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Background: One factor that may negatively impact male reproductive health is the illegal use of testosterone and anabolic-androgenic steroids. This study aimed to evaluate the prevalence of testosterone use in recreational athletes, as well as factors associated with its use, and to determine the profile of a person using testosterone. Methods: A cross-sectional analysis of data from an anonymous, online questionnaire of men recruited from gyms, randomly selected in Wroclaw, Poland, has been performed. The minimal sample size was evaluated with the univariate logistic regression model. The association between testosterone use and other factors was also evaluated with the univariate logistic regression model. Results: A total of 35% of respondents used testosterone. The main purposes of testosterone use were the improvement of training effects and the improvement of body shape. The respondents most likely to use testosterone and other anabolic-androgenic steroids were men aged 26-35, whose earnings were at the level of the middle class or higher, who were married, had children, had training experience of at least 6 months, exercised at least once a week, took part in weightlifting competitions, were managers in a corporation or enterprise, or were self-employed. Most of the people using testosterone had self-treated side effects. Conclusions: The profile of the person most likely to use testosterone corresponds to the characteristics of men in optimal socio-demographic conditions for reproduction. These results indicate that this is a significant social problem that may impact male reproductive health.
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This narrative review provides an overview of scientific studies on dietary supplements that may affect circulating testosterone (T) levels to explore which substances are scientifically proven to increase T concentration. We also review the scientific literature for their potential mechanisms and laboratory test changes triggered by their use. Based on the analysis of existing data on substances used to increase endogenous T levels, especially double-blind placebo-controlled randomized clinical trials, we selected 2 herbal extracts with the best documented positive effects on T levels, Withania somnifera root and root extracts/leaves and seed extracts of Trigonella foenum-graecum. Although these substances have different postulated mechanisms of action, both significantly increase T levels in men. Withania somnifera may inhibit the effects of cortisol and prolactin on the hypothalamic-pituitary-gonadal axis and directly affect the hypothalamus. Trigonella foenum-graecum seeds contain the active substance diosgenin, which is a precursor for sex hormone synthesis in gonads.
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Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis.
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The present study investigated whether Rho-associated protein kinase (RhoA/ROCK) signaling pathway inhibitor simvastatin inhibits matrix metalloproteinase 2 (MMP-2) activity in a rat ischemia-reperfusion injury (I/Ri) model by inhibiting the RhoA/ROCK pathway and reducing MMP-2 mRNA levels. Isolated rat hearts were subjected to aerobic perfusion or I/Ri control. The effect of simvastatin was assessed in hearts subjected to I/Ri. We determined cardiac mechanical function, the content of RhoA, phosphorylated myosin light chain subunit 1 (phospho-MYL9), troponin I, MMP-2, and MMP-2 mRNA in the heart homogenates, as well as MMP-2 activity in heart tissue. We showed that treatment with simvastatin caused improvement in the contractile function of the heart subjected to I/Ri which was accompanied by a decrease of MMP-2 activity in heart tissue along with inhibition of RhoA pathway, expressed in a reduction in both RhoA and its downstream product-phosphorylated myosin light chain (phospho-MYL9) in hearts treated with simvastatin. MMP-2 inactivation is not due to inhibition of MMP-2 m-RNA synthesis caused by inhibition of RhoA/ROCK pathway and is due, at least in part, to the direct drug action. The protective effect of simvastatin on systolic function in the acute ischemia-reperfusion model does not appear to be related to reduced MMP-2 activation, but other mechanisms related with the inhibition RhoA/ROCK pathway.
