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Medicina (Kaunas, Lithuania) Nov 2020Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its related precursors. AASs are widely used illicitly by... (Review)
Review
Anabolic-androgenic steroids (AASs) are a group of synthetic molecules derived from testosterone and its related precursors. AASs are widely used illicitly by adolescents and athletes, especially by bodybuilders, both for aesthetic uses and as performance enhancers to increase muscle growth and lean body mass. When used illicitly they can damage health and cause disorders affecting several functions. Sudden cardiac death (SCD) is the most common medical cause of death in athletes. SCD in athletes has also been associated with the use of performance-enhancing drugs. This review aimed to focus on deaths related to AAS abuse to investigate the cardiac pathophysiological mechanism that underlies this type of death, which still needs to be fully investigated. This review was conducted using PubMed Central and Google Scholar databases, until 21 July 2020, using the following key terms: "((Sudden cardiac death) OR (Sudden death)) AND ((androgenic anabolic steroid) OR (androgenic anabolic steroids) OR (anabolic-androgenic steroids) OR (anabolic-androgenic steroid))". Thirteen articles met the inclusion and exclusion criteria, for a total of 33 reported cases. Of the 33 cases, 31 (93.9%) were males while only 2 (61%) were females. Mean age was 29.79 and, among sportsmen, the most represented sports activity was bodybuilding. In all cases there was a history of AAS abuse or a physical phenotype suggesting AAS use; the total usage period was unspecified in most cases. In 24 cases the results of the toxicological analysis were reported. The most detected AASs were nandrolone, testosterone, and stanozolol. The most frequently reported macroscopic alterations were cardiomegaly and left ventricular hypertrophy, while the histological alterations were foci of fibrosis and necrosis of the myocardial tissue. Four principal mechanisms responsible for SCD have been proposed in AAS abusers: the atherogenic model, the thrombosis model, the model of vasospasm induced by the release of nitric oxide, and the direct myocardial injury model. Hypertrophy, fibrosis, and necrosis represent a substrate for arrhythmias, especially when combined with exercise. Indeed, AAS use has been shown to change physiological cardiac remodeling of athletes to pathophysiological cardiac hypertrophy with an increased risk of life-threatening arrhythmias.
Topics: Adolescent; Adult; Anabolic Agents; Athletes; Death, Sudden, Cardiac; Female; Humans; Male; Testosterone; Testosterone Congeners
PubMed: 33158202
DOI: 10.3390/medicina56110587 -
Wounds : a Compendium of Clinical... Jul 2020Compression therapy is the gold standard treatment for venous leg ulcers (VLUs); however, with adjunctive pharmacological therapies and poor patient adherence using... (Review)
Review
Compression therapy is the gold standard treatment for venous leg ulcers (VLUs); however, with adjunctive pharmacological therapies and poor patient adherence using compressive dressings, clinicians are looking to find the advantage in treating VLUs. This literature review focuses on the efficacy of pharmacological agents, quality of life using agents in addition to compression therapy, and cost effectiveness to indicate the best outcomes for pharmacological treatment of VLUs. The following available venotonic, hemorheologic, and fibrinolytic agents were reviewed for oral management in treating VLUs: pentoxifylline, flavonoids (diosmin, hidrosmin, rutosides, and micronized purified flavonoid fraction, Vasculera), Red-Vine-Leaf-Extract AS 195, Ruscus, Ginkgo biloba, Centella asiatica, Pycnogenol (French maritime pine bark), escin/horse chestnut extract, nutritional supplements (ie, zinc and magnesium, glycosaminoglycans [sulodexide], mesoglycans), Axaven, cilostazol, fibrinolytic enhancers (stanozolol and defibrotide), calcium dobesilate, aspirin, antibiotics (antimicrobials, doxycycline, levamisole), diuretics, cinnarizine, naftazone, and benzarone. Venous leg ulcer pharmacological treatment options were searched in the English language from February 2020 to March 2020 using numerous databases and sites, such as PubMed. Drugs used adjunctively with compression therapy that facilitate healing in long-standing or large VLUs include micronized purified flavonoid fraction, pentoxifylline, sulodexide, and mesoglycan.
Topics: Bandages; Fibrinolytic Agents; Humans; Leg Ulcer; Quality of Life; Varicose Ulcer; Wound Healing
PubMed: 33166265
DOI: No ID Found -
Journal of Veterinary Research Jun 2023Because of the activities and effects they induce, hormones are prohibited for use for anabolic purposes in farm animals intended for slaughter, which is regulated in...
