Gastric mucosal PGE2 levels in gastric nonulcer and ulcer patients with chronic renal failure or without renal diseases and in healthy subjects

PGE2-like immunoactivity in mucosal specimens from gastric corpus and antrum was measured in individuals with chronic uremia or without renal diseases in absence or presence of gastric ulcerations and in healthy subjects. Regardless the group of patients, compared to normal mucosa, a significant decrease in PGE2-like immunoactivity (50-70%) was found in mucosa from atrophic, but not from superficial gastritis. Whenever patients of the control group or patients with renal diseases suffered from ulcers, PGE2-like immunoactivity, compared to nonulcer subjects, revealed a decrease of about 60-70% in the nonulcerated mucosa. Compared to nonulcerated mucosa, the tissue of the ulcer rim in all patients with gastric ulcer showed a relative increase in PGE2-like immunoactivity, eg, PGE2-like immunoactivity was twice as high in tissue from the ulcer rim. The output of PGE2-like immunoactivity into the gastric juice of subjects without renal diseases was comparable to that found in patients with chronic uremia in both basal and pentagastrin-stimulated conditions. We therefore conclude that gastric mucosal formation is probably not influenced by chronic uremia.     

Decreased prostaglandin E2 immunoactivity of gastric mucosa in portal hypertension

PGE2-like immunoactivity was measured radioimmunologically in specimens from gastric corpus mucosa in (a) healthy subjects, (b) patients without liver disease in the absence or presence of gastric ulcer, and (c) patients with alcoholic cirrhosis in the absence or presence of gastric ulcer, further divided into subgroups without or with portal hypertension. The PGE2-like immunoactivity was almost the same in subjects without liver disease and in cirrhotic patients without portal hypertension. A significantly decreased PGE2-like immunoactivity was found in patients with portal hypertension, especially in cases of congestion in the mucosa. A further decrease of the PGE2-like immunoactivity could be found whenever gastric corpus ulcer was present. This decrease is statistically significant. We therefore concluded that a decrease in the PGE2-like immunoactivity in the gastric mucosa of cirrhotic patients is closely related to portal hypertension. Congestion in the mucosa, thought to be a relevant factor in the pathogenesis of the mucosal PGE2 deficiency, might also play a role.     

Enzyme Immunoassay of Gastric Luminal Prostaglandin E2 in Duodenal Ulcer Disease

A highly sensitive enzyme immunoassay was used to determine gastric juice prostaglandin E2 (PGE2) levels in control subjects with or without gastritis and in both active or inactive duodenal ulcer patients. Mean pentagastrin-stimulated PGE2 concentration was significantly lower in patients with duodenal ulcer than in control subjects considered as a whole group (with or without gastritis). However, no such difference was found between duodenal ulcer patients and controls showing histologically normal gastric mucosa. On the other hand, controls with chronic superficial gastritis had PGE2 levels significantly higher than those of histologically normal subjects and duodenal ulcer patients. Therefore, it seems unlikely that an absolute gastric PGE2 deficiency is involved in the pathogenesis of duodenal ulcer disease. However, the possibility that PGE2 synthesis could be deficient in relation to the prevailing level of mucosal inflammation cannot be excluded.     

Upper gastrointestinal mucosal lesions in chronic renal failure.

The upper gastrointestinal mucosa was studied endoscopically in 182 patients (140 males, 42 females) with chronic renal failure prior to hemodialysis. Endoscopy revealed normal mucosa in 77 patients (42.3%), inflammatory mucosal lesions in 88 (48.4%), peptic ulcer in 16 (8.8%; duodenal 15, gastric 1) and Barrett's ulcer in one patient. Upper gastrointestinal bleeding was noted at presentation in 16 (8.8%) cases and was associated with erosive gastritis, duodenitis and duodenal ulcer in 11, 3 and 2 patients respectively. Thus patients with chronic renal failure had a high prevalence of inflammatory mucosal changes.     

Simultaneous measurement of in vitro gastroduodenal prostaglandin E2 synthesis and degradation in peptic ulcer disease

The ability of mucosal specimens from the stomach and duodenum to synthesize and degrade prostaglandin E2 has been determined in normal subjects and peptic ulcer patients. Significant reduction in fundic PGE2 synthesis capacity was observed in gastric ulcer patients. There was also significant reduction in the PGE2 degradation capacity of antral, fundic, and duodenal mucosal specimens in gastric ulcer patients. Patients with gastritis showed significant elevation of both antral and fundic PGE2 synthesis capacity compared with normal but no alteration in PGE2 degradation. No differences were observed in PGE2 synthesis and degradation rates in patients with duodenal ulcer. The results argue in favour of an association between impairment of PGE2 metabolism in the mucosa of patients with gastric but not duodenal ulceration.     

