ABSTRACT
Islet transplantation has become a well-established therapy for select patients with type 1 diabetes. Viability and engraftment can be compromised by the generation of oxidative stress encountered during isolation and culture. We evaluated whether the administration of BMX-001 (MnTnBuOE-2-PyP5+ [Mn(III) meso-tetrakis-(N-b-butoxyethylpyridinium-2-yl)porphyrin]) and its earlier derivative, BMX-010 (MnTE-2-PyP [Mn(III) meso-tetrakis-(N-methylpyridinium-2-yl)porphyrin]) could improve islet function and engraftment outcomes. Long-term culture of human islets with BMX-001, but not BMX-010, exhibited preserved in vitro viability. Murine islets isolated and cultured for 24 hours with 34 µmol/L BMX-001 exhibited improved insulin secretion (n = 3 isolations, P < .05) in response to glucose relative to control islets. In addition, 34 µmol/L BMX-001-supplemented murine islets exhibited significantly reduced apoptosis as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling, compared with nontreated control islets (P < .05). Murine syngeneic islets transplanted under the kidney capsule at a marginal dose of 150 islets revealed 58% of 34 µmol/L BMX-001-treated islet recipients became euglycemic (n = 11 of 19) compared with 19% of nontreated control islet recipients (n = 3 of 19, P < .05). Of murine recipients receiving a marginal dose of human islets cultured with 34 µmol/L BMX-001, 92% (n = 12 of 13) achieved euglycemia compared with 57% of control recipients (n = 8 of 14, P = .11). These results demonstrate that the administration of BMX-001 enhances in vitro viability and augments murine marginal islet mass engraftment.
Subject(s)
Apoptosis/drug effects , Biomimetic Materials/pharmacology , Diabetes Mellitus, Experimental/prevention & control , Islets of Langerhans/drug effects , Metalloporphyrins/pharmacology , Animals , Cells, Cultured , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Glucose/pharmacology , Graft Survival , Humans , Insulin/metabolism , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Islets of Langerhans Transplantation , Male , Mice , Mice, Inbred BALB C , Oxidation-Reduction , Superoxide Dismutase/metabolismABSTRACT
A study a petrochemical plant examined the work environment and effects caused by combinations of multiple stressors in the working area. Work stressors and some health effects were perceived more prevalent among shiftworkers. Efficient contermeasures to protect and improve workers' health, should include the wholeness of the work environment, as well as the work organization
Subject(s)
Industry , Petroleum , Working ConditionsABSTRACT
Compreende 3 subprojetos. O primeiro estudo sobre Trabalho em Turnos de Revezamento Contínuo objetiva avaliar as possíveis repercussöes no trabalho em turnos nos âmbitos biológico, do desempenho no trabalho, das relaçöes sócio-familiares. A metodologia utilizada baseou-se em obter e comparar informaçöes a partir de uma amostragem dos trabalhadores através de entrevistas, questionários, perfis, protocolos e auto-avaliaçöes. O segundo estudo Análise Ergonômica do Trabalho em Sala de Controle fez uma avaliaçäo qualitativa inicial que permitiu estabelecer o perfil da carga de trabalho dos operadores das salas de controle principais com terminais de vídeo. Faz recomendaçöes para se identificar e/ou prevenir os problemas potenciais de saúde relacionados a este trabalho. O terceiro estudo Características Individuais, Familiares e do Trabalho objetivou avaliar e comparar, através de um questionário, as condiçöes de trabalho e de vida dos trabalhadores em turnos e diurnos que compunham a amostra real do estudo, dividida em quatro grandes áreas (CAC)