Epidermal growth factor in gastric ulcer healing by nocloprost, a stable prostaglandin E2 derivative.
BACKGROUND
The gastroprotective and ulcer-healing properties of prostaglandins, especially in gastric ulcers induced by non-steroidal anti-inflammatory drugs, are well established. Ulcer healing is an active process of filling the mucosal defect with migrating and proliferating epithelial cells combined with angiogenesis in granulation tissue at the ulcer bed. Growth factors, especially epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are crucial in the regulation of the reconstruction of damaged mucosal structures.


METHODS
In this double-blind, randomized, prospective study 40 patients with gastric ulcer were treated with nocloprost, a stable prostaglandin E2 derivative, or with ranitidine. All subjects underwent endoscopy before and after 4 and 8 weeks of anti-ulcer therapy. During endoscopy mucosal biopsies were performed for determination of EGF content in gastric mucosa at the ulcer margin and in the intact mucosa. Additionally, EGF output in saliva and its plasma concentrations were determined in all subjects before and during the treatment.


RESULTS
The gastric ulcer healing rate after 4 weeks was significantly higher in patients treated with nocloprost than in those treated with ranitidine (63% versus 39%, respectively). At initial examination the EGF content in the gastric mucosa obtained from the ulcer edge was significantly higher than that in the intact mucosa. There was a significant increase in the EGF content in both the ulcer margin and the intact mucosa in subjects treated with nocloprost but not in patients under treatment with ranitidine. Similarly, patients treated with nocloprost had significantly higher EGF output in saliva and higher EGF concentration in plasma throughout the anti-ulcer therapy.


CONCLUSIONS
Nocloprost is superior to ranitidine in the treatment of chronic gastric ulcers, and these effects could be due, at least in part, to higher expression and mucosal content of EGF in the ulcer area.
Konturek
J W
JW
Dept. of Medicine B, University of Münster, Germany.
Hengst
K
K
Konturek
S J
SJ
Domschke
W
W
D000328:Adult; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use*; D011899:Ranitidine / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
D000897:Anti-Ulcer Agents; D011461:Prostaglandins F, Synthetic; D004815:Epidermal Growth Factor; C048895:nocloprost; D011899:Ranitidine