Acute upper gastrointestinal hemorrhage in patients with chronic renal disease

In order to reassess the role of duodenal ulcers as a cause of acute upper gastrointestinal hemorrhage in patients with chronic renal failure, 20 consecutive patients with moderate to severe chronic renal failure and a comparison group of patients without renal disease who were seen for acute upper gastrointestinal hemorrhage were reviewed. Gastric bleeding sites (gastric ulcer in 35 percent and gastritis in 20 percent) rather than duodenal ulcers were the most common sources of bleeding and were significantly associated with the use of ulcerogenic drugs. Patients with renal disease in whom acute upper gastrointestinal hemorrhage developed had significantly more morbidity and a trend toward higher mortality than the comparison group of patients without renal disease. It is concluded that gastric mucosal lesions, at least in part due to the use of ulcerogenic drugs, are the most common cause of significant acute upper gastrointestinal hemorrhage in patients with chronic renal failure.     

Phospholipid composition of human gastric mucosa: a study of endoscopic biopsy specimens.

Gastric mucosal phospholipids, and in particular those of the surface layer, play an important part in mucosal barrier function. This study examined whether the phospholipid composition of the full thickness gastric mucosa is changed in peptic ulcer disease and gastritis. The phospholipid composition of gastric mucosa from endoscopic biopsy specimens in 28 subjects (eight healthy controls, 12 patients with duodenal ulcer, and eight with chronic atrophic gastritis) was studied. In addition, the phospholipid composition of gastric mucosa was compared with that of duodenal mucosa in 10 patients with duodenal ulcer. As expected phosphatidylcholine and phosphatidylethanolamine prevailed in all three groups. Lysolecithin was the smallest component in the duodenal ulcer and chronic atrophic gastritis groups. The phosphatidylethanolamine value was higher in duodenal ulcer and lower in chronic atrophic gastritis compared with the control group. In chronic atrophic gastritis there was an appreciable amount of phosphatidylglycerol that was not present in patients with duodenal ulcer or in the control group. There was no significant difference in phospholipid composition between antral and duodenal sites in duodenal ulcer patients. In conclusion, the phospholipid composition of gastric mucosa changes in human gastrointestinal diseases but its relation to cellular functions needs further study.     

Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol.

The distribution of mucosal PGE2-like activity was determined by bioassay technique in the body and antrum of the stomach and in the duodenum of healthy subjects and duodenal ulcer patients before and after administration of aspirin, paracetamol, or histamine. In healthy subjects, the oxyntic, antral and duodenal mucosa was found to be capable of generating large amounts of PGE2, which were not significantly different from those found in duodenal ulcer patients. No correlation was found between the generation of PGE2 and gastric acid secretory status or serum gastrin level. Aspirin-and to a much lesser extent, paracetamol-caused a dramatic reduction in the ability of the gastric mucosa to biosynthesis PGE2 and this was accompanied by marked side-effects and injury to the gastric mucosa. Administration of histamine caused small but significant reduction in the biosynthesis of PGE2 but it was accompanied by marked mucosal damage. This study indicates that the gastric and duodenal mucosa is capable of generating PGE2-like activity which may be involved in the mechanism that protects the mucosa against the damage caused by aspirin.     

肝硬化患者胃黏膜前列腺素E2的研究

目的研究肝硬化患者胃黏膜前列腺素E2(PGE2)及意义。方法选取肝硬化患者60例及慢性胃炎、非溃疡性消化不良(NUD)患者各80例,行上消化道内镜检查,取胃窦及胃体各1块黏膜组织,用RIA法检测PGE2含量。结果(1)肝硬化组胃黏膜PGE2含量明显低于慢性胃炎及NUD组。(2)在肝硬化患者中,胃黏膜PGE2含量门脉高压胃病(PHG)组明显低于非PHG组,肝源性溃疡(HU)组亦明显低于非HU组,而与肝功能分级无关。结论(1)肝硬化胃黏膜防御机制减弱。(2)肝硬化胃黏膜PGE2的异常参与PHG及HU的形成。     

Micronutrient antioxidants in gastric mucosa and serum in patients with gastritis and gastric ulcer: does Helicobacter pylori infection affect the mucosal levels?

