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Bini E.I.,National Institute of Medical science and Nutrition Salvador Zubiran INCMNSZ | Bini E.I.,CONICET | D'Attilio L.,CONICET | Marquina-Castillo B.,National Institute of Medical science and Nutrition Salvador Zubiran INCMNSZ | And 8 more authors.
Tuberculosis | Year: 2015

Background The chronic nature of tuberculosis and the protracted immuno-inflammatory reactions are implied in a series of metabolic and immune-endocrine changes accompanying the disease. We explored components from the hypothalamous-pituitary-gonadal axis and their relationship with cytokines involved in disease immunopathology, in male TB patients. Methods Plasma samples from 36 active untreated pulmonary TB male patients were used to determine TNF-α, IFN-γ, TGF-β, IL-6, cortisol, dehydroepiandrosterone, testosterone, progesterone, estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by ELISA. Healthy controls corresponded to 21 volunteers without contact with TB patients and similar age (40 ± 16,8 years). Testicular histological samples from necropsies of patients dying from TB were immune-stained for IL-1β, TNF-α, IL-6 and IFN-γ. The TM3 mouse Leydig cell line was incubated with recombinants TNF-α, IFN-γ and TGF-β, supernatants were collected and used to measure testosterone by ELISA. Results Patients showed decreased levels of testosterone in presence of high amounts of LH, together with augmented IFN-γ, IL-6 and TGF-β levels. Testicular histological sections showed abundant presence of IL-1β, TNF-α, IL-6 and IFN-γ in interstitial macrophages, Sertoli cells and some spermatogonia. In vitro treatment of Leydig cells with these cytokines led to a remarkable reduction of testosterone production. © 2015 Elsevier Ltd.

Prado-Uribe M.-D.-C.,Mexican Social Security Institute | Soto-Abraham M.-V.,National Institute of Cardiology Dr Ignacio Chavez | Mora-Villalpando C.J.,Mexican Social Security Institute | Gallardo J.M.,Mexican Social Security Institute | And 4 more authors.
Archives of Medical Research | Year: 2013

Background and Aims: Thyroid hormones exert important effects on heart remodeling through mir-208. The process may have a role in myocardial changes in chronic kidney disease where thyroid abnormalities are common. In this study the effect of T4 supplementation on left ventricle (LV) remodeling in 5/6 nephrectomized rats (5/6Nx) was analyzed. Methods: 5/6Nx rats and 5/6Nx under T4 supplementation (5/6Nx+ T4) were compared with control (C) and thyroidectomized (Tx) rats. After 8 weeks of follow-up, LV was analyzed for α-MHC, β-MHC, TGF-β, and mir-208 expression, hydroxyproline content, and myocardial fibrosis. Serum collagenase activity was also analyzed. Results: Heart weight increased in 5/6Nx rats compared to C, which was prevented with T4 supplementation (C, 1.5 ± 0.04; 5/6Nx, 1.8 ± 0.09; 5/6Nx+ T4, 1.6 ± 0.07 g, p <0.05). The same pattern was seen for LV wall thickness, hydroxyproline content, LV fibrosis, andmRNA TGF-β expression (C, 0.47 ± 0.17; 5/6Nx, 10.55 ± 3.4; 5/6Nx+ T4, 3.01 ± 0.52, p <0.01). Tx rats had reduction in heart weight, increased LV wall thickness, and fibrosis. Collagenase activity did not change in any group. mRNA expression of α-, β-MHC, and TGF-β increased in 5/6Nx in comparison to C and 5/6Nx+ T4. Expression of mir-208 decreased in 5/6Nx groups, and levels were restored with T4 supplementation (4.21 ± 0.28, 3.39 ± 0.29, and 4.26 ± 0.37 RU, respectively, p <0.01). Conclusions: Decreased plasma level of thyroid hormones or sensitivity at tissue level observed in chronic kidney disease induced by 5/6Nx has an important effect in heart remodeling processes, some of it related or mediated by mir-208 and TGF-β expression in the heart. © 2013 IMSS.

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