Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation.Antiresorptive drugs decrease the activation frequency,thereby ...Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation.Antiresorptive drugs decrease the activation frequency,thereby determining a secondary decrease in bone formation rate and a low bone turnover.Bisphosphonates are today’s mainstay among antiresorptive treatment of osteoporosis.Also,oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover.Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis.Recombinant-human parathyroid hormone(PTH)has showed to increase bone formation and significantly decrease vertebral fractures in severe patients,but with a modest effect on nonvertebral fractures.The study of Wnt signaling pathway,that induces prevalently an osteoblastic activity,opens large possibilities to antagonists of Wnt-inhibitors,such as sclerostin antibodies and dickkopf-1 antagonists,with potential effects not only on trabecular bone but also on cortical bone.展开更多
A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progester...A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progesterone, estradiol benzoate, and chlormadinone acetate） was developed. Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps, the extracts obtained were derivatized with heptafluorbutyric （HBF） anhydride and analyzed by GC-MS. In the above method, the linear scope was 2.5-50 μg kg^-1. The range of the recoveries was 78.5-148% for diethylstilbestrol, 70.8-109% for methyltestosterone, 69.8-87.2% for norethindrone, 67.7-120% for 17α-ethynylestradiol, 82.8-103% for estradiol, 70.3-99.2% for 6α-methyl-17α-hydroxy-progesterone, 73.0-104% for estradiol benzoate, and 72.9- 91.8% for chlormadinone acetate. The range of the coefficients of variation within batches was 0.4-12%; the range of the coefficients of variation between batches was 6.4-11%. The limit of detections and the detection capability were 0.99 and 3.30 μg kg^-1 for diethylstilbestrol, 1.05 and 3.50 μg kg^-1 for methyltestosterone, 1.19 and 3.97 μg kg^-1 for norethindrone, 0.94 and 3.13 μg kg^-1 for 17α-ethynylestradiol, 1.45 and 4.83 μg kg^-1 for estradiol, 1.56 and 5.20 μg kg^-1 for 6α-methyl-17α- hydroxy-progesterone, 1.92 and 6.40 μg kg^-1 for estradiol benzoate, and 2.41 and 8.03 μg kg^-1 for chlormadinone acetate, respectively. These results showed that the method was widely available, accurate, and sensitive.展开更多
The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgeni...The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.展开更多
Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroid...Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re- growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.展开更多
The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary f...The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.展开更多
In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The p...In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.展开更多
Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-...Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the f irst reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.展开更多
Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athlete...Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.展开更多
The quantitative structure-property relationship(QSPR) of anabolic androgenic steroids was studied on the half-wave reduction potential(E1/2) using quantum and physico-chemical molecular descriptors. The descriptors w...The quantitative structure-property relationship(QSPR) of anabolic androgenic steroids was studied on the half-wave reduction potential(E1/2) using quantum and physico-chemical molecular descriptors. The descriptors were calculated by semi-empirical calculations. Models were established using partial least square(PLS) regression and back-propagation artificial neural network(BP-ANN). The QSPR results indicate that the descriptors of these derivatives have significant relationship with half-wave reduction potential. The stability and prediction ability of these models were validated using leave-one-out cross-validation and external test set.展开更多
Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid im...Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.展开更多
