leukotriene-b4 and Duodenal-Ulcer

Epidemiological evidence has suggested that the declining prevalence of duodenal ulcer disease may be attributable to rising consumption of polyunsaturated fatty acids, a hypothesis supported by in vitro evidence of toxicity of such substances to Helicobacter pylori. The objective of the present study was to establish whether this association is causal. Forty patients with proven infection with H. pylori and endoscopic evidence of past or present duodenal ulcer disease were randomized to receive either polyunsaturated fatty acids (PUFA group), in the form of capsules and margarine, or a placebo (control). Both groups received concurrent H2 antagonist therapy. Efficacy of therapy was determined endoscopically by assessment of ulcer healing while H. pylori status was determined by antral biopsy, urease (EC 3.5.1.5) culture and histological assessment of the severity of H. pylori infection. Antral levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were quantified. Compliance was monitored. Before treatment, both groups were comparable for severity of H. pylori infection, smoking status and levels of LTB4 and PGE2. Despite a significant difference in consumption of linoleic acid (19.9 (SE 1.6) g for PUFA group v. 6.7 (SE 0.8) g for controls (P < 0.01) and linolenic acid (2.6 (SE 0.2) g v. 0.6 (SE 0.03) g (P < 0.01) there was no significant change in either the severity of H. pylori infection or prostaglandin levels in either group at 6 weeks. Consumption of a considerable amount of PUFA does not inhibit the colonization of the stomach by H. pylori nor does this alter the inflammatory changes characteristic of H. pylori gastritis. We conclude that the association between duodenal ulceration and a low level of dietary PUFA is likely to be spurious, probably reflecting the effect of confounding factors such as affluence, social class or smoking.

Topics: Combined Modality Therapy; Dinoprostone; Double-Blind Method; Duodenal Ulcer; Fatty Acids, Unsaturated; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Leukotriene B4; Linoleic Acids; Linolenic Acids; Male; Middle Aged; Pyloric Antrum; Ranitidine; Treatment Failure

The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the effect of nizatidine on duodenal ulcer healing and generation of mucosal prostaglandin estradiol and inflammatory mediators. Fifty-five patients with endoscopically proven active duodenal ulcer received either nizatidine 300 mg or placebo, once nightly, for 4 weeks, when a second endoscopy was performed. Healing was defined as complete epithelialization of the ulcer crater. At both endoscopies mucosal biopsies were obtained for determination of prostanoids and inflammatory mediators. Nizatidine and placebo induced ulcer healing in 76% and 60.9% of the patients, respectively, but the difference did not reach statistical significance. Nizatidine treatment did not significantly affect mucosal leukotriene B4, leukotriene C4 or platelet activating factor generation. It is concluded, therefore, that the antisecretory effect is probably the main mechanism responsible for nizatidine's therapeutic effects in peptic ulcer disease.

Topics: Adult; Aged; Dinoprostone; Double-Blind Method; Duodenal Ulcer; Female; Gastric Mucosa; Gastroscopy; Humans; Leukotriene B4; Leukotriene C4; Male; Middle Aged; Nizatidine; Platelet Activating Factor; Radioimmunoassay; Risk Factors

Ketotifen is an anti-allergic agent that was recently shown to prevent experimental gastric and colonic mucosal injury. We studied the effect of ketotifen on indomethacin-induced small intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg indomethacin, 30 min after refeeding 24 h fasted rats. Total ulcer area (mm2), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured 24 h after indomethacin administration. Study groups received ketotifen 100 micrograms/ 100 g body weight 30 min before and 5 h after indomethacin administration, either i.p. or orally. There were 7-9 animals in each group. Ulcer area was significantly reduced by oral administration of ketotifen from 229 +/- 26 to 146 +/- 28 mm2. PGE2 level was reduced by ketotifen from 505 +/- 73 to 228 +/- 68 ng/mg protein, and LTB4 was reduced from 289 +/- 68 to 59 +/- 26 ng/mg protein. Intraperitoneal administration of ketotifen had no effect on any of the measured parameters. Ketotifen had a definite protective effect on small intestinal mucosa in the rat, which was accompanied by a reduction of mucosal inflammatory mediators. Ketotifen may have a role in the prevention or treatment of small intestinal damage induced by nonsteroidal anti-inflammatory drugs.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dinoprostone; Disease Models, Animal; Drug Evaluation, Preclinical; Duodenal Ulcer; Histamine H1 Antagonists; Indomethacin; Ketotifen; Leukotriene B4; Male; Rats; Rats, Wistar

Platelet-activating factor (PAF), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) generation by gastroduodenal mucosa was assessed in duodenal ulcer patients and in normal subjects, to elucidate their possible role in the pathogenesis of peptic ulcer disease. Endoscopic fundic, antral, and duodenal biopsy specimens were obtained from 35 duodenal ulcer patients on the day the diagnosis was established and from 42 normal controls. In duodenal ulcer patients PAF generation, determined by platelet aggregation, was two- to three-fold higher than its respective generation by normal subjects. LTB4 and LTC4 synthesis by cultured antral and duodenal mucosa obtained from duodenal ulcer patients was twofold higher than their synthesis by normal subjects. Fundic LTB4 and LTC4 generation was similar in ulcer patients and controls. In 11 patients PAF, LTB4, and LTC4 generation was also assessed after 4 weeks of treatment resulting in ulcer healing and found to be significantly reduced when compared with their synthesis when the ulcer was active. These results thus suggest that PAF, LTB4, and LTC4 may have a role in the pathogenesis of duodenal ulcer, and therefore their modulation may have therapeutic benefits.

Topics: Adult; Cimetidine; Duodenal Ulcer; Duodenum; Female; Gastric Mucosa; Humans; Intestinal Mucosa; Leukotriene B4; Male; Middle Aged; Platelet Activating Factor; SRS-A