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1.
Med Sci Sports Exerc ; 56(6): 1118-1123, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38376993

RESUMEN

PURPOSE: This study examined the acute and long-term effects of nandrolone decanoate (ND) on fractional synthetic rates (FSR). METHODS: Male C57BL/6 mice were randomized into ND ( n = 20) or sham ( n = 20) groups. ND injections (10 g·kg -1 ·wk -1 ) started at 7 months of ages and continued for 6 wk. Ten animals from each group were randomly separated and examined 1 wk following drug cessation. The remaining animals were examined at 16 months of age. Animals were injected IP with 1.5 mL of deuterated water 24 h before euthanasia. The kidney, liver, heart, gastrocnemius, and soleus were extracted. Samples were analyzed for deuterated alanine enrichment in the bound protein and intracellular fraction by liquid chromatography tandem mass spectrometry to measure estimated FSR (fraction/day (F/D)) of mixed tissue. RESULTS: One-way ANOVA, with treatment and age as fixed factors, indicated that kidney FSR was greater ( P = 0.027) in ND (0.41 ± 0.02 F/D) than sham (0.36 ± 0.014F/D) and higher ( P = 0.003) in young (0.42 ± 0.2 F/D) than old (0.35 ± 0.01 F/D). Liver and heart FSR values were greater ( P ≤ 0.001) in young (0.79 ± 0.06 F/D and 0.13 ± 0.01 F/D, respectively) compared with old (0.40 ± 0.01 F/D and 0.09 ± 0.01 F/D, respectively), but not between ND and sham. Gastrocnemius FSR was ( P ≤ 0.001) greater in young (0.06 ± 0.01 F/D) compared with old (0.03 ± 0.002 F/D), and greater ( P = 0.006) in ND (0.05 ± 0.01 F/D) compared with sham (0.04 ± 0.003 F/D). Soleus FSR rates were greater ( P = 0.050) in young (0.13 ± 0.01 F/D) compared with old (0.11 ± 0.003 F/D), but not between ND (0.12 ± 0.01 F/D) and sham (0.12 ± 0.01 F/D). Old animals who had received ND displayed elevated FSR in the gastrocnemius ( P = 0.054) and soleus ( P = 0.024). CONCLUSIONS: ND use in young adult animals appeared to maintain long-term elevations in FSR in muscle during aging.


Asunto(s)
Envejecimiento , Hígado , Ratones Endogámicos C57BL , Proteínas Musculares , Músculo Esquelético , Animales , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Envejecimiento/metabolismo , Envejecimiento/fisiología , Proteínas Musculares/biosíntesis , Proteínas Musculares/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Nandrolona Decanoato/farmacología , Nandrolona Decanoato/administración & dosificación , Riñón/metabolismo , Riñón/efectos de los fármacos , Miocardio/metabolismo , Ratones , Andrógenos/administración & dosificación , Andrógenos/farmacología , Distribución Aleatoria , Nandrolona/farmacología , Nandrolona/administración & dosificación , Nandrolona/análogos & derivados , Anabolizantes/administración & dosificación , Anabolizantes/farmacología
2.
Rev. clín. esp. (Ed. impr.) ; 222(10): 612-620, dic. 2022. tab
Artículo en Español | IBECS | ID: ibc-212782

RESUMEN

El consumo de anabolizantes hormonales afecta no solamente a atletas profesionales, sino también a la población general (culturistas, clientes de gimnasios y adolescentes entre otros). En el primer caso su uso está prohibido y sancionado por la Agencia Mundial Anti-Dopaje y los comités olímpicos. Para los segundos es difícil establecer la prevalencia ya que muchos obtienen los productos a través de compras por Internet. Los motivos para su uso son diversos y se han descrito distintas formas de uso, así como diferentes tipologías de consumidores. Entre los efectos secundarios, el hipogonadismo es la causa más frecuente de consulta endocrinológica. En esta revisión se describen, tras una introducción general al dopaje, los antecedentes históricos de los andrógenos anabolizantes, su clasificación, las formas de uso, los efectos fisiológicos, los efectos adversos en diferentes órganos y sistemas, el tratamiento del hipogonadismo, así como los métodos de detección (AU)


The use of anabolic steroids affects not only professional athletes but also the general population (bodybuilders, gym clients, and adolescents). In the first case, its use is prohibited and sanctioned by the World Anti-Doping Agency and Olympic committees. For the other users, it is difficult to establish its prevalence since many obtain the products via the Internet. The reasons for its use are varied and different forms of use and other types of users have been described. Among the side effects of steroid use, hypogonadism is the most frequent cause for endocrinological consultation. After a general introduction to doping, this review describes the historical background of anabolic–androgenic steroids, their classification, forms of use, physiological effects, adverse effects on different organs and systems, treatment of hypogonadism, as well as detection methods (AU)


