[Gastroprotective effect of zinc sulfate in ethanol ulcer formation in rats].
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Biomedical subjects
Publications and source records attributed to V A Trapkov.
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Zinc concentrations were measured in blood and gastroduodenal mucosa of patients with duodenal ulcer in remission and exacerbation. These were found reduced in plasma but elevated in gastroduodenal mucosa. Healing of the ulcer lesion was associated with positive shifts in zinc metabolism which recovered normal values in ulcer remission. It is concluded that plasma and gastroduodenal levels of zinc reflect the stage of the pathological process in peptic ulcer.
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Scanning microcalorimetry is used to study heat denaturation of myosin "tail" helical fragments, light meromyosin and the LF-3 subfragment. It has been shown that all the data obtained were well explained by the existence of a set of quasi-independent cooperative regions. Probable location sites of separate cooperative regions in the helical part of the molecule are indicated. The obtained places of cooperative "breaks" are in a good agreement with the places of predominant cleavage of the myosin tail by proteolytic enzymes at its limited hydrolysis. The total denaturation enthalpy for each of the helical fragments per hydrogen bond at 100 degrees C is slightly less (5.4 +/- 0.8 kJ . mol-1) than the corresponding value for globular proteins.
The reversible inhibition of the enzymatic activity of trypsin by heparin was investigated. On the basis of an analysis of the Lineweaver-Burk and Dixon graphs, a noncompetitive nature of the inhibition of the BAPA amidase activity of trypsin by heparin was detected, and the values of Km and Ki were determined, equal to 3.1 . 10(-4) and 3.7-3.9 . 10(-7) M, respectively. A comparison of these values indicates a great affinity of heparin for the enzyme. It was shown that heparin inhibits the BAEE esterase activity of trypsin and at the same time has no inhibiting effect on acetyltrypsin. Considering that the acetylation of trypsin leads to selective blocking of the epsilon-amino groups, it was concluded that the epsilon-amino groups of the lysine residues of the trypsin molecule participate in the interaction with heparin.
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The 5-day pretreatment of rats with zinc sulfate (50 or 150 mg/kg/day per os) significantly reduce the rate, the number, and area of cystamine-induced duodenal lesions in rats. Pretreatment with zinc sulfate in a dose of 15 mg/kg/day over a 5-day period or single administration of zinc sulfate (50 mg/kg) did not markedly reduce the above-mentioned lesion parameters. The administration of zinc sulfate (50 or 150 mg/kg/day per os) during 7 days results in a dose-dependent, significant decrease in the area of chronic acetate-induced gastric and duodenal lesions in rats. The results of clinical and experimental study indicate that zinc-containing compounds can be successfully used both for prophylaxis and treatment of duodenal ulcer.
Specialised system for computer assisted prediction of antiulcer activity of chemical compounds on the basis of their structural formulae is described. Predicted activity spectrum includes antiulcer activity, antisecretory and gastroprotective effects; H2- and M1-receptors blockade, H+, K(+)-ATPase inhibition as the mechanisms of antisecretory effect. It is shown that the average prediction accuracy is 83% in leave-one-out cross validation and 82% for the independent test set. Prediction made for about 300 new chemical compounds provides the selection of 20 potential antiulcer agents, 9 of them were synthesised and tested, 5 compounds have potent antiulcer activity. The discovered antiulcer agents are classified as New Chemical Entry because antiulcer and close effects have not been earlier for any compound of this chemical series.