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Drug Testing and Analysis Sep 2020Anabolic androgenic steroids (AASs) comprise a class of synthetic androgens resulting from chemical modifications of testosterone, known for their illicit consumption,... (Comparative Study)
Comparative Study
Anabolic androgenic steroids (AASs) comprise a class of synthetic androgens resulting from chemical modifications of testosterone, known for their illicit consumption, which can result inextensive side effects. Extraction procedures applied to the analysis of their formulations are still limited to a few methodologies, despite the increasing numbers of confiscations of AASs. In this sense, the aims of this work were to evaluate the extraction of active ingredients from formulations of anabolic agents using solid-liquid or liquid-iquid, ultrasonic bath, ultrasonicprobe, and microwave-assisted extraction. The results indicated that the extraction procedures influenced the detected concentration of AASs, as the use of ultrasonic probe and microwave irradiation increased the overall extraction of anabolic agents compared with solid-liquid, liquid-liquid, and ultrasonic bath. Regarding oxymetholone, for instance, the microwave-assisted extraction and ultrasonic probe extracted, respectively, 37.46 ± 1.36 and 35.69 ± 0.98 mg/tablet, while solid-liquid extracted 29.63 ± 0.40 mg/tablet of the activeingredient. Therefore, alternative methods such as microwave-assisted extraction or theultrasonic probe could be used for the analysis of formulations of AASs assisting with the identification of illicit and toxic components.
Topics: Anabolic Agents; Chemical Fractionation; Doping in Sports; Liquid-Liquid Extraction; Microwaves; Solid Phase Extraction; Tablets; Testosterone Congeners; Ultrasonics
PubMed: 32537903
DOI: 10.1002/dta.2877 -
Leukemia Research Nov 2016Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant...
Angiogenesis occurs in response to tissue ischemia and wound healing, and contributes to the pathogenesis of a variety of diseases, such as benign and malignant neoplasia. Several studies have measured bone marrow microvessel density (MVD) in MDS patients and acute myeloid leukemia (AML) patients transformed from MDS, and MVD was higher in MDS patients than controls, but was lower than in AML patients. Vascular endothelial growth factor (VEGF) is expressed in bone marrow blast cells, and an autocrine VEGF signaling mechanism has been established in MDS. Increased bone marrow angiogenesis and VEGF concentrations are adverse prognostic features in all of these patients. In this study, 69 patients were treated in two groups: hypomethylating agents or supportive care with oxymetholone±pyridoxine. We evaluated the MVD and VEGF expression of paraffin-embedded bone marrow samples from patients. We also investigated the relationship between angiogenesis-related biomarkers including MVD, VEGF expression, and clinical factors. The patient median age was 65 years, and the median follow-up duration was 28 months. MVD assessment among subtypes of WHO MDS classification showed that the MVD of RCUD was significantly lower than in other types (p=0.02). However, there was no significant difference in VEGF expression according to the subtype of MDS. Although MVD and VEGF expression did not differ between risk groups based on the IPSS, the low risk group tended to have lower expression of angiogenesis-related biomarkers. MDS patients receiving hypomethylating agents had significantly lower MVD expression in responders than in non-responders (6.13±3.38 vs. 9.89±2.10, respectively, p=0.039). In a consecutive evaluation at the time of diagnosis and 3 months after the initial treatment, the group with a decrease or no change of MVD had a higher response rate compared to that in the group with an increase of MVD (92.9% vs. 58.8%, respectively, p=0.045). Adverse prognostic factors included older age, MDS type other than RCUD, a higher IPSS risk group, and abnormal cytogenetics. Although angiogenesis-related markers did not demonstrate any significant prognostic association with survival, MVD (≥10n/mm) and a strong expression of VEGF seemed to be associated with lower survival rate. These data suggested that the MVD value might be helpful in predicting responsiveness to treatment, especially in MDS patients treated with hypomethylating agents. Although angiogenesis-related markers including VEGF did not demonstrate a significant association with survival outcomes, we observed that high MVD and strong VEGF expression seemed to be associated with lower survival rate. Therefore, biologic markers related to angiogenesis might have a potential as prognostic factors for MDS patients.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bone Marrow Examination; Humans; Immunosuppressive Agents; Microvessels; Middle Aged; Myelodysplastic Syndromes; Neovascularization, Pathologic; Oxymetholone; Prognosis; Pyridoxine; Retrospective Studies; Survival Rate; Vascular Endothelial Growth Factor A; Young Adult
PubMed: 27639703
DOI: 10.1016/j.leukres.2016.08.012 -
Molecular and Cellular Endocrinology Jun 2023Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17β-estradiol (estradiol)...