Asunto(s)
Humanos , Anabolizantes/administración & dosificación , Andrógenos/administración & dosificación , Hipogonadismo/inducido químicamente , Doping en los Deportes , Anabolizantes/efectos adversos , Andrógenos/efectos adversos , Hipogonadismo/terapia
3.
Int J Mol Sci ; 23(2)2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35055125

RESUMEN

PTH induces phosphorylation of the transcriptional coregulator NACA on serine 99 through Gαs and PKA. This leads to nuclear translocation of NACA and expression of the target gene Lrp6, encoding a coreceptor of the PTH receptor (PTH1R) necessary for full anabolic response to intermittent PTH (iPTH) treatment. We hypothesized that maintaining enough functional PTH1R/LRP6 coreceptor complexes at the plasma membrane through NACA-dependent Lrp6 transcription is important to ensure maximal response to iPTH. To test this model, we generated compound heterozygous mice in which one allele each of Naca and Lrp6 is inactivated in osteoblasts and osteocytes, using a knock-in strain with a Naca99 Ser-to-Ala mutation and an Lrp6 floxed strain (test genotype: Naca99S/A; Lrp6+/fl;OCN-Cre). Four-month-old females were injected with vehicle or 100 µg/kg PTH(1-34) once daily, 5 days a week for 4 weeks. Control mice showed significant increases in vertebral trabecular bone mass and biomechanical properties that were abolished in compound heterozygotes. Lrp6 expression was reduced in compound heterozygotes vs. controls. The iPTH treatment increased Alpl and Col1a1 mRNA levels in the control but not in the test group. These results confirm that NACA and LRP6 form part of a common genetic pathway that is necessary for the full anabolic effect of iPTH.


Asunto(s)
Anabolizantes/administración & dosificación , Células Madre Embrionarias/citología , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Chaperonas Moleculares/genética , Hormona Paratiroidea/administración & dosificación , Anabolizantes/farmacología , Animales , Línea Celular , Membrana Celular/metabolismo , Células Madre Embrionarias/efectos de los fármacos , Células Madre Embrionarias/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Técnicas de Sustitución del Gen , Ratones , Chaperonas Moleculares/metabolismo , Mutagénesis Sitio-Dirigida , Osteoblastos/metabolismo , Osteocitos/metabolismo , Hormona Paratiroidea/farmacología , Fosforilación , Transducción de Señal/efectos de los fármacos , Microtomografía por Rayos X
4.
Bioorg Med Chem Lett ; 54: 128440, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34742889

RESUMEN

The continuing investigation of SAR of 3-aminothieno[2,3-b]pyridine-2-carboxamide derivatives has been described. In this study, C4-piperidine derivatives with polar functional groups were synthesized to develop orally available bone anabolic agents. The optimized compound 9o (DS96432529), which exhibited the best PK profile and high in vitro activity, showed the highest in vivo efficacy in this series. Moreover, significant synergistic effects were observed following co-administration of DS96432529 and alendronate or parathyroid hormone. The mechanism of action is most likely mediated through CDK8 inhibition.


Asunto(s)
Anabolizantes/farmacología , Huesos/efectos de los fármacos , Descubrimiento de Drogas , Administración Oral , Anabolizantes/administración & dosificación , Anabolizantes/química , Relación Dosis-Respuesta a Droga , Humanos , Estructura Molecular , Relación Estructura-Actividad
5.
Meat Sci ; 182: 108615, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34352620

RESUMEN

The impacts of several hormonal growth promotants (HGP) on Warner-Bratzler Shear Force (WBSF), desmin degradation ratio (DDR) and collagen content (COLL) were assessed. Treatments within feedlot and pasture finished steer carcasses (n = 60, n = 40, respectively) were control (CON-100-F and CON-400-P), oestradiol HGPs (OES-100-F and OES-400-P) and trenbolone acetate/oestradiol HGPs (TBA+OES-100-F only). The longissimus lumborum (LL), gluteus medius (GM), infraspinatus (IS), semitendinosus (ST,) and the LL and biceps femoris (BF) were collected from feedlot and pasture finished steers, respectively. All muscles were aged between 3 and 35 days. The LL from TBA+OES-100-F carcasses had increased WBSF and decreased DDR, which varied in magnitude with ageing (P < 0.05). The GM from OES-100-F steers also had lower DDR (P < 0.05). The feedlot HGP treatments had no impact on the WBSF of the IS, ST or GM and no impact on COLL in the LL. The OES-400-P had no impact on WBSF, DDRor COLL for both muscles (P > 0.05).


