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3.
ACG Case Rep J ; 3(2): 127-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26958568

RESUMO

We present a 24-year-old combat veteran who underwent extensive work-up for elevated aminotransferases, including liver biopsy, with no underlying pathology identified. Subsequent investigations showed elevated creatinine kinase and aldolase. The patient was later diagnosed with biopsy-proven dysferlin-deficient muscular dystrophy. Persistent transaminase elevation despite negative liver work-up should prompt clinicians to consider extrahepatic sources of enzyme elevation. Promptly correlating aminotransferase elevation with musculoskeletal pathology may present an opportunity for clinicians to detect myopathies such as muscular dystrophy in their preclinical stages.

8.
Transplantation ; 92(7): 745-51, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21869742

RESUMO

BACKGROUND: Development of pretransplantation islet culture strategies that preserve or enhance ß-cell viability would eliminate the requirement for the large numbers of islets needed to restore insulin independence in type 1 diabetes patients. We investigated whether glial cell line-derived neurotrophic factor (GDNF) could improve human islet survival and posttransplantation function in diabetic mice. METHODS: Human islets were cultured in medium supplemented with or without GDNF (100 ng/mL) and in vitro islet survival and function assessed by analyzing ß-cell apoptosis and glucose stimulated insulin release. In vivo effects of GDNF were assessed in streptozotocin-induced diabetic nude mice transplanted under the kidney capsule with 2000 islet equivalents of human islets precultured in medium supplemented with or without GDNF. RESULTS: In vitro, human islets cultured for 2 to 10 days in medium supplemented with GDNF showed lower ß-cell death, increased Akt phosphorylation, and higher glucose-induced insulin secretion than islets cultured in vehicle. Human islets precultured in medium supplemented with GDNF restored more diabetic mice to normoglycemia and for a longer period after transplantation than islets cultured in vehicle. CONCLUSIONS: Our study shows that GDNF has beneficial effects on human islet survival and could be used to improve islet posttransplantation survival.


Assuntos
Diabetes Mellitus Experimental/cirurgia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Glucose/farmacologia , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Camundongos , Camundongos Nus , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina/efeitos adversos , Transplante Heterólogo
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