INTRODUCTION
Because of the activities and effects they induce, hormones are prohibited for use for anabolic purposes in farm animals intended for slaughter, which is regulated in the European Union by relevant legal provisions. Therefore, there is an obligation to monitor residues of hormones in animals and food of animal origin to ensure consumer safety. A hormone banned but used formerly for fattening cattle, stanozolol, and its metabolite 16β-OH-stanozolol are synthetic compounds that belong to a large group of steroid hormones. This study investigates residues of these compounds in animal urine.
MATERIAL AND METHODS
From 2006-2022, 2,995 livestock urine samples were tested for stanozolol residues in Poland as part of the National Residue Monitoring Programme. A liquid chromatography-tandem mass spectrometry method to determine stanozolol and 16β-OH-stanozolol in animal urine was developed and validated according to the required criteria. Urine sample analysis was based on enzymatic hydrolysis of hormones potentially present in it to the free form, extraction of them from the sample with a mixture of n-hexane and butyl alcohol, purification of an extract on an NH2 amine column and finally, instrumental detection.
RESULTS
The apparent recovery and precision parameters of the developed method were in line with the established criteria, while its decision limits CCα and detection capabilities CCβ were lower than the recommended concentration for analytical purposes set at 2 μg L (valid until December 15, 2022; currently set as 0.5 μg L).
CONCLUSION
All examined samples were compliant with the evaluation criteria.
PubMed: 38143825
DOI: 10.2478/jvetres-2023-0030 -
BMJ Clinical Evidence Dec 2011Leg ulcers usually occur secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders. Between... (Review)
Review
INTRODUCTION
Leg ulcers usually occur secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders. Between 1.5 and 3.0/1000 people have active leg ulcers. Prevalence increases with age to about 20/1000 in people aged over 80 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of standard treatments, adjuvant treatments, and organisational interventions for venous leg ulcers? What are the effects of advice about self-help interventions in people receiving usual care for venous leg ulcers? What are the effects of interventions to prevent recurrence of venous leg ulcers? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 101 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: compression bandages and stockings, cultured allogenic (single or bilayer) skin replacement, debriding agents, dressings (cellulose, collagen, film, foam, hyaluronic acid-derived, semi-occlusive alginate), hydrocolloid (occlusive) dressings in the presence of compression, intermittent pneumatic compression, intravenous prostaglandin E1, larval therapy, laser treatment (low-level), leg ulcer clinics, multilayer elastic system, multilayer elastomeric (or non-elastomeric) high-compression regimens or bandages, oral treatments (aspirin, flavonoids, pentoxifylline, rutosides, stanozolol, sulodexide, thromboxane alpha(2) antagonists, zinc), peri-ulcer injection of granulocyte-macrophage colony-stimulating factor, self-help (advice to elevate leg, to keep leg active, to modify diet, to stop smoking, to reduce weight), short-stretch bandages, single-layer non-elastic system, skin grafting, superficial vein surgery, systemic mesoglycan, therapeutic ultrasound, and topical treatments (antimicrobial agents, autologous platelet lysate, calcitonin gene-related peptide plus vasoactive intestinal polypeptide, freeze-dried keratinocyte lysate, mesoglycan, negative pressure, recombinant keratinocyte growth factor, platelet-derived growth factor).
Topics: Bandages; Debridement; Humans; Leg Ulcer; Low-Level Light Therapy; Occlusive Dressings; Ultrasonic Therapy; Varicose Ulcer; Wound Healing
PubMed: 22189344
DOI: No ID Found -
Allergologie Select 2018The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using... (Review)
Review
The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using prophylactic treatment. For treating acute attacks, plasma-derived C1 inhibitor (C1-INH) concentrates, a bradykinin B2 receptor antagonist, and a recombinant human C1-INH are available in Europe. In the United States, a plasma-derived C1-INH concentrate, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor were approved for the treatment of acute attacks. Fresh frozen plasma is also available for treating acute attacks. Short-term prophylactic treatment focuses on C1-INH and attenuated androgens. Long-term prophylactic treatments include attenuated androgens such as danazol, stanozolol, and oxandrolone, antifibrinolytics, and a plasma-derived C1-INH concentrate. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are admitted for self-administration and home therapy. So the number of management options increased considerably within the last few years thus helping to diminish the burden of HAE.