A new GC/MS method for detection and identification of 19 anabolic steroids in human urine is presented.The procedure involves adsorption and isolation on a macroporous XAD-2 resin,enzymatic hydrolysis,alkaline extrac...A new GC/MS method for detection and identification of 19 anabolic steroids in human urine is presented.The procedure involves adsorption and isolation on a macroporous XAD-2 resin,enzymatic hydrolysis,alkaline extraction,derivatization,GC separation and MS detec- tion.Gas chromatographic-mass spectrometric data illustrate artifacts arising from enzymatic hydrolysis of steroid glucuronides and the structural characterization of their metabolites. Using this method,metabolic studies of these steroids in human urine were made after their ingestion by normal and healthy male volunteers.This method was proven to be suitable for large-scale routine analysis of anabolic steroids and was used successfully in passing the doping control test held by the Medical Commission of the International Olympic Committee.展开更多
Dehydroepiandrosterone (DHEA) is a weak androgen and is shown to have anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory effects on mouse, rat and rabbit models. However, human clinical trials data d...Dehydroepiandrosterone (DHEA) is a weak androgen and is shown to have anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory effects on mouse, rat and rabbit models. However, human clinical trials data did not support animal findings and were inconclusive. These systemic differences in biological actions between rodents and humans were attributed to the low level of DHEA in rodents. In order to further understand the differences in biological functions between rodents and humans, we resorted to an in-vitroapproach involving mouse, rat and human cell lines to assess DHEA biological and anabolic functions separately and independently without systemic influence. Results indicated that DHEA was effective on mouse and rat cell lines but not on human cell lines, as observed in in-vivo studies. In addition, our in-vitrostudy showed that DHEA was able to induce myogenesis in mouse mesenchymal cells revealing its anabolic function, even though DHEA was considered as a weak androgen. This observation lent credence to the ban on DHEA by IOC medical commission, citing DHEA as an anabolic steroid. These in-vitro experiments suggested that the differences in biological actions of DHEA between rodents and humans existed not only in-vivo at the systemic level, but also in-vitro at the cellular level and thus paving the way to study the mechanism responsible for these differences at the cellular level itself.展开更多
Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity.Testosterone is known to cause muscle hypertrophy,reduced fat mass,and increased body strength.The st...Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity.Testosterone is known to cause muscle hypertrophy,reduced fat mass,and increased body strength.The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia.We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young,treated non-diabetic young,untreated diabetic young,and treated diabetic young rats,and 32 aged Wistar rats to groups of untreated non-diabetic elderly,treated non-diabetic elderly,untreated diabetic elderly,and treated diabetic elderly rats,with eight animals each group.The treated non-diabetic and treated diabetic groups received injections of 15 mg/kg weight Durateston^(TM).All the trained groups performed aquatic training with an overload of 5% of the body mass.Following the experiment,we anesthetized and euthanized the animals after exercise(exhaustion).Hemoglobin,erythrocytes,and hematocrit values were higher in the treated groups.The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups(p<0.05).As for the lipid profile,untreated rats had the highest values.Glucose concentration was higher at rest and after exercise in the untreated diabetic groups(p<0.05).Lactate was more elevated in the untreated diabetic groups,and the testosterone-treated groups performed the longest swimming time after the maximal test(p<0.05).The use of testosterone in conjunction with physical exercise improved physical performance in water,blood glucose,and lipid profiles.展开更多
