- Synthesis of a human long-term oxymetholone metabolite. [Journal Article]
- SSteroids 2019 Jun 20; :108430
- A long-term metabolite of the doping agent oxymetholone (OXM-M2, 17β-hydroxymethyl-2,17α-methyl-18-norandrost-13-en-3-one) which has been identified by GC-MS/MS was synthesized from commercially avai…
A long-term metabolite of the doping agent oxymetholone (OXM-M2, 17β-hydroxymethyl-2,17α-methyl-18-norandrost-13-en-3-one) which has been identified by GC-MS/MS was synthesized from commercially available materials. Two efficient synthetic routes to access both C-17 epimers of tentative metabolites were developed. The identity and molecular configuration of the in vivo metabolite: 17β-hydroxymethyl-2α,17α-methyl-18-norandrost-13-en-3-one was confirmed by single crystal X-ray diffraction.
- Nasturtium Officinale L. hydroalcoholic extract improved oxymetholone-induced oxidative injury in mouse testis and sperm parameters. [Journal Article]
- AAndrologia 2019 Apr 25; :e13294
- Testicular tissue and sex hormones are sensitive to the anabolic steroids (oxymetholone/OM) due to increased free radical damage and hormonal changes. The Nasturtium officinale L. have various antiox…
Testicular tissue and sex hormones are sensitive to the anabolic steroids (oxymetholone/OM) due to increased free radical damage and hormonal changes. The Nasturtium officinale L. have various antioxidant compounds. The aim of the present study was to investigate N. officinale effect on OM-induced oxidative injury in mouse testis and sperm parameters. Thirty BALB/c mice were divided into five groups, including control, OM (5 ml/kg) and three N. officinale doses (25, 50 and 100 mg/kg) + OM. At the end of the study (40 days), serum luteinising hormone (LH), follicle-stimulating hormone (FSH), testosterone, nitric oxide (NO) levels, ferric reducing ability of power (FRAP) and testis stereological factors were measured. The sperm parameters were evaluated. Liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI/MS) analysis was yielded a fingerprint of N. officinale phenolic constituents. 100 mg/kg of N. officinale extract significantly reduced the serum level of testosterone and a significant increase in LH and FSH in comparison with the control group. This dose also significantly improved the stereological factors and sperm parameters. 50 and 100 mg/kg of N. officinale extract significantly increased the testis tissue FRAP levels, and 100 doses reduced the serum levels of NO. Fourteen compounds and 34 peaks were identified in the extract with LC-ESI/MS. Nasturtium officinale extract has protective effects against testicular toxicity caused by OM.
- Supraphysiologic-dose anabolic-androgenic steroid use: A risk factor for dementia? [Review]
- NBNeurosci Biobehav Rev 2019; 100:180-207
- Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Dise…
Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.
- Oxymetholone-Induced Acute Renal Failure: A Case Report. [Case Reports]
- CJCaspian J Intern Med 2018; 9(4):410-412
- CONCLUSIONS: Rhabdomyolysis due to drug use and the consequent acute kidney injury are among the lethal risks associated with anabolic steroid abuse. In most cases, the symptoms are extensive and often misleading. Therefore, detailed history taking, physical scrutiny, paraclinical testing, and early diagnosis are crucial for rhabdomyolysis patients.
- Combined extracts of Garcinia mangostana fruit rind and Cinnamomum tamala leaf supplementation enhances muscle strength and endurance in resistance trained males. [Randomized Controlled Trial]
- JIJ Int Soc Sports Nutr 2018 Oct 22; 15(1):50
- CONCLUSIONS: GMCT supplementation is effective in increasing muscle strength, muscle size and, total lean mass, as well as endurance performance.
- Detection of adulterated drugs in traditional Chinese medicine and dietary supplements using hydrogen as a carrier gas. [Journal Article]
- PlosPLoS One 2018; 13(10):e0205371
- 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 h…
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.
