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Drug effects on the gastric mucosa in relation to ulcerogenesis.

Johnston, Brian. (1977) Drug effects on the gastric mucosa in relation to ulcerogenesis. Doctoral thesis, University of Surrey (United Kingdom)..

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It has been suggested that a gastric ulcer results when the ability of the stomach to defend itself against the aggressive forces of the gastric contents breaks down. The studies in this dissertation are concerned with the effects of agents on the synthesis of mucosal glycoproteins, the principle components of gastric mucus which constitutes the first line of defence of the gastric mucosa. Studies on the synthesis of mucosal glycoproteins, employing the in vitro incorporation of radiolabelled precursors, showed that human gastric ulcer was associated with a derangement of mucus synthesis characterised by decreased incorporation rates of N-acetylglucosamine. In contrast sulphate uptake appeared to be increased in disease states. Whereas predosing animals with mucosal damaging agents, such as ethanol, or a period of starvation,produced reductions, carbenoxolone and the E type prostaglandins, which have been shown to be beneficial in the treatment of ulceration, caused marked increases in the rate of incorporation of N-acetylglucosamine. Further studies with carbenoxolone indicated that the effect of the drug is on the degree of glycosylation of the glycoprotein rather than on the amount produced. It is suggested that carbenoxolone results in the production of a modified glycoprotein carbohydrate side chain, richer in N-acetylglucosamine, N-acetylgalactosamine, N-acetylneuraminic acid and fucose and depleted with respect to galactose. The drug also resulted in increased sulphation of mucosal glycoprotein. Carbenoxolone has also been investigated in relation to its effect on the release of lysosomal enzymes which have been shown to be elevated in drug induced gastric mucosal lesions. The results show that the drug is extremely membrane active causing lysis of lysosomal membranes at high concentrations (above 10[-4]M) and stabilization at lower concentrations (10[-5]M). The significance of these findings with relation to ulceration and the beneficial action of anti-ulcerogenic drugs is discussed.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
Johnston, Brian.
Date : 1977
Contributors :
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1977.
Depositing User : EPrints Services
Date Deposited : 22 Jun 2018 12:59
Last Modified : 06 Nov 2018 16:52

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