Influence of Helicobacter pylori on gastric secretion. Study on variously associated gastric body, fundus and antrum chronic gastritis

Among the various themes related to Helicobacter pylori (HP) which is still a subject of discussion, there is the possible influence of this bacterium on gastric secretory physiology. In the present study, an evaluation has been carried out of stimulated gastrinemia, stimulated acid secretion and total peptic activity in gastric juice in the course of a paradigmatic condition, as autonomous chronic gastritis, in order to reveal possible modifications induced by the HP infection. In cases of HP positive chronic superficial antral gastritis associated either with normal body-fundic mucosa or with superficial gastritis, there is a significant increase of stimulated gastrinemia in comparison to HP negative groups and controls. In the course of body-fundic atrophic and preatrophic chronic gastritis associated either with antral superficial chronic gastritis or with antral atrophic gastritis, there are no statistically significant differences between HP positive and HP negative subjects. As regards acid and pepsin secretion no significant differences emerge in any group between HP positive and HP negative subjects. In the HP positive subjects with antral superficial gastritis and higher gastrin values the study of acid and pepsin secretion has yielded no significant variations. From the results of this study it emerges how gastric secretory parameters vary exclusively according to the histologic state of gastric mucosa. Therefore, the lesion action of HP may mainly be attributed to a direct action, rather than to substantial gastric secretory changes.     

Prevalence of Helicobacter pylori infection and gastric mucosal abnormalities in chronic pancreatitis

OBJECTIVE: Chronic pancreatitis is often associated with abnormal gastric acid secretion. However, previous studies have taken into consideration neither the potential role of Helicobacter pylori (H. pylori) infection nor histological features of the gastric mucosa in this context. The aim of this study was to analyze the prevalence of H. pylori infection as well as the pattern of gastritis in patients with chronic pancreatitis. METHODS: Forty patients with chronic alcoholic pancreatitis were included in the study: 40 patients with alcoholic liver cirrhosis and normal exocrine pancreatic function and 40 asymptomatic nonalcoholic subjects matched for age and sex used as control subjects. Endoscopy was performed in all patients, and five biopsy specimens from the antrum (three from the gastric body and two from the cardia) were taken for histological grading of gastritis and H. pylori assessment. RESULTS: Prevalence of H. pylori infection was similar in subjects with chronic pancreatitis (38%), asymptomatic subjects (28%) and liver cirrhosis (30%). Topography and expression of H. pylori-associated chronic gastritis was also not different among the three groups of subjects. In H. pylori-negative subjects, the presence of moderate to severe chronic antral gastritis was significantly more common in patients with chronic pancreatitis (40%) than in subjects with liver cirrhosis (18%) and in asymptomatic subjects (14%) (p < 0.05). No difference was found among the three groups of patients with regard to gastritis activity, atrophy, and intestinal metaplasia in the various gastric regions. The chronicity grade of gastritis did not correlate with the severity of pancreatic insufficiency. CONCLUSION: Prevalence of H. pylori infection is not different in patients with chronic pancreatitis as compared with subjects alcoholic liver cirrhosis and asymptomatic subjects. A severe H. pylori-negative chronic gastritis is more common in patients with chronic pancreatitis. This chronic inflammation of the gastric mucosa could contribute to determining the changes in gastric physiology described in patients with chronic pancreatitis.     

Gastric acid secretion in chronic atrophic gastritis and chronic (superficial) gastritis

Basal and pentagastrin-stimulated peak acid outputs were determined in 21 subjects with chronic atrophic gastritis and 10 subjects with chronic superficial gastritis. All subjects were Caucasian. The histological diagnosis was based on multiple gastric biopsy specimens obtained through a fibregastroscope. Comparison of the results with those of a previously reported Caucasian control group show that the mean basal acid outputs of subjects with chronic (superficial) gastritis were significantly higher than that of controls and subjects with chronic atrophic gastritis. No significant difference was found in the mean peak acid outputs of controls and subjects with chronic atrophic gastritis or chronic (superficial) gastritis.     

