Malhotra an d colleagues (1965,1967a, 1967b, 1970) postulated th at the increased m astication required to eat a north Indian chapatti diet, as com pared w ith the sloppy south Indian rice diet, resulted in an increased output of saliva. This increased saliva not only protected developm ent of ulcer by its buffering action, b u t also by its high concentration of epiderm al grow th factor which has a cytoprotective effect and prom otes the healing
of duodenal ulcer. How ever, in Africa, and in some parts of India, w here a sloppy diet is consum ed th at does not require m astication, there is no correlation betw een such a diet and the incidence of duodenal ulceration (Tovey 1994).
1.2.1.5.iii MUCOSAL IRRITATION
There is evidence that fresh rice b ran oil or unm illed rice m ay have a protective effect against ulceration. It has been show n that du rin g storage rice b ran oil undergoes lipolysis and peroxidation, resulting in the
production of ketoaldehydes w hich are ulcerogenic in an anim al m odel (Jayaraj, Rees, Tovey, W hite 1986). These change are initiated by the lipase present in rice germ w hich is released during milling. This phenom enon may account partly for the high incidence of duodenal ulcer w herever refined or polished rice is the staple diet. It is commonly th o u g h t that consum ption of spices is an im portant aetiological factor in the duodenal ulceration, b u t there is no evidence for this: the consum ption of peppers is high in m any low incidence areas such as north India, Indonesia, and Malaysia (Tovey 1994).
1.2.1.6 SMOKING
In 1927 Barnett was the first person to notice that duodenal ulcer seem ed to be m ore com m on in habitual sm okers than in non-sm okers, although he d id n o t believe that the association w as m eaningful. H arrison et al (1979) review ed six major studies and found th at the m ean prevalence of duodenal ulcer in sm okers com pared w ith non-sm okers was 1.9:1. A subsequent epidemiological survey show ed that in m en, 75% of the attributable risk of duodenal ulcer could be abolished by rem oving
(statistically) exposure to sm oking and alcohol, alone or com bination (Piper et al 1984). More recently, an endoscopic survey of 1200 outpatients found a prevalence ratio of 1.8:1 (Ainley et al 1986). Doctors often advise their patients w ith duodenal ulcer to stop smoking; there is
epidem iological evidence of an association betw een cigarette sm oking and duodenal ulcer (Friedman et al 1974), and some patients notice that
sm oking increases their sym ptom s.
There is evidence that stopping sm oking increases the rate of healing of a duodenal ulcer (Korman et al 1981, Sonnenberg et al 1981). The incidence of duodenal ulcer in outpatients w ith dyspepsia is higher in sm okers than in non-sm okers. W hitfield & Hobsley (1985 & 1987) m easured m axim al gastric secretion after stim ulation w ith histam ine in pre-operative DU patients. They noticed that the smokers secreted significantly m ore gastric juice th an non-sm okers. They suggested that chronic sm oking, at least in men, increases maximal gastric secretion and thereby plays an im portant role in the aetiology of DU. Roxburgh, W hitfield and Hobsley (1992) suggested that acute sm oking decreases gastric secretion, leading to antral hypoacidity. This hypoacidity, induced by regular sm oking, results in an increase in parietal cell mass via a feed-back m echanism m ediated by gastrin, w hich explains the increase in the m axim al gastric secretion in chronic smokers. Similarly Lindell et al (1993) also found a reduction in gastric secretion after acute smoking. The authors of this study have postulated th at sm oking increases the susceptibility to ulcer form ation not only by increasing the stim ulated gastric secretion b u t also possibly by the very high concentration of nicotine in gastric juice affecting the
cytoprotective properties of the mucosa. It is also possible that nicotine m ay have a direct toxic effect on epithelial cells.
The prevalence of DU is higher in smokers than non-sm okers (Edw ards 1959, W hitfield & Hobsley 1987), and correlates directly w ith the num ber of cigarettes sm oked (Whitfield & Hobsley 1985, E dw ard 1959, Ainley et al 1986). There are various m echanism by w hich sm oking m ight cause the DU. W hitfield & Hobsley (1985 & 1987) suggested that chronic sm oking increases gastric secretion, which leads to increased duodenal acidification. Smoking also increases m otility and it m ay reduce the pancreatic secretion (Kaufman et al 1990). It has been suggested that cigarette sm oking exerts its effect by decreasing m ucosal resistance, inhibiting the ability of the m ucosa to regenerate (Kaufman et al 1990). Sonnenberg (1982) suggested th at
nicotine reduces the m ucosal blood flow. Cooper et al (1957) claimed that smoking reduces m ucus production. Quim by et al (1986) suggested that endogenous prostaglandin production is reduced by sm oking, w hich affects m ucosal regeneration.
A insw orth et al (1993) in their prospective study m easured duodenal bicarbonate secretion in smokers and non-sm okers; they reported a decrease in duodenal mucosal bicarbonate secretion in smokers. They suggested th at reduced bicarbonate secretion in duodenal m ucosa explains at least in p art the role of cigarette sm oking in the pathogenesis of
duodenal ulcer disease.
Zhang et al (1994) in an anim al study claimed that cigarette sm oking produced a reduction in m esenteric blood flow; they speculated that the vasoconstrictive effect of sm oking on m esenteric vessels m ay be involved in the potentiation of acid-induced duodenal m ucosal injury. Kato et al (1992) suggested that cigarette smoking depresses prostaglandin synthesis, and thus reduces its protective effect against the developm ent of duodenal ulcer.
1.2.1.7 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
It is not clear how NSAIDs produce ulcers, b u t the ulcers seems to be
"nonspecific" and not necessarily related to the m ucosal exposure to gastric juice since N SAID -induced ulcers occur throughout the intestine.
How ever, in the d u o d en u m it seems certain that NSAIDs produce chronic relapsing ulcer disease. It has been proposed that NSAID drugs are
ulcerogenic because they interfere w ith the m etabolism of prostaglandins in the alim entary m ucosa (Soil et al 1989). For example, it seems that NSAIDs inhibit the cyclo-oxgenase system of gastric m ucosa and therefore decrease the production of "mucosally protective" prostaglandins. Indeed, the deficit produced by NSAIDs can be corrected by supplying exogenous prostaglandin analogues. The injurious effects of NSAIDs m ay be partly systemic, as they can be reproduced by parenteral adm inistration of these drugs, and also partly due to the local dam aging effects of the preparations, w hich are lessened by enteric coating (Schoen et al 1989).
NSAIDs m ay injure the alim entary mucosa by directing the m etabolism of prostaglandin precursors, such as arachidonic acid, into potentially
dangerous pathw ays, such as the 5-lipoxygenase system, resulting in the production of leukotrienes and active oxygen radicals. In addition NSAIDs also result in the production of platelet aggregating factor, the latter being the m ost im portant endogenous ulcerogen an d therefore the most im portant m echanism w hereby NSAIDs dam age the gastroduodenal mucosa (W ormsley 1990).
How ever, a num ber of studies have show n little correlation betw een the inhibition of prostaglandin production and the degree of N SAID -induced mucosal damage. Therefore direct toxic effects, attributable to nonionic diffusion of the drugs into the gastric m ucosal cells may be injurious and perm it additional dam age from lum inal factors such as gastric juice and bile salts (Schoen et al 1989, W hittle 1983).