Background:There are many forms of anabolic steroids,including stanozolol(Winstrol),which are popular for their muscle-building effects but dangerous to the heart.This pre-sent work is aimed at evaluating the pharmaco...Background:There are many forms of anabolic steroids,including stanozolol(Winstrol),which are popular for their muscle-building effects but dangerous to the heart.This pre-sent work is aimed at evaluating the pharmacologica impact of allicin,a natural attribute obtained from garlic,on obstructing cardiac injury in rabbits that received stanozolol.Methods:Thirty rabbits were divided into three groups:control,stanozolol-treated,and stanozolol plus allicin.Cardiac function was assessed by measuring troponin,creatine kinase(CK),Galectin-3,and GDF-15.Oxidative stress and antioxidant markers,includ-ing malondialdehyde(MDA),glutathione,and catalase,were analyzed.Inflammatory mediators such as C-reactive protein(CRP),interleukin-6(IL-6),NF-κB,iNOS,nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were evaluated.Lipid profile parameters,including total cholesterol,low-density lipoprotein(LDL),and high-density lipoprotein(HDL),were measured.Histopathological examina-tion assessed myocardial damage,fibrosis,and collagen deposition.Results:Stanozolol administration significantly increased cardiac damage markers,oxidative stress,and inflammatory mediators while causing dyslipidemia,characterized by elevated LDL and total cholesterol and reduced HDL.Allicin co-administration effectively countered these effects by reducing oxidative stress and inflammation,restoring antioxidant balance,and improving lipid profiles.Histopathological analysis revealed severe myocardial disor-ganization,necrosis,and fibrosis in the stanozolol group,whereas the allicin-treated group exhibited preserved myocardial structure with reduced collagen deposition.Conclusion:Allicin significantly mitigates stanozolol-induced cardiotoxicity by reduc-ing oxidative stress,inflammation,lipid dysregulation,and myocardial damage,as evidenced by biochemical and histopathological findings.These results suggest that allicin may serve as a potential therapeutic agent to counteract the cardiovascular risks associated with anabolic steroid use.展开更多
Antiresorptive drugs are widely used for treatment of osteoporosis and cancer bone metastasis,which function mainly through an overall inhibition of osteoclast.However,not all osteoclasts are“bone eaters”;preosteocl...Antiresorptive drugs are widely used for treatment of osteoporosis and cancer bone metastasis,which function mainly through an overall inhibition of osteoclast.However,not all osteoclasts are“bone eaters”;preosteoclasts(pOCs)play anabolic roles in bone formation and angiogenesis through coupling with osteoblasts and secreting platelet derived growth factor-BB(PDGF-BB).In this study,a bone-targeted pH-responsive nanomaterial was designed for selectively eliminating mature osteoclasts(mOCs)without affecting pOCs.Biocompatible cerium nano-system(CNS)was guided to the acidic extracellular microenvironment created by mOCs and gained oxidative enzymatic activity.Oxidative CNS decreased the viability of mOCs through accumulating intracellular reactive oxygen species and enhancing calcium oscillation.Non-acid secreting anabolic pOCs were thus preserved and kept producing PDGF-BB,which lead to mesenchymal stem cell osteogenesis and endothelial progenitor cell angiogenesis via PI3K-Akt activated focal adhesion kinase.In treating osteoporotic ovariectomized mice,CNS showed better protective effects compare with the current first line antiresorptive drug due to the better anabolic effects marked by higher level of bone formation and vascularization.We provided a novel anabolic therapeutic strategy in treating bone disorders with excessive bone resorption.展开更多
Anabolic androgenic steroids (AAS) have several adverse effects on the cardiovascular system that may lead to a sudden cardiac death (SCD).We herein report a case involving a 24-year-old male,AAS abuser with intramusc...Anabolic androgenic steroids (AAS) have several adverse effects on the cardiovascular system that may lead to a sudden cardiac death (SCD).We herein report a case involving a 24-year-old male,AAS abuser with intramuscular delivery in the 6 months before,who suffered a cardiorespiratory arrest at home's bathtub when returning from New Year's party.A forensic autopsy was performed according to the guidelines of the Association for European Cardiovascular Pathology (AECVP).The body showed hypertrophy of skeletal musculature,with low amount of subcutaneous fat and no signs of injury (body mass index,BMh 26.8 kg/m^(2)).On internal examination,there were multiorgan congestion,acute pulmonary edema,and cardiomegaly (420 g) with severe coronary atherosclerosis and superimposed acute occlusive thrombosis at the left main trunk and left anterior descendant.Areas of scarring were located at the intersection between the posterior wall and the posterior third of the septum (postero-septal).At histology,acute myocardial infarction at the anterior third of the septum and the anterior wall,and subacute myocardial infarction at apical septum and apical posterior wall were detected.Other findings were small intramyocardial vessel disease and myocytes hypertrophy.Chemicotoxicological analysis in blood showed ethanol ((0.90 ±0.05) g/L),stanazolol (11.31 μg/L),nandrolone (2.05μg/L) and testosterone (<1.00μg/L).When confronted with a sudden death in a young athlete we must pay attention to the physical phenotype that may suggest AAS abuse and perform a detailed examination of the heart.Chemicotoxicological analysis is a key to establish the relationship between SCD and AAS abuse.展开更多