Dose uniformity of ferromagnetic seed implants in tissue with discrete vasculature: a numerical study on the impact of seed characteristics and implantation techniques

There is evidence of a two-way interaction between gastric acid secretion and H. pylori-associated gastritis. Gastric acid secretion influences the density of H. pylori colonisation, its distribution within the stomach and the severity of the mucosal inflammatory response to the infection. In addition, H. pylori gastritis alters gastric acid secretion. In subjects with a predominant antral gastritis, it increases acid secretion predisposing to duodenal ulcer, whereas in others with predominant body gastritis, acid secretion is impaired and the subjects have an increased risk of gastric cancer. The two-way interaction between acid secretion and H. pylori gastritis is observed when H. pylori-positive subjects are treated with proton pump inhibitor agents. The inhibition of acid secretion induces a body gastritis and this inflammation of the body mucosa inhibits acid secretion thus augmenting the anti-secretory effect of the drug. In this article, we discuss the interaction between gastric acid secretion and H. pylori gastritis and its importance in determining disease outcome.     

Helicobacter pylori inhibits the secretory activity of gastric parietal cells in patients with chronic gastritis. An ultrastructural study

BACKGROUND: Previous in vitro studies suggested that Helicobacter pylori may inhibit the acid secretion of gastric parietal cells. The aim of this study was to investigate ultrastructurally the influence of H. pylori infection on the gastric parietal cell function in vivo. METHODS: This study comprised 28 patients with chronic gastritis. Biopsy specimens were taken from the gastric body in all cases and examined by electron microscopy. Gastric parietal cells were counted in each ultrathin section and classified into secretory and non-secretory types. The pH of the gastric juice was also measured in all patients. RESULTS: The number of parietal cells in the secretory phase was significantly lower in H. pylori-infected (n = 16) patients than in those (n = 12) without H. pylori infection. The intragastric pH was significantly higher in patients with H. pylori-associated gastritis than in those without H. pylori infection. Parietal cells in secretory phase tended to decrease in proportion to the activity of the gastric mucosal inflammation. CONCLUSIONS: The results of this investigation suggests that H. pylori-associated gastritis is related to a decreased secretory activity of the gastric parietal cells.     

Urinary procoagulant activity and tissue factor levels in patients with diabetes mellitus

BACKGROUND: Usually, atrophic body gastritis has been considered an autoimmune disease characterized by the presence of parietal cell antibodies. Previous investigations into the role of Helicobacter pylori infection have obtained conflicting results. The aim of this study was to investigate the prevalence and role of H. pylori in a prospectively investigated population of patients with corpus-predominant atrophic gastritis. PATIENTS AND METHODS: A consecutive series of 67 newly diagnosed cases of atrophic body gastritis was derived from a screening of 326 patients with unexplained anemia or dyspepsia. Criteria for diagnosis were fasting hypergastrinemia, pentagastrin-resistant achlorhydria, and histological confirmation of body atrophy. In all 67 patients, H. pylori infection was evaluated independently by histological assay and urease test. The gastritis status of both the fundic and antral mucosa were graded according to the Sydney system. Parietal cell and intrinsic factor antibodies also were determined. RESULTS: Active H. pylori infection was present in 26.8% of our patients and allowed us to identify a patient's subpopulation with a significantly smaller degree of body mucosa damage as shown by functional parameters (gastrin, gastric acid secretion, pepsinogen I) and histological assessment. In this subpopulation, a higher prevalence of gastric cancer familial history was found. Presence of parietal cell antibodies showed a similar prevalence in H. pylori-positive and H. pylori-negative patients (61.1% vs. 69.4%) and was not associated with significant functional and histological differences. Cure of infection determined an evident improvement of corporal atrophy as well as a reduction of hypergastrinemia. CONCLUSION: Active H. pylori infection, a potential cause of oxyntic gland atrophy, is found in one-fourth of patients with newly diagnosed atrophic body gastritis.     

