.
Nielsen, JJ, Low, SA
Current osteoporosis reports. 2020;(5):449-459
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Abstract
PURPOSE OF REVIEW Compared with the current standard of implanting bone anabolics for fracture repair, bone fracture-targeted anabolics would be more effective, less invasive, and less toxic and would allow for control over what phase of fracture healing is being affected. We therefore sought to identify the optimal bone-targeting molecule to allow for systemic administration of therapeutics to bone fractures. RECENT FINDINGS We found that many bone-targeting molecules exist, but most have been developed for the treatment of bone cancers, osteomyelitis, or osteoporosis. There are a few examples of bone-targeting ligands that have been developed for bone fractures that are selective for the bone fracture over the body and skeleton. Acidic oligopeptides have the ideal half-life, toxicity profile, and selectivity for a bone fracture-targeting ligand and are the most developed and promising of these bone fracture-targeting ligands. However, many other promising ligands have been developed that could be used for bone fractures.
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Kidney disease associated with androgenic-anabolic steroids and vitamin supplements abuse: Be aware!
Parente Filho, SLA, Gomes, PEAC, Forte, GA, Lima, LLL, Silva Júnior, GBD, Meneses, GC, Martins, AMC, Daher, EF
Nefrologia. 2020;(1):26-31
Abstract
The excessive chase for beauty standards and the rise of muscle dysmorphia have ultimately led to an increase in androgenic-anabolic steroids (AAS) and intramuscular injections of vitamins A, D and E (ADE) abuse, which is associated with several adverse effects and has become a public health issue. This review of literature discusses kidney injury associated with the use of AAS and ADE, highlighting the mechanisms of acute and chronic renal lesion, such as direct renal toxicity, glomerular hyperfiltration and hypercalcemia. Future perspectives regarding evaluation and early diagnosis of kidney injury in these patients are also discussed.
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Indirect clinical markers for the detection of anabolic steroid abuse beyond the conventional doping control in athletes.
Christou, GA, Christou, MA, Žiberna, L, Christou, KA
European journal of sport science. 2019;(9):1276-1286
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Abstract
Growing analytical challenges have arisen for the detection of misuse of androgenic anabolic steroids (AAS) in athletes the last years. Therefore, consideration of additional indirect markers can substantially aid the efforts to detect AAS abuse in athletes. Moreover, this approach can also help physicians to suspect AAS abuse when treating athletes. Laboratory markers highly indicative of AAS abuse in athletes include the considerable downregulation of high density lipoprotein-cholesterol, elevation of haematocrit or serum γ-glutamyl transpeptidase levels and for males reduced serum levels of both luteinizing hormone and follicle-stimulating hormone. Moreover, physical signs suggestive of current AAS abuse are hypertension, apparent changes in behaviour making the athlete more irritable and aggressive and the sudden appearance of acne vulgaris in an adult athlete with no recent history of acne, while testicular atrophy and gynecomastia raise suspicion of current or past AAS abuse in male athletes.
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Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping.
Solimini, R, Rotolo, MC, Mastrobattista, L, Mortali, C, Minutillo, A, Pichini, S, Pacifici, R, Palmi, I
European review for medical and pharmacological sciences. 2017;(1 Suppl):7-16
Abstract
Anabolic Androgenic Steroids (AAS) abuse and misuse is nowadays a harmful habit involving both professional or recreational athletes, as well as general population. AAS are also frequently present in over-the-counter dietary supplements without being declared in the list of ingredients, leaving consumers unaware of the risks of adverse effects. Indeed, health risks of AAS consumption in pharmaceutical preparations or dietary complements seem still underestimated and under-reported. The variety of complications due to AAS misuse involves cardiovascular, central nervous, musculoskeletal and genitourinary systems of both males and females; psychiatric and behavioral effects, damages to metabolic system, skin and mainly liver. For instance, relevant concern has been raised by the AAS hepatotoxicity including adenoma, hepatocellular carcinoma, cholestasis, and peliosis hepatis. The present review reports the information available on the hepatotoxic effects of AAS use in professional and amateur athletes.
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Branched-chain amino acids and muscle protein synthesis in humans: myth or reality?