Asunto(s)
Anabolizantes/administración & dosificación , Colágeno/análisis , Desmina/metabolismo , Estradiol/administración & dosificación , Músculo Esquelético/química , Acetato de Trembolona/administración & dosificación , Animales , Bovinos , Dieta/veterinaria , Masculino , Carne Roja/análisis , Resistencia al Corte
6.
Neurosci Lett ; 761: 136104, 2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34256105

RESUMEN

AIMS: Oxandrolone (OXA) is a synthetic steroid used for the treatment of clinical conditions associated with catabolic states in humans, including children. However, its behavioral effects are not well known. Our goal was to evaluate the anxiety-like behavior induced in young adult rats after the treatment of juvenile animals with OXA. METHODS: Four-week-old male rats were separated into three groups: Control (CON), therapeutic-like OXA dose (TD), and excessive OXA dose (ED), in which 2.5 and 37.5 mg/kg/day of OXA were administered via gavage for four weeks for TD and ED, respectively. Behavior was evaluated through the elevated plus maze (EPM) and open field (OF) tests. Protein expression of catalase (CAT), superoxide dismutase (SOD), Tumor necrosis factor-α (TNF-α), and dopamine receptor 2 (DrD2) were analyzed in tissue samples of the hippocampus, amygdala, and prefrontal cortex by Western Blot. RESULTS: OXA induced anxiety-like behaviors in both TD and ED animals; it decreased the time spent in the open arms of the EPM in both groups and reduced the time spent in the central zone of the OF in the TD group. In the hippocampus, CAT expression was higher in TD compared with both control and ED animals. No differences were found in the amygdala and prefrontal cortex. TNF-α, SOD, and DrD2 levels were not altered in any of the assessed areas. CONCLUSIONS: Treatment of juvenile rats with OXA led to anxiety-like behavior in young adult animals regardless of the dose used, with minor changes in the antioxidant machinery located in the hippocampus.


Asunto(s)
Anabolizantes/toxicidad , Ansiedad/etiología , Hipocampo/efectos de los fármacos , Oxandrolona/toxicidad , Anabolizantes/administración & dosificación , Animales , Catalasa/metabolismo , Hipocampo/crecimiento & desarrollo , Hipocampo/metabolismo , Masculino , Oxandrolona/administración & dosificación , Ratas , Ratas Wistar , Receptores de Dopamina D2/metabolismo , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
7.
Med Sci Sports Exerc ; 53(8): 1778-1794, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34261998

RESUMEN

This consensus statement is an update of the 1987 American College of Sports Medicine (ACSM) position stand on the use of anabolic-androgenic steroids (AAS). Substantial data have been collected since the previous position stand, and AAS use patterns have changed significantly. The ACSM acknowledges that lawful and ethical therapeutic use of AAS is now an accepted mainstream treatment for several clinical disorders; however, there is increased recognition that AAS are commonly used illicitly to enhance performance and appearance in several segments of the population, including competitive athletes. The illicit use of AAS by competitive athletes is contrary to the rules and ethics of many sport governing bodies. Thus, the ACSM deplores the illicit use of AAS for athletic and recreational purposes. This consensus statement provides a brief history of AAS use, an update on the science of how we now understand AAS to be working metabolically/biochemically, potential side effects, the prevalence of use among athletes, and the use of AAS in clinical scenarios.


Asunto(s)
Anabolizantes/administración & dosificación , Doping en los Deportes/legislación & jurisprudencia , Hormonas Esteroides Gonadales/administración & dosificación , Atletas , Consenso , Humanos , Prevalencia , Sociedades Médicas , Deportes , Medicina Deportiva
8.
Behav Brain Res ; 414: 113475, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34280460

RESUMEN

Oxandrolone (OXA) is an androgen and anabolic steroid (AAS) that is used to reverse weight loss associated with some medical conditions. One of the side effects of OXA is its potential to induce depressive symptoms. Growing evidence suggested that neuroinflammation and cytokines play crucial roles in sickness behavioral and associated mood disturbances. Previous studies showed that metformin attenuated neuroinflammation. This study investigated the potential protective role of metformin against OXA-induced depression-like behavior and neuroinflammation. Twenty- four Wistar male rats were randomly grouped into four groups: the control group (Control) received only vehicle; the oxandrolone group (OXA) received oxandrolone (0.28 mg/kg, i.p); the metformin group (MET) received metformin (100 mg/kg, i.p); and the oxandrolone / metformin group (OXA + MET) received both oxandrolone (0.28 mg/kg, i.p) and metformin (100 mg/kg, i.p). These treatments were administered for fourteen consecutive days. Behavioral tests to measure depression-like behavior were conducted before and after treatments. qRT-PCR was used to measure the relative expression of proinflammatory and anti-inflammatory cytokines in the hippocampus and hypothalamus. The results showed that oxandrolone induced depression-like behavior and dysregulated pro-/anti-inflammatory cytokines, while metformin attenuated these effects. These findings suggest that metformin is a potential treatment to reverse the depressive effects induced by oxandrolone that involve neuroinflammatory effects.