Bovine urine was centrifuged.Added the internal standard(ZER-d4 and DES-d8) into the supernate.The extract was cleaned up by two immunoaffinity columns respectively.A C8 analytical column was used and the analytes wer...Bovine urine was centrifuged.Added the internal standard(ZER-d4 and DES-d8) into the supernate.The extract was cleaned up by two immunoaffinity columns respectively.A C8 analytical column was used and the analytes were chromatographed by acetonitrile-water(70:30,v/v).With HPLC-MS/MS,data acquisition was achieved by using atmospheric pressure chemical ionization (APCI) in negative scan mode and multiple reaction monitoring (MRM) determination mode.Quantification was made by internal standarad method.The limits of determination of DES and DEN are 0.05 ng·g-1,the recovery level was 80 %-106% between 0.5 and 10 ng·g-1.The limits of determination of HEX and ZER are 0.025 ng·g-1,the recovery level was 83%-104% between 0.25 and 5 ng·g-1.展开更多
Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human ...Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.展开更多
We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the my...We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity （AR△ZF2） versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR△ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, IEf2 and calcineurin Aa, was increased in AR△ZF2 muscle, and the expression of all but p57kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.展开更多
A highly sensitive method was developed for the simultaneous determination of 8 steroid hormones in high-fat fish tissues using ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The 8 s...A highly sensitive method was developed for the simultaneous determination of 8 steroid hormones in high-fat fish tissues using ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The 8 steroid hormones were extracted from the tissues with diethyl ether.Differing from other common purification methods,the extract solutions were cleaned by gel permeation chromatography(GPC) using ethyl acetate-cyclohexane solution(1:1,v/v) as the mobile phase.The separation of target compounds was carried out by a BEH C18 column and a gradient elution consisting of acetonitrile and 0.2% aqueous formic acid(v/v).The compounds were detected under the multiple reaction monitoring(MRM) mode and quantified with external standard method.This method was validated with respect to linearity,specificity,accuracy and precision.A linearity with correlation coefficient larger than 0.995 was achieved in the range of 0.5 to 50 ng m L^(-1).The average recoveries at the spiked levels of 1.0,5.0,and 10.0 μg kg^(–1) varied between 81.7% and 90.8%,with the relative standard deviations(n=5) ranged from 3.50% to 10.0%.The limit of quantification(LOQ) for 8 steroid hormones ranged from 0.2 to 1.5 μg kg^(-1).It was concluded that this method can be successfully applied for the determination of 8 steroid hormones in complicated matrices including high-fat fish tissues.展开更多
文摘Vertebral and nonvertebral fractures prevention is the main goal for osteoporosis therapy by inhibiting bone resorption and/or stimulating bone formation.Antiresorptive drugs decrease the activation frequency,thereby determining a secondary decrease in bone formation rate and a low bone turnover.Bisphosphonates are today’s mainstay among antiresorptive treatment of osteoporosis.Also,oral selective estrogen receptor modulators and recently denosumab have a negative effect on bone turnover.Agents active on bone formation are considered a better perspective in the treatment of severe osteoporosis.Recombinant-human parathyroid hormone(PTH)has showed to increase bone formation and significantly decrease vertebral fractures in severe patients,but with a modest effect on nonvertebral fractures.The study of Wnt signaling pathway,that induces prevalently an osteoblastic activity,opens large possibilities to antagonists of Wnt-inhibitors,such as sclerostin antibodies and dickkopf-1 antagonists,with potential effects not only on trabecular bone but also on cortical bone.
