Endothelin-1 Drives Epithelial-Mesenchymal Transition In Hypertensive Nephroangiosclerosis

BACKGROUND: Tubulointerstitial fibrosis, the final outcome of most kidney diseases, involves activation of epithelial mesenchymal transition (EMT). Endothelin‐1 (ET‐1) activates EMT in cancer cells, but it is not known whether it drives EMT in the kidney. We therefore tested the hypothesis that tubulointerstitial fibrosis involves EMT driven by ET‐1. METHODS AND RESULTS: Transgenic TG[mRen2]27 (TGRen2) rats developing fulminant angiotensin II–dependent hypertension with prominent cardiovascular and renal damage were submitted to drug treatments targeted to ET‐1 and/or angiotensin II receptor or left untreated (controls). Expressional changes of E‐cadherin and α‐smooth muscle actin (αSMA) were examined as markers of renal EMT. In human kidney HK‐2 proximal tubular cells expressing the ET(B) receptor subtype, the effects of ET‐1 with or without ET‐1 antagonists were also investigated. The occurrence of renal fibrosis was associated with EMT in control TGRen2 rats, as evidenced by decreased E‐cadherin and increased αSMA expression. Irbesartan and the mixed ET‐1 receptor antagonist bosentan prevented these changes in a blood pressure–independent fashion (P < 0.001 for both versus controls). In HK‐2 cells ET‐1 blunted E‐cadherin expression, increased αSMA expression (both P < 0.01), collagen synthesis, and metalloproteinase activity (P < 0.005, all versus untreated cells). All changes were prevented by the selective ET(B) receptor antagonist BQ‐788. Evidence for involvement of the Rho‐kinase signaling pathway and dephosphorylation of Yes‐associated protein in EMT was also found. CONCLUSIONS: In angiotensin II–dependent hypertension, ET‐1 acting via ET(B) receptors and the Rho‐kinase and Yes‐associated protein induces EMT and thereby renal fibrosis

O usuário remoto de uma biblioteca acadêmica

Os avanços tecnológicos trouxeram para as bibliotecas o desafio de atender às necessidades de informação de um novo tipo de usuário - o usuário remoto. Com o objetivo de conhecer esse usuário, no contexto acadêmico, foi realizado estudo para saber como a internet é usada, definindo-se quais os tipos de usuários, necessidades de informação e qual a demanda temática. Foram analisadas 314 mensagens eletrônicas recebidas pela Biblioteca/CIR: Centro de Informação e Referência em Saúde Pública da Faculdade de Saúde Pública, da Universidade de São Paulo (São Paulo/Brasil), no período de agosto de 1999 a agosto de 2000. Dentre os resultados obtidos os principais foram: a grande maioria dos usuários remotos da Biblioteca são do próprio país, no caso o Brasil (91,7%). Destes, 41,7% são do Estado de São Paulo e 27,4%, da cidade de São Paulo. Quanto à categoria, a área acadêmica deteve a maior demanda dos serviços remotos (46,2%), sendo 30,5% de alunos e 5,7% de professores. Quanto ao tipo de demanda, a busca de assuntos liderou os pedidos com 51,6%, seguido de serviços de comutação bibliográfica, com 18%. Os assuntos mais procurados foram os da área de atuação da Biblioteca - saúde pública -, com 66,8%, segundo a categoria SP do DeCS - Descritores em Ciências da Saúde, da Bireme (Sistema Latino Americano e do Caribe em Ciências da Saúde). Outras categorias do DeCS foram objeto de procura, como a categoria C (Doenças), com 14,5%. As questões foram qualificadas como "simples", "de média complexidade" e "complexas". Para respostas às questões simples, a disponibilização de um serviço de resposta a "Perguntas Freqüentes" (FAQ "Frequently Asked Questions") no web site da Biblioteca poderia melhor atender às necessidades do usuário remoto. Para as demais, a especialização do bibliotecário na área da saúde e a integração da biblioteca com especialistas, devem ser considerados visando o melhor desempenho no atendimento do usuário remoto de bibliotecas acadêmicas.Palavras-Chave: Usuário remoto; Tecnologia em biblioteca