Asunto(s)
Anabolizantes/efectos adversos , Antiinflamatorios/farmacología , Citocinas/efectos de los fármacos , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Metformina/farmacología , Enfermedades Neuroinflamatorias/inducido químicamente , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Oxandrolona/efectos adversos , Anabolizantes/administración & dosificación , Animales , Antiinflamatorios/administración & dosificación , Conducta Animal/efectos de los fármacos , Depresión/inmunología , Depresión/metabolismo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Hipocampo/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/inmunología , Hipotálamo/metabolismo , Interleucina-10 , Interleucina-1beta/efectos de los fármacos , Interleucina-6 , Masculino , Metformina/administración & dosificación , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Oxandrolona/administración & dosificación , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/efectos de los fármacos
9.
Front Endocrinol (Lausanne) ; 12: 678797, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34177807

RESUMEN

Background: Gonadotropin-releasing hormone agonist (GnRHa) is the gold standard in the treatment of Central Precocious Puberty (CPP) with progressive puberty and accelerative growth. However, GnRHa treatment is reported to result in growth deceleration and prevents growth plate development which leads to a reduction in height velocity. Stanozolol (ST) has been used to stimulate growth in patients with delayed growth and puberty, nevertheless, the effects and mechanisms of ST on CPP with GnRHa treatment are currently unclear. Methods and Results: In the current study, we recorded the following vital observations that provided insights into ST induced chondrogenic differentiation and the maintenance of normal growth plate development: (1) ST efficiently prevented growth deceleration and maintained normal growth plate development in rats undergoing GnRHa treatment; (2) ST suppressed the inhibitory effect of GnRHa to promote chondrogenic differentiation; (3) ST induced chondrogenic differentiation through the activation of the JNK/c-Jun/Sox9 signaling pathway; (4) ST promoted chondrogenic differentiation and growth plate development through the JNK/Sox9 signaling pathway in vivo. Conclusions: ST mitigated the inhibitory effects of GnRHa and promoted growth plate development in rats. ST induced the differentiation of chondrocytes and maintained normal growth plate development through the activation of JNK/c-Jun/Sox9 signaling. These novel findings indicated that ST could be a potential agent for maintaining normal bone growth in cases of CPP undergoing GnRHa treatment.


Asunto(s)
Anabolizantes/uso terapéutico , Desarrollo Óseo/efectos de los fármacos , Hormona Liberadora de Gonadotropina/agonistas , Pubertad Precoz/tratamiento farmacológico , Estanozolol/uso terapéutico , Anabolizantes/administración & dosificación , Animales , Línea Celular , Condrocitos/efectos de los fármacos , Quimioterapia Combinada , Placa de Crecimiento/efectos de los fármacos , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Estanozolol/administración & dosificación
10.
BMJ Case Rep ; 14(2)2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33637513

RESUMEN

A severe case of COVID-19 was observed in an otherwise healthy 28-year-old man who had taken oxandrolone 40 mg/day as an anabolic steroid. The patient had been taking oxandrolone for enhanced bodybuilding 30 days prior to presenting to an outpatient clinic with COVID-19 symptoms. The patient reported that his symptoms have rapidly worsened over the course of 4 days prior to presenting at the clinic. As part of an experimental antiandrogen treatment for hyperandrogenic men suffering from COVID-19, he was administered a single 600 mg dose of the novel antiandrogen proxalutamide. Twenty-four hours after administration of this dose, marked improvement of symptoms and markers of disease severity were observed. To our knowledge, this is the first case that potentially links anabolic steroid use to COVID-19 disease severity.