基金supposed by the Projects of Agricultural Standards for Veterinary Drug Residues,China
文摘A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progesterone, estradiol benzoate, and chlormadinone acetate） was developed. Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps, the extracts obtained were derivatized with heptafluorbutyric （HBF） anhydride and analyzed by GC-MS. In the above method, the linear scope was 2.5-50 μg kg^-1. The range of the recoveries was 78.5-148% for diethylstilbestrol, 70.8-109% for methyltestosterone, 69.8-87.2% for norethindrone, 67.7-120% for 17α-ethynylestradiol, 82.8-103% for estradiol, 70.3-99.2% for 6α-methyl-17α-hydroxy-progesterone, 73.0-104% for estradiol benzoate, and 72.9- 91.8% for chlormadinone acetate. The range of the coefficients of variation within batches was 0.4-12%; the range of the coefficients of variation between batches was 6.4-11%. The limit of detections and the detection capability were 0.99 and 3.30 μg kg^-1 for diethylstilbestrol, 1.05 and 3.50 μg kg^-1 for methyltestosterone, 1.19 and 3.97 μg kg^-1 for norethindrone, 0.94 and 3.13 μg kg^-1 for 17α-ethynylestradiol, 1.45 and 4.83 μg kg^-1 for estradiol, 1.56 and 5.20 μg kg^-1 for 6α-methyl-17α- hydroxy-progesterone, 1.92 and 6.40 μg kg^-1 for estradiol benzoate, and 2.41 and 8.03 μg kg^-1 for chlormadinone acetate, respectively. These results showed that the method was widely available, accurate, and sensitive.
文摘The use of testosterone replacement therapy （TRT） for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids （AAS） within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal （HPG） axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.
文摘Anabolic steroid abuse is common among athletes and is associated with a number of medical complications. We describe a case of a 27-year-old male bodybuilder with multiple hepatic adenomas induced by anabolic steroids. He initially presented with tumor hemorrhage and was treated with left lateral hepatic segmentectomy. Regression of the remaining tumors was observed with cessation of steroid use. However, 3 years and a half after his initial hepatic segmentectomy, he presented with recurrent tumor enlargement and intraperitoneal hemorrhage in the setting of steroid abuse relapse. Given his limited hepatic reserve, he was conservatively managed with embolization of the right accessory hepatic artery. This is the first reported case of hepatic adenoma re- growth with recidivistic steroid abuse, complicated by life-threatening hemorrhage. While athletes and bodybuilders are often aware of the legal and social ramifications of steroid abuse, they should continue to be counseled about its serious medical risks.
基金Support was provided by a Career Development Award (RCR, BX001284) from the Veterans Administration
文摘The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.
基金We thank the Shanghai Municipal Committee of Science and Technology(Grant Nos.:20XD1423400,23ZR1460900 and 20DZ2201100)Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine(Grant No.:ZY(2021e2023)-0501)+2 种基金Shanghai Science and Technology Development Fund from Central Leading Local Government(Grant No.:YDZX20223100001004)National Natural Science Foundation of China(Grant No.:21672249)Expenditure Budget Program of Shanghai University of Traditional Chinese Medicine(Grant Nos.:2020LK051,and 2021LK001).
文摘In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.
文摘Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the f irst reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.
基金supported by YAKHA Sport,Franceby the Platform 3A,funded by the European Regional Development Fund+3 种基金the French Ministry of Research,Higher Education and Innovationthe Provence-Alpes-Côte-d'Azur regionthe Departmental Council of Vauclusethe Urban Community of Avignon。
文摘Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.
基金Project supported by the Postdoctoral Science Foundation of Central South University,ChinaProject(2015SK20823)supported by Science and Technology Project of Hunan Province,China+2 种基金Project(15A001)supported by Scientific Research Fund of Hunan Provincial Education Department,ChinaProject(CX2015B372)supported by Hunan Provincial Innovation Foundation for Postgraduate,ChinaProject supported by Innovation Experiment Program for University Students of Changsha University of Science and Technology,China
文摘The quantitative structure-property relationship(QSPR) of anabolic androgenic steroids was studied on the half-wave reduction potential(E1/2) using quantum and physico-chemical molecular descriptors. The descriptors were calculated by semi-empirical calculations. Models were established using partial least square(PLS) regression and back-propagation artificial neural network(BP-ANN). The QSPR results indicate that the descriptors of these derivatives have significant relationship with half-wave reduction potential. The stability and prediction ability of these models were validated using leave-one-out cross-validation and external test set.
