RESUMO
Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing a secondary infection with a different serotype progress to the severe form of the disease, called dengue hemorrhagic fever. In this study, the vaccine potential of three tetravalent and conserved synthetic peptides derived from DENV envelope domain I (named Pep01) and II (named Pep02 and Pep03) was evaluated. Human dengue IgM/IgG positive serum (n=16) showed reactivity against Pep01, Pep02 and Pep03 in different degrees. Mice immunization experiments showed that these peptides were able to induce a humoral response characterized by antibodies with low neutralizing activity. The spleen cells derived from mice immunized with the peptides showed a significant cytotoxic activity (only for Pep02 and Pep03), a high expression of IL-10 (P<0.01) and a reduced expression of TNF-α and IFN-gamma (P<0.001) compared to DENV-1 infected splenocytes. Thus these peptides, and specially the Pep03, can induce a humoral response characterized by antibodies with low neutralizing activities and probably a T cell response that could be beneficial to induce an effective immune response against all DENV serotypes and do not contributed to the immunopathogenesis. However, further studies in peptide sequence will be required to induce the production of neutralizing antibodies against all four DENV serotypes and also to improve immunogenicity of these peptides.
Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Testes Imunológicos de Citotoxicidade , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/genética , Vírus da Dengue/genética , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Camundongos , Testes de Neutralização , Linfócitos T Citotóxicos/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/genéticaRESUMO
Introdução: Queimaduras em crianças são uma das causas mais frequentes de internação e de mortalidade por fatores externos no Brasil. Crianças com mais de 30% de Superfície Corporal Queimada (SCQ) evoluem com hiperglicemia pós-traumática e resistência aos efeitos da insulina, situação que prejudica a função imune, aumenta o risco de infecção, compromete a cicatrização e aumenta a mortalidade. O controle da hiperglicemia, com o uso da insulinoterapia, já na assistência intensiva, diminui a morbidade e mortalidade e aumenta a sensibilidade à insulina. Objetivo: Identificar a alteração da sensibilidade à insulina em crianças queimadas. Método: Revisão Sistemática, realizada busca na base de dados Pubmed referente aos anos de 2009 a 2013. Resultados: Os estudos mostraram que a queimadura, nas crianças com mais de 30% de SCQ, está relacionada à hiperglicemia, aumento de catecolaminas plasmáticas, fatores inflamatórios, aumento da incidência de sepse e mortalidade. A resistência à insulina está relacionada à hiperglicemia, à via inflamatória, aos ácidos graxos livres, ao stress do retículo endoplasmático e à diminuição da oxidação mitocondrial. A insulinoterapia intensiva diminuiu a morbidade e a mortalidade dos pacientes. Crianças permaneceram com resistência à insulina por até três anos pós-injúria. Conclusão: A persistência da hiperglicemia pós-traumática e dos fatores inflamatórios, bem como o estresse do retículo endoplasmático e a diminuição da oxidação mitocondrial na criança queimada, contribuem para a resistência à insulina em até três anos após a injúria. O manejo da hiperglicemia no paciente crítico com o uso da insulinoterapia intensiva diminuiu a morbidade e a mortalidade nos estudos analisados, inclusive contribuindo para o aumento da sensibilidade à insulina e consequente diminuição de sua resistência...
Introduction: Burns in children are one of the most frequent causes of hospitalization and mortality by external causes in Brazil. Children over 30% TBSA (Total body surface area) evolve with posttraumatic hyperglycemia and resistance to insulins effects, a situation that impairs immune function, increases the risk of infection, impairs wound healing and increases mortality. The control of hyperglycemia by insulin, as in intensive care reduce morbidity and mortality and improves insulin sensitivity. Objective: To identify the change in insulin sensitivity in burned children. Methods: Systematic Review, carried out search in the Pubmed database for the years 2009 to 2013. Results: Studies have shown that burns in children over 30% TBSA, is related to hyperglycemia, increased plasma catecholamines, inflammatory factors, increased incidence of sepsis and mortality. Insulin resistance is related to hyperglycemia, the inflammatory pathway, the free fatty acids, endoplasmic reticulum stress and decreased mitochondrial oxidation. Intensive insulin therapy decreased the morbidity and mortality of patients. Children remained insulin resistance post-injury up to three years. Conclusions: The persistence of posttraumatic hyperglycemia and inflammatory factors as well as the endoplasmic reticulum stress and decreased mitochondrial oxidation in burned children contribute to insulin resistance by up to three years after the injury. Management of hyperglycemia in critically ill patients through intensive insulin therapy decreased morbidity and mortality in the assessed studies, including contributing to increased insulin sensitivity and consequentreduction of its resistance. It was observed that the target of 130 mg/dl in severely child is recommended, with indications of strict glycemic control to avoid hypoglycemic episodes. Increased vitamin A in these children, as well as increased risk of developing diabetes mellitus 2 are issues that need further studies for ...