Asunto(s)
Anabolizantes/efectos adversos , Antagonistas de Andrógenos/administración & dosificación , Tratamiento Farmacológico de COVID-19 , Oxandrolona/efectos adversos , Oxazoles/administración & dosificación , Tiohidantoínas/administración & dosificación , Adulto , Anabolizantes/administración & dosificación , Progresión de la Enfermedad , Humanos , Masculino , Oxandrolona/administración & dosificación , Sustancias para Mejorar el Rendimiento/efectos adversos , SARS-CoV-2 , Índice de Severidad de la Enfermedad
11.
Physiol Rep ; 9(3): e14730, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33527754

RESUMEN

Fucoidan is a sulfated polysaccharide found in a range of brown algae species. Growing evidence supports the long-term supplementation of fucoidan as an ergogenic aid to improve skeletal muscle performance. The aim of this study was to investigate the effect of fucoidan on the skeletal muscle of mice. Male BL/6 mice (N = 8-10) were administered a novel fucoidan blend (FUC, 400 mg/kg/day) or vehicle (CON) for 4 weeks. Treatment and control experimental groups were further separated into exercise (CON+EX, FUC+EX) or no-exercise (CON, FUC) groups, where exercised groups performed 30 min of treadmill training three times per week. At the completion of the 4-week treatment period, there was a significant increase in cross-sectional area (CSA) of muscle fibers in fucoidan-treated extensor digitorum longus (EDL) and soleus fibers, which was accompanied by a significant increase in tibialis anterior (TA) muscle force production in fucoidan-treated groups. There were no significant changes in grip strength or treadmill time to fatigue, nor was there an effect of fucoidan or exercise on mass of TA, EDL, or soleus muscles. In gastrocnemius muscles, there was no change in mRNA expression of mitochondrial biogenesis markers PGC-1α and Nrf-2 in any experimental groups; however, there was a significant effect of fucoidan supplementation on myosin heavy chain (MHC)-2x, but not MHC-2a, mRNA expression. Overall, fucoidan increased muscle size and strength after 4 weeks of supplementation in both exercised and no-exercised mice suggesting an important influence of fucoidan on skeletal muscle physiology.


Asunto(s)
Anabolizantes/administración & dosificación , Contracción Muscular/efectos de los fármacos , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Resistencia Física/efectos de los fármacos , Polisacáridos/administración & dosificación , Crecimiento del Músculo Esquelético/efectos de los fármacos , Administración Oral , Animales , Masculino , Ratones Endogámicos C57BL , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/genética , Mitocondrias Musculares/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , Factores de Tiempo
12.
Arch Dis Child ; 106(1): 74-76, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-31862699

RESUMEN

The UK Turner syndrome (TS) study examined the effect on final height of oxandrolone 0.05 mg/kg/day (maximum dose 2.5 mg) versus placebo from 9 years of age; and delaying ethinylestradiol induction of puberty by 2 years from 12 (E12) to 14 (E14) years in growth hormone-treated girls with TS. The study ran from 1999 to 2013. By 2011, eighty-two of 92 participants had reached final height and an interim analysis using the Super-Imposition by Translation And Rotation model showed significant increases in final height with both oxandrolone and E14. The analysis has been repeated now that all 92 patients have reached final height. Oxandrolone still significantly increased final height by 4.1 cm (95% CI 1.6 to 6.6, n=92) compared with 4.6 cm previously. However, the E14 effect was no longer significant at 2.7 cm (95% CI -0.8 to 6.1, n=56) compared with 3.8 cm previously.


Asunto(s)
Anabolizantes/uso terapéutico , Oxandrolona/uso terapéutico , Síndrome de Turner/tratamiento farmacológico , Anabolizantes/administración & dosificación , Estatura , Niño , Esquema de Medicación , Femenino , Humanos , Masculino , Oxandrolona/administración & dosificación , Resultado del Tratamiento , Reino Unido
13.
Drug Test Anal ; 13(1): 217-222, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33037775

RESUMEN

Hair and urine concentrations of the nonsteroidal selective androgen receptor modulator GSK2881078 were examined following single oral administration to investigate its hair incorporation and estimate the general suitability of hair testing for selected androgen receptor modulators. Hair segments were collected following a single dose of 1.5 mg GSK2881078 by repeated shaving of scalp hair at Week 0 (blank), Week 1 (representing the pre-application period), Week 3 (ideally focusing the time of incorporation), and Weeks 5 and 9 (post-administration period). The intact compound and various (at least 4) hydroxy-metabolites exhibited similar elimination profiles. The peak urinary concentration (approximately 920 pg/ml) was observed after 8 h and is reduced to the detection limit (2 pg/ml) on Day 42 following administration of 760 µg GSK2881078. Correspondingly, hair concentrations of GSK2881078 (intact compound only) following a single oral dose of 1.5 mg GSK2881078 reached a peak concentration of 1.7 pg/mg in the segments collected 3 weeks post administration, representing the time of ingestion. The concentration rapidly declined to trace amounts of 0.7 (Week 5) and 0.2 pg/mg (Week 9), respectively. In conclusion, measurement of the intact compound GSK2881078 is feasible for both urine and hair analysis. However, concentrations in hair after single oral administration are in the low pg/mg range and can only be detected, if the segments cover the administration period.