Human adrenocortical H295R cells have been validated by the OECD Test Guideline 456 to detect chemicals disrupting testosterone and 17β-estradiol (estradiol) biosynthesis. This study evaluated a novel approach to detect disturbances of steroidogenesis in H295R cells, exemplified by prochloraz and five anabolic steroids. Steroid profiles were assessed by an untargeted LC-MS-based method, providing a relative quantification of 57 steroids annotated according to their accurate masses and retention times. Such a panel of steroids included several mineralocorticoids, glucocorticoids, progestins and adrenal androgens. The coverage of a high number of metabolites in this extended steroid profiling facilitated grouping of chemicals with similar effects and detecting subtler differences between chemicals. It allowed, for example, distinguishing between the effects of turinabol and oxymetholone, supposed to act similarly in a previous characterization including only nine adrenal steroids. Furthermore, the results revealed that product/substrate ratios can provide superior information on altered enzyme activities compared to individual metabolite levels. For example, the 17α-hydroxypregnenolone/pregnenolone ratio was found to be a more sensitive marker for detecting 17α-hydroxylase inhibition by prochloraz than the corresponding individual steroids. These results illustrate that chemical grouping and calculation of product/substrate ratios can provide valuable information on mode-of-action and help prioritizing further experimental work.
Topics: Humans; Anabolic Androgenic Steroids; Cell Line, Tumor; Steroids; Estradiol
PubMed: 37037411
DOI: 10.1016/j.mce.2023.111929 -
Oxidative Medicine and Cellular... 2015The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic...
The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation.
Topics: Animals; Antioxidants; Body Weight; Creatine Kinase; Cytokines; Dietary Supplements; Ethanol; Fruit; Immunohistochemistry; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred ICR; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Plant Extracts; Schisandra; Sciatic Nerve
PubMed: 26064425
DOI: 10.1155/2015/872428 -
British Journal of Haematology Jun 2020Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood...
Progressive cytopenia is a serious complication among paediatric patients with inherited bone marrow failure syndromes (IBMFS). Androgens have been used to improve blood counts in different bone marrow failure conditions. Little is known about efficacy and toxicity with new androgens (i.e., danazol) in different types of IBMFS. We identified 29 patients from the Canadian Inherited Marrow Failure Registry, who received oxymetholone or danazol. Sixteen (55%) had haematological response including patients with unclassified IBMFS (45%). Danazol showed a better toxicity profile and similar efficacy compared to oxymetholone. Androgens are an effective and safe option to ameliorate bone marrow failure in IBMFS.
Topics: Adolescent; Adult; Androgens; Bone Marrow Failure Disorders; Canada; Cell Lineage; Child; Child, Preschool; Combined Modality Therapy; Danazol; Disease Progression; Drug Substitution; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Middle Aged; Oxymetholone; Pancytopenia; Registries; Thrombocytopenia; Treatment Outcome; Virilism
PubMed: 32128787
DOI: 10.1111/bjh.16445 -
PloS One 2018Helium, a minor component of natural gas and radioactive minerals, is most commonly used as a carrier in gas chromatography-mass spectrometry (GC-MS). Its scarcity leads...