O pesquisador da Educação Ambiental: reflexões sobre sua formação inicial e continuadaThe researcher of Environmental Education: reflections on his initial and continued formation

O presente artigo objetiva identificar e problematizar a formação inicial e continuada dos pesquisadores em Educação Ambiental. Para tanto, procedeu-se uma investigação sobre a trajetória da formação de autores de artigos científicos em Educação Ambiental (EA). Para a seleção dos autores, optou-se por um recorte de trabalhos relacionados à EA formal. Os artigos foram selecionados a partir das palavras-chave: Educação Ambiental; Educação Formal; Escola; em dois periódicos nacionais, sendo um na área de Extensão Universitária e outra de Pesquisa em Educação Ambiental. A investigação da formação dos autores analisados ocorreu por meio da pesquisa de seus currículos na Plataforma Lattes. A análise da formação inicial dos autores dos artigos revelou que a maioria tem formação inicial na área de Ciências Biológicas. Ao analisar a formação continuada percebemos que ocorreu uma migração para área de Ciências Humanas. Esses resultados apontam para a importância da abordagem das Ciências Naturais, mesmo com suas limitações, no que se refere à perspectiva crítica, no sentido de comprometimento com a causa ambiental. Comprometimento que impulsiona esses profissionais a enfrentarem barreiras epistemológicas, mudando para as ciências humanas, em sua formação continuada, e, dessa forma, suprindo as carências impostas pela área rumo à criticidade

Increased expression of interleukin-22 in patients with giant cell arteritis

GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis

Optimization of Laboratory Diagnostics of Primary Biliary Cholangitis: When Solid-Phase Assays and Immunofluorescence Combine

The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved, thanks to innovative analytical opportunities, such as enzyme-linked immunosorbent assays (ELISA) and multiple immunodot liver profile tests, based on recombinant or purified antigens. This study aimed to identify the best diagnostic test combination to optimize PBC diagnosis. Between January 2014 and March 2017, 164 PBC patients were recruited at the hospitals of Parma, Modena, Reggio-Emilia, and Piacenza. Antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were assayed by indirect immunofluorescence (IIF), ELISA, and immunodot assays (PBC Screen, MIT3, M2, gp210, and sp100). AMA-IIF resulted in 89.6% positive cases. Using multiple immunodot liver profiles, AMA-M2 sensitivity was 94.5%, while anti-gp210 and anti-sp100 antibodies were positive in 16.5% and 17.7% of patients, respectively. PBC screening yielded positive results in 94.5% of cases; MIT3, sp100, and gp210 were detected by individual ELISA test in 89.0%, 17.1%, and 18.9% of patients, respectively. The association of PBC screening with IIF-AMA improved the diagnostic sensitivity from 89.6% to 98.2% (p &lt; 0.01). When multiple immunodot liver profile testing was integrated with AMA-IIF, the diagnostic sensitivity increased from 89.1% to 98.8% (p &lt; 0.01). The combination of IIF with solid-phase methods significantly improved diagnostic efficacy in PBC patients

Endothelin-1 (ET-1) modulates epithelial-mesenchymal transition (EMT), which contributes to kidney tubulo-interstitial fibrosis in angiotensin II-dependent hypertension

The origin of myofibroblasts remains uncertain, but studies suggest that the epithelial cells may acquire a fibroblast-like phenotype via epithelial-mesenchymal transition (EMT). Objective of the study was to investigate whether EMT may contribute to the development of kidney fibrosis in a model of angiotensin II-dependent hypertension and to identify the role of ET-1 via ETA/ETB receptors. Transgenic rats TGRen2 (n=35) received for 4 weeks one of the following treatments a) irbesartan, b) bosentan, non selective ETA /ETB receptor antagonist, c) BMS-182874, selective ETA,antagonist, d) BMS+irbesartan, e) placebo. EMT was assessed by investigating coexpression of a marker of epithelial cell (E-cadherin) and one of myofibroblast (S100A4 or alfa-SMA) with double immunofluorescence. Specific immunoreactivity was measured using QWinStandard Leica ImageTMsoftware. A reduction in blood pressure was found only with irbesartan, whereas both bosentan and irbesartan significantly lowered tubulo-interstitial fibrosis. Coexpression of E-cadherin and S100A4, or E-cadherin and alfa-SMA, markedly decreased in the tubular cells of TGRen2 treated with irbesartan or bosentan. Alfa-SMA expression decreased after irbesartan, bosentan and BMS+irbesartan, but not after BMS. S100A4 expression was reduced after irbesartan, bosentan and BMS+irbesartan. E-cadherin increased only after irbesartan. Coexpression of the markers of myofibroblasts and kidney epithelial cells, by demonstrating the development of EMT during the onset of kidney hypertension-induced damage, suggests a crucial role of EMT in the pathogenesis of Ang II-mediated fibrosis. The reduction of myofibroblast markers not only after irbesartan, but also after blockade of ETA/ETB receptors, suggests an involvement of ET-1 in the development of Ang II-mediated EMT