文摘Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.
文摘A new GC/MS method for detection and identification of 19 anabolic steroids in human urine is presented.The procedure involves adsorption and isolation on a macroporous XAD-2 resin,enzymatic hydrolysis,alkaline extraction,derivatization,GC separation and MS detec- tion.Gas chromatographic-mass spectrometric data illustrate artifacts arising from enzymatic hydrolysis of steroid glucuronides and the structural characterization of their metabolites. Using this method,metabolic studies of these steroids in human urine were made after their ingestion by normal and healthy male volunteers.This method was proven to be suitable for large-scale routine analysis of anabolic steroids and was used successfully in passing the doping control test held by the Medical Commission of the International Olympic Committee.
文摘Dehydroepiandrosterone (DHEA) is a weak androgen and is shown to have anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory effects on mouse, rat and rabbit models. However, human clinical trials data did not support animal findings and were inconclusive. These systemic differences in biological actions between rodents and humans were attributed to the low level of DHEA in rodents. In order to further understand the differences in biological functions between rodents and humans, we resorted to an in-vitroapproach involving mouse, rat and human cell lines to assess DHEA biological and anabolic functions separately and independently without systemic influence. Results indicated that DHEA was effective on mouse and rat cell lines but not on human cell lines, as observed in in-vivo studies. In addition, our in-vitrostudy showed that DHEA was able to induce myogenesis in mouse mesenchymal cells revealing its anabolic function, even though DHEA was considered as a weak androgen. This observation lent credence to the ban on DHEA by IOC medical commission, citing DHEA as an anabolic steroid. These in-vitro experiments suggested that the differences in biological actions of DHEA between rodents and humans existed not only in-vivo at the systemic level, but also in-vitro at the cellular level and thus paving the way to study the mechanism responsible for these differences at the cellular level itself.
文摘Prolonged hyperglycemia conditions are a risk factor for chronic degenerative diseases such as diabetes and obesity.Testosterone is known to cause muscle hypertrophy,reduced fat mass,and increased body strength.The study aimed to verify possible alterations and differences in the influence of testosterone on the physical performance in post-exercise conditions of young and old animals with alloxan-induced hyperglycemia.We randomly assigned 32 young Wistar rats to groups of untreated non-diabetic young,treated non-diabetic young,untreated diabetic young,and treated diabetic young rats,and 32 aged Wistar rats to groups of untreated non-diabetic elderly,treated non-diabetic elderly,untreated diabetic elderly,and treated diabetic elderly rats,with eight animals each group.The treated non-diabetic and treated diabetic groups received injections of 15 mg/kg weight Durateston^(TM).All the trained groups performed aquatic training with an overload of 5% of the body mass.Following the experiment,we anesthetized and euthanized the animals after exercise(exhaustion).Hemoglobin,erythrocytes,and hematocrit values were higher in the treated groups.The treated diabetic elderly group had the highest leukocyte and neutrophil counts compared to the untreated young groups(p<0.05).As for the lipid profile,untreated rats had the highest values.Glucose concentration was higher at rest and after exercise in the untreated diabetic groups(p<0.05).Lactate was more elevated in the untreated diabetic groups,and the testosterone-treated groups performed the longest swimming time after the maximal test(p<0.05).The use of testosterone in conjunction with physical exercise improved physical performance in water,blood glucose,and lipid profiles.
基金the College of Pharmacy, Mustansiriyah University, for providing the necessary facilities and support to carry out this research.
