1000 resultados para Apoptose Teses
Resumo:
O cuidado s necessidades emocionais de crianas hospitalizadas vem merecendo ateno dos profissionais de enfermagem em nosso pas, embora ainda no de modo generalizado. A possibilidade de brincar sabidamente atenua o sofrimento, especialmente na infncia, justificando-se a importncia deste tema. Assim, este trabalho teve como objetivo analisar a produo acadmica dos enfermeiros brasileiros sobre o uso do brinquedo na ateno criana em cuidado hospitalar, nos programas de ps-graduao stricto sensu. O levantamento foi feito no Portal CAPES, CEPEn, IBICT e consulta s referncias dos trabalhos. Das quinze teses/dissertaes encontradas na literatura pode-se encontrar catorze, que foram analisadas e constituem o corpus do presente estudo. O brinquedo foi mais utilizado no pr e ps-operatrio, por enfermeiros docentes, com crianas pr-escolares e escolares, pais e enfermeiros. Os trabalhos analisados reforam os resultados positivos desta prtica. Recomendamos que as enfermeiras pediatras utilizem o brinquedo em todas as instituies onde a criana necessite de cuidado.
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Estudo histrico-social sobre a emergncia das profisses de nutricionista e de assistente social, entre os anos 30 e meados do sculo 20. O trabalho trata das circunstncias do surgimento dos cursos de nutrio e de servio social no interior da Escola Anna Nery/UFRJ, e compara as funes desempenhadas por enfermeiras, nutricionistas e assistentes sociais poca. As fontes primrias de pesquisa encontram-se no Centro de Documentao da Escola de Enfermagem Anna Nery/UFRJ e incluem documentos escritos e depoimento oral. As fontes secundrias foram artigos, livros e teses. A anlise de textos e documentos evidenciou que a Escola teve papel decisivo na emergncia dessas novas profisses, que vieram contribuir para uma melhor organizao e funcionamento dos servios de sade e para a prestao de uma assistncia mais completa clientela. Ao mesmo tempo, sua caracterstica feminina veio, ainda, favorecer a insero de mulheres no mercado de trabalho qualificado na rea da sade.
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Pesquisa bibliogrfica que buscou identificar como os conflitos e sentimentos das mulheres portadoras de HIV/Aids so abordados na literatura nacional e os caminhos propostos para uma abordagem de cuidado integral. Os dados foram coletados em novembro de 2006, na base de dados LILACS, utilizando as palavras-chave: mulheres, sentimentos, HIV, Aids, sofrimento, depresso e medo e como critrio de incluso o fato de os estudos terem sido divulgados nos ltimos cinco anos. A amostra ficou constituda de catorze pesquisas (quatro teses, duas dissertaes e oito artigos). O mtodo de anlise de contedo permitiu identificar trs categorias temticas: o olhar do pesquisador, o que seu olhar identifica e o seu olhar para alm do corpo fsico - as quais revelam a necessidade de abordar as mulheres considerando todo o seu contexto enquanto ser humano, incluindo questes de vulnerabili-dade, ideologia social de gnero, promoo da auto-estima e exerccio da cidadania.
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Abstract : Apoptosis is an evolutionarily conserved cellular suicide mechanism that can be triggered by activation of various pathways, such as the Fas-Pathway. Upon stimulation by its specific ligand (FasL), present at the surface of Cytotoxic Τ lymphocytes, the death receptor Fas initiates a signaling cascade culminating in the activation of cellular caspases, leading thus to cell death of the target cell (e.g. transformed cell). Dysregulation of apoptosis in general, and of Fas pathway in particular, was shown to contribute to pathogenesis of cancers and many human diseases. Even though, during the last decades the molecular mechanisms of apoptosis have been widely studied, it is important to better understand the mechanisms leading to apoptosis, to improve our understanding of pathological processes, and generate more subtle apoptosis-modulating therapies to fight cancer and other diseases. In order to identify new components of the Fas signaling pathway, a screen based on the mechanism of RNA interference was undertaken. After a first and a second manual whole-kinome screen, we identified several strong positive hits that showed a protection against Fas ligand-induced apoptosis with distinct siRNAs, notably STK11, an interesting tumor suppressor mutated in several sporadic and inherited cancers. The STK11 functional characterization reveals that this kinase represents an apically acting general pro-apoptotic