title: Effect of omeprazole dose, nonsteroidal anti-inflammatory agents, and smoking on repair mechanisms in acute peptic ulcer bleeding.
abstract: BACKGROUND
  Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Kuopio University Hospital, Box 100, 70029, Kuopio, Finland, tuomora@gmail.com.
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rantanen
authors.forename: Marianne
authors.initials: M
authors.lastname: Udd
authors.forename: Teemu
authors.initials: T
authors.lastname: Honkanen
authors.forename: Pekka
authors.initials: P
authors.lastname: Miettinen
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.forename: Lassi
authors.initials: L
authors.lastname: Rantanen
authors.forename: Risto
authors.initials: R
authors.lastname: Julkunen
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.forename: Niku
authors.initials: N
authors.lastname: Oksala
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage* / Q000627:therapeutic use; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D009853:Omeprazole