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Metaloproteinase 2 da Matriz , Traumatismo por Reperfusão , Sinvastatina , Quinases Associadas a rho , Animais , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Cadeias Leves de Miosina/metabolismo , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Sinvastatina/farmacologia , Troponina I/metabolismo , Proteínas rho de Ligação ao GTP , Quinases Associadas a rho/metabolismoRESUMO
Matrix metalloproteinase 2 (MMP-2) is activated in hearts upon ischemia-reperfusion (IR) injury and cleaves sarcomeric proteins. It was shown that carvedilol and nebivolol reduced the activity of different MMPs. Hence, we hypothesized that they could reduce MMPs activation in myocytes, and therefore, protect against cardiac contractile dysfunction related with IR injury. Isolated rat hearts were subjected to either control aerobic perfusion or IR injury: 25 min of aerobic perfusion, followed by 20 min global, no-flow ischemia, and reperfusion for 30 min. The effects of carvedilol, nebivolol, or metoprolol were evaluated in hearts subjected to IR injury. Cardiac mechanical function and MMP-2 activity in the heart homogenates and coronary effluent were assessed along with troponin I content in the former. Only carvedilol improved the recovery of mechanical function at the end of reperfusion compared to IR injury hearts. IR injury induced the activation and release of MMP-2 into the coronary effluent during reperfusion. MMP-2 activity in the coronary effluent increased in the IR injury group and this was prevented by carvedilol. Troponin I levels decreased by 73% in IR hearts and this was abolished by carvedilol. Conclusions: These data suggest that the cardioprotective effect of carvedilol in myocardial IR injury may be mediated by inhibiting MMP-2 activation.
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BACKGROUND: Acute myocarditis often progresses to heart failure because there is no effective, etiology-targeted therapy of this disease. Simvastatin has been shown to be cardioprotective by decreasing matrix metalloproteinases' (MMPs) activity. The study was designed to determine whether simvastatin inhibits MMPs activity, decreases the severity of inflammation and contractile dysfunction of the heart in experimental autoimmune myocarditis (EAM). METHODS: Simvastatin (3 or 30 mg/kg/day) was given to experimental rats with EAM by gastric gavage for 21 days. Then transthoracic echocardiography was performed, MMPs activity and troponin I level were determined and tissue samples were assessed under a light and transmission electron microscope. RESULTS: Hearts treated with simvastatin did not show left ventricular enlargement. As a result of EAM, there was an enhanced activation of MMP-9, which was significantly reduced in the high-dose simvastatin group compared to the low-dose group. It was accompanied by prevention of myofilaments degradation and reduction of severity of inflammation. CONCLUSIONS: The cardioprotective effects of simvastatin in the acute phase of EAM are, at least in part, due to its ability to decrease MMP-9 activity and subsequent decline in myofilaments degradation and suppression of inflammation. These effects were achieved in doses equivalent to therapeutic doses in humans.
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Inflamação/tratamento farmacológico , Metaloproteases/genética , Miocardite/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Cardiotônicos/farmacologia , Ecocardiografia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Metaloproteases/antagonistas & inibidores , Modelos Animais , Miocardite/genética , Miocardite/imunologia , Miocardite/patologia , Ratos , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/prevenção & controleRESUMO
The use of specific medicine up to several months before a doping control is not be reported on the doping control form, while the drug could then still be detectable in urine in case of a very slow elimination. It may lead to a positive test result. For example, dorzolamide, a carbonic anhydrase inhibitor for topical ophthalmic application, has a very slow elimination rate via the renal route (half-life > 4 months). This substance can be a source of unintended anti-doping rule violations.
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Inibidores da Anidrase Carbônica/administração & dosagem , Dopagem Esportivo/prevenção & controle , Sulfonamidas/administração & dosagem , Tiofenos/administração & dosagem , Administração Oftálmica , Adulto , Inibidores da Anidrase Carbônica/farmacocinética , Feminino , Meia-Vida , Humanos , Sulfonamidas/farmacocinética , Tiofenos/farmacocinética , Fatores de TempoRESUMO
Not required for Clinical Vignette.