Helicobacter pylori prevalence in acquired immunodeficiency syndrome

Helicobacter pylori is consistently reported with high prevalence in HIV-negative patients with chronic gastritis and active ulcer disease. This study is an evaluation of the prevalence of H. pylori in AIDS patients, and the association with chronic gastritis, erosions, and ulcer disease. Seventy-three AIDS patients referred for the evaluation of gastrointestinal symptoms underwent upper endoscopy and antral gastric biopsy. Histologic gastritis was diagnosed and degree of activity graded on hematoxylin-eosin stain. H. pylori organisms were identified by acridine orange stain. A single pathologist evaluated the biopsy specimens. H. pylori was found in 15% (11 of 73) of AIDS patients. Histologic chronic active gastritis was evident in 94.5% (69 of 73) of the study group. H. pylori was identified in 15.9% (11 of 69) of biopsy specimens with histologic chronic active gastritis. The organism was more common in biopsy specimens with a higher grade of activity in the chronic gastritis. Endoscopic erosions or ulcers were noted in 11 patients (seven gastric, four duodenal). H. pylori was present in 18% (2 of 11) of AIDS patients with erosions or ulcers. The prevalence of H. pylori in AIDS patients with histologic chronic active gastritis is much lower than the prevalence previously reported for HIV-negative patients with similar pathology. The low prevalence observed does not implicate H. pylori as the causal agent in most chronic active gastritis in the AIDS population. Impaired acid secretion may reduce colonization of gastric mucosa and explain the low rate of H. pylori observed.     

Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma

Helicobacter pylori (HP) infection, a cause of multifocal atrophic gastritis, is considered an important factor related to the evolution of the human gastric mucosa from normal to intestinal-type adenocarcinoma. We examined cell proliferation and both double and single strand DNA damage in situ in 35 patients undergoing gastrectomy for adenocarcinoma with HP-infected gastric mucosa by immunolocalization of Ki-67, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, and in situ nick translation. We also studied the distribution of intraepithelial neutrophils by elastase immunolocalization. HP infection was confirmed in all cases by serum anti-HP antibodies, ureas testing, and histopathological examination. HP-infected gastric mucosa was classified according to the degree of inflammation and intestinal metaplasia. Ki-67, terminal deoxynucleotidyl transferase-mediated labeling, in situ nick translation, and intraepithelial neutrophil indices all increased with the progression of gastritis and were highest in glands with incomplete intestinal metaplasia. All indices were lowest in gastric glands with complete intestinal metaplasia. Significant positive correlations were observed among these markers. Increased proliferative activity in HP-associated chronic gastritis in response to cell damage or injury was clearly demonstrated, suggesting that both HP-associated toxins and intraepithelial neutrophils are important in HP-related gastric epithelial injury. Increased cell turnover associated with incomplete intestinal metaplasia may result in DNA instability and subsequent development of intestinal-type gastric adenocarcinoma in HP-infected mucosa.     

Uremia in the rat affects gastric cell growth and differentiation

The aim of this study was to determine if hypertrophy of different tissues seen in uremic rats included gastrointestinal hypertrophy and an increase in parietal cell mass that might explain the increased acid secretion we previously reported. Chronic renal failure was induced by subtotal nephrectomy. Despite a lower total body weight, uremic rats had a significantly greater stomach weight (33%), corpus area (13%), corpus mucosal height (19%), and parietal (32%) and enterochromaffin-like (ECL, 54%) cell density, but a 16% decrease in mucous neck cell region height. These findings suggest that uremia leads to gastric stem cell stimulation with differentiation favoring parietal and ECL cells over mucous cells. In addition, in uremic rats there was an increase in height of the duodenal mucosa, but not of the ileal or transverse colon mucosa. In conclusion, the present study shows that uremia in the rat promotes hypertrophy of the stomach with cell differentiation favoring parietal cells over mucus cells. The increase in parietal cell mass may explain the increased acid secretion in these rats.     

Pathology of Helicobacter infection

The colonization of gastric mucosa by Helicobacter pylori (H.p.) is a special form of chronic bacterial infection characterized by long term persistence of microbes because cause of an inefficiency of local immune responses. The resulting chronic gastritis causes decisive transformations of gastric mucosa. They comprise the acquisition of an active mucosa-associated lymphoid tissue as well as the development of glandular atrophy and intestinal metaplasia in the stomach. Both transformations change normal gastric functions, and create abnormal microenvironments with an increased risk for gastric cancer and lymphoma. Own recent investigations indicate, that the distribution and severity of chronic gastritis might be decisively influenced by a rise of antigastric autoimmune reactivity during the H.p. infection. The histologic examination of gastric biopsy samples is essential for an exact diagnosis of the complex pathogenic processes in chronic gastritis. In the future special emphasis of histologic analyses has to be put on the subtypes of gastritis, which are prone for complications and on the evaluation of gastritis remission after H.p. eradication.     

