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Title: A study of experimental gastric ulcers and erosions
Author: MacDonald, Allan
ISNI:       0000 0001 3614 9075
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1976
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Various models for an experimental study of gastric ulcers and erosions were sought and high incidences of erosion or ulceration were obtained using stress (Restraint), antiinflammatory drugs (phenylbutazone, aspirin), a corticosteroid (prednisolone) and physical or chemical trauma (electrocautery or acetic acid). Reproducible results were obtained only by carefully controlling variables such as sex, bodyweight, temperature and season. Histochemically,erosions and ulcers were associated with a loss of mucus, particularly from the regenerative zone of the mucosa. Biochemical studies after erosion formation confirmed the decrease in mucus content and also showed an altered carbohydrate composition of the mucus. Studies of mucous glycoprotein synthesis by measuring the rate of incorporation of labelled carbohydrate and amino acid suggested that one mode of action of stress and ulcerogenic drugs may be inhibition of the glycosylation of the mucus glycoprotein and hence a decreased synthesis of glycoprotein or the synthesis of a modified glycoprotein or both. Prostaglandins E[1], E[2] and F[2] were found to decrease the incorporation of carbohydrate and amino acid. This effect may be produced by stimulation of adenyl cyclase and elevation of cyclic AMP levels as the dibutyryl analogue of cyclic AMP and a phosphodiesterase inhibitor, theophylline were found to have similar effects. The dibutyryl analogue of cyclic GMP was found to have no effect on glycoprotein synthesis. Glycaemia was also found to be important as hypoglycaemia decreased glycoprotein synthesis and increased the susceptibility to erosion formation. It appears that a constant supply of glucose to the mucosal cells is necessary for synthesis of the mucus glycoprotein and normal cell function. The drug carbenoxolone sodium and an analogue cicloxolone sodium were shown to be effective against stress-induced erosions and also promoted the healing of electrocautery ulcers. The mechanism of action may be allied with increased mucus synthesis as both drugs were shown to increase the glycosylation of mucus glycoproteins.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available