文摘Background:There are many forms of anabolic steroids,including stanozolol(Winstrol),which are popular for their muscle-building effects but dangerous to the heart.This pre-sent work is aimed at evaluating the pharmacologica impact of allicin,a natural attribute obtained from garlic,on obstructing cardiac injury in rabbits that received stanozolol.Methods:Thirty rabbits were divided into three groups:control,stanozolol-treated,and stanozolol plus allicin.Cardiac function was assessed by measuring troponin,creatine kinase(CK),Galectin-3,and GDF-15.Oxidative stress and antioxidant markers,includ-ing malondialdehyde(MDA),glutathione,and catalase,were analyzed.Inflammatory mediators such as C-reactive protein(CRP),interleukin-6(IL-6),NF-κB,iNOS,nitric oxide(NO),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were evaluated.Lipid profile parameters,including total cholesterol,low-density lipoprotein(LDL),and high-density lipoprotein(HDL),were measured.Histopathological examina-tion assessed myocardial damage,fibrosis,and collagen deposition.Results:Stanozolol administration significantly increased cardiac damage markers,oxidative stress,and inflammatory mediators while causing dyslipidemia,characterized by elevated LDL and total cholesterol and reduced HDL.Allicin co-administration effectively countered these effects by reducing oxidative stress and inflammation,restoring antioxidant balance,and improving lipid profiles.Histopathological analysis revealed severe myocardial disor-ganization,necrosis,and fibrosis in the stanozolol group,whereas the allicin-treated group exhibited preserved myocardial structure with reduced collagen deposition.Conclusion:Allicin significantly mitigates stanozolol-induced cardiotoxicity by reduc-ing oxidative stress,inflammation,lipid dysregulation,and myocardial damage,as evidenced by biochemical and histopathological findings.These results suggest that allicin may serve as a potential therapeutic agent to counteract the cardiovascular risks associated with anabolic steroid use.
基金This work was funded by the State Key Program of National Natural Science of China(No.81930067)the Nature Science Foundation of China(81802166)AMU Southwest Hospital funding for young investigators(XZ-2019-505-005).
文摘Antiresorptive drugs are widely used for treatment of osteoporosis and cancer bone metastasis,which function mainly through an overall inhibition of osteoclast.However,not all osteoclasts are“bone eaters”;preosteoclasts(pOCs)play anabolic roles in bone formation and angiogenesis through coupling with osteoblasts and secreting platelet derived growth factor-BB(PDGF-BB).In this study,a bone-targeted pH-responsive nanomaterial was designed for selectively eliminating mature osteoclasts(mOCs)without affecting pOCs.Biocompatible cerium nano-system(CNS)was guided to the acidic extracellular microenvironment created by mOCs and gained oxidative enzymatic activity.Oxidative CNS decreased the viability of mOCs through accumulating intracellular reactive oxygen species and enhancing calcium oscillation.Non-acid secreting anabolic pOCs were thus preserved and kept producing PDGF-BB,which lead to mesenchymal stem cell osteogenesis and endothelial progenitor cell angiogenesis via PI3K-Akt activated focal adhesion kinase.In treating osteoporotic ovariectomized mice,CNS showed better protective effects compare with the current first line antiresorptive drug due to the better anabolic effects marked by higher level of bone formation and vascularization.We provided a novel anabolic therapeutic strategy in treating bone disorders with excessive bone resorption.
文摘Anabolic androgenic steroids (AAS) have several adverse effects on the cardiovascular system that may lead to a sudden cardiac death (SCD).We herein report a case involving a 24-year-old male,AAS abuser with intramuscular delivery in the 6 months before,who suffered a cardiorespiratory arrest at home's bathtub when returning from New Year's party.A forensic autopsy was performed according to the guidelines of the Association for European Cardiovascular Pathology (AECVP).The body showed hypertrophy of skeletal musculature,with low amount of subcutaneous fat and no signs of injury (body mass index,BMh 26.8 kg/m^(2)).On internal examination,there were multiorgan congestion,acute pulmonary edema,and cardiomegaly (420 g) with severe coronary atherosclerosis and superimposed acute occlusive thrombosis at the left main trunk and left anterior descendant.Areas of scarring were located at the intersection between the posterior wall and the posterior third of the septum (postero-septal).At histology,acute myocardial infarction at the anterior third of the septum and the anterior wall,and subacute myocardial infarction at apical septum and apical posterior wall were detected.Other findings were small intramyocardial vessel disease and myocytes hypertrophy.Chemicotoxicological analysis in blood showed ethanol ((0.90 ±0.05) g/L),stanazolol (11.31 μg/L),nandrolone (2.05μg/L) and testosterone (<1.00μg/L).When confronted with a sudden death in a young athlete we must pay attention to the physical phenotype that may suggest AAS abuse and perform a detailed examination of the heart.Chemicotoxicological analysis is a key to establish the relationship between SCD and AAS abuse.