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Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , HumanosRESUMO
AIMS: Acute myocarditis is a potentially lethal inflammatory heart disease that frequently precedes the development of dilated cardiomyopathy and subsequent heart failure. At present, there is no effective standardized therapy for acute myocarditis, besides the optimal care of heart failure and arrhythmias in accordance with evidence-based guidelines and specific etiology-driven therapy for infectious myocarditis. Carvedilol has been shown to be cardioprotective by reducing cardiac pro-inflammatory cytokines present in oxidative stress in certain heart diseases. However, effects of carvedilol administration in acute myocarditis with its impact on matrix metalloproteinases' (MMPs) activation have not been elucidated. METHODS AND RESULTS: Carvedilol in 3 doses (2, 10, and 30 mg/kg) was given daily to 3 study groups of rats (n = 8) with experimental autoimmune myocarditis by gastric gavage for 3 weeks. In comparison to untreated rats (n = 8) with induced myocarditis, carvedilol significantly prevented the left ventricle enlargement and/or systolic dysfunction depending on the dose in study groups. Performed zymography showed enhanced MMP-2 activity in untreated rats, while carvedilol administration reduced alterations. This was accompanied by prevention of troponin I release and myofilaments degradation in cardiac muscle tissue. Additionally, severe inflammatory cell infiltration was detected in the nontreated group. Carvedilol in all doses tested, had no impact on severity of inflammation. The severity of inflammation did not differ between study groups and in relation to the untreated group. CONCLUSIONS: The protective effects of carvedilol on heart function observed in the acute phase of experimental autoimmune myocarditis seem to be associated with its ability to decrease MMP-2 activity and subsequently prevent degradation of myofilaments and release of troponin I while not related to suppression of inflammation.
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Doenças Autoimunes/tratamento farmacológico , Carbazóis/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Miocardite/tratamento farmacológico , Propanolaminas/farmacologia , Doença Aguda , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/farmacologia , Animais , Doenças Autoimunes/patologia , Carbazóis/administração & dosagem , Carvedilol , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Inflamação/tratamento farmacológico , Inflamação/patologia , Miocardite/patologia , Propanolaminas/administração & dosagem , Ratos , Ratos Endogâmicos Lew , Índice de Gravidade de DoençaRESUMO
In addition to different injuries, infections are the most common reason for giving up training altogether or reducing its volume and intensity, as well as a lack of opportunities to participate in sports competitions. Nowadays, a slow but constant re-emergence of pertussis, especially among teenagers and young adults, including athletes, can be observed. This paper describes an outbreak of pertussis among professional Polish shooters, focusing on the transmission of Bordetella pertussis infection between members of the national team, its influence on performance capacity and adverse event analysis. From 9 June, 2015 to 31 July, 2015, a total of 4 confirmed and suspected cases of pertussis were reported among members of the Polish Sport Shooting National Team, their relatives and acquaintances. Pertussis significantly decreased exercise performance of the first athlete, a 35-year-old woman, interrupted her training, and finally resulted in failure to win a medal or quota place. Pertussis also significantly decreased performance of the second athlete, a 25-year-old shooter. The other cases emerged in their families. Whooping cough is a real threat to athletes and should be prevented. Preventive measures include appropriate immunization, constant medical supervision, as well as early isolation, diagnostic tests and treatment of all infected sport team members. Regular administration of booster doses of the acellular pertussis vaccine (Tdpa) every 5 years seems reasonable.
