Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of tissue-type plasminogen activator (t-PA) was investigated in the gastric ulcer formation induced by microvascular derangement. The rat stomach was exposed and repeated electrical stimuli (irritation) were applied on the small arterial wall close to the lesser curvature to induce mucosal ischemia followed by hyperemia. The t-PA activity in the regional blood of the stomach was significantly elevated as early as 5 min after the irritation. Immunohistochemical study using anti-t-PA monoclonal antibody revealed that t-PA was detectable in the endothelial cells of capillaries and collecting venules, suggesting the involvement of endothelium-mediated fibrinolytic activity in the irritation-induced ulcer formation. Pretreatment of SOD or allopurinol significantly attenuated the irritation-induced t-PA activation, suggesting that the t-PA activity was modulated by xanthine oxidase-associated superoxide anions. CV-6209, a selective antagonist of platelet-activating factor (PAF), also prevented the activation of t-PA as well as ulcer formation, providing a concept that PAF may be associated with the local fibrinolytic activation which may cause hemorrhagic changes in the gastric mucosal microvasculature. The present study supports the hypothesis that increased t-PA activity may reflect the microvascular endothelial damages caused by vasomotor derangement and suggests that oxygen-derived free radicals may participate in the regulation of endothelium-derived fibrinolytic activities in the mucosal microvasculature.
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PMID:Involvement of superoxide anion and platelet-activating factor in increased tissue-type plasminogen activator during rat gastric microvascular damages. 165 Sep 66

Peripheral blood monocytes from healthy subjects, patients with gastric precancer disease (chronic gastric ulcer, stomach polyps and chronic atrophic gastritis) and different stages of gastric cancer were used. Spontaneous and lipopolysaccharide (LPS)-stimulated TNF-like factors production by monocytes was significantly higher in the precancer gastric disease patients than in the healthy subjects. At the same time the spontaneous capacity of monocytes to produce NTF-like factors was 2.5 lower in the gastric cancer patients compared to the healthy subjects. Moreover, in 5/13 of the gastric cancer patients in TNF-like factors production by the LPS-stimulated and non-stimulated monocytes was 1 unit/ml less. Spontaneous and reactive CL indexes were higher in the cancer patients monocytes than in the healthy subjects. The obtained results suggest that reactive oxygen species production can be an alternative mechanism by which a cytotoxic action of monocytes is regulated.
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PMID:[Changes in the profile of cytotoxic mediator monocytes in patients with cancer and precancerous conditions of the stomach]. 185 63

In this article, the evidence for the involvement of free radicals in some of the gastrointestinal disorders is reviewed. Oxygen radicals are partially reduced oxygen species that include superoxide, and hydroxyl radicals, and hypophthalous acids. Most cells possess numerous antioxidant enzymes and scavengers to protect themselves from these injurious agents; the rate of production of reactive oxygen metabolites may exceed the capacity of the antioxidant defenses thus resulting in tissue damage. The gastrointestinal tract is particularly well endowed with the enzymatic machinery necessary to form large amounts of oxygen radicals. Sources of radicals in the gastrointestinal tract include mucosal xanthine oxidase and NADPH oxidase found in the resident phagocytotic leukocytes (macrophages, neutrophils, eosinophils) of the lamina propria. Other sources of oxygen radicals in the gastrointestinal tract involve ischemia and reperfusion, drug ingestion, diet and radiation therapy. Recent studies have demonstrated the involvement of oxygen radicals following active episodes of small-intestinal ischemia, ulcerative colitis, pancreatitis and gastric ulcer. In contrast to cell antioxidants, control of tissue free radical levels is now pharmacologically feasible and perhaps justified for specific diseases. However, carefully designed and controlled clinical trials are needed.
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PMID:Oxygen radicals: their role in selected gastrointestinal disorders. 186 20

In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer.
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PMID:Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer. 207 Sep 80

We evaluated the role of oxygen free radicals in the induction of acute stress gastric ulcer in rats. After 12 hr of immobility, ulcers of up to 4 mm were observed in the gastric mucosa. Pretreatment with allopurinol, a xanthine oxidase inhibitor, produced a significant reduction in the number and size of lesions (p < 0.0001). No protection was afforded by aluminum hydroxide or ranitidine alone, but enhanced protection was observed when given in association to allopurinol. A secondary role for H ions is suggested by these findings. Our results support the hypothesis of a role of oxygen free radicals in the pathogenesis of stress gastric ulcers. Allopurinol might be used in conditions predisposing to stress in patients.
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PMID:[The etiopathogenesis of the acute stress ulcer. The role of oxygen free radicals]. 215 40

