The experiments confirm the presence of a lipid in certain staple foods that have protective and healing properties in experimental peptic ulcer animal models. The differences in the prevalence of duodenal ulceration between different regions in some developing countries with a high prevalence of Helicobacter pylori infection might be explained by the presence or absence of protective lipids or ulcerogenic factors in the staple diet.

SUMMARY In India there are regions of high incidence and regions of low incidence of duodenal ulcer. Rats prefed for two weeks on diets from low incidence areas developed significantly fewer rumenal ulcers after pyloric ligation than rats fed on diets from high incidence areas. The protective action was found in various individual items of food taken from the diets of low incidence areas.

The varying geographical prevalence of duodenal ulceration has suggested a relationship to staple diet. Previous experiments on animal peptic ulcer models showed that certain foods, particularly the lipid fraction, are ulceroprotective. This paper reports experiments on animal models further to investigate the nature of the protective substances in the most active lipid, that of horse gram. The free fatty acids and triglycerides, sterols, sterol esters and phospholipids from horse gram were extracted and tested for protective activity on rat peptic ulcer models: the pyloric ligation model which is chronic, involving 14 days pre-feeding, and two acute models using ethanol or cysteamine to induce ulceration. The results showed that sterol esters, but not sterols, were protective in the pyloric ligation model. Sterols were protective in the acute models using ethanol-induced and cysteamine-induced ulceration. Phospholipids were protective in both types of model. The free fatty acids and triglycerides gave no protection using the pyloric ligation model. The presence of sterols, sterol esters and phospholipids in the lipid fraction of foods in staple diets may account for the low prevalence of duodenal ulcer in certain geographical areas, despite a uniformly high prevalence of Helicobacter pylori infection.

These results suggest that the factor of diet may well explain the regional differences in the prevalence of duodenal ulceration between North and South India and China where other etiologic factors are similar.

The effect of mexiletine administration on steady-state plasma theophylline concentrations was studied in eight normal healthy men in a prospective open label nonrandomized two-way crossover trial. Repeated doses of 300 mg of sustained-release theophylline were given every 12 hours for 9 days. Mexiletine hydrochloride, 200 mg every 8 hours, was given for five consecutive doses starting on the morning of day 6. Mexiletine increased theophylline levels in all subjects. Mean predose (trough) levels rose from 8.1 +/- 0.1 microgram.ml-1 to 13.4 +/- 0.6 micrograms.ml-1 and AUC(0-12) from 96.8 +/- 9.1 to 160.2 +/- 3.7 micrograms.ml-1.hr. Plasma clearance was reduced by mexiletine from 44.7 +/- 5.1 to 25.4 +/- 1.2 ml.hr-1. Both N-demethylated metabolites of theophylline were decreased by 60% by mexiletine, whose levels remained within its therapeutic range. Theophylline levels returned to pre-mexiletine values when this drug was discontinued. Mexiletine reduces theophylline clearance and increases its plasma concentration by inhibiting N-demethylation of theophylline. Plasma theophylline levels should be monitored when mexiletine is added.

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The ulcerogenic and protective effects of various rice fractions in the diet were studied in the pylorus ligated ulcer model in the rat. Oil present in rice and particularly rice bran becomes ulcerogenic on storage and in this model results in a significant increase in the median (range) numbers of ulcers from six (one to ten) to nine (six to 15) (P less than 0.05). The ulcerogenic effect of stored rice bran oil was reversed by cysteine which significantly reduced the ulcer incidence from 100% to 60% (P less than 0.005) and the numbers of ulcers from 26 (six to 70) to one (zero to four) (P less than 0.001). Fresh rice bran significantly reduced the numbers of ulcers from six (one to ten) to one (one to four) (P less than 0.05). Similarly, unmilled rice and freshly milled newly harvested rice was also shown to be protective in this model by significantly reducing the ulcer incidence from 87.5% to 50% and 0% respectively (P values less than 0.025) and the numbers of ulcers from three (zero to 17) to one (zero to one) and zero (zero to zero) respectively (P values less than 0.001). These results could in part explain the geographical distribution of duodenal ulceration, where the incidence is high in all the rice eating areas of the world, and provide a plausible hypothesis to explain the mechanism of dietary ulcerogenesis.

SUMMARY In duodenal ulceration the Alcian blue staining acid mucosubstances in goblet cells are reduced and the goblet cells themselves disappear. At the same time periodic acid-Schiff (PAS) staining neutral mucosubstances appear in the cells of the surface epithelium. These changes have been measured quantitatively with the help of a Vickers M86/0010 Scanning and Integrated Microdensitometer. During healing the changes are reversed. It is suggested that these changes suggest a metaplasia towards a gastric type mucosa as a protective response to the presence of ulceration.Mucosubstances in the human duodenum are normally secreted from goblet cells in the epithelium of the villi as well as from Brunners glands lying in the submucosa (Fig. 1)