Asunto(s)
Anabolizantes/orina , Cabello/química , Indoles/orina , Anabolizantes/administración & dosificación , Anabolizantes/análisis , Anabolizantes/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Humanos , Indoles/administración & dosificación , Indoles/análisis , Indoles/metabolismo , Límite de Detección , Espectrometría de Masas/métodos , Receptores Androgénicos/metabolismo , Detección de Abuso de Sustancias/métodos
14.
J Am Coll Nutr ; 40(1): 53-60, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32186977

RESUMEN

OBJECTIVE: Beef protein extracts are growing in popularity in recent years due to their purported anabolic effects as well as to their potential benefits on hematological variables. The present randomized, controlled, double-blind, cross-over study aimed to analyze the effects of beef protein supplementation on a group of male elite triathletes (Spanish National Team). METHODS: Six elite triathletes (age, 21 ± 3 years; VO2max, 71.5 ± 3.0 ml·kg·min-1) were randomly assigned to consume daily either 25 g of a beef supplement (BEEF) or an isoenergetic carbohydrates (CHO) supplement for 8 weeks, with both conditions being separated by a 5-week washout period. Outcomes, including blood analyses and anthropometrical measurements, were assessed before and after each 8-week intervention. RESULTS: No effects of supplement condition were observed on body mass nor on skinfold thicknesses, but BEEF induced significant and large benefits over CHO in the thigh cross-sectional area (3.02%, 95%CI = 1.33 to 4.71%; p = 0.028, d = 1.22). Contrary to CHO, BEEF presented a significant increase in vastus lateralis muscle thickness (p = 0.046), but differences between conditions were not significant (p = 0.173, d = 0.87). Although a significantly more favorable testosterone-to-cortisol ratio (TCR) was observed for BEEF over CHO (37%, 95% CI = 5 to 68%; p = 0.028, d = 1.29), no significant differences were found for the hematological variables (i.e., iron, ferritin, red blood cell count, hemoglobin or hematocrit). CONCLUSION: Beef protein supplementation seems to facilitate a more favorable anabolic environment (i.e., increased TCR and muscle mass) in male elite triathletes, with no impact on hematological variables.


Asunto(s)
Anabolizantes , Composición Corporal , Suplementos Dietéticos , Animales , Bovinos , Humanos , Masculino , Anabolizantes/administración & dosificación , Atletas , Estudios Cruzados , Método Doble Ciego , Recuento de Eritrocitos , Ferritinas/sangre , Hematócrito , Hemoglobinas/análisis , Hierro/sangre , Carne Roja , Adolescente , Adulto Joven
15.
Drug Test Anal ; 13(5): 1034-1047, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33277807

RESUMEN

Selective androgen receptor (AR) modulators (SARMs) are potent anabolic agents with a high potential of misuse in horseracing and equestrian sports. In this study, we applied label-free proteomics to discover plasma protein biomarkers in geldings (castrated horses) after administration with a popular SARM named RAD140. Tryptic peptides were prepared from plasma samples and analyzed by nano-flow ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (nano-UHPLC-HRMS/MS) using data-independent acquisition (DIA) method. Orthogonal projection on latent structure-discriminant analysis (OPLS-DA) has led to the development of a predictive model that could discriminate RAD140-administered samples from control samples and could also correctly classify 18 out of 19 in-training horses as control samples. The model comprises 75 proteins with variable importance in projection (VIP) score above 1. Gene Ontology (GO) enrichment analysis and literature review have identified upregulation of AR-regulated clusterin, and proteins associated with inflammation (haptoglobin, cluster of differentiation 14 [CD14], and inter-alpha-trypsin inhibitor heavy chain 4 [ITIH4]) and erythropoiesis (glycosylphosphatidylinositol-specific phospholipase D1 [GPLD1]) after RAD140 administration. Their changes were confirmed by selected reaction monitoring (SRM) experiments. Similar effects have been reported by the use of androgens and other SARMs. This is the first reported study that describes the use of a proteomic biomarker approach to detect horses that have been administered with RAD140 by applying label-free proteomic profiling of plasma samples. These results support the concept of a biomarker-driven approach to enhance the doping control of RAD140 and potentially other SARMs in the future.