modulator of the extrinsic pathway (FasL, TRAIL, TNF-induced apoptosis), but not of the intrinsic apoptotic pathway. The STK11 action on the Fas pathway was shown to be dependent on its kinase activity, but independent of AMPK, a well-characterized STK11 downstream substrate. Furthermore, STK11 was shown to interact with caspase-8, a major mediator of the extrinsic pathway, and modulate its activity through an unclear mechanism that may involve an STK11-dependant caspase-8 phosphorylation. This modification may allow a proper caspase-8 polyubiquitination and activation in p62 sequestosmes aggregates, but may also increase the activation of caspase-8 at the DISC level. In addition, we observed that STK11 modulate not only the apoptotic pathway induced by Fas engagement, but also FasL-induced JNK and NF- KB, sustaining an upstream role of this kinase in the pathway. In conclusion, our report reveals that STK11 is an important pro-apoptotic modulator of the Fas pathway in particular, and extrinsic pathway in general. Our finding could explain, at least partially, why inactivating mutations of the kinase leads to cancer, by allowing resistance to apoptosis and accordingly evasion of immune surveillance. Rsum : L'apoptose est un mcanisme de suicide cellulaire, conserv dans diverses espces, et qui au niveau molculaire est dclench par diffrentes voies de signalisation, comme par exemple lors de l'activation du rcepteur Fas. La liaison du ligand FasL au rcepteur de la mort Fas, induit une cascade de signalisation qui conduit l'activation des caspases. Les lymphocytes Τ cytotoxiques peuvent utiliser la voie Fas pour induire la mort et se dbarrasser de cellules dangereuses pour le reste de l'organisme, tel que les cellules transformes. La dysrgulation de l'apoptose en gnral, et de la voie Fas en particulier, peut contribuer diverses maladies telles que le cancer. Mme si ces dernires dcennies, les mcanismes molculaires conduisant l'apoptose ont t extensivement tudis, il reste nanmoins important de mieux comprendre le phnomne d'apoptose, pour amliorer notre comprhension des processus pathologiques, mais surtout dans le but de dvelopper de nouvelles thrapies ciblant l'apoptose contre le cancer et d'autres pathologies. Pour identifier de nouveau constituants de la voie Fas, un criblage gntique bas sur l'interfrence l'ARN a t entrepris. Aprs un premier et un deuxime criblage d'une librairie du kinome, nous avons identifi diffrentes protines qui pourraient jouer un rle positif dans la voie Fas, et en particulier la protine suppresseur de tumeur STK11, qui est frquemment mute dans divers cancers sporadiques et hrditaires. La caractrisation fonctionnelle de STK11 a rvl que cette kinase tait un modulateur apical de la voie extrinsque de l'apoptose en gnral (Fas, TNF, TRAIL), mais pas de la voie intrinsque. L'action de STK11 sur la voie Fas est dpendante de sa fonction kinase, mais indpendante de l'AMPK, un substrat bien caractris de STK11. De plus, STK11 interagt avec la caspase-8, un constituant majeur de la voie Fas, et module son activit, par un mcanisme encore peu clair qui pourrait impliquer une phosphorylation de la caspase-8 par STK11. Cette modification pourrait permettre une activation optimale de la caspase-8 en jouant un rle dans le processus de polyubiquitination de la caspase-8, phnomne qui semble tre important pour l'activation de la caspase-8 dans des agrgats protiques avec p62, mais qui pourrait aussi augmenter son activation au niveau du DISC. Finalement, nous avons observ que STK11 modulait non seulement la voie apoptotique dclenche par l'activation de Fas, mais aussi les voies non-apoptotiques de Fas, comme JNK et NF-KB. En conclusion notre tude, rvle que STK11 est un important modulateur pro- apoptotique de la voie Fas, et de la voie extrinsque en gnral. Cette dcouverte pourrait expliquer, du moins partiellement, pourquoi les mutations inactivatrices de STK11 conduisent au cancer, par une augmentation de la rsistance l'apoptose et donc par l'vasion de la surveillance immunitaire.
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O estudo uma reviso narrativa de teses e dissertaes concludas no perodo de 2000 a 2009 produzidas pelo Grupo de Pesquisa Enfermagem Obsttrica e Neonatal e pelo Ncleo de Estudos e Pesquisa em Aleitamento Materno da Escola de Enfermagem da Universidade de So Paulo que focalizaram os fatores maternos e perinatais que repercutem na sade neonatal. A produo cientfica evidencia alinhamento com as diretrizes estabelecidas pelos rgos de sade nacionais e internacionais para a promoo da sade neonatal e infantil.