Wolfe, RR
Journal of the International Society of Sports Nutrition. 2017;:30
Abstract
The branched chain amino acids (BCAAs) are leucine, valine and isoleucine. A multi-million dollar industry of nutritional supplements has grown around the concept that dietary supplements of BCAAs alone produce an anabolic response in humans driven by a stimulation of muscle protein synthesis. In this brief review the theoretical and empirical bases for that claim are discussed. Theoretically, the maximal stimulation of muscle protein synthesis in the post-absorptive state in response to BCAAs alone is the difference between muscle protein breakdown and muscle protein synthesis (about 30% greater than synthesis), because the other EAAs required for synthesis of new protein can only be derived from muscle protein breakdown. Realistically, a maximal increase in muscle protein synthesis of 30% is an over-estimate because the obligatory oxidation of EAAs can never be completely suppressed. An extensive search of the literature has revealed no studies in human subjects in which the response of muscle protein synthesis to orally-ingested BCAAs alone was quantified, and only two studies in which the effect of intravenously infused BCAAs alone was assessed. Both of these intravenous infusion studies found that BCAAs decreased muscle protein synthesis as well as protein breakdown, meaning a decrease in muscle protein turnover. The catabolic state in which the rate of muscle protein breakdown exceeded the rate of muscle protein synthesis persisted during BCAA infusion. We conclude that the claim that consumption of dietary BCAAs stimulates muscle protein synthesis or produces an anabolic response in human subjects is unwarranted.
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Effects of pharmacological interventions on muscle protein synthesis and breakdown in recovery from burns.
Diaz, EC, Herndon, DN, Porter, C, Sidossis, LS, Suman, OE, Børsheim, E
Burns : journal of the International Society for Burn Injuries. 2015;(4):649-57
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Abstract
OBJECTIVE The pathophysiological response to burn injury disturbs the balance between skeletal muscle protein synthesis and breakdown, resulting in severe muscle wasting. Muscle loss after burn injury is related to increased mortality and morbidity. Consequently, mitigation of this catabolic response has become a focus in the management of these patients. The aim of this review is to discuss the literature pertaining to pharmacological interventions aimed at attenuating skeletal muscle catabolism in severely burned patients. DATA SELECTION Review of the literature related to skeletal muscle protein metabolism following burn injury was conducted. Emphasis was on studies utilizing stable isotope tracer kinetics to assess the impact of pharmacological interventions on muscle protein metabolism in severely burned patients. CONCLUSION Data support the efficacy of testosterone, oxandrolone, human recombinant growth hormone, insulin, metformin, and propranolol in improving skeletal muscle protein net balance in patients with severe burns. The mechanisms underlying the improvement of protein net balance differ between types and dosages of drugs, but their main effect is on protein synthesis. Finally, the majority of studies have been conducted during the acute hypermetabolic phase of the injury. Except for oxandrolone, the effects of drugs on muscle protein kinetics following discharge from the hospital are largely unknown.
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U.S. Army Research on Pharmacological Enhancement of Soldier Performance: Stimulants, Anabolic Hormones, and Blood Doping.
Friedl, KE
Journal of strength and conditioning research. 2015;:S71-6
Abstract
The level playing field of competitive sports is an irrelevant concern in asymmetrical warfare. However, there is a common theme of pressure to use performance-enhancing drugs because athletic or military opponents may be using them to advantage. This interest is fueled by personal anecdotes, misconceptions, and myths, and decisions to use or not to use pharmacological interventions may ignore available scientific data. The U.S. Army has led research in this area, with an abundance of published data extending back to World War II. Behavioral effects have been a consistent concern. A key conclusion to be drawn from this research is that although there may be specialized applications for some of these interventions, the majority of soldiers will gain the greatest performance benefits from effective physical and mental training programs combined with good principles of rest and nutrition. Furthermore, the perceived need to improve human biology with drugs may be solving the wrong problem, trying to fit the human to the demands of poorly conceived tactics, tasks, and equipments instead of capitalizing on human capabilities.
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Polypharmacy among anabolic-androgenic steroid users: a descriptive metasynthesis.