Helium, a minor component of natural gas and radioactive minerals, is most commonly used as a carrier in gas chromatography-mass spectrometry (GC-MS). Its scarcity leads to limited availability and higher costs. In this experiment, hydrogen from a safe source of a hydrogen generator was tested as a substitutive carrier gas for the detection of adulterant in traditional Chinese medicine (TCM) and food supplements by GC-MS analysis. We found that the limits of detection (LODs) of using hydrogen were from 10 to 1000 μg/g. The levels of LODs tested among 170 drugs remain the same whether hydrogen or helium was used as a carrier gas with the exception of 7 drugs-benzbromarone, estradiol benzoate, bezafibrate, mefenamic acid, oxymetholone, piperidenafil and cetilistat. The real sample analysis results using hydrogen were as satisfactory as those using helium. In addition, the retention time was shortened after the chromatographic performance was optimized. In summary, it is worth considering hydrogen as a carrier gas due to its affordable costs, energy efficiency, carbon reduction and chromatographic advantages to detect adulterated drugs in TCM and dietary supplement using GC-MS.
Topics: Chlorzoxazone; Dietary Supplements; Drug Contamination; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Helium; Humans; Hydrogen; Limit of Detection; Oxymetholone; Pyrimidinones; Sildenafil Citrate; Sulfones
PubMed: 30304050
DOI: 10.1371/journal.pone.0205371 -
Journal of the International Society of... Oct 2018A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically evaluated physical performance and muscle strength enhancing ability of GMCT in a preclinical mouse model followed by a 42-days double-blind placebo controlled human trial in resistance trained adult males.
METHODS
Four groups of Swiss albino mice (20-30 g body weight) (n = 6) were fed a standard laboratory diet and given Carboxymethylcellulose sodium (CMC), 150 mg/kg GMCT (GMCT-150), 300 mg/kg GMCT (GMCT-300) or 50 mg/kg Oxymetholone (OXY) via oral gavage for 21 days. On day 22, the animals' physical performance and muscle strength were assessed in a forced swimming test (FST) and forelimb grip strength experiment, respectively. In the human trial, thirty-eight resistance-trained young adults (mean age 26.32 ± 4.39 years, body weight 67.79 ± 12.84 kg, BMI 22.92 ± 3.54 kg/m) completed the trial. The participants received either GMCT (n = 19; 800 mg daily) or matched placebo (n = 19) for 42 days. As primary variables, 1-RM bench press, 1-RM leg press, and leg extension repetitions were measured at baseline and on days 14, 28 and 42 of the intervention. Anthropometric parameters and serum markers such as free testosterone, insulin-like growth factor 1 (IGF-1), insulin and lactate were also measured before and after the intervention.
RESULTS
GMCT-300 mice showed significant improvement in swimming time (GMCT: 395.3 ± 81.70 s vs. CMC: 271.6 ± 56.86 s; p = 0.0166), distance (GMCT: 341.22 ± 65.88 m vs. CMC: 260.84 ± 49.15 m; p = 0.0461) and grip strength (GMCT: 43.92 ± 6.97 N vs. CMC: 35.0 ± 6.92 N; p = 0.0490), compared with the CMC group. At the end of the 42-day human trial, the per protocol analyses reveal that mean changes from baseline 1-RM bench press (GMCT: 23.47 ± 10.07 kg vs. PL: 3.42 ± 2.06 kg; p < 0.0001), leg press (GMCT: 29.32 ± 16.17 kg vs. PL: 5.21 ± 1.72 kg; p < 0.0001), number of leg extension repetitions (GMCT: 6.58 ± 2.57 vs. PL: 2.05 ± 1.22; p < 0.0001) in GMCT group were significantly improved, compared with placebo. Intergroup difference analyses show that the changes from baseline left arm (GMCT: 1.09 ± 0.36 cm vs. PL: 0.68 ± 0.42 cm; p = 0.0023), right arm (GMCT: 1.50 ± 0.44 cm vs. PL: 1.11 ± 0.43 cm; p = 0.0088) circumference and lean mass (GMCT: 2.29 ± 2.09 kg vs. PL: 0.52 ± 2.58 kg; p = 0.0404) in GMCT group were also significantly improved, compared with placebo. In comparison to placebo, GMCT supplementation did not improve free testosterone, IGF-1, insulin or lactate levels. Parameters of clinical biochemistry, hematology, urine and vital signs of the participants were within the normal range.