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Summary Resolution of the inflammation is as important as its induction. In this thesis, we investigated the contributions of two prominent factors involved in inflammation, Tumour Necrosis Factor (TNF) and neutrophils. We studied their role in the resolution f the inflammatory lesion induced by the infection with the protozoan parasite Leishmania major. In mice susceptible to infection with L. major, unhealing lesions are characterized by an elevated number and sustained presence of inflammatory neutrophils in the infected tissue, illustrating an acute inflammatory process. In contrast, mice from resistant strains, which resolve their lesions, can control the presence of neutrophils at the site of infection. Neutrophil persistence in the infected tissue may result from several events including an increased survival of neutrophils mediated by factors produced by the pathogen or the microenvironment. Following infection with L. major, the cellular composition of the inflammatory lesion differs significantly between susceptible and resistant mice and a higher proportion of macrophages is present in the lesions of resistant strains. In an attempt to clarify the factors involved in neutrophil persistence, we investigated the mechanisms modulating neutrophil cell death. We demonstrated that macrophages could induce neutrophil apoptosis in a process involving TNF. TNF is an essential cytokine with pro- and anti-inflammatory properties, which is expressed as a transmembrane protein that can be cleaved releasing the secreted form. Our data show the essential role of the transmembrane form of TNF (mTNF) in the induction of neutrophil apoptosis by macrophages, revealing macrophages and mTNF as important regulators of neutrophil apoptosis. TNF is critical in the resolution of the inflammatory lesion induced by L. major infection, and in L. major resistant strains its absence results in increased swelling of the lesions. We investigated the contribution of mTNF in the outcome of L. major infection. Our data demonstrate that following infection with L. major, mTNF is sufficient to support the resolution of the inflammatory lesion and optimal parasite killing. In addition, we show that the presence of mTNF is essential to induce neutrophil clearance in the infected tissue. While the persistence of neutrophils is deleterious for the host, we could demonstrate an early anti-inflammatory role of neutrophils. Altogether, this study demonstrates the importance of mTNF in the induction of neutrophil apoptosis, a process involved in the resolution of the inflammatory lesion induced by L. major infection. Rsum La rsolution de l'inflammation est toute aussi importante que son initiation. Durant ce travail de thse, nous avons tudi les contributions de deux facteurs importants impliqus dans l'inflammation, le TNF (Facteur Ncrosant des Tumeurs) et les neutrophiles, dans la rsolution de la lsion inflammatoire induite par l'infection avec le parasite protozoaire Leishmania major. Chez les souris sensibles l'infection avec L. major, des lsions importantes qui ne gurissent pas se dveloppent ; celles-ci sont caractrises par un nombre lev et une prsence soutenue de neutrophiles dans les tissus infects, ce qui illustre un processus inflammatoire aigu. Au contraire, les souris rsistantes l'infection qui gurissent leurs lsions, sont capables de contrler la prsence des neutrophiles au site d'infection. La persistance des neutrophiles dans la lsion inflammatoire peut tre la consquence de plusieurs vnements, dont une augmentation de la survie des neutrophiles induite par des facteurs produits par le pathogne ou le micro-environnement. Suite l'infection avec L. major, la composition cellulaire de la lsion inflammatoire est significativement diffrente entre les souris sensibles et rsistantes l'infection, et une plus grande proportion de macrophages est prsente dans les lsions des souris rsistantes. Dans l'objectif de clarifier les facteurs impliqus dans la persistance des neutrophiles dans les tissus infects par L. major, nous avons tudi les mcanismes de rgulation de la mort des neutrophiles. Nous avons dmontr que les macrophages pouvaient induire l'apoptose des neutrophiles dans un procd impliquant le TNF. Le TNF est une cytokine aux proprits pro- et anti-inflammatoires, exprime sous une forme transmembranaire qui peut tre clive pour relcher la forme scrte. Nos expriences illustrent le rle essentiel de la forme transmembranaire du TNF (mTNF) dans l'induction de l'apoptose des neutrophiles par les macrophages. L TNF est une cytokine importante dans la rsolution de la raction inflammatoire induite par L. major, et chez les souris rsistantes l'absence de TNF provoque des lsions inflammatoires plus importantes. Nous avons tudi la contribution du mTNF dans la rsolution de l'infection avec L. major. Nos rsultats dmontrent que suite une infection avec le parasite, la prsence du mTNF est suffisante pour gurir la lsion inflammatoire et contrler efficacement la rplication du parasite. De plus, le mTNF joue un rle essentiel dans l'limination des neutrophiles du tissu infect. Alors que la persistance des neutrophiles est nocive pour l'hte, nous avons montr que les neutrophiles avaient un rle prcoce anti-inflammatoire. En rsum, cette tude rvle l'importance du mTNF dans l'induction de l'apoptose des neutrophiles par les macrophages, un procd impliqu dans la rsolution de la lsion inflammatoire induite par l'infection avec L. major.