Free radicals (FRs) play an important role in the pathogenesis of gastroduodenal mucosal inflammation, peptic ulcer disease, and probably even gastric cancer. Various micronutrients protect the gastric mucosa by scavenging FRs. Only limited data is available regarding the concentration of micronutrients in the gastric mucosa in patients with gastritis and peptic ulcer disease. Our aim was to analyze micronutrient antioxidant concentrations in the antral mucosa in patients with gastritis and gastric ulcer and to determine the influence of Helicobacter pylori infection on gastric mucosal antioxidants in patients with gastritis and gastric ulcer. Patients who underwent upper endoscopy for evaluation of dyspepsia were included in the study. Ascorbic acid, alpha-tocopherol, alpha-carotene, beta-carotene, total carotenoids, lutein, cryptoxanthin, and lycopene levels were measured in the sera and antral mucosal biopsies in these patients. The diagnosis of H. pylori was confirmed by histology, urease test (CLO) and serology. Patients with negative endoscopic findings and normal histology and no H. pylori infection served as controls. In patients with gastritis, alpha-tocopherol levels were reduced in serum and mucosa irrespective of H. pylori status, whereas carotenoids and ascorbic acid levels were similar to controls. However, in patients with gastric ulcer, serum and mucosal levels of all micronutrient antioxidants were markedly decreased compared with both controls and patients with gastritis. The degree of depletion of antioxidants was similar in patients with either H. pylori-induced or nonsteroidal antiinflammatory drug (NSAID)-induced ulcers. Patients with gastric ulcer have very low gastric antioxidant concentrations compared to patients with gastritis and normal mucosa. This depletion in antioxidants seems to be a nonspecific response and was not related to H. pylori infection.     

Gastric mucosal prostaglandin E2 levels in cirrhosis and portal hypertension

Prostaglandin E2 (PGE2) tissue levels were measured, using radioimmunoassay, in specimens from the gastric antral mucosa in (a) healthy subjects, (b) patients without liver diseases in the absence or presence of gastric ulcers, and (c) patients with alcoholic cirrhosis in the absence or presence of gastric ulcers. These groups were divided further into subgroups with or without portal hypertension. PGE2 tissue levels in subjects without liver diseases were not significantly different from those of cirrhotic patients without portal hypertension. However, in cirrhotic patients with portal hypertension, the PGE2 content was significantly lower, especially in the presence of congestion in the mucosa (about 70-80%). When a gastric antral ulcer was present, a further statistically significant decrease of the PGE2 levels was observed. It was concluded that a decrease in the PGE2 tissue levels in the gastric mucosa of cirrhotic patients is related to the presence of portal hypertension. Congestion in the mucosa, as a pathogenetically relevant factor for mucosal PGE2 deficiency, may play a role.     

Sulfation of glycolipids by human gastric mucosa in disease

The activity levels of sulfotransferase enzymes involved in the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to mucosal membrane and mucus gel glycolipids were studied in fundic and antral mucosal biopsies of patients with severe and chronic gastritis, gastric atrophy, gastric ulcer, and gastric cancer. With sulfotransferase which catalyzes the sulfation of mucus triglucosyl glyceroglucolipid increase in enzyme activity over the control was observed in patients with chronic and severe gastritis, and gastric atrophy, while a decrease in activity was noted in patients with gastric ulcer and gastric cancer. The differences were significant at p less than 0.001 for severe gastritis, gastric ulcer and gastric cancer. The increase in activity of sulfotransferase enzyme involved in the sulfation of membrane galactosylceramide over the control was observed in antral and fundic mucosa of all patients. Significant (p less than 0.001) differences were found in patients with severe gastritis, gastric atrophy and gastric ulcer. The results indicate that considerable changes in the activities of the mucosal sulfotransferase enzymes involved in the synthesis of membrane and secretory sulfolipids occur in gastric disease.     

Gastric and Duodenal Mucosal Prostaglandin Concentrations in Gastric or Duodenal Ulcer Disease: Relationships with Demographics, Environmental, and Histological Factors, including Helicobacter pylori

We measured gastric and duodenal mucosal prostaglandin concentrations in 69 patients with active or inactive duodenal or gastric ulcer disease and 26 non-ulcer controls. Each underwent endoscopy enabling us to obtain multiple biopsies from the gastric body and antrum and from the duodenal bulb and postbulbar duodenum for measurement of mucosal prostaglandin concentrations, as well as a single biopsy from each region for mucosal histology. Using a multivariate linear regression model, we found that neither gastric nor duodenal ulcer disease significantly affected gastric or duodenal mucosal prostaglandin concentrations. Mucosal prostaglandin concentrations were similar at the edge of the ulcer and in the adjacent non-ulcerated mucosa. Neither gender symptoms, smoking, use of H2-receptor antagonists, disease activity, nor Helicobacter pylori infection had an independent effect on mucosal prostaglandins in any region. Gastritis in the body of the stomach was associated with significantly higher prostaglandins, while older age was associated with significantly lower gastric and duodenal prostaglandins. Gastroduodenal mucosal prostaglandins are thus not altered in patients with active or inactive peptic ulcer disease, even when multiple demographic and histologic variables are taken into consideration.     

