Duodenal ulcer models

Recent data in our laboratories indicated the possible involvement of central and peripheral dopamine binding sites in the pathogenesis of duodenal ulceration. Structure activity studies with duodenal ulcerogens implicated dopamine as a putative mediator and/or modulator in duodenal ulceration. Using the cysteamine- or propionitrile-induced duodenal ulcer model in rats, we found that dopamine agonists (e.g., bromocriptine, lergotrile,... 

Administration of cysteamine enhances inflammatory reaetions. Cysteamine is used to induce experimental duodenal ulcer model using animals. 

Salim (1992d) has performed several studies using reser-pine to produce a chronic model of peptic ulceration in rats. Administration of allopurinol, DMSO, cysteine or methionine-S-methylsulphonium chloride protected against injury. In addition allopurinol and DMSO were found to stimulate healing in this model. In an acute model of duodenal ulceration induced by pentagastrin and carbachol allopurinol, DMSO, cysteine or methionine-S-methylsulphonium chloride all protected against injury. 

Duodenal ulcer is about four times more prevalent than gastric ulcer in this part of the world (J.,2). Until recently, however, animal models have been available mostly for gastric... 

The duodenal ulcerogenic action of propionitrile and cysteamine was confirmed and extended by several authors (J, 8, 25-32). The model, especially the rapidly developing cysteamine-induced duodenal ulcer, was actually introduced in several laboratories to routinely test drugs for anti-ulcer activity (7.8,27.33). The cysteamine model, a simple, fast, and inexpensive procedure, became especially useful after a chronic form of duodenal ulcer was developed ( ) and similarities between the model and human duodenal ulceration were noted (7-10). 

Maintenance and repair of duodenal and gastric collagen and elastin connective tissue components also seems to be an important copper-dependent enzyme function in preventing or repairing duodenal or gastric ulcers. Induction or facilitation of de novo synthesis of lysyl oxidase by copper complexes [16] merits consideration to account for the observed rapid and normal replacement of connective tissue components in the surgically placed gastric ulcer model [178]. 

Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers A model of the relationship between ulcer healing and acid suppression. Gastroenterology 1990 99 345-351. 

Figure 11. A hypothetical model of the causation of duodenal ulcer. Gastric acid activates bacterial urease in antral organisms, but most of the NH3 is converted to NH4. When the juice empties into the duodenum, more NH3 is present due to the higher pH. This permeant gas can then rapidly enter duodenal cells and can result in increased cell apoptosis and ulceration.

As an example of potential clinical application of the proposed theoretical model, preliminary results of a phase I clinical trial are described below. We estimated the values of relaxation time and ratio Max/Max in adolescents with different results of endoscopy. We found that the mean relaxation time was significantly longer in subjects with a severe gastric and duodenal inflammation, namely, with ulcers and erosions compared to a healthy control group (p<0.05). The exhaled air of patients with milder forms of the disease and of the control group caused faster sensor relaxation after their interaction (Table 7.1). 

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