Androgens Contribute to Sex Differences in Myocardial Remodeling under Pressure Overload by a Mechanism Involving TGF-β

Background: In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Methodology/Principal Findings: Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-bs, Smads 2 and 3, collagens, fibronectin, b-myosin heavy chain and a-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson’s trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-bs and the treatment with a neutralizing antibody to TGF-b prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-bs and TGF-b target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-b expression was confirmed i

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cooperation between physiologists and geneticists in the research of causes and mechanisms of genetic hypertension. Two years have elapsed and the genes important for the development of essential hypertension or genetic hypertension of the rat still remain to be identified. In the present article “The phenotypic patterns of essential hypertension are the key to identifying high blood pressure genes “ Paul Korner (2010) has summarized his ideas why defining the phenotype needs to be done adequately. The paper is based on his recent book (Korner 2007) about pathophysiological mechanisms important in essential hypertension and some types of genetic hypertension in rats. In this book he has compared the operation of the circulatory contro

Low-back Pain Disorders as Occupational Diseases in the Czech Republic and 22 European Countries: Comparison of National Systems, Related Diagnoses and Evaluation Criteria

International audienceAim: Low-back pain diseases (LBPD) belong to the most frequent diagnoses determined by general practitioners, and constitute one of the most common reasons for sick leave and permanent disability pension in the Czech Republic and other European countries. Epidemiological studies have shown a statistically significant association between LBPD and certain types of occupational burden. However, in the Czech Republic, LBPD caused by overload and/or whole-body vibrations have not yet been included in the list of occupational diseases. The aim of this study was to collect and compare the systems, criteria and diagnoses used to recognize LBPD as occupational diseases in other European countries.Methods: A questionnaire focused on LBPD was distributed and answered by specialists in occupational diseases in European countries. It included items concerning LBPD in the national list of occupational diseases, and work-related and diagnostic criteria that need to be fulfilled for recognizing LBPD as occupational diseases and possible awarding compensations to the patients.Results: In 13 countries out of the 23 countries studied, LBPD caused by overload can be recognized as occupational, providing that the diagnosis is sufficiently proven and exposure criteria and/or listed occupation are met and duration of exposure is confirmed (Belgium, Denmark, France, Germany, Hungary, Italy, Lithuania, Macedonia, Netherlands, Romania, Slovakia, Sweden, and Switzerland). LBPD due to vibrations can be also recognized as occupational in 14 countries. In 8 countries LBPD are not accepted as occupational unless they are caused by an injury at work. Specific criteria to evaluate occupational exposure of patients with LBPD were set in Belgium, Denmark, France, Germany, Lithuania, Macedonia, Netherlands, and Slovakia. In other countries, the evaluation is done at an individual basis.Conclusions: In practice, the assessment of occupational overload and its contribution to the development of LBPD as well as its inclusion in the compensation system are important for several reasons. Firstly, it may be considered essentially preventable. Secondly, cases with a significant contribution of occupational aetiology may be viewed as occupational diseases for which compensation may be claimed, as it is the case in many European countries. Importantly, inclusion of LBPD in the list of occupational diseases or another system of compensation may be viewed as a preventive measure as it increases the visibility of this problem not only for the workers, but especially for the employers