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Rsum : Les anticorps monoclonaux ont une place de plus en plus prpondrante dans le traitement des lymphomes et leucmies. Dans cette tude, trois anticorps monoclonaux murins, dirigs contre les antignes CDS, CD71 et HLA-DR exprims la surface des cellules de leucmies lymphodes chroniques (LLC), ont t valus. In vitro, les anticorps radiomarqus ont montrs des bonnes liaisons spcifiques sur les diffrentes cellules cibles. L'anti-CD71 inhibait la prolifration de la plupart des lignes cellulaires testes avec une accumulation des cellules en phase S prcoce du cycle cellulaire. L'anti-HLA-DR inhibait aussi la prolifration des lignes leucmique JOK1-5.3 et lymphode Daudi. Cette inhibition tait associe une agrgation des cellules. Aucune induction d'apoptose n'a pu tre clairement observe avec ces anticorps. L'anti-CD5 n'a montr aucun effet d'inhibition de croissance in vitro. In vivo, l'injection des anticorps individuellement augmentait significativement la survie mdiane de souris SCID greffes avec des cellules JOK1-5.3 en i.p. De plus, l'anticorps antiCD5 combin l'anti-HLA-DR ou l'anti-CD71, sous certaines conditions, inhibait compltement le dveloppement tumoral dans la quasi totalit des souris traites avec une augmentation significative de l'efficacit compare aux anticorps seuls. L'augmentation de l'efficacit thrapeutique des anticorps monoclonaux par les cytokines, dont l'IL-2, a dj t montre dans la littrature. Au regard du meilleur comportement de l'IL-2 sous la forme complexe un anticorps anti-IL-2, nous avons valu l'efficacit de l'IL-2/anti-IL-2 seul ou combins au rituximab chez diffrents modles tumoraux s.c. (BL60.2, Daudi, Ramos) ou i.p. (JOK15.3) de souris SCID. Le complexe IL-2/anti-IL-2 a montr un effet anti-tumoral dans les souris greffes avec BL60.2 et Daudi. Le traitement IL-2/anti-IL-2 combin au rituximab a montr une efficacit accrue chez des souris avec BL60.2 par rapport au rituximab seul. En revanche, nous n'avons pas observ de diffrence avec IL-2/anti-IL-2 seul.Aussi, nous avons valu l'utilisation de l'agent couplant tri-fonctionnel TMEA pour produire des anticorps bispecifiques. Les expriences prliminaires avec les anticorps rituximab et herceptine, ont mis en vidence sur gel SDS-Page la formation de dimers (~100kDa) et de trimers (~150kDa). Les anticorps bispecifiques sont composs d'un fragment Fab' d'une spcificit et de un ou deux fragments Fab' de l'autre spcificit permettant de moduler la capacit de liaison. Nous avons enfin montr qu'une construction anti-CD5/anti-CD20 tait capable de se lier indpendamment ou simultanment ses antignes cibles. En conclusion, ce travail a montr l'efficacit thrapeutique des trois anticorps monoclonaux tudis dans un model de LLC in vivo, et plus particulirement l'intrt de certaines combinaisons. D'autre part, nous avons montr l'efficacit anti-tumorale du complexe IL-2/anti-IL-2 in vivo. Des tudes futures devront permettre de dfinir un rgime favorable pour augmenter l'efficacit de la thrapie avec les anticorps monoclonaux. Enfin, nous avons montr la faisabilit d'utiliser l'agent couplant TMEA pour produire des anticorps bispcifiques fonctionnels.Abstract : Monoclonal antibody (mAb) therapy has become an integral part in different treatments of lymphomas and leukaemias. In this study, we describe three murine mAbs directed against the CD5, CD71 and HLA-DR antigens expressed on chronic lymphocytic leukaemia cells (CLL). In vitro, radiolabeled purified mAbs showed good specific binding on live target cells. Anti-CD71 mAb inhibited proliferation of most cell lines with an accumulation of responding cells in early S-phase of the cell cycle, but without induction of apoptosis. Anti-HLA-DR mAb showed proliferation inhibition of leukaemia JOK1-5.3 and lymphoid Daudi cells, associated with cell aggregation, but again no specific sign of apoptosis was observed. Anti-CD5 mAb did not show any growth inhibitory effect in vitro. In vivo, in a model of SCID mice grafted i.p. with JOK1-5.3 cells, injection of individual mAbs induced significant prolongation of median survival, up to complete inhibition of tumour growth in some mice. Antibody combination of anti-CD5 with anti-HLA-DR or anti-CD71, evaluated in an early treatment, completely inhibited tumour growth in most mice, with a significant efficacy enhancement as compared to mAb used as single agents. Previous reports described the improved efficacy of mAb therapy when combined with cytokines such as IL-2. Relying further on the improved efficacy of IL-2 when administered as an immune complex with