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The influence of components and some schemata of antiulcerous therapy on content and activity of monooxigenase system's enzymes in mucous membrane of stomach are studied on the model of experimental stomach ulcer in rats. It is established, that among components of antiulcerous therapy such as omeprazole, clarithromycin and metronidazole inhibit content and activity of MOS enzymes. Tinidazol, amoxicillin and azithromycin do not affect the function of MOS. Rifampicin and pantoprazole induce enzyme system of monooxigenase. In triple therapy with omeprazole, clarithromycin and metronidazole the inhibit effect of preparations to system of MOS is exponentiated and it leads to suppression of mucous cytoprotaction of gastro duodenal zone. Triple therapy of ulcerous disease with pantoprazole, rifampicin and azithromycin is effective planning to stimulate defense mechanisms of the organism.

Levels were assayed and compared of metabolic enzymes--thymidine and adenosine--in gastric mucosa tissues and blood serum from patients with gastric ulcer disease and gastric cancer (age--30-60 yrs). Enzymatic levels matched to the highest degree in cases of ulcer disease aggravated by chronic atrophic gastritis and precancerous alterations (dysplasia, metaplasia). Elevated concentrations of thymidine kinase and phosphorylase and adenosine desaminase were identified both at foci of ulceration (p > 0.001, p > 0.05, respectively) and in blood serum in all age brackets. Moreover, blood serum assay confirmed the view that changes in serum enzyme levels are suggestive of those in tissue enzymatic profile. Our data established a direct correlation between accumulated effect of level changes, on the one hand, and risk of neoplastic transformation of gastric mucosa in ulcer patients, on the other.

Frequently recurrent stomach ulcers are ulcers that exacerbate 2-3 times per year. Indolent ulcers are ulcers for which there is no healing during three months of continuous treatment.

Aim: To assess activity of superoxide dismutase and catalase in acute ulcer and in the end of its treatment with antisecretory (omeprasole and zaran), anti-Helicobacter (metronidasole) and antioxidant (alpha-tocopherol) drugs in patients with duodenal ulcer., Materials and Methods: 126 patients with duodenal ulcer were divided into 6 groups: group 1 patients had Helicobacter pylori (HP+) and were given omeprasole; group 2 patients had HP and were given omeprasole + metronizarole; group 3 patients were free of HP and received metronidasole + alpha-tocopherol; group 4 HP+ patients received zaran; group 5 HP+ patients got zaran = metronidasole; group 6 free of HP received zaran + alpha-tocopherol. The patients were examined using esophagogastroduodenoscopy, roentgenoscopy of the stomach, tests of the gastric juice., Results: An acute phase of ulcer was accompanied with enhanced activity of superoxide dismutase and low activity of catalase in mucosal biopsies from ulcer lesion and periulcer zone. In remission, antioxidant system resumed normal activity depending on the kind of the combined therapy. The combination omeprasole + metronidasole was more effective in HP eradication than zaran + metronidasole. Effect of alpha-tocopherol was poor., Conclusion: It is suggested that HP stimulates lipid peroxidation and thus maintains inflammation in gastric and duodenal mucosa.

Regulation of lipid peroxidation is realized not only by antioxidant enzymes but by natural antioxidants as well. We have lately succeeded, together with the students, in identifying antioxidant properties of quaternary ammonium compounds, which fact makes it possible for the above properties to gain extensive applicability in a setting where there is this variety of disbolism. One of such drug preparations is ethonium. The article contains information about uses of ethonium in the tablet dose form. The tablets are of little toxicity, they stimulate the oxidation-reduction processes and proved to be effective in experimental gastric and duodenal ulcers.

It was shown on an experimental model of chronic gastric ulcer in rats that administration of microsomal oxidation inductors benzonal (benzobarbital) and phenobarbital in a dose of 50 mg/kg for 10 days significantly increases the content of cytochrome P-450 in the gastric mucosa. The increased content of P-450 promotes stimulation of the synthesis of mucosal barrier glycoproteins. The cytoprotective effect of famotidine in a dose of 100 mg/kg and sucralfate in a dose of 400 mg/kg proved to be much weaker than that of the inductors.