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OBJECTIVE: To investigate whether alterations in the phosphorylation status of matrix metalloproteinase 2 (MMP-2) in the heart may be protective in the setting of ischaemia-reperfusion (IR) injury. DESIGN: In-vitro heart function and biochemical research study. SETTING: University basic science laboratory. INTERVENTIONS: Male Sprague-Dawley rats, weighing 250-350 g. Isolated rat hearts were perfused at constant pressure either aerobically for 75 min or subjected to 20 min of global, no-flow ischaemia followed by 30 min of reperfusion. MAIN OUTCOME MEASURES: Heart mechanical function, MMP-2 activity and troponin I levels. RESULTS: The serine/threonine phosphatase inhibitor okadaic acid (OA) improved the recovery of mechanical function compared with control IR hearts and prevented the loss of troponin I. OA significantly reduced protein phosphatase 2A, but not protein phosphatase 1, activity in perfused hearts. IR stimulated the activation and release of MMP-2 into the coronary effluent in the first 2 min of reperfusion. This was accompanied by a decrease in the remaining activity and protein level of MMP-2 in heart tissue determined at the end of the reperfusion. OA did not alter the IR-stimulated release of MMP-2 into the coronary effluent, but reduced the decrease in MMP-2 in reperfused hearts. The immunoprecipitation of heart homogenates using anti-phosphoserine antibody showed that MMP-2 is phosphorylated. The dephosphorylation of MMP-2 by alkaline phosphatase treatment of homogenates prepared from IR hearts treated with OA significantly increased MMP-2 activity. CONCLUSIONS: These results suggest that the phosphorylation status of MMP-2 is important in its contribution to myocardial IR injury.
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Metaloproteinase 2 da Matriz/metabolismo , Traumatismo por Reperfusão Miocárdica/enzimologia , Fosfatase Alcalina/farmacologia , Animais , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Coração/efeitos dos fármacos , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/enzimologia , Ácido Okadáico/farmacologia , Ácido Okadáico/uso terapêutico , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 1/antagonistas & inibidores , Proteína Fosfatase 1/metabolismo , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/metabolismo , Ratos , Ratos Sprague-Dawley , Troponina I/metabolismoRESUMO
The isolated perfused mammalian heart preparation was established in 1897 by Oscar Langendorff. The method was developed on the basis of the isolated perfused frog heart established by Elias Cyon at the Carl Ludwig Institute of Physiology in Leipzig, Germany in 1866. Observations made using both methods at the end of the 19th and at the beginning of the 20th century led to important discoveries, forming the basis for our understanding of heart physiology. This included the role of temperature, oxygen and calcium ions for heart contractile function, the origin of cardiac electrical activity in the atrium, the negative chronotropic effect of vagus stimulation and the chemical transmission of impulses in the vagus nerve by acetylcholine. Langendorff himself demonstrated that the heart receives its nutrients and oxygen from blood via the coronary arteries and that cardiac mechanical function is reflected by changes in the coronary circulation. The method underwent many modifications but its general principle remains the same today. Blood, or more commonly crystalloid perfusates, are delivered into the heart through a cannula inserted in the ascending aorta, either at constant pressure or constant flow. Retrograde flow in the aorta closes the leaflets of the aortic valve and as a consequence, the entire perfusate enters the coronary arteries via the ostia at the aortic root. After passing through the coronary circulation the perfusate drains into the right atrium via the coronary sinus. The simplicity of the isolated mammalian heart preparation, the broad spectrum of measurements which can be done using this method, its high reproducibility and relatively low cost make it a very useful tool in modern cardiovascular and pharmacological research, in spite of a few shortcomings. In the last decade the method has brought many important advances in many areas including ischemia-reperfusion injury, cell-based therapy and donor heart preservation for transplant.
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Cardiologia/história , Coração/fisiologia , Mamíferos/fisiologia , Modelos Cardiovasculares , Perfusão/métodos , Animais , Circulação Coronária/fisiologia , História do Século XIX , História do Século XX , História do Século XXI , Técnicas In Vitro , Contração Miocárdica/fisiologiaRESUMO
Arterial hypertension may result from renal artery stenosis. In this type of hypertension renin-angiotensin-aldosterone system is activated and patients often produce signs of hyperaldosteronism. It must be distinguished from primary hyperaldosteronism in order to chose a proper therapy. In this paper we describe a case of a 65-years-old man with severe arterial hypertension, which was difficult to control pharmacologically. The patient revealed symptoms which suggested primary hyperaldosteronism (except normal plasma renin activity). Only imaging techniques allowed diagnose of renal artery stenosis and carry out successful percutaneous angioplasty of renal artery.