Expression of the TGF-beta1 system in human testicular pathologies

In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO) and hypospermatogenesis (H) are commonly found. In these pathologies, Leydig cell hyperplasia (LCH) is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5), and the co-receptor endoglin in human biopsies from patients with idiopathic infertilityFil: Gonzalez, Candela Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Matzkin, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Frungieri, Monica Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Terradas, Claudio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos"Carlos G. Durand"; Argentina. Instituto Médico IPREFER; ArgentinaFil: Ponzio, Roberto . Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Puigdomenech, Elisa. Instituto Médico IPREFER;; ArgentinaFil: Levalle, Oscar. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos"Carlos G. Durand"; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Gonzalez Calvar, Silvia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Altered expression of aromatase, estrogen receptors and progesterone receptors in human leydig cell hyperplasia

Testicular function is regulated by pituitary hormones and also by paracrine and autocrine factors. A number of reports have pointed out the importance of estrogens and progesterone in male reproductive tract. Recently, we have reported in testicular biopsies from men with Sertoli Cell Only Syndrome (SCO) or Hypospermatogenesis (H) with Leydig cell hyperplasia (LCH) an increase in the expression of the TGFB1 and its receptors ALK1 and endoglin, which are involved in the proliferation of Leydig cells. The aim of the present work was to analyze the expression of aromatase, estrogen and progesterone receptors (ERs, PR) in pathological testicular biopsies with SCO or H with and without LCH. The ERs and CYP19 proteins were detected in the Leydig cells from all pathological biopsies analyzed. Biopsies with SCO or H with LCH showed an increment in the immunostaining of CYP19 and ERs in the Leydig cells respect to biopsies without LCH. The gene expression of CYP19 was increased in SCO or H biopsies with LCH respect to SCO and H biopsies without LCH. PR was localized in Leydig cells and showed a significant increment in biopsies with LCH respect from biopsies without LCH. The gene expression of both PRA and PRB was increased in biopsies with LCH respect to biopsies without LCH. In concussion, alterations in the gene expression of aromatase, ERs, and PR and the likely interactions of these systems with locally produced factors such as growth factors and cytokines, might lead to Leydig cell proliferation in testicular pathology.Fil: Gonzalez, Candela Rocio. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Inserra, Pablo Ignacio Felipe. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Terradas, Claudio. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Carlos Durand; ArgentinaFil: Ponzio, Roberto Oscar. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Puigdomenech, Elisa. No especifíca;Fil: Levalle, Oscar. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Carlos G. Durand"; ArgentinaFil: Vitullo, Alfredo Daniel. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Calandra, Ricardo Saul. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gonzalez de Calvar, Silvia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Vídeos agregam valor ao trabalho do professor de ciências da saúde

O trabalho apresenta exemplos de vídeos produzidos para o ensino médico. Justifica o uso de vídeos nesta área para apoiar a visualização de fenômenos cuja observação in loco depende de situações não reprodutíveis - como cirurgias ou dissecações - ou exigem alta capacidade de abstração dos alunos, no caso de fenômenos microscópicos, químicos, ou moleculares. Defende que os vídeos não induzem à passividade dos alunos,, se forem produzidos de forma criativa e coerente, explorando os recursos da linguagem de vídeo associados ao potencial da tecnologia digital. Os exemplos também apresentam recursos de produção e edição, salientando-se a intenção didática ou pedagógica que gerou a escolha por um ou outro recurso. Sugere que vídeos educacionais contribuem para a aprendizagem dos alunos e agregam valor ao trabalho do professor, porque apóiam arepresentação e a exposição do conhecimento e podem constituir objeto de estudo, pesquisa e profissionalização de equipes de produção, em todas as instituições que pretendematualizar sua base tecnológica, segundo necessidades impostas pelo Séc. XXI

Histidine decarboxylase inhibitors attenuate the pro angiogenic activity of Leydig tumor cells: Potential neoadjuvant therapy for the treatment of leydigiomas?