Endothelin-1 (ET-1) modulates epithelial-mesenchymal transition (EMT), which contributes to kidney tubulo-interstitial fibrosis in angiotensin II-dependent hypertension

The origin of myofibroblasts remains uncertain, but studies suggest that the epithelial cells may acquire a fibroblast-like phenotype via epithelial-mesenchymal transition (EMT). Objective of the study was to investigate whether EMT may contribute to the development of kidney fibrosis in a model of angiotensin II-dependent hypertension and to identify the role of ET-1 via ETA/ETB receptors. Transgenic rats TGRen2 (n=35) received for 4 weeks one of the following treatments a) irbesartan, b) bosentan, non selective ETA /ETB receptor antagonist, c) BMS-182874, selective ETA,antagonist, d) BMS+irbesartan, e) placebo. EMT was assessed by investigating coexpression of a marker of epithelial cell (E-cadherin) and one of myofibroblast (S100A4 or alfa-SMA) with double immunofluorescence. Specific immunoreactivity was measured using QWinStandard Leica ImageTMsoftware. A reduction in blood pressure was found only with irbesartan, whereas both bosentan and irbesartan significantly lowered tubulo-interstitial fibrosis. Coexpression of E-cadherin and S100A4, or E-cadherin and alfa-SMA, markedly decreased in the tubular cells of TGRen2 treated with irbesartan or bosentan. Alfa-SMA expression decreased after irbesartan, bosentan and BMS+irbesartan, but not after BMS. S100A4 expression was reduced after irbesartan, bosentan and BMS+irbesartan. E-cadherin increased only after irbesartan. Coexpression of the markers of myofibroblasts and kidney epithelial cells, by demonstrating the development of EMT during the onset of kidney hypertension-induced damage, suggests a crucial role of EMT in the pathogenesis of Ang II-mediated fibrosis. The reduction of myofibroblast markers not only after irbesartan, but also after blockade of ETA/ETB receptors, suggests an involvement of ET-1 in the development of Ang II-mediated EMT

Capacitação no uso das bases Medline e Lilacs: avaliação de conteúdo, estrutura e metodologia

Avaliação dos resultados da capacitação de usuários de buscas informatizadas do Curso de Acesso às Bases em cd-rom Medline e Lilacs, modalidade do Programa Educativo da Biblioteca/CIR da Faculdade de Saúde Pública da USP, oferecido a docentes e alunos da pós-graduação em saúde pública. O universo de estudo foi constituído de 92 participantes entre 1993 e 1995. Os egressos do curso opinaram sobre o seu conteúdo, estrutura, metodologia, material didático e demais aspectos específicos à organização de capacitação desse nível. Concluiu-se que o Curso Medline e Lilacs está atendendo às necessidades dos usuários das buscas informatizadas, precisando de algumas adequações, as quais são apontadas neste artigo

SERVIÇOS E PRODUTOS DO SIBi/USP: descrição dos processos essenciais, gerenciais e de apoio

