Mucosal defense

Prostaglandins, one of the most important epithelial growth factors, inhibit gastric acid secretion and have numerous mucosal protective effects, the most important of which include the stimulation of both mucus and phospholipid production, promotion of bicarbonate secretion, and increased mucosal cell turnover. Damage to the mucosal defense system is the primary method by which HP or NSAIDs cause peptic ulcers. 

Misoprostol is a synthetic prostaglandin E2 analog that exogenously replaces prostaglandin stores. The minimum effective dose shown to inhibit acid secretion and promote mucosal defense is 400 meg/day. Misoprostol use is limited by a high frequency of bothersome gastrointestinal effects such as abdominal pain, flatulence, and diarrhea. In placebo-controlled studies diarrhea occurred with twice the frequency in the... 

Problems with other normal mucosal defense mechanisms may also contribute to the development of GERD, including prolonged acid clearance time from the esophagus, delayed gastric emptying, and reduced mucosal resistance. 

Most peptic ulcers occur in the presence of acid and pepsin when HP, NSAIDs, or other factors disrupt normal mucosal defense and healing mechanisms. Acid is an independent factor that contributes to disruption of mucosal integrity. Increased acid secretion has been observed in patients with DU and may result from HP infection. Patients with GU usually have normal or reduced rates of acid secretion. 

Alterations in mucosal defense induced by HP or NSAIDs are the most important cofactors in peptic ulcer formation. Mucosal defense and repair mechanisms include mucus and bicarbonate secretion, intrinsic epithelial cell defense, and mucosal blood flow. Maintenance of mucosal integrity and repair is mediated by endogenous prostaglandin production. 

PGE and PGI2 are the main prostaglandins synthesized by gastric mucosa. They decrease acid secretion and improve mucosal defense mechanism by ... 

Lamont, J.T. 1992. Mucus The front line of intestinal mucosal defense. In Neuro-immuno physiology of the gastrointestinal mucosa, implications for inflammatory diseases, eds. R.H. Stead, M.H. Perdue, H. Cook, D.W. Powel, and K.E. Barrett, 190. New York New York Academy of Sciences. 

Takeeda M, Hayashi Y, Yamato M, et al. Roles of endogenous prostaglandins and cyclooxygenase izoen-zymes in mucosal defense of inflamed rat stomach. J Physiol Pharmacol. 2004 55 193-205. 

Antacids are weak bases that react with gastric hydrochloric acid to form a salt and water. Although their principle mechanism of action is reduction of intragastric acidity, they may also promote mucosal defense mechanisms through stimulation of mucosal prostaglandin production. After a meal, approximately 45 meq/h of hydrochloric acid is secreted. A single dose of 156 meq of antacid... 

Bi L.C. and Kaunitz J.D. (2003) Gastroduodenal mucosal defense an integrated protective response. Curr Opin Gastroenterol. 19, 526-532 Bradbury N.A. (2000) Protein kinase A-mediated secretion of mucin from human colonic epithelial cells. J Cell Physiol 185, 408-415... 

The innate nonadaptive mucosal defense system of the airways of healthy individuals is a highly efficient primary defense for the elimination of... 

Tomee JFC, Hiemstra PS, Heinzel-Wieland R, Kauffman HF Antileukoprotease An endogenous protein in the innate mucosal defense against fimgi. J Infect Dis 1997 176 740-747. 

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