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1.
J Pediatr Endocrinol Metab ; 27(5-6): 549-54, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24468605

RESUMO

BACKGROUND: Antiepileptics may affect cortisol metabolism through CYP3A4. There is little known about ethosuximide. CLINICAL CASE: Our patient is a 12-year-old girl with salt-wasting congenital adrenal hyperplasia (CAH) owing to 21 hydroxylase deficiency. A standard treatment regimen was initiated with satisfactory results until the age of 6 years, when she developed absence seizures treated with ethosuximide. She received such therapy until the age of 12 years, at which point ethosuximide was discontinued. During ethosuximide administration, she experienced worsening control of CAH disease activity that responded to progressive increases in hydrocortisone dose up to 28 mg/m2 per day. Despite high doses of hydrocortisone, she suffered no cushingoid symptoms. Her requirements for high glucocorticoid replacement doses resolved shortly after ethosuximide was discontinued. We provide data over 6 years demonstrating a correlation between adrenal hormone secretion, cortisol requirements and ethosuximide dose. CONCLUSION: This is the first case demonstrating an interaction between ethosuximide and hydrocortisone clearance in the treatment of salt-wasting CAH.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Anticonvulsivantes/efeitos adversos , Etossuximida/efeitos adversos , Hidrocortisona/metabolismo , Hidrocortisona/uso terapêutico , Criança , Interações Medicamentosas , Epilepsia Tipo Ausência/complicações , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tônico-Clônica/complicações , Epilepsia Tônico-Clônica/tratamento farmacológico , Feminino , Humanos
2.
J Clin Invest ; 120(12): 4466-77, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21099112

RESUMO

Excessive iron absorption is one of the main features of ß-thalassemia and can lead to severe morbidity and mortality. Serial analyses of ß-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with ß-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in ß-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in ß-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with ß-thalassemia and related disorders.


Assuntos
Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia beta/tratamento farmacológico , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Sequência de Bases , Primers do DNA/genética , Modelos Animais de Doenças , Eritropoese/efeitos dos fármacos , Expressão Gênica , Hepcidinas , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/metabolismo , Ferro da Dieta/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Camundongos Transgênicos , Proteínas Recombinantes/genética , Proteínas Recombinantes/uso terapêutico , Talassemia beta/sangue , Talassemia beta/metabolismo
3.
Ann N Y Acad Sci ; 1202: 221-5, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20712796

RESUMO

Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with beta-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in beta-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in beta-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Sobrecarga de Ferro/metabolismo , Proteínas de Membrana/metabolismo , Talassemia beta/metabolismo , Anemia/etiologia , Anemia/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Terapia Genética , Vetores Genéticos/genética , Proteína da Hemocromatose , Hepcidinas , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/uso terapêutico , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia , Proteínas de Membrana/genética , Proteínas de Membrana/uso terapêutico , Talassemia beta/complicações , Talassemia beta/genética , Talassemia beta/terapia
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