Diethyldithiocarbamate (DDC), an inhibitor of Cu,Zn-superoxide dismutase (SOD), at a dose of 500 mg/kg or aminotriazole (AT), an inhibitor of catalase, at a dose of 2,000 mg/kg reduced slightly gastric mucosal SOD activity, did not change gastric mucosal blood flow (GMBF), and did not cause gastric ulcers. However, when both DDC and AT were administered together, gastric mucosal SOD activity and GMBF remarkably decreased, and gastric ulcers appeared. Moreover, the administration of SOD attenuated gastric ulcer induced by DDC plus AT. These results suggested that SOD may play an important role in the gastric mucosal defense mechanisms against active oxygen species.
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PMID:Gastric mucosal protection and superoxide dismutase. 284 84

The effects of misoprostol on human gastric mucosal hemodynamics were examined in a double-blind, placebo-controlled, parallel study in 12 healthy male volunteers. Six subjects received 200 micrograms of misoprostol and six received placebo. The index of mucosal blood volume and mucosal blood hemoglobin oxygen saturation (Hb-SO2) were measured at 20 locations in the stomach using reflectance spectrophotometry during endoscopy prior to and after administration of the study drug. Mucosal blood volume index increased by approximately 10 to 25 percent throughout the stomach without a significant change in mucosal Hb-SO2 following treatment with misoprostol. The increase in mucosal blood volume index was statistically significant for 16 of the 20 locations (p less than or equal to 0.05). Placebo produced no significant change in mucosal blood volume and mucosal Hb-SO2. These findings suggest that misoprostol may have the potential effect of accelerating gastric ulcer healing by improving gastric mucosal hemodynamics, in addition to its gastric acid antisecretory activity.
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PMID:Misoprostol-induced changes in gastric mucosal hemodynamics. A double-blind parallel study in human volunteers. 311 40

In 50 patients with gastric ulcer indices of oxygen tension (pO2) levels were investigated in correlation with the concentration of prostaglandins (E and F2 alpha), prostacyclin, thromboxane as well as with values of transmucous difference of potentials in different parts of the gastric mucosa, they were compared with 30 healthy controls. It has been assumed that the detected increase of reverse diffusion of hydrogen ions (the appearance of positive values of the transmembranous potential) and disorder of the ratio of prostanoids in favor of vasoconstrictors lead to a decrease in the blood flow and pO2 in the periulcerative zone of the patients with gastric ulcer. Hypoxia of the gastric mucosa is regarded as an important pathogenetic factor of ulcerogenesis.
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PMID:[The role of local factors regulating vascular blood flow in the development of hypoxia of the gastric mucosa in peptic ulcer]. 324 60

During the last decade, evidence increased that microcirculatory disorders play a pivotal role in the development of mucosal injury, and, hence, formation of gastric ulcer. Mucosal microcirculation is altered at least by two distinct mechanisms: Stimulation of acid secretion leads to a rise of blood flow in the acid-secreting areas, and, concomitantly, due to a steal-phenomenon to a decrease of mucosal capillary perfusion of the antrum, which results in temporary ischemia. In addition, surface noxae-induced release of potent mediators, such as histamine, leukotrienes, thromboxane, platelet-activating factor and reactive oxygen metabolites cause vasoconstriction, capillary stasis and increase of microvascular permeability (loss of endothelial integrity), which aggravate mucosal injury. Therefore, therapeutic strategies should consider leukotriene-synthesis inhibitors, histamine-, thromboxane- and platelet-activating factor receptor antagonists, oxygen radical scavengers, as well as counteracting mediators and hormones, such as prostaglandins and somatostatin, inasmuch as these compounds have been shown to additionally prevent mucosal microvascular injury, in particular capillary perfusion failure and loss of endothelial integrity, during gastric ulcer formation.
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PMID:[Microcirculation of gastric mucosa in pathogenesis of stomach ulcer]. 751 63

Blood flow plays an important role in protection of normal gastric mucosa and in the protection and healing of damaged mucosa. Blood flow contributes to protection by supplying the mucosa with oxygen and HCO3-, and by removing H+ and toxic agents diffusing from the lumen into the mucosa. Low mucosal blood flow predisposes to injury, whereas high blood flow protects against injurious agents. Superficial mucosal damage is followed by increased blood flow which supports the healing process and prevents superficial lesions from developing into deep ones. The hypermic response increases the supply of HCO3- to the mucosa and increases the resistance of the injured mucosa against back diffusing H+ and aggressive drugs such as ethanol (adaptive protection). Mucosal ischemia contributes to gastric ulceration in various clinical conditions such as hemorrhagic shock, stress, aorta aneurysm and after proximal gastric vagotomy. Blood vessels are damaged in gastric ulcers. During ulcer healing blood flow returns to normal. Stimulated or inhibited angiogenesis in the granulation tissue effects the healing of a gastric ulcer.
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PMID:The role of blood flow in gastric mucosal defence, damage and healing. 753 77


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