anti-IL-2 mAb, we evaluated the anti-tumour effect of the IL-2/anti-IL-2 complex alone or combined with rituximab in subcutaneous (BL60.2, Daudi, Ramos) or i.p. (JOK1-5.3) tumour models in SCID mice. The IL-2/anti-IL-2 complex demonstrated an anti-tumour effect in BL60.2 and Daudi grafted SCID mice. Combination of IL-2/anti-IL-2 treatment with rituximab showed increased efficacy as compared to rituximab alone in BL60.2 grafted mice. However, no difference was observed with IL-2/anti-IL-2 complex alone in these experiments. Finally, we evaluated the feasibility of producing bispecific antibodies (bsAbs) using a trifunctional coupling agent, called TMEA. In preliminary experiments coupling rituximab with herceptine Fab' fragments we obtained the formation of dimers (~100kDa) and trimers (~150kDa) as observed on SDS-Page gel. This method allowed us to produce bsAb with one Fab' fragments of one specificity and one or two Fab' fragments of the second specificity. An anti-CD5/anti-CD20 bsAb was shown to bind targeted antigen either independently or simultaneously. In conclusion, these data show that the three mAbs were all able to induce significant growth inhibition of the JOK1-5.3 cell line in vivo, and efficacy was enhanced when used in combination. IL2/anti-IL-2 complex displayed anti-tumour efficacy in vivo. Further evaluation is necessary to define the most favourable combination to improve mAb therapy. BsAb were produced using the tri-functional agent allowing antibody fragments with relatively good binding. The poor yield obtained with such chemical couplings limited the use of these constructs in preclinical experiments.
Resumo:
Esta pesquisa documental teve como objetivo refletir sobre o estado da arte na Enfermagem brasileira acerca do cuidado ao recm-nascido em UTI neonatal. A fonte de pesquisa foi o Banco de Teses e Dissertaes da Associao Brasileira de Enfermagem. Foram identificados 81 estudos. A anlise dos dados foi feita em duas etapas: primeiro realizamos a caracterizao dos trabalhos; aps, organizamos o material a partir de dados evidentes nos estudos, dando lugar s categorias temticas: cuidado centrado nos aspectos fisiolgicos do recm-nascido; a famlia que acompanha os cuidados ao recm-nascido em UTI neonatal; e a equipe de sade que atua no cuidado ao recm-nascido em UTI neonatal. Constatamos que a pesquisa em enfermagem busca novas formas de cuidar, e proporciona uma aproximao entre a teoria e a prtica, garantindo sua sustentao enquanto profisso, e contribuindo na produo de conhecimento em neonatologia.
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Trata-se de um estudo documental, descritivo, com abordagem quantitativa, com o objetivo de caracterizar a produo da ps-graduao brasileira na rea da enfermagem no trinio 2007-2009, com nfase na temtica gerenciamento em enfermagem. As informaes foram obtidas no banco de dados da CAPES, que disponibiliza resumos de dissertaes e teses. O material foi analisado e categorizado segundo as reas/campos e respectivas linhas de pesquisa, definidas pela rea de Enfermagem. A anlise da produo em geral foi descritiva e analtica/crtica no campo organizacional, especificamente, na temtica do gerenciamento. Os resultados mostraram algumas mudanas na produo no trinio, quando comparada aos estudos anteriores, destacando-se o crescimento da rea/campo assistencial, manuteno da organizacional e queda na rea/campo profissional. Na temtica de gerenciamento houve o predomnio de estudos sobre avaliao em sade, concepes/percepes sobre planejamento/organizao, do trabalho-servios e educao permanente.
Resumo:
O estudo objetivou analisar o perfil profissional das egressas do Programa de Ps-Graduao em Enfermagem da Universidade Federal da Bahia na rea de gerenciamento em enfermagem. Trata-se de estudo descritivo e exploratrio, desenvolvido atravs de pesquisa documental. Foram utilizados dados dos Currculos Lattes ede documentos do Programa coletados atravs de formulrio. A populao foi constituda por egressas na Linha de Pesquisa Organizao e Avaliao dos Sistemas de Cuidado Sade, que desenvolveram dissertaes/teses relacionadas ao Gerenciamento em Enfermagem/Sade. Os dados foram armazenados no software Microsoft Excel e, em seguida, transferidos para o programa estatstico STATA 9.0. Os resultados indicaram que a maioria das egressasso mulheres, originrias do estado da Bahia, concluintes do curso entre 2000 e 2011; docentes de instituies pblicas que continuaram na atividade acadmica aps a concluso do curso. Esses resultados apontam o Programa como um espao acadmico comprometido com a preparao de pesquisadoras.