Thymoma in dogs: 23 cases (1980-1991)

OBJECTIVE: To assess the efficacy of misoprostol for the treatment of chronic erosive gastritis and associated symptoms. METHODS: We performed a double-blind controlled trial, administering 200-micrograms misoprostol tablets or placebo twice daily for 2 months to 48 patients with symptomatic chronic erosive gastritis. Symptomatology was assessed by means of a standard questionnaire at the beginning and at the end of the study, as well as endoscopic and histologic changes of the gastric mucosa. RESULTS: At the end of the treatment period, a significant reduction in symptom score was observed in misoprostol-treated (from 86.6 +/- 66.2 to 17.6 +/- 18.2, p < 0.001) but not in placebo-treated patients. Endoscopic score was significantly reduced at the end of the treatment period in the misoprostol group, compared with that of the placebo group (p < 0.05). A significant reduction in the activity of histologic gastritis was observed only in patients on misoprostol. The prevalence of gastric colonization by Helicobacter pylori was rather low (30%), and no effect of treatment was observed. CONCLUSIONS: Patients with symptomatic chronic erosive gastritis seem to profit from treatment with misoprostol: the treatment with misoprostol, but not with placebo, was effective in significantly reducing the extent of symptoms. Such an improvement was associated with a substantial improvement in the endoscopic and histologic appearance of the gastric mucosa.     

Diagnosis of otitis media with effusion by acoustic reflectometry

Colonization of human gastric mucosa with Helicobacter pylori leads to chronic active gastritis and induces the occurrence of an acquired mucosa-associated lymphoid tissue (MALT) in the stomach. This remodelling of the gastric mucosa together with chronic antigen persistence may induce autoimmune reactions. The aim of this study was to investigate humoral autoimmune reactions to human gastric mucosa in H. pylori gastritis and their clinical relevance. Sera from patients with dyspeptic symptoms were tested for presence of IgG immunoglobulins against H. pylori. Gastric infection with H. pylori and alterations of gastric mucosa were demonstrated by histological examination of gastric biopsy specimens. All sera were tested for reactivity against human gastric mucosa by immunohistochemistry. Two different in-situ binding sites of antigastric autoantibodies were observed. Binding to canalicular structures within parietal cells was significantly correlated with antibodies to H. pylori, elevated basal gastrin levels and atrophy of gastric corpus glands. Our data indicate that autoimmune reactions to antigens in the human gastric mucosa occur in H. pylori gastritis and that they may play a role in the pathogenesis of the disease.     

Synthetic implants in the reconstruction of the ossicular chain

OBJECTIVE: To determine whether there is a relationship between overexpression of c-met oncoprotein and stage of human gastric mucosal lesions, and its significance. METHOD: Immunohistochemical staining was used in 157 cases of endoscopic biopsies with c-met monoclonal antibody, S-19, which was raised against the human c-met gene product. RESULTS: overexpresion of c-met oncoprotein was detected in 3/30 cases (10%) of superficial gastritis, 4/33 cases (12.1%) of chronic atrophic gastritis, 10/31 cases (32.3%) of intestinal mataplasia, 10/30 cases (33.3%) of dysplasia, and 10/30 cases (33.3%) of gastric carcinoma. The positive staining rate was higher in intestinal mataplasia (54.8%), dysplasia (56.7%), carcinoma (53.3%) than in two kinds of simple chronic gastritis (P < 0.05). The positive staining was obviously located in luminal membrane of mucosal cells. The positive cells were mainly situated in proliferative cell zone of gastric glands. Moreover, the weak staining only in this zone was shown in two of the three normal mucosa. CONCLUSIONS: The overexpression of c-met may be involved in proliferation of gastric mucosa. It is possible that persistent overexpression of c-met oncoprotein is associated with the malignant transformation of gastric mucosal cells.     

Helicobacter pylori in patients undergoing periodic hemodialysis

Forty-nine haemodialyzed patients have been submitted consecutively, under informed consent, to endoscopy with multiple antral gastric mucosa biopsies for Helicobacter pylori (HP) identification, performed by urease, microscopic and cultural tests, as well as histologic examination. Patients have been considered HP negative when negative for all tests; positivity for HP has been correlated with gastritis histologically evaluated according to Whitehead; at endoscopy, blood samples for HP specific IgG, IgA, IgM have been collected; patient's life style concerning smoke, alcohol and drugs as FANS has been investigated as well. HP prevalence in our haemodialyzed patients is 38.8 per cent, similar to general population submitted to endoscopy; a statistically significant correlation between HP and gastritis and specific IgG, but no correlation between HP and age, dialysis duration, IgA, IgM, smoking, alcohol or drugs consumption has been found.     

