Monochloramine-induced cytolysis to cultured rat gastric mucosal cells: role of glutathione and iron in protection and injury.

Helicobacter pylori (H. pylori) infection plays a role in the pathogenesis of peptic ulceration as well as active chronic gastritis. Possible mechanisms of H. pylori-induced mucosal injury include the generation of toxic monochloramine (NH2Cl) from oxidant (HOCl)--which is a product of activated neutrophils-and ammonia (NH3), which is a metabolite of H. pylori urease. To clarify mechanisms by which NH2Cl induces cytolysis, we determined the effects of glutathione (GSH) alteration and iron chelation on NH2Cl-induced damage in cultured rat gastric mucosal cells, because these are involved in oxidant injury. Cytotoxicity was quantified by chromium 51 release from prelabeled cells that were exposed to NH2Cl or hydrogen peroxide (H2O2). Although both NH2Cl and H2O2 caused a time-related and dose-dependent increase in 51Cr release, NH2Cl was more cytotoxic than H2O2. Pretreatment with extracellular GSH caused a right shift of the dose-response curve for NH2Cl, whereas pretreatment with diethyl maleate (a depletor of cellular GSH) rendered cells less resistant to NH2Cl. Iron chelation with 1,10-phenanthroline or deferoxamine failed to influence NH2Cl injury, whereas such treatment was protective against H2O2. Intracellular GSH seems to play an important role as a potent defense system against NH2Cl, as observed in H2O2-induced damage. However, the mechanisms of NH2Cl-induced damage seem to be distinctly different from cytolysis by H2O2 in terms of the mediation of cellular iron.     

Antigastric autoantibodies inHelicobacter pylori infection: role in gastric mucosal inflammation

The aim of the study was to ascertain whether there is an association between the presence of serum parietal cell autoantibodies (PCA) and: (1) Helicobacter pylori infection; (2) the presence and degree of gastritis and intestinal metaplasia; and (3) the H. pylori infecting strain. Gastric mucosal biopsies were obtained from 49 consecutive patients in order to assess and grade gastritis, make a histological diagnosis, and culture and genotype H. pylori. H. pylori infection was present in 26 patients (group 1), had been present in 17 patients (group 2), and the remaining 6 (group 3) had never had the infection. The infecting strain was cagA positive in 21 of 26 group 1 patients. Positive PCA results were found in 84%, 76%, and 14% of patients in groups 1, 2, and 3, respectively. PCA results were correlated with anti-H. pylori antibody titers (P<0.05). In group 2 patients, PCA were associated with the degree of antral gastritis (Fisher's exact test P<0.05). cagA status was not associated with the presence of PCA (chi2=0.68, NS). The frequency of positive findings for PCA in group 2 was higher in patients with (90%) than in those without (50%) intestinal metaplasia. In conclusion: (1) H. pylori infection is associated with the production of PCA, which, after eradication of the infection, persist and might contribute to the persistent antral chronic gastritis and intestinal metaplasia; (2) the gastric lesions associated with infections sustained by the more-virulent H. pylori strains do not appear to be due to the induction of antigastric autoantibodies.     

Epinephrine protects against severe acute gastric bleeding in rats: role of nitric oxide and glutathione

The aim of this study was to examine the effect of the systemic administration of epinephrine against severe acute gastric bleeding in rats. Epinephrine decreased gastric hemorrhage not only before but also after lipopolysaccharide-induced severe acute gastric bleeding. Epinephrine ameliorated severe gastric hemorrhage and decreased gastric mucosal lipid peroxidation through alpha- and beta-adrenoceptors. Epinephrine modulated alpha-adrenoceptors to increase the levels of gastric mucosal nitric oxide and glutathione. Nitric oxide synthase inhibitors potently reversed the effects of epinephrine on gastric mucosal glutathione. Thus, epinephrine might act through alpha-adrenoceptors to increase the levels of gastric mucosal nitric oxide and glutathione and thus protect against severe acute gastric bleeding in rats.     