- 1H NMR determination of adulteration of anabolic steroids in seized drugs. [Journal Article]
- SSteroids 2018; 138:47-56
- Counterfeiting and adulteration of pharmaceuticals is a prevalent problem worldwide and represents a major health risk to the population, with anabolic steroids being one of the main classes of drugs…
Counterfeiting and adulteration of pharmaceuticals is a prevalent problem worldwide and represents a major health risk to the population, with anabolic steroids being one of the main classes of drugs consumed and obtained from dubious sources. In this work, we propose the use of the 1H NMR technique to evaluate formulations containing anabolic steroids, with analysis of 40 samples of anabolic drugs that are used in injectable and capsule forms. The samples analyzed presented the following active ingredients: testosterone propionate, testosterone phenylpropionate, testosterone isocaproate, testosterone decanoate, testosterone cypionate, testosterone undecanoate, stanozolol, drostanolone propionate, trenbolone acetate, oxymetholone, and methandrostenolone. The 1H NMR spectroscopic measurements were performed using a 600 MHz Bruker Avance III spectrometer, with deuterated chloroform (CDCl3) containing 0.1% TMS as solvent. Of the 40 samples analyzed, eight did not show the presence of the active principle stated on the label. Three types of adulteration were found in the analyzed samples: absence of the active ingredient, adulteration with other substances, and concentration values below those indicated on the label. Sildenafil citrate was found in four samples. The GC-MS technique was used to confirm the adulteration results found using 1H NMR. Quantitative determination by NMR was performed using internal standard and ERETIC 2 methods, and the results obtained were statistically the same.
- StatPearls: Immunodeficiency [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Immunodeficiency results from a failure or absence of elements of the immune system including lymphocytes, phagocytes and complement system. These immunodeficiencies can be either primary such as Bru…
Immunodeficiency results from a failure or absence of elements of the immune system including lymphocytes, phagocytes and complement system. These immunodeficiencies can be either primary such as Bruton’s disease or secondary as the one caused by HIV infection. Primary Immunodeficiency B-cell Deficiencies X- linked Agammaglobulinemia (Bruton’s disease): First described by Bruton. X-linked disorder. Found in male babies expressed around 5 to 6 months of age (maternal IgG disappears). In boys, pre-B cells did not differentiate into mature B lymphocytes. There is a mutation in the gene that encodes for a tyrosine kinase protein. Low level of all immunoglobulins (IgG, IgA, IgM, IgD and IgE) is present. Infants with X-linked agammaglobulinemia suffer from recurrent bacterial infections: otitis media, bronchitis, septicemia, pneumonia, and arthritis, and Giardia lamblia causes intestinal malabsorption. Intermittent injections of large amounts of IgG keep the patient alive, but a patient may die at a younger age if infection with antibiotic-resistant bacteria occurs. Bone marrow transplantation is critical. Selective Immunoglobulin IgA Deficiencies : IgA deficiency is more common than other deficiencies of immunoglobulins.. These patients are more prone to recurrent sinus and lung infections. A malfunctioning in heavy-chain gene switching may cause this problem. Treatment should not include gammaglobulin preparations to prevent hypersensitivity reactions. T-cell Immunodeficiencies Congenital thymic Aplasia (DiGeorge Syndrome): Tetany is present. Fungal and viral infections are common. A transplant of the fetal thymus is needed to correct this deficiency. Chronic Mucocutaneous Candidasis: Selective defect in functioning of T-cells. Patient with this disorder usually have a normal T-cell mediated immunity to microorganisms other than Candida. B-cells function is normal. Disorders affect both genders, and it is inherited. Patient in addition to the above will have other disorders like parathyroid deficiencies. Antifungals are useful. Hyper-IgM syndrome: This disorder is characterized by bacterial infections including pneumonia, meningitis, otitis, among others that start in early childhood. High levels of IgM. Other immunoglobulins are defective. Lymphocytes are normal in numbers. The gene encoding the CD40 ligand on T lymphocytes is faulty. B and T lymphocyte cooperation in the immune response is compromised. The failure to interact with CD40 results in an inability of the B cell to switch from the production of IgM to the other classes of antibodies. Immunoglobulin therapy is recommended. Interleukin-12 receptor deficiency: Mycobacterial infections are frequent due to the lack of the interleukin-12 receptor. Treatment involves selective antimicrobials. T-cell and B-cell Deficiencies Severe combined immunodeficiency disease (SCID): There is a failure of early stem cells to differentiate into T and B lymphocytes. Deficiency of the interleukin-2 receptor is the most prevalent. Other problems are due to defective genes encoding ZAP-70, Janus kinase 3 and the genes involved in the DNA recombination of immune cells receptors: RAG1 and RAG2. Clinically characterized by a variety of infections, including those caused by opportunistic pathogens. Selective antibiotics, antivirals, and antifungals are available after the pathogen identification. Immunosuppressive therapy is not needed after allograft transplantation. Wiskott-Aldrich syndrome: This syndrome is associated with normal T-cell numbers with