PubMed: 31826031
DOI: 10.5414/ALX1561E -
Neuroscience and Biobehavioral Reviews May 2019Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk... (Review)
Review
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.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Androgens; Animals; Brain; Dementia; Humans; Hypogonadism; Oxidative Stress; Phosphorylation; Risk Factors; Testosterone Congeners; tau Proteins
PubMed: 30817935
DOI: 10.1016/j.neubiorev.2019.02.014 -
BMJ Clinical Evidence Sep 2008Leg ulcers usually occur secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders. Between... (Review)
Review
INTRODUCTION
Leg ulcers usually occur secondary to venous reflux or obstruction, but 20% of people with leg ulcers have arterial disease, with or without venous disorders. Between 1.5 and 3.0/1000 people have active leg ulcers. Prevalence increases with age to about 20/1000 in people aged over 80 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of standard treatments, adjuvant treatments, and organisational interventions for venous leg ulcers? What are the effects of interventions to prevent recurrence of venous leg ulcers? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 80 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: compression bandages and stockings, cultured allogenic (single or bilayer) skin replacement, debriding agents, dressings (cellulose, collagen, film, foam, hyaluronic acid-derived, semi-occlusive alginate), hydrocolloid (occlusive) dressings in the presence of compression, intermittent pneumatic compression, intravenous prostaglandin E1, larval therapy, laser treatment (low-level), leg ulcer clinics, multilayer elastic system, multilayer elastomeric (or non-elastomeric) high-compression regimens or bandages, oral treatments (aspirin, flavonoids, pentoxifylline, rutosides, stanozolol, sulodexide, thromboxane alpha(2) antagonists, zinc), peri-ulcer injection of granulocyte-macrophage colony-stimulating factor, short-stretch bandages, single-layer non-elastic system, skin grafting, superficial vein surgery, systemic mesoglycan, therapeutic ultrasound, self-help (advice to elevate leg, advice to keep leg active, advice to modify diet, advice to stop smoking, advice to reduce weight), and topical treatments (antimicrobial agents, autologous platelet lysate, calcitonin gene-related peptide plus vasoactive intestinal polypeptide, freeze-dried keratinocyte lysate, mesoglycan, negative-pressure recombinant keratinocyte growth factor, platelet-derived growth factor).
Topics: Bandages; Debridement; Humans; Leg Ulcer; Occlusive Dressings; Ultrasonic Therapy; Varicose Ulcer; Wound Healing
PubMed: 19445798
DOI: No ID Found -
Analytical and Bioanalytical Chemistry Feb 2023Potential scenarios as to the origin of minute amounts of banned substances detected in doping control samples have been a much-discussed problem in anti-doping analysis...
Investigations into the concentration and metabolite profiles of stanozolol and LGD-4033 in blood plasma and seminal fluid using liquid chromatography high-resolution mass spectrometry.
Potential scenarios as to the origin of minute amounts of banned substances detected in doping control samples have been a much-discussed problem in anti-doping analysis in recent years. One such debated scenario has been the contamination of female athletes' urine with ejaculate containing doping agents and/or their metabolites. The aim of this work was to obtain complementary information on whether relevant concentration ranges of doping substances are excreted into the ejaculate and which metabolites can be detected in the seminal fluid (sf) and corresponding blood plasma (bp) samples. A method was established to study the concentration and metabolite profiles of stanozolol and LGD-4033-substances listed under anabolic substances (S1) on the World Anti-Doping Agency's Prohibited List-in bp and sf using liquid chromatography high-resolution mass spectrometry (LC-HRMS). For sf and bp, methods for detecting minute amounts of these substances were developed and tested for specificity, recovery, linearity, precision, and reliability. Subsequently, sf and bp samples from an animal administration study, where a boar orally received stanozolol at 0.33 mg/kg and LGD-4033 at 0.11 mg/kg, were measured. The developed assays proved appropriate for the detection of the target substances in both matrices with detection limits between 10 and 40 pg/mL for the unmetabolized drugs in sf and bp, allowing to estimate the concentration of stanozolol in bp (0.02-0.40 ng/mL) and in sf (0.01-0.25 ng/mL) as well as of LGD-4033 in bp (0.21-2.00 ng/mL) and in sf (0.03-0.68 ng/mL) post-administration. In addition, metabolites resulting from different metabolic pathways were identified in sf and bp, with sf resembling a composite of the metabolic profile of bp and urine.
Topics: Male; Animals; Female; Swine; Stanozolol; Reproducibility of Results; Tandem Mass Spectrometry; Substance Abuse Detection; Chromatography, Liquid; Plasma; Doping in Sports; Anabolic Agents
PubMed: 36441233
DOI: 10.1007/s00216-022-04456-y -
Frontiers in Medicine 2021Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Bone marrow mononuclear cells from 10...