O Modelo de Gestão do Sistema Integrado de Bibliote\ud cas da Universidade de São Paulo\ud (SIBi/USP) incorpora conceitos e ferramentas de ger\ud enciamento que permeiam as\ud organizações modernas para garantir melhores índice\ud s de desempenho sistêmico e prestar\ud serviços com qualidade e eficiência aos usuários. C\ud omo parte do Modelo está a\ud identificação e a descrição detalhada dos processos\ud de trabalho do Sistema, assim como o\ud estabelecimento de alguns indicadores de desempenho\ud . A partir do\ud trabalho inicial, foi\ud elaborado um levantamento complementar para identif\ud icação dos processos que\ud abrangessem o conjunto do Sistema de forma ampla. O\ud s dados foram dispostos em\ud planilhas para melhor visualização, especialmente q\ud uanto aos macro processos, processos,\ud sub processos e atividades. Os processos foram sepa\ud rados em essenciais, gerenciais e de\ud apoio, além de elencadas as atividades pertinentes\ud a cada um deles, bem como as\ud instruções técnicas e fluxos de trabalho. Foram est\ud abelecidos alguns indicadores, tendo por\ud referência os da IFLA já estudados por outro Grupo\ud de Trabalho. Daquele estudo quatro\ud indicadores foram testados e validados pelo SIBi/US\ud P por meio de aplicação piloto em\ud algumas das Bibliotecas do Sistema e outros foram d\ud efinidos no estudo atual. Com isso foi\ud possível mapear os processos e as atividades desenv\ud olvidas pelo conjunto de Bibliotecas\ud sendo que cada Biblioteca, em função de sua especia\ud lidade e especificidade pode adequar\ud o seu mapeamento. A definição de um núcleo básico d\ud e indicadores objetiva viabilizar a\ud concretização da missão e dos objetivos em consonân\ud cia com a política do SIBI/USPThe Management Model of the Integrated Library Syst\ud em, University of São Paulo\ud (SIBi/USP) incorporates concepts and management too\ud ls that permeate modern\ud organizations to ensure better systemic performance\ud indexes and provide services\ud with quality and efficiency to users. Is part of th\ud e model, the identification and the\ud detailed description of the essential processes, ma\ud nagement and support, as well as\ud the establishment of some performance indicators. F\ud rom the initial work, we designed\ud a complementary survey to identify the processes co\ud vering the whole of the System.\ud Data were arranged in sheets for easy viewing, espe\ud cially with regard to macro \ud processes, processes, sub processes and activities.\ud The processes were divided into\ud essential, managerial and support. At that time, we\ud re listed the activities under each\ud processes and their technical instructions and work\ud flows. It were established some\ud indicators, using model IFLA already studied by oth\ud er Working Group. In this study\ud four indicators have been tested and validated by S\ud IBi/USP through pilot application\ud in some of the Library System and others were defin\ud ed in the current study. It was\ud possible to map the processes and activities undert\ud aken by all Libraries of SIBi/USP,\ud and each of them, depending on their specialty and\ud specificity can do its own\ud mapping. The definition of a core of indicators can\ud enable the achievement of the\ud mission and objectives in line with the policy of S\ud IBI/US

Evaluation of 99th percentile and reference change values of a high-sensitivity cTnI method: A multicenter study

Abstract Background The Italian Society of Clinical Biochemistry (SIBioC) and the Italian Section of the European Ligand Assay Society (ELAS) have recently promoted a multicenter study (Italian hs-cTnI Study) with the aim to accurately evaluate analytical performances and reference values of the most popular cTnI methods commercially available in Italy. The aim of this article is to report the results of the Italian hs-cTnI Study concerning the evaluation of the 99th percentile URL and reference change (RCV) values around the 99th URL of the Access cTnI method. Materials and methods Heparinized plasma samples were collected from 1306 healthy adult volunteers by 8 Italian clinical centers. Every center collected from 50 to 150 plasma samples from healthy adult subjects. All volunteers denied the presence of chronic or acute diseases and had normal values of routine laboratory tests (including creatinine, electrolytes, glucose and blood counts). An older cohort of 457 adult subjects (mean age 63.0 years; SD 8.1 years, minimum 47 years, maximum 86 years) underwent also ECG and cardiac imaging analysis in order to exclude the presence of asymptomatic cardiac disease. Results and conclusions The results of the present study confirm that the Access hsTnI method using the DxI platform satisfies the two criteria required by international guidelines for high-sensitivity methods for cTn assay. Furthermore, the results of this study confirm that the calculation of the 99th percentile URL values are greatly affected not only by age and sex of the reference population, but also by the statistical approach used for calculation of cTnI distribution parameters