Elevation of TFF1 gene expression during healing of gastric ulcer at non-ulcerated sites in the stomach: semiquantification using the single tube method of polymerase chain reaction

BACKGROUND: The Trefoil factor family 1 (TFF1), one of the trefoil peptides, has been considered to play protective and reparative roles of experimentally induced ulcers in the stomach. However, the alteration of the TFF1 mRNA in the non-ulcerated areas of living human gastric mucosa in gastric ulcer is not well known. We examined TFF1 gene expression at non-ulcerated sites during the healing of a gastric ulcer by semiquantitative determination of the TFF1 mRNA. METHODS: Gastric mucosal biopsy specimens were taken before and after the healing of the gastric ulcer from seven consecutive patients and from seven patients diagnosed with non-ulcer dyspepsia (NUD). The relative value of TFF1 mRNA (RTFF1) was calculated by the single tube method of polymerase chain reaction (ST-PCR) and Southern hybridization. Immunohistochemistry using monoclonal antibodies was performed to confirm the presence of the TFF1 peptide. The status of Helicobacter pylori and the severity of gastritis were investigated simultaneously. RESULTS: The mean relative values of TFF1 mRNA at both the gastric angle (RTFF1AS) and the gastric body (RTFF1BS) of patients with gastric ulcers at the healed stage were significantly higher than those at the open stage (P< 0.05). The mean RTFF1AS at both the open and healed stages were lower than those of RTFF1BS at the open and healed stages, respectively, The mean RTFF1B at the open stage was lower than that in NUD (not significant), but the mean of RTFF1B at the healed stage was significantly higher than that in NUD. The RTFF1AS and RTFF1BS of all patients did not correlate with H. pylori status nor with the severity of gastritis. The induction of TFF1 mRNA at the non-ulcerated background sites seemed not to be related to the status of H. pylori or to the severity of gastritis. CONCLUSIONS: These results suggest that the increased levels TFF1 mRNA during the healing of gastric ulcers might be closely related to the protection and the cell differentiation at the non-ulcerated areas of living human gastric mucosa.     

Interrelationships among gastric mucosal morphology,secretion, and motility in peptic ulcer disease

Pathophysiologic abnormalities associated with ulcer disease include gastritis (particularly of the antral mucosa), excessive duodenogastric reflux, and altered motor activity of the stomach. It is not known whether these abnormalities are interrelated and whether they occur during periods of ulcer inactivity. We have tested the hypothesis that the morphological abnormalities of the gastric mucosa in inactive ulcer disease are proportional to an alteration of the gastric luminal milieu itself due to abnormal secretory and motor function. Thus, multiple endoscopic biopsies and 24-hr physiologic measurements were performed in 12 patients with well-documented ulcers in the past (seven type I gastric ulcer patients, five duodenal ulcer patients), now clinically and endoscopically in remission. Seven healthy individuals underwent similar studies and served as controls. Histologic quantification of inflammation and metaplasia (expressed as a gastritis index) was found to be significantly different among groups (P<0.01). Gastric ulcer patients exhibited a higher gastritis index than controls, while duodenal ulcer patients were intermediate. A significant inverse relationship was found between gastritis index and postprandial motility index (R ²=0.59,P<0.01) and a nonsignificant trend between gastritis index and fasting motility index. There was no difference among groups or detectable associations between gastritis index and intragastric pH or bile acid concentration. We conclude that gastric mucosal disease, expressed as gastritis index, persists during inactive ulcer disease. There is an association with antral hypomotility, which is more strongly manifested postprandially. It is not associated with gastric pH or bile acid concentration. Gastric mucosal inflammation and antral hypomotility predispose to ulceration rather than simply accompanying it.This work was supported in part by grant AM 26428 from the National Institutes of Health.     