Asunto(s)
Anabolizantes/administración & dosificación , Proteínas Sanguíneas/análisis , Cromatografía Líquida de Alta Presión/veterinaria , Doping en los Deportes , Caballos/sangre , Nitrilos/administración & dosificación , Orquiectomía , Oxadiazoles/administración & dosificación , Proteoma , Proteómica , Detección de Abuso de Sustancias/veterinaria , Espectrometría de Masas en Tándem/veterinaria , Anabolizantes/síntesis química , Animales , Biomarcadores/sangre , Masculino , Nitrilos/síntesis química , Oxadiazoles/síntesis química , Reproducibilidad de los Resultados
16.
Drug Test Anal ; 12(11-12): 1561-1569, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33119965

RESUMEN

The detection of clostebol misuse in sports has been growing recently, especially in Italy, due to the ample availability of pharmaceutical formulations containing clostebol acetate (Trofodermin®) and the use of more sensitive instrumentation by the antidoping laboratories. Most of these cases have been claimed to be related to a nonconscious use of the drug or through contact with relatives or teammates using it. We have investigated, through the application of the well-known and currently used gas chromatographic mass spectrometric procedures, the likelihood of these allegations and have demonstrated that after a single transdermal administration of 5 mg of clostebol acetate and a transient contact with the application area, it is possible to generate adverse analytical findings in antidoping controls. We have reviewed the Phase I and Phase II clostebol metabolism in order to generate evidences that may help the sport authorities reviewing these cases. The main clostebol metabolite (4-chloro-androst-4-en-3α-ol-17-one, M1) generally used at the screening level as well as other three metabolites (M2-M4) are mainly excreted as glucuronides, whereas M5 (4ζ-chloro-5ζ-androstan-3ß-ol-17-one) is predominantly excreted as sulfate. Neither the 5α-reductases activity (impaired by the presence of the chlorine in C4) nor specific sulfotransferases present in the skin allowed a clear distinction of the administration route. Studies with a larger number of volunteers and probably investigating another physiological fluid allowed in antidoping such as blood are needed for a deeper investigation. It is not unreasonable to establish a reporting level for M1, maybe creating some false negatives but excluding nonintentional doping scenarios.


Asunto(s)
Anabolizantes/administración & dosificación , Doping en los Deportes/prevención & control , Neomicina/administración & dosificación , Absorción Cutánea/fisiología , Testosterona/análogos & derivados , Administración Cutánea , Anabolizantes/metabolismo , Doping en los Deportes/métodos , Combinación de Medicamentos , Femenino , Humanos , Italia , Masculino , Neomicina/metabolismo , Absorción Cutánea/efectos de los fármacos , Crema para la Piel/administración & dosificación , Testosterona/administración & dosificación , Testosterona/metabolismo , Testosterona/orina
17.
Sci Signal ; 13(647)2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32873724

RESUMEN

Anabolic androgenic steroids (AAS) have medical utility but are often abused, and the effects of AAS on reward circuits in the brain have been suggested to lead to addiction. We investigated the previously reported correlations between AAS and the endogenous µ-opioid system in the rewarding properties of AAS in mice. We found that a single injection of a supraphysiological dose of natural or synthetic AAS strengthened excitatory synaptic transmission in putative ventral tegmental area (VTA) dopaminergic neurons. This effect was associated with the activation of µ-opioid receptors (MORs) and an increase in ß-endorphins released into the VTA and the plasma. Irreversible blockade of MORs in the VTA counteracted two drug-seeking behaviors, locomotor activity and place preference. These data suggest that AAS indirectly stimulate a dopaminergic reward center of the brain through activation of endogenous opioid signaling and that this mechanism mediates the addictive effects of AAS.


Asunto(s)
Neuronas Dopaminérgicas/fisiología , Plasticidad Neuronal/fisiología , Receptores Opioides mu/metabolismo , Recompensa , Esteroides/farmacología , Anabolizantes/administración & dosificación , Anabolizantes/farmacología , Animales , Neuronas Dopaminérgicas/citología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Ratones , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Nandrolona/administración & dosificación , Nandrolona/farmacología , Plasticidad Neuronal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Esteroides/administración & dosificación , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Área Tegmental Ventral/citología , Área Tegmental Ventral/metabolismo , Área Tegmental Ventral/fisiología , betaendorfina/sangre , betaendorfina/metabolismo
18.
Korean J Gastroenterol ; 76(3): 167-170, 2020 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-32969366

RESUMEN

Hepatic disorders with prominent cholestasis can be caused by a range of conditions, and anabolic androgenic steroids have been considered a cause of protracted cholestasis. A 29-year-old man who had taken an anabolic androgenic steroid analogue for 2 months visited the hospital complaining of jaundice and indigestion. After stopping the medication, the hyperbilirubinemia tended to decrease, but a transiently elevated aminotransferase level was observed. The endogenous testosterone level also decreased initially but recovered soon after. The liver function profiles were normalized after 2 months of conservative management. This case emphasizes that close drug history taking, including anabolic steroids, is important for identifying the cause of unexplained persistent jaundice.