CONCLUSION
GMCT supplementation is effective in increasing muscle strength, muscle size and, total lean mass, as well as endurance performance.
TRIAL REGISTRATION
Clinical Trial Registry of India (CTRI/2015/01/005374), Registered on Jan 07, 2015; CTRI Website URL - http://ctri.nic.in.
Topics: Adult; Animals; Cinnamomum; Double-Blind Method; Fruit; Garcinia mangostana; Humans; Insulin; Insulin-Like Growth Factor I; Lactic Acid; Male; Mice; Muscle Strength; Physical Endurance; Plant Extracts; Plant Leaves; Resistance Training; Testosterone; Young Adult
PubMed: 30348185
DOI: 10.1186/s12970-018-0257-4 -
International Journal of Molecular... Mar 2018The present study assessed the beneficial skeletal muscle‑preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM‑2001 (Polycan) (EAP) on...
The present study assessed the beneficial skeletal muscle‑preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM‑2001 (Polycan) (EAP) on dexamethasone (DEXA)‑induced catabolic muscle atrophy in mice. To investigate whether EAP prevented catabolic DEXA‑induced muscle atrophy, and to examine its mechanisms of action, EAP (100, 200 and 400 mg/kg) was administered orally, once a day for 24 days. EAP treatment was initiated 2 weeks prior to DEXA treatment (1 mg/kg, once a day for 10 days) in mice. Body weight alterations, serum biochemistry, calf thickness, calf muscle strength, gastrocnemius muscle thickness and weight, gastrocnemius muscle antioxidant defense parameters, gastrocnemius muscle mRNA expression, histology and histomorphometry were subsequently assessed. After 24 days, DEXA control mice exhibited muscle atrophy according to all criteria indices. However, these muscle atrophy symptoms were significantly inhibited by oral treatment with all three doses of EAP. Regarding possible mechanisms of action, EAP exhibited favorable ameliorating effects on DEXA‑induced catabolic muscle atrophy via antioxidant and anti‑inflammatory effects; these effects were mediated by modulation of the expression of genes involved in muscle protein synthesis (AKT serine/threonine kinase 1, phosphatidylinositol 3‑kinase, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4) and degradation (atrogin‑1, muscle RING‑finger protein‑1, myostatin and sirtuin 1). Therefore, these results indicated that EAP may be helpful in improving muscle atrophies of various etiologies. EAP at 400 mg/kg exhibited favorable muscle protective effects against DEXA‑induced catabolic muscle atrophy, comparable with the effects of oxymetholone (50 mg/kg), which has been used to treat various muscle disorders.
Topics: Aldehydes; Animals; Antioxidants; Ascomycota; Body Weight; Catalase; Dexamethasone; Extracellular Space; Glutathione; Male; Malondialdehyde; Mice, Inbred ICR; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Nitric Oxide Synthase Type II; Organ Size; Poly(ADP-ribose) Polymerases; Polysaccharides; RNA, Messenger; Reactive Oxygen Species; Superoxide Dismutase; Tyrosine
PubMed: 29138805
DOI: 10.3892/ijmm.2017.3251 -
QJM : Monthly Journal of the... Aug 2014
Topics: Adult; Anabolic Agents; Humans; Infarction; Kidney; Male; Oxymetholone; Performance-Enhancing Substances; Polycythemia; Substance-Related Disorders; Tomography, X-Ray Computed; Weight Lifting
PubMed: 24557731
DOI: 10.1093/qjmed/hcu042 -
British Journal of Haematology Oct 2019
Topics: Adult; Aged; Aged, 80 and over; Androgens; Danazol; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Oxymetholone; Retrospective Studies; Thrombocytopenia; Treatment Outcome; Young Adult
PubMed: 31368111
DOI: 10.1111/bjh.16121