Heat-shock-proteins-antibodies in patients with Helicobacter pylori associated chronic gastritis

Twenty eight patients (15 F, 13 M mean age 37.7 SD +/- 9.93 range 22-55) affected by Helicobacter Pylori infection associated gastritis were studied. HSP 70 Antibodies were found in 21.4% of patients and their mean values were significantly higher in the patients than in the subjects affected by gastritis HP negative used as controls (p = 0.05). This datum was confirmed by Western blotting. The presence of HSP 70 antibodies in the sera of those patients may support the link between the protein and the development and persistence of chronic inflammation in the gastric mucosa.     

Fixed-ratio discrimination training as replacement therapy in Parkinson''s disease: studies in a 6-hydroxydopamine-treated rat model

Stimulated acid secretion in portal hypertensive gastropathy is blunted and could be due to defective signal transduction in the parietal cell. Therefore, an attempt was made to study the levels of second messengers in parietal cells in experimental extrahepatic portal hypertensive gastropathy. Our aim was to measure acid secretion, intracellular free calcium, calcium transport, cyclic AMP, and ATP levels in the parietal cells isolated from the gastric mucosa of portal hypertensive rats. Acid secretion using acridine orange, intracellular free calcium using Fura-2/AM, calcium influx and efflux by 45CaCl2 and cyclic AMP by RIA kits were measured in unstimulated and histamine- and carbachol-stimulated isolated parietal cells in rats with partial portal vein ligation and sham operation. ATP was measured by HPLC. In portal hypertensive gastropathy, stimulated acid secretion was blunted, and there was a decrease in basal intracellular free calcium. Calcium influx and efflux were at a higher level, and there was a decrease in elevation of intracellular free calcium and cyclic AMP levels with secretagogues. There was also a decrease in ATP. In conclusion, there exists a low energy state in addition to multiple aberrations at the second messenger level in parietal cells in portal hypertensive gastropathy.     

Helicobacter pylori detection by polymerase chain reaction in gastric juice and its correlation with the histology (Giemsa)]

HP infection is involved in the pathogenesis of several gastroduodenal diseases, as type B chronic gastritis, duodenal and gastric ulcer, MALT lymphoma and gastric cancer. The recent availability of molecular techniques, specifically the PCR, allow us to detect very low amounts of the bacterium. The aim of the study is to evaluate the presence of HP in gastric juice by PCR technique and to correlate this findings with histology (Giemsa) of gastric mucosa. Gastric juice PCR positive findings were found in 10/31 (32.3%) HP positive patients at histology. We concluded that HP in gastric juice is possible to detect by molecular techniques. In our study 32.3% of the patients showed the presence of HP in gastric juice.     

Changes in parietal and mucous cell mass in the gastric mucosa of normal subjects with age: a morphometric study

Whether or not the gastric mucosa undergoes significant changes in normal aging subjects is still open to debate. In 51 subjects undergoing endoscopy and lacking any significant endoscopic or histologic modification we evaluated mucosal thickness, gland number, numbers of parietal, chief and mucous cells at the fundus and of mucopeptic cells at the antrum, with a morphometric method, subgrouping the patients according to their age class. Our findings demonstrate that the number of parietal cells tends to increase with age and, on the other hand, the number of mucous cells is reduced in elderly subjects (p < 0.05). When considering the parietal-to-mucous cell ratio, this is significantly increased (p = 0.0005) with age. Acid secretion being an offensive factor and mucus a fundamental component of the gastric mucosal barrier, these findings suggest an increased susceptibility of the gastric mucosa to damage in the elderly.     

Effect of electroacupuncture on gastric acid secretion and gut hormones

21 patients with mild type of chronic superficial gastritis were selected in this study. The effect of electroacupuncture in Zhongwan (RM12), Neiguan (P6) and Sanyinjiao (Sp6) on gastric acid secretion, serum gastrin, plasma somatostatin, plasma motilin concentration and erythrocyte acetylcholinesterase (AchE) activity were observed. The results were as follows: There were significant decreases in gastric acid output, serum gastrin concentration and AchE activity (P < 0.05), but no significant changes in plasma somatostatin and motilin concentration (P > 0.05) after simultaneous electroacupuncture in Zhongwan, Neiguan and Sanyinjiao.     

Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.