Gastric juice acidity was examined in 131 patients with gastric ulcer. In 31 (23.7%) patients it appeared to be high, in 57 (43.5%)-normal, in 42 (32.8%)-low. In 28.6% cases the pepsin concentration was high, in 26.5%-normal, in 44.9% - low. In elder patients, patients with cardial ulcer, plural and combined ulcers, big size ulcers, long-term ulcer anamnesis the rate of low acidity increases. Among patients with unsatisfactory results of conservative treatment 15.8% had high acidity and 38.7% low acidity. Low acidity is an unfavorable prognostic factor.

Administration of lysosomes and lysosome enzymes into the submucous base of intact rats' stomachs did not result in ulceration. Premedication by histamine, serotonin (combined and separated) and ACTH did not increase sensibility of mucous membrane to lysosome enzymes. Prednisolone-premedication provoked the decrease of mucous membrane resistance to free lysosome enzymes and appearance of ulcerative lesions in the point of enzyme applications. Free lysosome enzymes are able to produce ulcerative lesions. This process is going on with the participation of prednisolone.

In 77 patients with gastric ulcer disease, the activity of alkaline phosphatase of gastric juice and its fractions was studied at the late period after resection of the stomach. Activity of thermolabile and thermostable fraction of alkaline phosphatase was the lowest in patients who underwent creation of transverse Billroth-II anastomosis, indicating that it was more physiologic as compared to Hofmeister--Finsterer modification of anastomosis in relation to the barrier (sphincter) function, and thus prevented reflux of the intestinal contents into the stomach.

The paper is concerned with evaluation of the activity of the intracellular enzymes of lymphocytes--succinate dehydrogenase and alpha-glycerophosphate dehydrogenase of mitochondria, in patients with peptic ulcer running a different course to define their importance in the disease prediction. Aggravation of peptic ulcer was found to result at first in marked activation of lymphocyte energy supply including that at the expense of the formation of new cellular populations. Later the count of lymphocytes with a high enzymatic activity was found to decline together with a reduction of enzymatic activity. The retention of the indicated changes after ulcer healing serves a prognostically unfavourable sign of the further disease course.

Concentrations of 5-, 12-, 15-HETE versus myeloperoxidase activity in the periulcerous area were investigated in 40 peptic ulcer patients. A control group consisted of 20 healthy subjects. In ulcer patients the activity of lipoxygenase pathway of metabolism of arachidonic acid and myeloperoxidase was enhanced. This is likely to promote chronic inflammation of the mucosa in the periulcerous area, this inflammation being an important prognostic factor for ulcerogenesis.

In the experiments on Wistar rats we showed that administration of ulcerogenic drugs (cinchophen, acetylsalicylic acid, butadione, indomethacin etc.) produced the alterations of free activity of lysosomal enzymes in the homogenates of ulcerated stomachs, presumably the significant elevation of the activity of cathepsins (more often cathepsin with optimum of activity at pH 5.5) and the significant reduction of free activity of acid nucleases (more often of DNA-ase). The alterations of free activity of lysosomal enzymes were as in cases with gastric ulcerations as in cases with unaffected stomachs.

An examination of 100 patients with ulcer disease of the stomach duodenum and 20 practically healthy people has shown that the level of extracellular antioxidant enzyme defense (ceruloplasmin) is higher than those in practically healthy people. This dependence was most pronounced in the group of patients requiring surgical interventions. In the process of treatment the level of ceruloplasmin activity gradually decreased, without reaching normal values. The level of ceruloplasmin activity in patients with ulcer disease of the stomach and duodenum are thought to characterize the state of compensatory reactions in these patients.

The activity of enzymes of the antioxidant system and pO2 in the gastric mucosa (GM) was studied in patients with gastric ulcer. The various enzymes differed in activity. Along with low activity of superoxide dismutase (SOD), glutathione peroxidase (GP), and glutathione reductase (GR), both normal and increased values were encountered. In GM hypoxia the GP activity increased in the peri-ulcerous zone. There was no statistically significant increase of SOD activity and reduction of GR activity.

In examination of 51 patient with acute gastrointestinal bleeding of ulcer etiology, the activity of lysosomal enzymes, peroxide oxidation of lipids were increased, the activity of antioxidant system was decreased. This can lead to inhibition of proliferative processes, stipulating the severity of blood loss, course of the postoperative period, the incidence of postoperative complications, and lethality.

