title: Gastroduodenal mucosal defense: an integrated protective response.
abstract: OBJECTIVE
  The remarkable resistance of the mucosal lining the upper gastrointestinal tract to concentrated gastric acid remains one of the biggest unsolved mysteries of upper gastrointestinal physiology. Even with the discovery of the involvement of Helicobacter pylori in gastroduodenal injury, the mechanism by which the organism causes injury remains unresolved. In the past year, there have been striking findings regarding trefoil peptides, the protective effect of regulatory peptides such as adrenomedullin, and the influence of H. pylori on the junctions that join the epithelial cells.
  
  
  RESULTS
  Trefoil peptide-2-deficient mice were more susceptible to gastric injury from nonsteroidal anti-inflammatory agents, confirming that trefoil peptides increased the barrier properties of the pre-epithelial mucus gel. With regard to H. pylori, the gastric mucosa of mice deficient in the tyrosine phosphatase receptor type Z were not damaged by H. pylori vacuolating cytotoxin. Proton pump inhibition appears to be equally or more effective in upper gastrointestinal mucosal protection compared with other interventions such as exogenous prostaglandins or H. pylori eradication.
  
  
  CONCLUSIONS
  Peptic ulcer disease, although declining in prevalence, appears to be increasing in virulence, perhaps because of the overall aging of the population and improved intensive care unit care. Although H. pylori and nonsteroidal anti-inflammatory drugs have been identified as key pro-ulcerogenic factors, many ulcers may also result from a deficiency of other, unknown host protective factors. A more detailed understanding of the host factors involved in mucosal protection will thus help identify novel therapeutic targets aimed at the prevention and treatment of upper gastrointestinal mucosal injury.
authors.affiliation: Long Beach VA Medical Center, Long Beach, California, USA.
authors.forename: Luke C
authors.initials: LC
authors.lastname: Bi
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kaunitz