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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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Preliminary effect and feasibility of physiotherapy with strength training and protein-rich nutritional supplement in combination with anabolic steroids in cross-continuum rehabilitation of patients with hip fracture: protocol for a blinded randomized controlled pilot trial (HIP-SAP1 trial).
Hulsbæk, S, Ban, I, Aasvang, TK, Jensen, JB, Kehlet, H, Foss, NB, Bandholm, T, Kristensen, MT
Trials. 2019;(1):763
Abstract
BACKGROUND A 2014 Cochrane review evaluating the effect of anabolic steroids after hip fracture concluded that the quality of the studies was insufficient to draw conclusions on the effects and recommended further high-quality trials in the field. Therefore, the aim of this pilot trial is to determine the preliminary effect and feasibility of a 12-week multimodal intervention consisting of physiotherapy (with strength training), protein-rich nutritional supplement and anabolic steroid on knee-extension muscle strength and function 14 weeks after hip fracture surgery. METHODS We plan to conduct a randomized, placebo-controlled pilot trial with 48 patients operated for acute hip fracture. The patients are randomized (1:1) to either (1) physiotherapy with protein-rich nutritional supplement plus anabolic steroid or (2) physiotherapy with protein-rich nutritional supplement plus placebo. Outcome assessments will be carried out blinded at baseline (3-10 days after surgery) and at 14 weeks after entering the trial. Primary outcome is the change from baseline to follow-up in maximal isometric knee-extension muscle strength in the fractured limb. Secondary outcomes are physical performance test, patient-reported outcomes, and measures of body composition. DISCUSSION If the trial is found feasible and the results show an indication of anabolic steroid being a relevant addition to further enhance the recovery of muscle strength and function in an enhanced recovery after surgery program, this trial will constitute the basis of a larger confirmatory trial. TRIAL REGISTRATION ClinicalTrials.gov, NCT03545347. Preregistered on 4 June 2018.
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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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Direct quantitation of endogenous steroid sulfates in human urine by liquid chromatography-electrospray tandem mass spectrometry.
Esquivel, A, Alechaga, É, Monfort, N, Ventura, R
Drug testing and analysis. 2018;(11-12):1734-1743
Abstract
A method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the direct quantitation of endogenous steroid sulfates has been developed to be able to evaluate these metabolites as biomarkers to detect the misuse of endogenous androgenic anabolic steroids in sports. For sample preparation, a mixed-mode solid-phase extraction was optimized to eliminate the glucuronide fraction in the washing step thus obtaining only the sulfate fraction. Chromatographic separation was optimized to achieve adequate resolution between isomers. The electrospray ionization and the product ion mass spectra of the sulfates were studied in order to obtain the most specific and selective transitions. The method was validated for quantitative purposes for 11 steroid sulfates obtaining satisfactory values for linearity, accuracy, and intra- and inter-day precision (relative standard deviation better than 16.2%). Limits of quantitation ranged between 0.5 and 2 ng/mL. Extraction recoveries for sulfate metabolites were between 90 and 94%. Matrix effect ranged from 90 to 110% showing the absence of significant ion suppression/enhancement. Samples were found to be stable after 2 freeze/thaw cycles. The applicability of the method was checked by the analysis of 75 urine samples from healthy volunteers (54 males, 37 Caucasian and 17 Asian, and 21 Caucasian females) to evaluate the concentration levels of endogenous sulfate metabolites in basal conditions.
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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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Anabolic effects of leucine-rich whey protein, carbohydrate, and soy protein with and without β-hydroxy-β-methylbutyrate (HMB) during fasting-induced catabolism: A human randomized crossover trial.
Rittig, N, Bach, E, Thomsen, HH, Møller, AB, Hansen, J, Johannsen, M, Jensen, E, Serena, A, Jørgensen, JO, Richelsen, B, et al
Clinical nutrition (Edinburgh, Scotland). 2017;(3):697-705
Abstract
BACKGROUND Protein-rich beverages are widely used clinically to preserve muscle protein and improve physical performance. Beverages with high contents of leucine or its keto-metabolite β-hydroxy-β-methylbutyrate (HMB) are especially anabolic in muscle, but it is uncertain whether this also applies to catabolic conditions such as fasting and whether common or separate intracellular signaling cascades are involved. OBJECTIVE To compare a specific leucine-rich whey protein beverage (LWH) with isocaloric carbohydrate- (CHO), soy protein (SOY), and soy protein +3 g HMB (HMB) during fasting-induced catabolic conditions. DESIGN Eight healthy lean male subjects underwent four interventions (LWH, CHO, SOY, and HMB) using a randomized crossover design. Each trial included a 36 h fast and consisted of a 3 h basal fasting period and a 4 h 'sipping' period. RESULTS Forearm net balances of phenylalanine (NBphe, measure of net protein loss) improved for all groups (p < 0.05), but more prominently so for LWH and HMB compared with SOY (p < 0.05). Muscle protein phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets eukaryotic translation factor 4E-binding protein 1 (4EBP1) and ribosomal S6 kinase 1 (S6) were distinctly increased during LWH consumption (p < 0.05). The ratio between autophagy protein microtubule-associated protein 1 light chain-3β II and I (LC3II/LC3I, a measure of autophagy activity) was decreased during LWH and SOY intake compared with the fasting period (p < 0.05). CONCLUSION LWH and HMB have superior anabolic effects on muscle protein kinetics after 36 h of fasting, and LWH distinctly activates the mTOR pathway. These novel findings suggest that leucine-rich whey protein and/or HMB are specifically beneficial during fasting-induced catabolic conditions.
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Anabolic steroids for rehabilitation after hip fracture in older people.