Free glutamine content and phosphate-dependent glutaminase activity were studied in the biopsy specimens from the tissue of ulcer, polyps, carcinoma and the surrounding gastric mucosa of patients with precancerous diseases and carcinoma of the stomach. The glutamine content in carcinoma was not significantly different from that in the normal gastric mucosa. The glutamine level in the gastric mucosa remote from the tumour was considerably higher than normal. In case of polyposis of the stomach glutamine was present in the polyps and absent in the remote gastric mucosa. A marked glutaminase activity was revealed in the carcinoma of the stomach, but its level did not differ from the normal or in the case of precancerous diseases.

Experiments were performed on white rats with experimental acetate ulcer of the stomach and intestine. At the height of destruction of gastric mucosa tissue (60 minutes from the onset of ulcer formation) a consistent increase in acid phosphatase secretion was recorded. This process was accompanied, as a rule, by significant elevation of proteolytic activity (pH 6.5-7.0) in tissue extract obtained from the affected area. It is suggested that the increased proteolytic activity observed at pH 6.5-7.0 in the tissue extract from the ulcerous area is most likely related to the release of lysosomal proteases at the height of tissue destruction. It thus appears that ulcer of the gastric mucosa induced by acetic acid application is determined by interstitial proteolytic activity of cathepsins that are released during the destruction of lysosomal membranes.

Lipid peroxidation, a state of the antioxidative system and activity of acid phosphatase were studied in mucosal membrane of 53 patients with ulcerous disease of stomach. Increase of the acid phosphatase activity in cytoplasm, activation of lipid peroxidation and inhibition of the antioxidative system were detected in ulcer border and periulcerous region. These alterations in lipid peroxidation and the state of the antioxidative system were considered as distinct pathogenetic factors responsible for deterioration of lysosomal membranes and contributing to chronic and relapsing development of ulcerous disease.

Lysozyme concentration in the gastric juice of 34 patients with peptic ulcer and 10 practically healthy persons was studied. In the patients with peptic ulcer the lysozyme levels in the gastric juice were found to be lower. A significant decrease in the lysozyme concentration was observed in the patients suffering from peptic ulcer for more than 2 years. During the first months of the disease increased levels of lysozyme were recorded. Relationship between the lysozyme concentration in the gastric juice and the acidity of the gastric contents was shown. Decreased concentrations of lysozyme were more pronounced in the patients with increased levels of hydrochloric acid.

The method of Okabe was used to induce experimental gastric ulcer in rats. The content of serotonin and histamine was determined in gastric mucosa extracts. The spectrum of proteolytic enzymes and proteolytic activity in gastric mucosa extracts were determined by polyacrylamide gel disc electrophoresis at varying pH. It was found that in "acetate" gastric ulcer the rats had the increased content of serotonin in the gastric mucosa followed by the elevated histamine content. In the early stages of "acetate" ulcer the proteolytic activity was detectable at pH 6.5-7. At the same time there took place a reconstruction of the spectrum of proteolytic enzymes. Analogous changes in the spectrum of proteolytic enzymes of gastric mucosa extracts and occurrence of the proteolytic activity at pH 6.5-7 were also recorded after serotonin administration (30 mg/kg) to intact rats. Thus it has been demonstrated that the increased serotonin output is implicated in the changes seen in the enzymatic spectrum and in the occurrence of proteolytic activity at high pH (6.5-7). The latter might be related to the release of lysosomal proteases responsible for intratissular proteolysis in the gastric mucosa and for ulcer formation.

An antitryptic activity and effect of trypsin and chymotrypsin, administered parenterally, on the activity were studied in blood serum of patients, subjected to surgical operations. The antitryptic activity and content of alpha1- and alpha2-globulins were shown to increase in blood serum of patients within 5 days of the postoperative period. Intramuscular administration of the proteolytic enzymes within 5 days decreased the anti-tryptic activity and content of alpha1- and alpha2-globulins in blood serum.