Sagoe, D, McVeigh, J, Bjørnebekk, A, Essilfie, MS, Andreassen, CS, Pallesen, S
Substance abuse treatment, prevention, and policy. 2015;:12
Abstract
BACKGROUND As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS) users has been published. METHOD We systematically reviewed and synthesized qualitative/descriptive literature gathered from searches in electronic databases and by inspecting reference lists of relevant literature to investigate AAS users' polypharmacy. We adhered to the recommendations of the UK Economic and Social Research Council's qualitative research synthesis manual and the PRISMA guidelines. RESULTS A total of 50 studies published between 1985 and 2014 were included in the analysis. Studies originated from 10 countries although most originated from United States (n=22), followed by Sweden (n=7), England only (n=5), and the United Kingdom (n=4). It was evident that prior to their debut, AAS users often used other licit and illicit substances. The main ancillary/supplementary substances used were alcohol, and cannabis/cannabinoids followed by cocaine, growth hormone, and human chorionic gonadotropin (hCG), amphetamine/meth, clenbuterol, ephedra/ephedrine, insulin, and thyroxine. Other popular substance classes were analgesics/opioids, dietary/nutritional supplements, and diuretics. Our classification of the various substances used by AAS users resulted in 13 main groups. These non-AAS substances were used mainly to enhance the effects of AAS, combat the side effects of AAS, and for recreational or relaxation purposes, as well as sexual enhancement. CONCLUSIONS Our findings corroborate previous suggestions of associations between AAS use and the use of other licit and illicit substances. Efforts must be intensified to combat the debilitating effects of AAS-associated polypharmacy.
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Multimodal nutrition/anabolic therapy for wasting conditions.
Balstad, TR, Kaasa, S, Solheim, TS
Current opinion in clinical nutrition and metabolic care. 2014;(3):226-35
Abstract
PURPOSE OF REVIEW Significant progress has been made in the field of defining and describing the pathophysiology of wasting conditions such as cachexia. The number of new promising drugs, nutritional therapy alternatives, and exercise/rehabilitation programs is increasing. The purpose of this review is to give an overview of recent clinical findings from intervention studies investigating multimodal anabolic therapies utilizing drug, nutritional, and/or exercise interventions in order to counteract wasting. RECENT FINDINGS Anabolic agents such as ghrelin and selective androgen receptor modulators are under late-phase clinical testing and hold promise as new therapies, and their ability to mitigate weight loss and improve muscle mass and physical function is evaluated. In the past 2 years, eight new studies investigating interventions with anabolic potential in wasting have been published, among which three of these studies were multimodal. SUMMARY Targeted anabolic therapies aiming to prevent or reverse wasting might involve a combination of anabolic pharmacologic drugs, nutrition, and physical exercise working concurrently to enhance muscle protein synthesis and reduce breakdown. Some anabolic pharmacological interventions demonstrate the potential to improve muscle mass, but the multimodal interventions seem in greater extent to also demonstrate improvement in physical function.
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Anabolic agents: recent strategies for their detection and protection from inadvertent doping.
Geyer, H, Schänzer, W, Thevis, M
British journal of sports medicine. 2014;(10):820-6
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Abstract
According to the World Anti-Doping Agency (WADA) Prohibited List, anabolic agents consist of exogenous anabolic androgenic steroids (AAS), endogenous AAS and other anabolic agents such as clenbuterol and selective androgen receptor modulators (SARMs). Currently employed strategies for their improved detection include the prolongation of the detection windows for exogenous AAS, non-targeted and indirect analytical approaches for the detection of modified steroids (designer steroids), the athlete's biological passport and isotope ratio mass spectrometry for the detection of the misuse of endogenous AAS, as well as preventive doping research for the detection of SARMs. The recent use of these strategies led to 4-80-fold increases of adverse analytical findings for exogenous AAS, to the detection of the misuse of new designer steroids, to adverse analytical findings of different endogenous AAS and to the first adverse analytical findings of SARMs. The strategies of the antidoping research are not only focused on the development of methods to catch the cheating athlete but also to protect the clean athlete from inadvertent doping. Within the past few years several sources of inadvertent doping with anabolic agents have been identified. Among these are nutritional supplements adulterated with AAS, meat products contaminated with clenbuterol, mycotoxin (zearalenone) contamination leading to zeranol findings, and natural products containing endogenous AAS. The protection strategy consists of further investigations in case of reasonable suspicion of inadvertent doping, publication of the results, education of athletes and development of methods to differentiate between intentional and unintentional doping.