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O estudo das teses e dissertaes produzidas pelo Grupo de Pesquisa Gnero, Sade e Enfermagem, da Escola de Enfermagem da Universidade de So Paulo, teve por objetivo descrever e analisar a produo do saber construdo pelo grupo, seu produto e processo de construo. Os resultados mostram uma produo expressiva no conjunto de estudos de gnero no cenrio nacional, revelando que o aprofundamento da compreenso dos fenmenos sociais sob a tica de gnero tem trazido avanos no s no mbito da pesquisa, como da interveno. No campo das prticas em sade e de enfermagem, tem se mostrado capaz de revelar os limites e as potencialidades que as permeiam.
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SUMMARY : The present work addresses several aspects of cell cycle regulation, cell fate specification and cell death in the central nervous system (CNS), specifically the cortex and the retina. More precisely, we investigated the role of Bmi1, a polycomb family gene required for stem cell proliferation and self-renewal, in the development of the cerebral cortex, as well as in the genesis of the retina. These data, together with studies published during the last two decades concerning cell cycle re-activation in apoptotic neurons in the CNS, raised the question of a possible link between regulation of the cell cycle during development and during retinal degeneration. 1. The effects of Bmi1 loss in the cerebral cortex : Consistently with our and others' observations on failure of Bmi9-/- stem cells to proliferate and self-renew in vitro, the Bmi9-/- cerebral cortex presented slight defects in proliferation in stem/progenitor cells compartments in vivo. This was in accordance with the pattern of Bmi1 expression in the developing forebrain. The modest proliferation defects, compared to the drastic consequences of Bmi9 loss in vitro, suggest that cell-extrinsic mechanisms may partially compensate for Bmi1 deletion in vivo during cortical histogenesis. Nevertheless, we observed a decreased proliferating activity in neurogenic regions of the adult telencephalon, more precisely in the subventricular zone, showing that Bmi1 controls neural stem/progenitor proliferation during adulthood in vivo. Our data also highlight an increased production of astrocytes at birth, and a generalized gliosis in the adult Bmi9-/- brain. Importantly, glial progenitors and astrocytes retained the ability to proliferate in the absence of Bmi1. 2. The effects of Bmi1 loss in the retina : The pattern of expression of Bmi1 during development and in the adult retina suggests a role for Bmi1 in cell fate specification and differentiation rather than in proliferation. While the layering and the global structure of the retina appear normal in Bmi1 /adult mice, immunohistochemcal analysis revealed defects in the three major classes of retinal interneurons, namely: horizontal, bipolar and amacrine cells. Electroretinogram recordings in Bmi9-/- mice are coherent with the defects observed at the histological level, with a reduced b-wave and low-profile oscillatory potentials. These results show that Bmi1 controls not only proliferation, but also cell type generation, as previously observed in the cerebellum. 3. Cell cycle events and related neuroprotective strategies in retinal degeneration : In several neurodegenerative disorders, neurons re-express cell cycle proteins such as cyclin dependent kinases (Cdks) prior to apoptosis. Here, we show for the first time that this is also the case during retinal degeneration. Rd1 mice carry a recessive defect (Pdebrd/rd) that causes retinal degeneration and serves as a model of retinitis pigmentosa. We found that photoreceptors express Cdk4 and Cdk2, and undergo DNA synthesis prior to cell death. To interfere with the reactivation of Cdk-related pathways, we deleted E2fs or Brni1, which normally allow cell cycle progression. While deleting E2f1 (downstream of Cdk4/6) in Rd1 mice provides only temporary protection, knocking out Bmi1 (upstream of Cdks) leads to an extensive neuroprotective effect, independent of p16ink4a or p19arf, two tumor suppressors regulated by Bmi1. Analysis of Cdks and the DNA repair-related protein Ligase IV showed that Bmi1 acts downstream of DNA repair events and upstream of Cdks in this neurodegenerative mechanism. Expression of Cdks during an acute model of retinal degeneration, light damage-induced photoreceptor death, points to a role for Bmi1 and cell cycle proteins in retinal degeneration. Considering the similarity with the cell cycle-related apoptotic pathway observed in other neurodegenerative diseases, Bmi1 is a possible general target to