Disc-electrophoretic investigation of proteases of the gastric juice of dogs under normal conditions and in experimental atophan ulcer of the stomach demonstrated that in fasting dogs ulceration was accompanied by marked quantitative changes in the protease spectrum. Fraction No. 6 showed a significant elevation against the background of total reduction of proteolytic fraction of the gastric juice in sham feeding of ulcerated dogs. Sham feeding replete ulcerated dogs indicated a marked increase of fractions No.1 and No.2. The noted changes of the gastric juice protease spectrum may be of ulcerogenic significance.

Total and non-sedimentable activities of lysosomal proteinases were studied in rat gastric mucose under conditions of normal state and of ulcer development as well as after treatment of the ulcer area with contrical and with the mixture containing contrical and medical glue MK-8. Both total activity of cathepsins A, B, C and D and their non-sedimentable activity were increased by 32-102% and 44-94%, respectively, under conditions of ulcerogenesis. Contrical and the mixture of the drug with glue MK-8 normalized the enzymatic activity studied; the mixture containing the inhibitor was the most effective. Inhibitors of proteinases combined with medical plastificators might be used in local treatment of stomach ulcerous disease.

Gastric acidity was evaluated, using the histamine test (Key's test), measurement of nocturnal gastric secretion and gastric pH-metry, in 174 patients with gastric ulcers. Acidity proved to be lowered in 25% of gastric ulcers patients, normal in 30% and increased in nearly half of the patients. Intragastric proteolysis was studied in 48 individuals, including 27 patients with peptic ulcers and 21 normal controls. It was found to be normal in the overwhelming majority of peptic ulcer patients (74%). It is concluded that intragastric proteolysis can only be regarded as an aggressive factor, resulting in the formation of a gastric ulcer, when it is combined with high acidity.

New data have been made available which confirm the existence of differing quateron sensitivity of tissular monaminoxidases possessing dissimilar substrate specificity. An experimental neurogenic dystrophy of the stomach is attended on the whole by an activated deamidization of monamines, but there could be seen marked differences in the ability to intensify oxidation depending upon the localization of the mitochondrial monaminoxidases in various parts of the stomach. When introduced to intact animals in a dose of 5 mg/kg quateron tends to lower the activity of mitochondrial monaminoxidases in individual receptor areas of the stomach with respect to norepinephrine and, especially, serotonin. In such instances preliminary introduction of quateron prevents an activated oxidation of norepinephrine and serotonin, observed 24 hours after inflicting an injury. In the mechanisms governing deposition of catecholamines and serotonin in the gastric wall occurring under the effect of quateron a definite role plays also the inhibition of the mitochondrial monaminoxidases.

Activity of the main enzymes of pentose phosphate pathway of carbohydrate metabolism was studied in human mucosa of the stomach. In the mucosa glucose-6-phosphate dehydrogenase in gastric ulcer and 6-phosphogluconate dehydrogenase in normal stomach were shown to be less active as compared with these enzymatic activities in duodenal ulcer. A distinct decrease in the activity of glucose-6-phosphate dehydrogenase was observed in the ulcerous region, independently of the ulcer localization either in corpus ventriculi or in duodenum, as compared with the parts of the mucosa away from the impairment; the lowest enzymatic activity was estimated in the gastric ulcer zone. Activities of 6-phosphogluconate dehydrogenase and transketolase were the same in the ulcerous and normal mucosa and did not depend on the localization of the impairment. Contents of lactic and pyruvic acids were similar in mucosa of the stomach both in gastric and duodenal ulcer.

Lysosomal membrane stability has been studied in the gastric mucosa in response to mechanical damage caused by lysosomal fractionation and release of lysosomal enzymes from mucous cells into the gastric cavity of alive animals during induction of acetic ulcer or erosive damage of the gastric mucosa resulting from intraperitoneal introduction of histamine and serotonin. It has been found that all types of ulcerogenesis in the gastric mucosa led to the decrease in lysosomal membrane stability to mechanical stress in the course of lysosomal fractionation. In addition there was a substantial release of lysosomal enzymes into the gastric cavity in different types of ulcerogenesis. The decrease in lysosomal membrane stability combined with a subsequent development of ulcers and erosions in the gastric mucosa seems indicative of the fact that lysosomal enzymes take part in the initial formation of ulcers in the gastric mucosa.