RESUMO
BACKGROUND: Although islet cell transplantation is considered an ideal form of endocrine replacement for type I diabetes, clinical application in humans is still not feasible. New immunosuppressive strategies are clearly needed to control inexorable rejection. CD45 is a family of transmembrane protein tyrosine phosphatases critically involved in the regulation of lymphocyte activation signals. Anti-CD45RB monoclonal antibody can prevent rejection of murine renal allografts. METHODS: Here, we examine the consequences of targeting CD45 in murine islet cell transplantation. Diabetic mice recipients received islet allografts under the kidney capsule and were divided into seven groups. Recipients received no treatment (controls) or anti-CD45RB monoclonal antibody (mAb; MB23G2 or C363.16A) at different dosages and treatment intervals. RESULTS: All untreated control animals lost islet function, becoming hyperglycemic within 10-17 days after transplantation. Animals treated with either anti-CD45RB mAb showed a significant prolongation of islet allograft survival when compared with controls. Anti-CD45RB MB23G2 at 100 microg/day, given on days -1, 0, and 5 was particularly effective, inducing indefinite islet allograft survival in 60% of recipients. CONCLUSIONS: These results indicate that anti-CD45 mAbs are potent immunomodulatory agents, able to sustain indefinite islet allograft function after a short treatment course in the highly immunogenic model of islet transplantation.
Assuntos
Anticorpos Monoclonais/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/farmacologia , Transplante das Ilhotas Pancreáticas/imunologia , Antígenos Comuns de Leucócito/imunologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante HomólogoAssuntos
Constituição Corporal , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Transplante de Rim , Rim/anatomia & histologia , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/organização & administração , Superfície Corporal , Peso Corporal , Doença Crônica , Rejeição de Enxerto/etiologia , Humanos , Análise Multivariada , Análise de Regressão , Estudos Retrospectivos , Fatores de RiscoAssuntos
Teste de Histocompatibilidade , Transplante de Rim/imunologia , Transplante de Pâncreas/imunologia , Ciclosporina/uso terapêutico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/terapia , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/fisiologia , Muromonab-CD3/uso terapêutico , Transplante de Pâncreas/fisiologia , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Doadores de Tecidos , Resultado do TratamentoAssuntos
Anticorpos Monoclonais/uso terapêutico , Diabetes Mellitus Experimental/terapia , Sobrevivência de Enxerto/imunologia , Terapia de Imunossupressão/métodos , Transplante das Ilhotas Pancreáticas/imunologia , Antígenos Comuns de Leucócito/imunologia , Animais , Glicemia/metabolismo , Éxons , Transplante das Ilhotas Pancreáticas/fisiologia , Antígenos Comuns de Leucócito/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante Homólogo , Transplante IsogênicoAssuntos
Doenças Cardiovasculares/prevenção & controle , Transplante de Pâncreas/fisiologia , Ácidos Siálicos/sangue , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/cirurgia , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/cirurgia , Humanos , Transplante de Rim , Ácido N-Acetilneuramínico , Fatores de RiscoRESUMO
Through this study, the authors make a capital a critical analysis about the national conjuncture within the field of health, and settle a relationship with the problems experienced by the municipality of Londrina. They analyse the responsibility of Federal Government and their various sectors, regarding the insufficiency of financial resources to be used in the area, and by the bad management of these resources. The structure health services in Londrina is described in detail, emphasizing the importance of this town as the regional center for the whole of northern Paraná. Emphasis is given to the excess os patients, at the moment, mainly in relation to general hospitals, because of lack of availability of beds. At the end of the study, considerations about the legislation of SUS (Sistema único de Saúde) are made and several suggestions are presented, aiming at regularizing the situation in the Municipality of Londrina.
