3 resultados para Critical Pathways

em Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho"


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The inflammatory response is a protective process of the body to counteract xenobiotic penetration and injury, although in disease this response can become deregulated. There are endogenous biochemical pathways that operate in the host to keep inflammation under control. Here we demonstrate that the counter-regulator annexin 1 (AnxA1) is critical for controlling experimental endotoxemia. Lipopolysaccharide (LPS) markedly activated the AnxA1 gene in epithelial cells, neutrophils, and peritoneal, mesenteric, and alveolar macrophages-cell types known to function in experimental endotoxemia. Administration of LPS to AnxA1-deficient mice produced a toxic response characterized by organ injury and lethality within 48 hours, a phenotype rescued by exogenous application of low doses of the protein. In the absence of AnxA1, LPS generated a deregulated cellular and cytokine response with a marked degree of leukocyte adhesion in the microcirculation. Analysis of LPS receptor expression in AnxA1-null macrophages indicated an aberrant expression of Toll-like receptor 4. In conclusion, this study has detailed cellular and biochemical alterations associated with AnxA1 gene deletion and highlighted the impact of this protective circuit for the correct functioning of the homeostatic response to sublethal doses of LPS. Copyright © American Society for Investigative Pathology.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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The concept of resilience is often situated in a dominant discourse that reflects medical and developmentalist epistemology, in Western models, with the ideology of white people, and middle class hegemonic norms. Behavior that falls outside of the normal, or what is socially acceptable, is associated with riskiness and tacitly if not explicitly labeled as pathological, and then, not resilient. However, the context of social injustice of many young people at-risk can have drastic effects on them. When we offer institutions such as schools that do not understand their needs, they may refuse our services and some of them may engage in antisocial activities, since they are looking for personal validation, pathways to recognize themselves, and places and organizations that contribute to the building of their social identity. This paper analyses how the denial of support and resources for the wellbeing of young people can lead them to situations that are socially unacceptable, such as sexual exploitation and drug trafficking. The main argument is that these activities, in the absence of conventional mechanisms, may bring some benefit to the subjects. Benefits may be in material conditions, though strongly marked by issues of social inequality; or subjective, in gaining relationships with people outside the normative places and institutions for young people. Unconventional circumstances produce unconventional attitudes that are expressed in alternative forms of resilience.