reduced functions, which get progressively worse. IgM concentrations are reduced, but IgG levels are normal. Both IgA and IgE levels are elevated. These patients have a defective WASP which is involved in actin filament assembly. Immunodeficiency with ataxia-telangiectasia: This is a deficiency of T-cells associated with a lack of coordination of movement (ataxia) and dilation of small blood vessels of the facial area (telangiectasis). T-cells and their functions are diminished to various degrees. B-cell numbers and IgM concentrations are normal to low. IgG is often reduced, and IgA is considerably reduced. There is a high incidence of malignancy, especially leukemias, in these patients. MHC deficiency (Bare leukocyte syndrome): This subjects have have fewer CD4+ or CD8+ T lymphocytes that predispose to these individuals to be prone to recurrent infections. Antibody production is affected and predispose to bacteremia. Complement Deficiencies Hereditary angioedema: This disease has an autosomal dominant genetic pattern. Caused by C1 inhibitor deficiency. Clinically characterized by generalized edema including the one leading to acute suffocation. Therapy with oxymetholone and danazol can be helpful in correcting the defect. Recurrent infections: Frequent infections by extracellular bacteria may be caused by C3 deficiency. C5 deficiency predisposes to viral infections. Patients with deficiency of the membrane attack complex (MAC) are particularly susceptible to bacteremia caused by Neisseria species. Autoimmune diseases This are caused by C2 and C4 deficiencies and mimic systemic lupus erythematosus. Phagocyte Deficiencies Chronic granulomatous disease (CGD): It is mostly an X-linked disorder. It is clinically characterized by a defective NADPH that interferes with the intracellular ability of neutrophils to kill engulfed bacteria species. NAPDH oxidase is required for the generation of peroxidase and superoxides that will kill the organisms. The intracellular survival of the organisms leads to the formation of a granuloma, an organized structure consisting of mononuclear cells. These granulomas can become large enough to obstruct the stomach, esophagus, or bladder. Patients with this disease are very susceptible to opportunistic infection by certain bacteria and fungi especially with Serratia and Burkholderia. Nitroblue tetrazolium (NBT) dye reduction test confirms the diagnosis of CGD and the dichlorofluorescein (DCF) test is also useful. Aggressive therapy with wide spectrum antibiotics and antifungal agents is required. Leukocyte adhesion deficiency syndrome: Characterized by pyogenic infections including pneumonia and otitis. It is an autosomal recessive disease, and the faulty gene encodes for an integrin. There is an impaired adhesion and defective phagocytosis of bacteria. Treatment involves the use of selective antibiotics. Secondary Immunodeficiency Use of Drugs (Steroids) : Administration of steroids has direct effects on immune cell traffic and functions. T cells are more affected than B cells. Cytokine synthesis is inhibited. Nutrient Deficiencies : They are associated with impaired immune system. Affects cell-mediated immunity, antibody production, phagocyte function, complement system and cytokine synthesis. Aggravated by infections. Multiple enzymes with important roles require zinc, iron and other micronutrients. Obesity : It may cause impaired immune responses. There is altered NK function. Cytotoxicity is compromised and the ability of phagocytes to kill microorganisms. Acquired Immune Deficiency Syndrome (AIDS) : Caused by human immunodeficiency virus (HIV), which is a retrovirus transmitted sexually, perinatally or blood products. Immune dysfunction results from the direct effects of HIV and impairment of CD4 T cells. HIV proteins may act as superantigens. There is decreased responses to antigens and mitogens. Interleukin-2 and other cytokines are decreased. Infected cells may be killed by HIV-1 specific CD8+ T cells. In HIV-1 infection neutralizing antibodies appear to be ineffective in controlling viral replication and infection.
- Trilineage Hematopoiesis Induced by Low-dose Eltrombopag in a Patient With Fanconi Anemia can be Used as a Bridge to Hematopoietic Stem Cell Transplant. [Journal Article]
- JPJ Pediatr Hematol Oncol 2019; 41(3):229-232
- Fanconi anemia (FA) is an autosomal recessive, progressive bone marrow failure disorder characterized by congenital defects and marked cancer predisposition. Hematopoietic stem cell transplant is the…
Fanconi anemia (FA) is an autosomal recessive, progressive bone marrow failure disorder characterized by congenital defects and marked cancer predisposition. Hematopoietic stem cell transplant is the therapy of choice for FA patients with progressive pancytopenia. These patients receive multiple transfusions for cytopenias. Oxymetholone has been used with variable success to improve cytopenias. Eltrombopag has been shown to induce bilineage or trilineage hematopoiesis in aplastic anemia and patients with myelodysplastic marrow. We report a case of FA where eltrombopag in conjunction with oxymetholone induced trilineage hematopoiesis and eliminated transfusion requirement before transplant, thereby enhancing favorable outcome after hematopoietic stem cell transplant.
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- GeneReviews®: Fanconi Anemia [BOOK]
- BOOKUniversity of Washington, Seattle: Seattle (WA)
- Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, i…
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, gastrointestinal tract, and genitourinary tract – are more common in individuals with FA.