Asunto(s)
Anabolizantes/efectos adversos , Andrógenos/efectos adversos , Ictericia/diagnóstico , Adulto , Anabolizantes/administración & dosificación , Anabolizantes/química , Andrógenos/administración & dosificación , Andrógenos/química , Bilirrubina/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Pancreatocolangiografía por Resonancia Magnética , Humanos , Ictericia/etiología , Ictericia/patología , Masculino , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
19.
Drug Test Anal ; 12(11-12): 1570-1580, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32959982

RESUMEN

The possibility of nutritional supplement contamination with minute amounts of the selective androgen receptor modulator (SARM) ostarine has become a major concern for athletes and result managing authorities. In case of an adverse analytical finding (AAF), affected athletes need to provide conclusive information, demonstrating that the test result originates from a contamination scenario rather than doping. The aim of this research project was to study the elimination profiles of microdosed ostarine and characterize the time-dependent urinary excretion of the drug and selected metabolites. Single- and multi-dose administration studies with 1, 10, and 50 µg of ostarine were conducted, and collected urine samples were analyzed by LC-MS/MS following solid-phase extraction or enzymatic hydrolysis combined with liquid-liquid extraction. In the post-administration samples, both the maximum urine concentrations/abundance ratios and detection times of ostarine and its phase-I and phase-II metabolites were found to correlate with the administered drug dose. With regard to the observed maximum levels of ostarine, the time points of peak urinary concentrations/abundance ratios, and detection windows, a high inter-individual variation was observed. However, the study demonstrated that a single oral dose of as little as 1 µg can be detected for up to 9 (5) days by monitoring ostarine (glucuronide), and hydroxylated metabolites (especially M1a) appear to offer a considerably shorter detection window. The obtained data on ostarine (metabolite) detection times and urinary concentrations following different administration schemes support the interpretation of AAFs, in particular when scenarios of proven supplement contamination are discussed and supplement administration protocols exist.


Asunto(s)
Anilidas/administración & dosificación , Anilidas/orina , Suplementos Dietéticos/análisis , Ingestión de Alimentos/fisiología , Contaminación de Alimentos/análisis , Detección de Abuso de Sustancias/métodos , Administración Oral , Anabolizantes/administración & dosificación , Anabolizantes/orina , Doping en los Deportes/prevención & control , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Humanos , Extracción Líquido-Líquido/métodos , Extracción Líquido-Líquido/normas , Masculino , Receptores Androgénicos/metabolismo , Extracción en Fase Sólida/métodos , Extracción en Fase Sólida/normas , Detección de Abuso de Sustancias/normas , Yogur/análisis
20.
Steroids ; 164: 108727, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32891681

RESUMEN

Nandrolone decanoate (ND) belongs to the class II of anabolic-androgenic steroids (AAS), which is composed of 19-nor-testosterone-derivatives. AAS represent a group of synthetic testosterone that is used in clinical treatment. However, these drugs are widely abused among individuals as a means of promoting muscle growth or enhancing athletic performance. AAS in general and ND in particular have been associated with several behavioral disturbances, such as anxiety, aggressiveness and depression. A factor that contributes to the development of depression is the brain activation of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of kynurenine pathway (KP). In the present study, we examined the involvement of KP in depressive phenotype induced by a ND treatment (10 mg/kg/day/s.c., for 28 days) that mimics human abuse system (e.g. supraphysiological doses) in C57B/6J mice. Our results showed that ND caused depressive like-behavior in the tail suspension test and anhedonic-like state measured in the sucrose preference test. ND administration decreased the levels of brain-derived neurotrophic factor and neurotrophin-3 and reduced Na+,K+-ATPase activity in the hippocampus, striatum and prefrontal cortex. We also found that ND elicited KP activation, as reflected by the increase of IDO activity and kynurenine levels in these brain regions. Moreover, ND decreased serotonin levels and increased 5-hydroxyindoleacetic acid levels in the brain. Treatment with IDO inhibitor 1-methyl-dl-trypthophan (1 mg/kg/i.p.) reversed the behavioral and neurochemical alterations induced by ND. These results indicate for the first time that KP plays a key role in depressive-like behavior and neurotoxicity induced by supraphysiologicaldoses of ND in mice.


Asunto(s)
Anabolizantes/administración & dosificación , Conducta Animal/efectos de los fármacos , Depresión/psicología , Quinurenina/metabolismo , Nandrolona Decanoato/administración & dosificación , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/enzimología , Cuerpo Estriado/metabolismo , Depresión/inducido químicamente , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Hipocampo/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/enzimología , Corteza Prefrontal/metabolismo , Triptófano/administración & dosificación , Triptófano/análogos & derivados
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