文摘Bovine urine was centrifuged.Added the internal standard(ZER-d4 and DES-d8) into the supernate.The extract was cleaned up by two immunoaffinity columns respectively.A C8 analytical column was used and the analytes were chromatographed by acetonitrile-water(70:30,v/v).With HPLC-MS/MS,data acquisition was achieved by using atmospheric pressure chemical ionization (APCI) in negative scan mode and multiple reaction monitoring (MRM) determination mode.Quantification was made by internal standarad method.The limits of determination of DES and DEN are 0.05 ng·g-1,the recovery level was 80 %-106% between 0.5 and 10 ng·g-1.The limits of determination of HEX and ZER are 0.025 ng·g-1,the recovery level was 83%-104% between 0.25 and 5 ng·g-1.
文摘Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.
文摘We aimed to determine the mechanisms of the anabolic actions of androgens in skeletal muscle by investigating potential androgen receptor （AR）-regulated genes in in vitro and in vivo models. The expression of the myogenic regulatory factor myogenin was significantly decreased in skeletal muscle from testosterone-treated orchidectomized male mice compared to control orchidectomized males, and was increased in muscle from male AR knockout mice that lacked DNA binding activity （AR△ZF2） versus wildtype mice, demonstrating that myogenin is repressed by the androgen/AR pathway. The ubiquitin ligase Fbxo32 was repressed by 12 h dihydrotestosterone treatment in human skeletal muscle cell myoblasts, and c-Myc expression was decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle, and increased in AR△ZF2 muscle. The expression of a group of genes that regulate the transition from myoblast proliferation to differentiation, Tceal7, p57Kip2, IEf2 and calcineurin Aa, was increased in AR△ZF2 muscle, and the expression of all but p57kip2 was also decreased in testosterone-treated orchidectomized male muscle compared to control orchidectomized male muscle. We conclude that in males, androgens act via the AR in part to promote peak muscle mass by maintaining myoblasts in the proliferative state and delaying the transition to differentiation during muscle growth and development, and by suppressing ubiquitin ligase-mediated atrophy pathways to preserve muscle mass in adult muscle.
基金supported by the Natural Science Foundation of Zhejiang Province,China(No.LY17C200009)the Foundation of Zhejiang Educational Committee(No.Y201328477)
文摘A highly sensitive method was developed for the simultaneous determination of 8 steroid hormones in high-fat fish tissues using ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The 8 steroid hormones were extracted from the tissues with diethyl ether.Differing from other common purification methods,the extract solutions were cleaned by gel permeation chromatography(GPC) using ethyl acetate-cyclohexane solution(1:1,v/v) as the mobile phase.The separation of target compounds was carried out by a BEH C18 column and a gradient elution consisting of acetonitrile and 0.2% aqueous formic acid(v/v).The compounds were detected under the multiple reaction monitoring(MRM) mode and quantified with external standard method.This method was validated with respect to linearity,specificity,accuracy and precision.A linearity with correlation coefficient larger than 0.995 was achieved in the range of 0.5 to 50 ng m L^(-1).The average recoveries at the spiked levels of 1.0,5.0,and 10.0 μg kg^(–1) varied between 81.7% and 90.8%,with the relative standard deviations(n=5) ranged from 3.50% to 10.0%.The limit of quantification(LOQ) for 8 steroid hormones ranged from 0.2 to 1.5 μg kg^(-1).It was concluded that this method can be successfully applied for the determination of 8 steroid hormones in complicated matrices including high-fat fish tissues.