NSAID-induced gastric mucosal damage

Gastric mucosal damage is a common side effect of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs may cause gastrointestinal symptoms, gastric erosions, peptic ulcers or upper gastrointestinal bleeding. Therefore, NSAIDs should be used cautiously in patients with a history of gastrointestinal lesions. Drugs that may be useful in preventing or treating NSAID-induced gastric mucosal injury are under intensive clinical investigation.     

Mechanism of reserpine-induced acute gastric mucosal injury in the rat: role of endogenous 5-hydroxytryptamine.

1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 +/- 2.1 mm2, mean +/- SEM). Coeliac ganglionectomy or the beta-adrenoceptor-blocking drug propranolol (5-15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The alpha-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 +/- 0.5 mm2 and 3 +/- 0.8 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM, P less than 0.01) and a dose of 15 mg/kg afforded complete protection. 2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P less than 0.05) increase was noted with 15 and 20 mg/kg (47.5 +/- 2.9 mm2 and 49.4 +/- 2.2 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM). 3. The results suggest that, in the rat, reserpine causes vagal alpha-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it.     

Pathogenesis of aspirin-induced gastric mucosal injury

It is necessary for some conditions to occur at the same time so that aspirin induced gastric mucosa injury occurs. The definite condition that is necessary for the development of gastric mucosa injury by aspirin is the direct injury with the aspirin and the presence of the gastric acid. The pathologic central mechanism is the inhibition of cyclooxygenase, the disturbance of microcirculation and pro-apoptotic signaling. At all events, it is a theme for gastroenterologists to establish a mean to prevent the gastric mucosa injury induced by aspirin.     

Near-total gastric necrosis caused by acute gastric dilatation

Gastric dilatation caused by psychogenic polyphagia or bulimia may, under extreme circumstances, progress to total gastric necrosis. We have described a patient in whom acute abdominal symptoms and signs developed while he was receiving psychiatric treatment. Laparotomy showed massive gastric dilatation with near-total infarction. Total gastrectomy with cervical esophagostomy, feeding and decompressing jejunostomies, and wide drainage of the gastric bed were done. After staged reconstruction, recovery was uneventful.     

第3章第1节急性胃粘膜病变

1 概况 1.1 定义 AGML是指机体遭到严重疾病或严重创伤而处于应激状态,以及胃肠接触某些药物引起胃肠粘膜急性浅表性糜烂、急性溃疡的统称,视为严重疾病或严重创伤的继发症(前者),或因病服用药物所致并发症(后者).     

胃黏膜糜烂和症状评分与胃排空的相关性研究

目的探讨慢性胃炎患者胃黏膜糜烂与否影响胃排空功能,以及症状学评分与胃排空功能的相关性。方法75例慢性胃炎患者经内镜检查分为黏膜糜烂组与无糜烂组,经问卷调查获得症状评分,然后进行钡条胃排空功能检测。比较黏膜糜烂组与无糜烂组的餐后5h胃排空率,进行症状评分与胃排空率的相关性分析。结果糜烂组5h胃排空率为(100．00±25．00)%(中位数±四分位数间距),钡条总排出率(该组患者排出钡条总数与吞入的钡条总数之比)为82．95%。无糜烂组5h胃排空率为(85．00±55．00)%,钡条总排出率为62．17%。两组间差异有统计学意义(P＜0．05)。上腹胀症状评分与胃排空率相关(r=-0．243,P＜0．05)。结论慢性胃炎患者胃黏膜糜烂可加速胃排空,上腹胀症状评分与胃排空率存在负相关性。     