Farooqi, V, Berg, ME, Cameron, ID, Crotty, M
Sao Paulo medical journal = Revista paulista de medicina. 2016;(5):467-468
Abstract
BACKGROUND Hip fracture occurs predominantly in older people, many of whom are frail and undernourished. After hip fracture surgery and rehabilitation, most patients experience a decline in mobility and function. Anabolic steroids, the synthetic derivatives of the male hormone testosterone, have been used in combination with exercise to improve muscle mass and strength in athletes. They may have similar effects in older people who are recovering from hip fracture. OBJECTIVES To examine the effects (primarily in terms of functional outcome and adverse events) of anabolic steroids after surgical treatment of hip fracture in older people. METHODS Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (10 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013 Issue 8), MEDLINE (1946 to August Week 4 2013), EMBASE (1974 to 2013 Week 36), trial registers, conference proceedings, and reference lists of relevant articles. The search was run in September 2013.Selection criteria: Randomized controlled trials of anabolic steroids given after hip fracture surgery, in inpatient or outpatient settings, to improve physical functioning in older patients with hip fracture.Data collection and analysis: Two review authors independently selected trials (based on predefined inclusion criteria), extracted data and assessed each study's risk of bias. A third review author moderated disagreements. Only very limited pooling of data was possible. The primary outcomes were function (for example, independence in mobility and activities of daily living) and adverse events, including mortality. MAIN RESULTS We screened 1290 records and found only three trials involving 154 female participants, all of whom were aged above 65 years and had had hip fracture surgery. All studies had methodological shortcomings that placed them at high or unclear risk of bias. Because of this high risk of bias, imprecise results and likelihood of publication bias, we judged the quality of the evidence for all primary outcomes to be very low.These trials tested two comparisons. One trial had three groups and contributed data to both comparisons. None of the trials reported on patient acceptability of the intervention.Two very different trials compared anabolic steroid versus control (no anabolic steroid or placebo). One trial compared anabolic steroid injections (given weekly until discharge from hospital or four weeks, whichever came first) versus placebo injections in 29 "frail elderly females". This found very low quality evidence of little difference between the two groups in the numbers discharged to a higher level of care or dead (one person in the control group died) (8/15 versus 10/14; risk ratio (RR) 0.75, 95% confidence interval (CI) 0.42 to 1.33; P = 0.32), time to independent mobilization or individual adverse events. The second trial compared anabolic steroid injections (every three weeks for six months) and daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women" who were followed up for one year after surgery. This trial provided very low quality evidence that anabolic steroid may result in less dependency, assessed in terms of being either dependent in at least two functions or dead (one person in the control group died) at six and 12 months, but the result was also compatible with no difference or an increase in dependency (dependent in at least two levels of function or dead at 12 months: 1/17 versus 5/19; RR 0.22, 95% CI 0.03 to 1.73; P = 0.15). The trial found no evidence of between-group differences in individual adverse events.Two trials compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One trial compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other trial compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both trials found some evidence of better function in the steroid plus group. One trial reported greater independence, higher Harris hip scores and gait speeds in the steroid plus group at 12 months. The second trial found fewer participants in the anabolic steroid group were either dependent in at least two functions, including bathing, or dead at six and 12 months (one person in the control group died) (1/17 versus 7/18; RR 0.15, 95% CI 0.02 to 1.10; P = 0.06). Pooled mortality data (2/51 versus 3/51) from the two trials showed no evidence of a difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one trial reported side effects of hoarseness and increased facial hair. The other trial reported better quality of life in the steroid plus group. AUTHORS' CONCLUSIONS The available evidence is insufficient to draw conclusions on the effects, primarily in terms of functional outcome and adverse events, of anabolic steroids, either separately or in combination with nutritional supplements, after surgical treatment of hip fracture in older people. Given that the available data points to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.
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High anabolic potential of essential amino acid mixtures in advanced nonsmall cell lung cancer.
Engelen, MPKJ, Safar, AM, Bartter, T, Koeman, F, Deutz, NEP
Annals of oncology : official journal of the European Society for Medical Oncology. 2015;(9):1960-1966
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Abstract
BACKGROUND Conventional nutritional supplements are not or only partly successful in inducing protein accretion in advanced cancer, suggesting an attenuated anabolic response. To prevent muscle wasting and its deleterious consequences, generating an anabolic response is crucial. Dietary essential amino acids (EAA) have anabolic properties in other wasting diseases; however, data in advanced cancer are lacking. PATIENTS AND METHODS In 13 patients with advanced nonsmall-cell lung cancer (NSCLC) (stage III and IV) and 11 healthy age-matched subjects, we measured protein synthesis and breakdown of the whole body, and net protein anabolism (difference between protein synthesis and breakdown) after intake of 14 g of free EAA with high leucine levels (EAA/leucine) versus a balanced amino acid mixture containing both EAA and non-EAA as present in whey protein, according to a randomized, double-blind, crossover design. RESULTS Protein synthesis and net protein anabolism were higher after intake of the EAA/leucine than the balanced amino acid mixture (P < 0.001), independent of presence of cancer. A highly significant linear relationship between net protein anabolism and the amount of EAA available in the systemic circulation (R(2): 0.85, P < 0.001) was found in both groups. The presence of muscle or recent weight loss, systemic inflammatory response, or length of survival did not influence this relationship. High leucine levels in the EAA/leucine mixture was of no anabolic benefit. CONCLUSIONS There is no anabolic resistance or attenuated anabolic potential to intake of 14 g of EAA/leucine or balanced amino acid mixture in advanced (mainly stage III) NSCLC. The high anabolic potential of dietary EAA in cancer patients is independent of their nutritional status, systemic inflammatory response or disease trajectory, suggesting a key role of EAA in new nutritional approaches to prevent muscle loss, thereby improving outcome of patients with advanced cancer. CLINICALTRAILSGOV NCT01172314.