prevent or delay neuronal death. RESUME : Ce travail aborde plusieurs aspects de la rgulation du cycle cellulaire, de la spcification du devenir des cellules et de la mort cellulaire dans le systme nerveux centrale (SNC), plus particulirement dans le cortex crbral et dans la rtine. Nous nous sommes intresss au gne Bmi1, appartenant la famille polycomb et ncessaire la prolifration et au renouvellement des cellules souches. Nous avons vis dissquer son rle dans le dveloppement du cortex et de la rtine. Ces donnes, ainsi qu'une srie de travaux publis au cours des deux dernires dcennies concernant la ractivation du cycle cellulaire dans les neurones en voie d'apoptose dans le SNC, nous ont ensuite pouss chercher un lien entre la rgulation du cycle cellulaire pendant le dveloppement et au cours de la dgnrescence rtinienne. 1. Les effets de l'inactivation de Bmi1 dans le cortex crbral : En accord avec l'incapacit des cellules souches neurales in vitro prolifrer et se renouveler en absence de Bmi1, le cortex crbral des souris Bmi1-/- prsente de lgers dfauts de prolifration dans les compartiments contenant les cellules souches neurales. Ceci est en accord avec le profil d'expression de Bmi1 dans le tlencphale. Les consquences de la dltion de Bmi1 sont toutefois nettement moins prononces in vivo qu'in vitro ; cette diffrence suggre l'existence de mcanismes pouvant partiellement compenser l'absence de Bmi1 pendant la corticogense. Nanmoins, l'observation d'une rduction de la prolifration dans la zone sous-ventriculaire, la zone majeure de neurogense dans le tlencphale adulte, montre que Bmi1 contrle la prolifration des cellules souche/prognitrices neurales chez la souris adulte. Nos rsultats dmontrent par ailleurs une augmentation de la production d'astrocytes la naissance ainsi qu'une gliose gnralise l'tat adulte chez les souris Bmi1-/-. Les progniteurs gliaux et les astrocytes conservent donc leur capacit prolifrer en absence de Bmi1. 2. Les effets de l'inactivation de Bmi1 dans la rtine : Le profil d'expression de Bmi1 pendant fe dveloppement ainsi que dans la rtine adulte suggre un rle de Bmi1 dans la spcification de certains types cellulaires et dans la diffrentiation plutt que dans la prolifration. Alors que la structure et la lamination de la rtine semblent normales chez les souris Bmi1-/-, l'analyse par immunohistochimie amis en vidence des dfauts au niveau des trois classes d'interneurones rtiniens (les cellules horizontales, bipolaires et amacrines). Les lectrortinogrammes des souris Bmi1-/- sont cohrents avec les dfauts observs au niveau histologique et montrent une rduction de l'onde b et des potentiels oscillatoires. Ces rsultats montrent que Bmi1 contrle la gnration de certaines sous-populations de neurones, comme dmontr auparavant au niveau de cervelet. 3. Ractivation du cycle cellulaire et stratgies thraoeutiaues dans les dgnrescences rtiniennes : Dans plusieurs maladies neurodgnratives, les neurones r-expriment des protines du cycle cellulaire telles que les kinases cycline-dpendantes (Cdk) avant d'entrer en apoptose. Nous avons dmontr que c'est aussi le cas dans les dgnrescences rtiniennes. Les souris Rd1 portent une mutation rcessive (Pde6brd/rd) qui induit une dgnrescence de la rtine et sont utilises comme modle animal de rtinite pigmentaire. Nous avons observ que les photorcepteurs expriment Cdk4 et Cdk2, et entament une synthse d'ADN avant de mourir par apoptose. Pour interfrer avec la ractivation les mcanismes Cdk-dpendants, nous avons inactiv les gnes E2f et Bmi1, qui permettent normalement la progression du cycle cellulaire. Nous avons mis en vidence que la dltion de E2f1 (en aval de Cdk4/6) dans les souris Rd1 permet une protection transitoire des photorcepteurs. Toutefois, l'inactivation de Bmi1 (en amont des Cdk) est corrle une neuroprotection bien plus durable et ceci indpendamment de p16ink4a et p19arf, deux suppresseurs de tumeurs normalement rguls par Bmi1. L'analyse des Cdk et de la ligase IV (une protine implique dans les mcanismes de rparation de l'ADN) a montr que Bmi1 agit en aval des vnements de rparation de l'ADN et en amont des Cdk dans la cascade apoptotique dans les photorcepteurs des souris Rd1. Nous avons galement observ la prsence de Cdk dans un modle aigu de dgnrescence rtinienne induit par une exposition des animaux des niveaux toxiques de lumire. Nos rsultats suggrent donc un rle gnral de Bmi1 et des protines du cycle cellulaire dans les dgnrescences de la rtine. Si l'on considre la similarit avec les vnements de ractivation du cycle cellulaire observs dans d'autres maladies neurodgnratives, Bmi1 pourrait tre une cible thrapeutique gnrale pour prvenir la mort neuronale.