Los tumores de células de Leydig (TCL) son tumores endócrinos del intersticio testicular, cuya incidencia se encuentra en aumento. Los síntomas incluyen feminización o virilización en pacientes prepuberales, y pérdida de libido, disfunción eréctil, infertilidad y/o ginecomastia en adultos. Si bien son usualmente benignos, cuando malignizan en adultos no responden a radio y quimioterapia. Múltiples trabajos han reportado que la histidina decarboxilasa (HDC), enzima que cataliza la conversión de L-histidina en histamina (HA), tiene un rol importante en el desarrollo de tumores. A su vez, en nuestro laboratorio demostramos que la HA induce la proliferación de células de Leydig tumorales (CLT) murinas, mientras que la inhibición de HDC disminuye su proliferación y capacidad esteroidogénica. Además, observamos elevada expresión de HDC en TCL pediátricos vs. controles de distintos estadios de madurez sexual; y se ha descrito que ratones knock out para HDC poseen una angiogénesis incompleta. Para evaluar el rol de HDC en la modulación de la angiogénesis se empleó la línea de CLT de rata R2C, principal modelo utilizado en estudios de Leydigioma. También se realizaron estudios en TCL pediátricos. Los medios condicionados por las CLT R2C estimularon la angiogénesis tanto in vitro como in vivo (empleando HUVEC y analizando el grado de vascularización de membranas corioalantoideas de codorniz, respectivamente). El efecto in vitro se revirtió al tratar previamente las CLT R2C con α-metil-DL-histidinadihidrocloruro, inhibidor específico de HDC. A su vez, tanto la HA como los medios condicionados provenientes de TCL pediátricos, produjeron un aumento en la proliferación de las HUVEC. Nuestros resultados sugieren que las CLT producen HA y otros factores proangiogénicos, y que la inhibición selectiva de HDC atenúa la capacidad proangiogénica de las CLT. En base a estos resultados y evidencias previas del laboratorio, inhibidores específicos de HDC podrían ser utilizados como potencial terapia neoadyuvante en TCL.Leydig Cell tumors (LCT) are a rare group of endocrine tumors in the testicular interstitium. Between 1 and 3% of testicular malignances in adults and 4% in prepubertal children belong to LCT. An increasing incidence of this type of neoplasia has been reported recently all around the world. Particularly, a strong relationship between LCT and the use of anabolic steroids (which are commonly used nowadays) has been reported recently. In prepubertal boys, symptoms include feminization or virilization, depending on the major circulating steroid (estradiol or testosterone respectively). Adult patients show loss of libido, penile dysfunction, infertility and/or gynecomastia. Although the etiology still is unknown, several studies indicate that tumoral Leydig cells have an excessive production of insulin-like growth factor (IGF-1), as well as aromatase (CYP19) overexpression, which causes an enormous amount of estrogens (particularly estradiol, E2), and both factors play an important role in tumorigenesis. While usually benign, when LCT became malignant in adults they respond poorly to radio and chemotherapy. Likewise, it has been reported that both therapies increase the incidence of several tumors. All these data imply the need of new therapeutic targets to avoid the chirurgical dissection of the testes and the consequences of the hormonal therapies associated, which implicate not only the loss in reproductive function, but also psychological disorders. Several publications have reported that histidine decarboxylase (HDC), the only enzyme capable of catalyzing the conversion from L-histidine to histamine (HA) in mammals, has an important role in the development of several types of tumors, such as colorectal, breast and melanoma. At the same time, in our laboratory we have reported that HA induces cell proliferation of murine Leydig cells, and complementary, this cell proliferation decreases when inhibiting selectively HDC, as well as steroid synthesis (progesterone and E2). Also, we observed a higher expression of HDC in pediatric LCT (n = 3) than normal controls corresponding to different stages of sexual maturation (n = 9). It has been described that HDC knock out mice have an incomplete angiogenesis, and also that MA-10 Leydig cells HDC expression correlates with vascular endothelial growth factor (VEGF). The aim of this study is to improve our knowledge about the role of HDC in LCT biology, particularly, the angiogenesis modulation. We used the R2C Leydig cell line, the most used model for in vitro studies of Leydigioma, because it overexpresses CYP19 and constitutively produces high levels of IGF-1 and E2, as well as human LCT. R2C and pediatric LCT angiogenic capability was evaluated in vitro by measuring proliferation of human umbilical vein endothelial cells (HUVEC). In addition, we verified R2C cells angiogenic capability in vivo, using quail embryo vasculature (chorioallantoic membrane assay). Both models have been validated for the study of angiogenesis. Conditioned medium obtained from R2C cell culture stimulated angiogenesis in vitro (p <0.001) as well as in vivo (p <0.001). The in vitro effect was reverted with a previous treatment on the R2C cell culture using α-methyl-DL-histidine hydrochloride (α-MHD, 10 µM), a specific HDC activity inhibitor (p <0.001). Finally, human conditioned medium from pediatric LCT increased HUVEC proliferation (p <0.01). In the same way, the analyzed patients showed higher testosterone and estradiol levels than normal serum concentrations, which was in concordance to phenotypical features observed in presence of LCT. Our results indicate that tumoral Leydig cells (TLC) produce HA, as well as other angiogenic factors, and it could be stimulating the vascular endothelium. The selective inhibition of HDC attenuates the pro-angiogenic capability in TLC. Considering all these results and previous observations of our laboratory, specific inhibitors of HDC could be used, in the future, as a potential therapeutic target for the treatment of LCT.Fil: Abiuso, Adriana María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Varela, María Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Haro Durand, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Besio Moreno, Marcos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ponzio, Roberto Oscar. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Rivarola, Marco Aurelio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belgorosky, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Berensztein, Esperanza Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Endocrinología; ArgentinaFil: Mondillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Análise interpretativa das dermatoses mais frequentes em Porto Alegre - Rio Grande do Sul - Brasil

Análise interpretativa das dermatoses mais frequentes em Porto Alegre - Rio Grande do Sul - Brasi

Consenso em criptococose - 2008

Univ Sao Paulo, Fac Med, Div Clin Mol Infecciosas, Hosp Clin, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Med, Sao Paulo, BrazilUniv Estadual Campinas, Hosp Clin, Inst Infectol Emilio Ribas, Campinas, SP, BrazilFundacao Oswaldo Cruz, Dept Microbiol Immunol & Parasitol, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, BrazilUniv Fed Parana, Fac Med, Dept Saude Comunitaria, BR-80060000 Curitiba, Parana, BrazilUniv Fed Rio Grande do Sul, Fac Med, Dept Clin Med, Porto Alegre, RS, BrazilUniv Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Sao Paulo, BrazilInst Doencas Trop Natan Portela, Teresina, PI, BrazilUniv Sao Paulo, Fac Med, Dept Mol Infecciosas & Parasitarias, Sao Paulo, BrazilUniv Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Campinas, SP, BrazilUniv Fed Uberlandia, Fac Med, BR-38400 Uberlandia, MG, BrazilFac Med Triangulo Mineiro, Dept Clin Med, Uberaba, MG, BrazilInst Infectol Emilio Ribas, Sao Paulo, BrazilUniv Estadual Sao Paulo, Fac Med Botucatu, Dept Doencas Trop & Diagnost Imagem, Sao Paulo, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Med, Sao Paulo, BrazilWeb of Scienc

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists