In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated. Copyright (C) 2003 John Wiley Sons, Ltd.

ATP-dependent K+ channels in renal ischemia reperfusion injury

ATP-dependent K+ channels (K-ATP) account for most of the recycling of K+ which enters the proximal tubules cell via Na, K-ATPase. In the mitochondrial membrane, opening of these channels preserves mitochondrial viability and matrix volume during ischemia. We examined KATP channel modulation in renal ischemia-reperfusion injury (IRI), using an isolated perfused rat kidney (IPRK) model, in control, IRI, IRI + 200 muM diazoxide (a K-ATP opener), IRI + 10 muM glibenclamide (a K-ATP blocker) and IRI + 200 muM diazoxide + 10 muM glibenclamide groups. IRI was induced by 2 periods of warm ischemia, followed by 45 min of reperfusion. IRI significantly decreased glomerular filtration rate (GFR) and increased fractional excretion of sodium (FENa) (p < 0.01). Neither diazoxide nor glibenclamide had an effect on control kidney function other than an increase in renal vascular resistance produced by glibenclamide. Pretreatment with 200 muM diazoxide reduced the postischemic increase in FENa (p < 0.05). Adding 10 muM glibenclamide inhibited the diazoxide effect on postischemic FENa (p < 0.01). Histology showed that kidneys pretreated with glibenclamide demonstrated an increase in injure in the thick ascending limb of outer medulla (p < 0.05). Glibenclamide significantly decreased post ischemic renal vascular resistance (p < 0.05). but had no significant effect on other renal function parameters. Our results suggest that sodium reabsorption is improved by K-ATP activation and blockade of K-ATP channels during IRI has an injury enhancing effect on renal epithelial function and histology. This may be mediated through K-ATP modulation in cell and or mitochondrial inner membrane.

Control of familial and renal cardiac diseases in English bull terriers: How to repair a damaged breed?

Control recommendations are presented for four genetic or familial diseases that cause significant morbidity and mortality in affected English Bull Terriers. Bull Terrier polycystic kidney disease is an autosomal dominant disease diagnosed by detecting a minimum of three renal cysts, with cysts present in both kidneys, and similarly affected family members to confirm the inherited nature of the cysts. Bull Terrier hereditary nephritis is an autosomal dominant disease diagnosed in otherwise normal animals with urinary protein: creatinine ratios persistently >0.3 and no significant urinary sediment, a family history of the disease, and characteristic glomerular basement membrane lesions. Mitral valve myxomatous degeneration and left ventricular outflow tract obstruction in Bull Terriers are familial diseases diagnosed by auscultating characteristic murmurs in affected animals. Excluding animals with these clinical signs from the breeding pool will reduce the prevalence rates of these diseases, however maintenance of an effective population size is also important. Providing breeders with information on genetics, including the risks associated with inbreeding and the benefits of outcrossing, is likely to improve canine breeding practices, thus increasing fitness and fecundity of these purebred dogs.

Boletim eletr??nico de bibliografias especializadas: pol??ticas p??blicas em direitos humanos

Os direitos humanos s??o os direitos essenciais a todos os seres humanos, sem que haja discrimina????o por ra??a, cor, g??nero, idioma, nacionalidade ou por qualquer outro motivo. Eles podem ser civis ou pol??ticos, como o direito ?? vida, ?? igualdade perante a lei e ?? liberdade de express??o. Podem tamb??m ser econ??micos, sociais e culturais, como o direito ao trabalho e ?? educa????o e coletivos, como o direito ao desenvolvimento. As Pol??ticas P??blicas em Direitos Humanos ?? tema deste boletim bibliogr??fico, o qual traz publica????es que mostram que estas n??o devem ser apenas programas governamentais, mas um instrumento de participa????o da sociedade civil na delimita????o do espa??o p??blico.

Sistema de pr??-qualifica????o de marcas e produtos m??dico-hospitalares do Inca

Para garantir a seguran??a no tratamento dos pacientes e aos profissionais de sa??de, foi criado o ???Sistema especial para pr??-qualifica????o de marcas e produtos??? para participa????o em licita????es de materiais hospitalares no Inca, devido ?? peculiaridade do paciente oncol??gico

A????es premiadas no 10?? Concurso Inova????o na Gest??o P??blica Federal

A publica????o apresenta o relato das 20 experi??ncias premiadas no 10?? Concurso Inova????o na Gest??o P??blica Federal e ?? uma importante fonte de refer??ncia de solu????es concretas para problemas enfrentados no dia-a-dia da administra????o p??blica. Nesta publica????o, o leitor encontrar?? iniciativas inovadoras nas seguintes ??reas: articula????o de parcerias, avalia????o de desempenho institucional, avalia????o e monitoramento de pol??ticas p??blicas, estabelecimento de padr??es de atendimento de servi??os, gerenciamento de pessoas e capacita????o, gerenciamento de informa????es, implementa????o de melhoria cont??nua, planejamento e gest??o estrat??gica, simplifica????o e agiliza????o de procedimentos

Redu????o da taxa de cancelamento de cirurgias atrav??s da otimiza????o do processo assistencial

O Centro Cir??rgico do Hospital de Cl??nicas de Porto Alegre realiza em torno de 46 cirurgias di??rias de m??dia e alta complexidade. O cancelamento de cirurgias gerava insatisfa????o e preju??zo direto ao paciente. O processo assistencial cir??rgico n??o era informatizado, o que dificultava a tomada de decis??o, por n??o dispor de dados fidedignos e abrangentes que mapeassem todos os eventos desse processo. Um trabalho rigoroso e detalhado de identifica????o das atividades, desde o atendimento ambulatorial do paciente cir??rgico at?? a realiza????o da cirurgia, proporcionou a informatiza????o do processo cr??tico, prevendo o registro das informa????es por quem realmente executa cada tarefa. O objetivo de subsidiar a tomada de decis??o foi alcan??ado. O resultado principal esperado ??? reduzir a taxa de cancelamento de cirurgias ??? foi obtido. A solu????o desse desafio simplificou e agilizou os procedimentos, qualificou a assist??ncia e humanizou o atendimento, refletindo diretamente na satisfa????o do paciente

Dimens??es do papel do Conanda na efetiva????o dos direitos humanos de crian??as e adolescentes para conselheiros nacionais: o debate sobre grandes eventos esportivos no Brasil

O contexto pol??tico e social brasileiro, desde as ??ltimas d??cadas do s??culo passado, tem sido marcado pelo processo de redefini????o do papel do Estado, a partir da universaliza????o dos direitos de cidadania, descentraliza????o administrativa e gest??o democr??tica das pol??ticas p??blicas. Trata-se, assim, de um novo formato institucional, legitimado pela Constitui????o Federal de 1988, integrante do processo de implementa????o da gest??o participativa, que ocorreu no Brasil principalmente a partir dos anos 90, nas esferas municipal, estadual e federal. Nesse novo formato institucional, surgem os Conselhos de Pol??ticas P??blicas como um novo padr??o de intera????o entre governo e sociedade, exigindo-se dos cidad??os uma atua????o efetiva, por meio de processos interativos, no ??mbito da gest??o p??blica. Esse modelo de gest??o absorve em sua estrutura v??rios segmentos da sociedade, constituindo o novo locus de articula????o pol??tica na defesa pela democratiza????o da gest??o das pol??ticas p??blicas, atrav??s dos quais sujeitos diversos interagem no processo de delibera????o, implementa????o, monitoramento, avalia????o e controle social das pol??ticas p??blicas, nas diversas tem??ticas e ??reas sociais. Este trabalho pretende analisar a capacidade do principal espa??o interinstitucional da inf??ncia e adolesc??ncia do Brasil de influenciar a agenda governamental e as pol??ticas p??blicas federais: o Conselho Nacional dos Direitos da Crian??a e do Adolescente (criado na d??cada de 1990). Para esta an??lise, a pesquisa foca no papel do Conanda na defesa, promo????o e prote????o dos direitos de crian??as e adolescentes no ??mbito do debate sobre grandes eventos esportivos no Brasil. Esta an??lise revela as possibilidades e limites do Conselho de influenciar na constitui????o da agenda p??blica na tem??tica, na decis??o dos agentes de Estado e na formula????o de pol??ticas, na perspectiva da efetiva????o dos direitos fundamentais constitucionais de crian??as e adolescentes