Prevalence of Helicobacter pylori in southern Indian controls and patients with gastroduodenal disease

Abstract The spiral organism Helicobacter pylori has been casually implicated in the genesis of various gastroduodenal diseases. Since these diseases are common in southern India, this study was undertaken to determine the prevalence of H. pylori in the gastric mucosa of asymptomatic adults and patients with various gastroduodenal diseases. H. pylori was detected in the gastric mucosa of 25 of 30 (83.3%) normal volunteers. Prevalence rates in the disease groups were also high, and included 38 of 41 patients with duodenal ulcer (92.6%), 13/16 with gastric ulcer (81.3%), and 85/119 subjects (71.4%) with non-ulcer dyspepsia. Light microscopic examination of the gastric mucosa provided the best method of detecting H. pylori. H. pylori colonization was significantly associated with histological abnormalities, mainly chronic atrophic gastritis (147) and superficial gastritis (11), while only three of 161 H. pylori positive patients had histologically normal antral mucosa. Ultrastructural examination revealed changes in the apical complex of the gastric mucosal cells in response to bacterial adhesion, with mucus depletion and cellular damage. Bacteria were also noted disrupting the tight junctions and entering the intercellular spaces. The high prevalence of H. pylori infection may explain the high incidence of gastritis, duodenal ulceration and gastric carcinoma in this population. However, in this population, the prevalence of infection in asymptomatic individuals was nearly as high as that in duodenal ulcer, underlining the need for further study to identify the differences in host response or bacterial pathogenicity that lead to the development of ulcer in only some individuals.     

Etiology and management of chronic gastritis

There are reasons to believe that chronic antral gastritis and chronic body gastritis are different clinical conditions. While both are associated with aging, chronic antral gastritis is much more commonly associated with gastric or duodenal ulcer. The natural history of chronic antral gastritis in asymptomatic normals and patients with peptic ulcer appears the same. Chronic body gastritis deteriorates rapidly with age in patients with gastric ulcer, but does not progress in patients with duodenal ulcer. With spontaneous healing of duodenal ulcer, chronic antral gastritis improves but persists. All these observations suggest that gastric ulcer, duodenal ulcer, and chronic antral gastritis are involved in a common mucosal inflammatory process. C. pylori occurs commonly on the antral mucosa affected by chronic gastritis, but is found to a much less extent at the site of peptic ulceration, and spontaneous ulcer healing is not affected by the presence of the organisms. It remains to be established whether C. pylori is the cause of chronic antral gastritis, is an aggravating factor of the gastritis, or is simply an inhabitant of the inflamed antral mucosa. Other known associations of chronic gastritis include pernicious anemia, bile reflux, and gastric cancer. Whether chronic antral or body gastritis is associated with clinical symptoms remains controversial. Histological improvement can be obtained with the use of prostaglandins, sucralfate, or bismuth compounds, which have one common property--they all possess mucosal-protective mechanisms.     

胃粘膜肥大细胞及其脱颗粒与Hp致病关系的探讨

目的：探讨胃粘膜肥大细胞（MC）及其脱颗粒与幽门螺杆菌（Hp）致病性的关系。方法：采用改良甲苯胺蓝染色法检测120例患者胃粘膜中MC计数及脱颗粒细胞所占比例。结果：1．Hp阳性患者胃粘膜MC计数及脱颗粒比显著高于Hp阴性患者（P＜0．01）;2．不同Hp感染胃病患者之间胃粘膜MC计数及脱颗粒比也有差异,消化性溃疡（PU）和慢性浅表性胃炎（CSG）患者胃粘膜MC计数及脱颗粒比显著高于慢性萎缩性胃炎（CAG）患者（P＜0．01）。结论：胃粘膜肥大细胞及其脱颗粒参与了Hp致病而导致胃粘膜受损。     

Enzyme activities in the gastric mucosa in duodenal ulcer patients

In a series of 45 consecutive duodenal ulcer patients (DU) the activities of 10 marker enzymes from the brush border, basolateral membrane, mitochondria, and lysosomes were determined by analysis of homogenized material taken with biopsy forceps through an endoscope from the antral and body part of the stomach. They were compared with the enzyme activities determined in controls with similar types of gastritis but without any evidence of peptic ulcer disease. All the DU patients had gastritis in the antral mucosa. In the body part, about 30% had gastritis. In the antral mucosa of DU patients the activities of the membrane and lysosomal enzymes were mostly increased when compared with the controls. In the gastric body mucosa of DU patients the activities of the lysosomal enzymes were mostly increased, whereas most of the membrane enzymes showed unchanged activities when compared with the corresponding controls. Monoamine oxidase activities were decreased or unaltered in both regions in these patients. The finding of enzymatic changes in the gastric mucosa of DU patients gives further support to an altered mucosal metabolism in these patients.