Follow-up endoscopic study of gastric mucosal changes secondary to gastric ulcer

A long-term follow-up gastrocamera photographic study of 481 patients with gastric ulcer was conducted at intervals of 3 weeks to 6 months. It showed that gastric ulcers could remain healed for 2 months to 6 years of observation, yet, recurrence of ulceration occurred in 79% including 18% with multiple occurences. Gastric polyp developed in 8 patients whose initial gastrophotography showed no such lesion in the original study. Furthermore, 7 cancers of the stomach developed at sites away from the initial benign ulcer foci. Six of these cases proved to be mucosal cancer and one was an advanced cancer. In 5 of 7 cases of malignancy, the cancer occurred distal to the initial ulcer foci and anaplastic adenocarcinoma was seen in 3 of these. The others were well differentiated adenocarcinomas. No correlation was found among histopathological type of cancer, depth of malignant invasion, location of the new growth or gastric juice acidity in these 7 cases of malignancy. It is concluded that a thorough and routine gastroscopic examination is indicated for all sorts of gastric disorders whether they are initial or follow-up cases.     

Mechanisms of direct gastric mucosal damage by NSAIDs

Since gastric mucosal membrane, that is the most important part of mucosal barrier, is a lipid-protein layer, ionized and water-soluble NSAIDs are restricted in their transport. In the highly acidic condition of gastric juice, however most of NSAIDs are non-ionized and fat-soluble, dissolve rapidly in lipid-protein layer, and is rapidly absorbed from the acid gastric contents. Within the gastric mucosal cells in neutral condition, NSAIDs are ionized and H+ ions are released. Intracellular NSAIDs cause impairment of gastric mucosal barrier by reduction and alteration of mucous secretion and/or reduction of mucosal ATP. Intracellular H+ ions provoke the mast cells to release histamine which causes mucosal micro-vascular damage. Finally, auto-digestion by gastric juice in this impaired mucosa makes the variegated mucosal lesions.     

Degradation of gastrin by gastric mucosal cells.

Specific binding of radiolabeled gastrin by gastric mucosal cells prepared from guinea pigs was detected and examined. Specific cell binding of gastrin was found to be both pH and temperature dependent. Maximum binding of radiolabeled gastrin by gastric mucosal cells was demonstrated at pH 7.4 and at 4 degrees C. Substantial degradation of 125I-gastrin occurred during incubation with gastric mucosal cells. Gastrin degradation was detected both by loss of immunological reactivity with antibodies to gastrin and by abolition of subsequent specific binding after prior incubation with gastric mucosal cells. Degradation of gastrin was most marked with incubations conducted at pH 7.4 and at low pH (pH 2.0), suggesting the activities of at least two gastrin-degrading enzyme systems in the gastric mucosal cell preparation.     

Physiological importance of calpains in gastric mucosal defense

The continuous and/or improper ingestion of irritants, including alcohol, NSAIDs, and Helicobacter pylori, often leads to serious gastropathies, affecting a wide range of people. A complex gastric defense system works to protect against these threats, for example by secreting mucus. Recently, by analysis of gene targeting mice for two gastrointestinal-tract-specific calpains, calpain-8 and calpain-9, we have demonstrated that they are cooperatively involved in the mucosal defense against stress-induced gastropathies. Calpains-8 and -9 are members of Ca2+ -dependent intracellular proteases comprising a superfamily in almost all eukaryotes, and form a functional complex, "G-calpain", expressed specifically in the mucus-producing cells. In this review, we show our recent results on calpains -8 and -9, and discuss gastric mucosal defense mechanisms involving them.     

胃黏膜皱襞巨大肥厚21例临床分析

目的 探讨良、恶性胃黏膜皱襞巨大肥厚的鉴别诊断。方法 胃镜诊断与黏膜活检、手术后病理诊断对照。结果 胃镜诊断21例胃黏膜皱襞巨大肥厚患者，其中弥漫性肥厚15例，局限性肥厚6例，常规病理活检仅发现7例恶性病变。术前胃镜诊断慢性胃黏膜肥厚性胃病8例，其中5例施行手术，均为恶性病变，误诊率这63．5％。结论 慢性胃黏膜肥厚性胃病(Menetrier)是少见的，胃黏膜皱襞巨大肥厚以恶性者居多。