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Dig Dis Sci ; 59(11): 2666-74, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25138901

RESUMO

BACKGROUND: Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown. AIMS: We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB. METHODS: There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls. RESULTS: Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p = 0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p = 0.0003) after treatment. CONCLUSIONS: Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high-dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/administração & dosagem , Omeprazol/administração & dosagem , Úlcera Péptica Hemorrágica/induzido quimicamente , Fumar/efeitos adversos , Adulto , Idoso , Antiulcerosos/uso terapêutico , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Omeprazol/uso terapêutico , Úlcera Péptica Hemorrágica/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
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