Resumo:
O estudo tem por objetivo identificar a produo cientfica sobre liderana no contexto da enfermagem produzida nos ltimos 10 anos (1999-2008). Trata-se de uma reviso bibliogrfica na base de dados LILACS, na qual foram includos trabalhos publicados no formato de artigos, teses, dissertaes, editoriais, apresentao de trabalho em eventos; em portugus, ingls ou espanhol; disponveis na ntegra no formato eletrnico. Optou-se pela construo de um formulrio para registrar os dados das produes, entre eles: referncia, procedncia dos manuscritos, ano, categoria, objetivos, metodologia e referencial terico. Encontraram-se 57 publicaes, das quais houve o predomnio de artigos originais, do tipo descritivo, no mbito hospitalar e a escassa utilizao de Teorias de Liderana fundamentando os estudos. A pesquisa aponta para a necessidade de adotar programas de desenvolvimento de lderes e projetos de educao permanente nos servios de sade, a fim de prepar-los para aplicar a liderana na enfermagem.
Resumo:
Trata-se de uma pesquisa documental que analisou a produo brasileira da ps-graduao stricto sensu em enfermagem relacionada hipertenso gestacional. Para tal, utilizou-se como fonte de pesquisa o Banco de Teses e Dissertaes da Associao Brasileira de Enfermagem. Identificaram-se 14 estudos produzidos entre 1979-2008, cuja produo concentrou-se na regio sudeste, entre 1996-2008. O processo analtico revelou a preocupao com a subjetividade das gestantes e com aspectos voltados assistncia de enfermagem. Mostrou, tambm, que a maioria dos estudos envolveu metodologia qualitativa e sob sustentao de teorias de enfermagem. A experincia vivida pelas gestantes hipertensas marcada por sentimentos negativos, por problemas socioeconmicos e influenciada pela forma de organizao familiar. A cultura das gestantes hipertensas desconsiderada e elas so assistidas em um contexto no qual a doena prioridade. Conclui-se que, apesar de alguns avanos cientficos, o tema no tem despertado o interesse merecido entre os enfermeiros que cursam ps-graduao.
Resumo:
Este trabalho tem por finalidade analisar a relao entre a estratgia na conduo da poltica externa cabo-verdiana e o seu crescimento e desenvolvimento econmico, de 1975 a 2008. Ou seja: At que ponto a estratgia seguida por Cabo Verde na conduo da poltica externa contribuiu para o seu desenvolvimento?. Esta a questo fulcral qual a presente dissertao procura responder. A anlise ser dividida em dois perodos, sendo que o primeiro corresponde ao perodo anterior abertura poltico-econmica de 1975 a 1991, e o segundo ao perodo posterior referida abertura de 1991 a 2008. A investigao baseia-se nas literaturas cabo-verdiana, portuguesa e outras consideradas relevantes para o efeito pretendido, entrevistas informais a alguns membros ou ex-membros de Governo e diplomatas cabo-verdianos, legislao e documentos oficiais sobre Cabo Verde, consultas na internet, bem como na prpria experincia vivida pelo autor deste trabalho, que tem acompanhado a evoluo do pas desde os primeiros anos aps a independncia. Conclui-se que, durante o perodo em estudo, a estratgia adoptada por sucessivos Governos na conduo da poltica externa do pas tem-se revelado determinante para o crescimento e desenvolvimento do arquiplago. A defesa do interesse nacional de Cabo Verde tem sido sempre o objectivo essencial dos governantes. Todavia, nos primeiros anos aps a independncia, sentiu-se, no pas, alguma influncia de pressupostos ideolgicos, o que tornou menos objectiva a conduo da poltica externa. Atravs das relaes externas de cooperao, das ajudas pblicas ao desenvolvimento, das parcerias, das remessas de emigrantes e de outros financiamentos, o pas tem conseguido progredir em vrias reas, a saber, nos domnios econmico, social, poltico e cultural. A abertura poltica e econmica a partir de 1991 foi um factor determinante para a credibilizao da poltica externa do pas no contexto internacional, o que contribuiu para o seu crescimento e desenvolvimento. Finalmente, analisam-se as possveis causas da cooperao deficitria entre frica e o arquiplago, bem como os principais objectivos alcanados por Cabo Verde a partir de 2005, nomeadamente a conquista do programa norte-americano Millennium Challenge Account (MCA), a elevao do arquiplago a Pas de Desenvolvimento Mdio (PDM), a parceria especial com a Unio Europeia, bem como a entrada para a Organizao Mundial do Comrcio (OMC), entre outros desafios da poltica externa cabo-verdiana.