Stanozolol and danazol are widely used in the treatment of aplastic anemia; however, their mechanisms of action are unclear. Bone marrow mononuclear cells from 10 patients newly diagnosed with aplastic anemia and 10 healthy volunteers were collected and cultured together with stanozolol, danazol, or blank control separately for marrow colony assays. K562 cell lines that had been incubated with stanozolol, danazol, or blank control were tested for erythroid or megakaryocytic differentiation. Meanwhile, CB6F1/Crl mice were injected with 1 × 10 C57BL/6 donor-originated lymphocytes after irradiation with 5 Gy total body irradiation to establish a model for immune-mediated bone marrow failure (aplastic anemia mouse model). Mice with aplastic anemia were treated with cyclosporin A monotherapy, cyclosporin A in combination with stanozolol, and cyclosporin A in combination with danazol for 30 days. Peripheral blood cell counts once a week and bone marrow colony assays at the end of 1 month were performed. The proportion of T cell subsets, level of inflammatory factors, erythropoietin, and thrombopoietin were detected before and after treatment. The levels of erythropoietin receptors on bone marrow mononuclear cells after treatment were tested using western blotting. In the experiments, the number of burst-forming units-erythroid; colony-forming units-granulocyte and macrophage; and colony-forming units-granulocyte, erythrocyte, monocyte, and megakaryocyte in the patients with aplastic anemia were significantly lower than that in the normal controls ( < 0.05). However, the number of colonies and mean fluorescence intensity of CD235a or CD41 expression in the harvested cultured cells were not significantly different among the different treatment groups in the patients with aplastic anemia, normal controls, and K562 cell lines. These results show that stanozolol and danazol produce no direct hematopoiesis-stimulating effects on progenitor cells. In the experiment, the mice with aplastic anemia treated with cyclosporin A and danazol exhibited the most rapid recovery of platelet; the platelet count returned to normal levels after 3 weeks of treatment, which was at least 1 week earlier than in the other groups. In contrast, mice treated with cyclosporin A and stanozolol exhibited the highest hemoglobin level at the end of treatment ( < 0.05). Bone marrow colony assays at 30 days showed that the number of burst-forming units-erythroid was the highest in mice treated with cyclosporin A and stanozolol, while the number of colony-forming units-granulocyte and macrophage was the highest in those treated with cyclosporin A and danazol. Compared to cyclosporin A monotherapy, additional stanozolol and danazol can both increase the level of regulatory T cells and upregulate interleukin-10, inhibiting the expression of tumor necrosis factor-α ( < 0.05). However, IL-2 was more effectively reduced by danazol than by stanozolol ( < 0.05). The cyclosporin A- and stanozolol-treated mice showed higher serum erythropoietin (corrected by hemoglobin level) and higher erythropoietin receptor levels in bone marrow mononuclear cells than the other groups ( < 0.05). Neither stanozolol nor danazol directly stimulated hematopoiesis . However, , stanozolol may exhibit an advantage in improving erythropoiesis, while danazol may induce stronger effects on platelets. Both danazol and stanozolol exhibited immunosuppressive roles. Stanozolol could enhance the secretion of erythropoietin and expression of erythropoietin receptor in bone marrow mononuclear cells.
PubMed: 34124083
DOI: 10.3389/fmed.2021.615195 -
BMC Veterinary Research Mar 2018Intra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring...
BACKGROUND
Intra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA. However, there is limited evidence on the anti-inflammatory and modulatory properties of stanozolol on articular tissues. The objective of the current study was to evaluate the effects of stanozolol on chondrocyte viability and gene expression in normal equine chondrocytes and an inflammatory in vitro system of OA (interleukin-1β (IL-1β) treated chondrocytes).
RESULTS
Chondrocytes from normal metacarpophalangeal joints of skeletally mature horses were exposed to four treatment groups: (1) media only (2) media+IL-1β (3) media+IL-1β + stanozolol (4) media+stanozolol. Following exposure, chondrocyte viability and the expression of catabolic, anabolic and structural genes were determined. General linear models with Dunnet's comparisons with Bonferroni's adjustment were performed. Cell viability was similar in all groups. Stanozolol treatment reduced gene expression of MMP-13, MMP-1, IL-6 and COX-2 in both normal and IL-1β treated chondrocytes. Stanozolol treatment reduced ADAMTS4 gene expression in normal chondrocytes. Stanozolol reduced the expression of COL2A1.
CONCLUSIONS
The current study demonstrates stanozolol has chondroprotective effects through downregulation of genes for pro-inflammatory/catabolic cytokines and enzymes associated with OA. However, there is no evidence of increased cartilage stimulation through upregulation of the anabolic and structural genes tested.
Topics: Animals; Anti-Inflammatory Agents; Chondrocytes; Horse Diseases; Horses; In Vitro Techniques; Interleukin-1beta; Lameness, Animal; Osteoarthritis; Stanozolol
PubMed: 29554899
DOI: 10.1186/s12917-018-1426-z