Helicobacter pylori and hormones.

Helicobacter pylori affects gastric acid secretion via several mechanisms. One of these is by changing gastric regulatory physiology. The infection elevates plasma gastrin levels and decreases gastric mucosal expression of the inhibitory peptide somatostatin. These changes may be due to products of H. pylori itself or inflammatory cytokines released in H. pylori infection: acid secretion is inhibited less by a low intra-gastric pH, infusions of cholecystokinin and gastric distention in infected persons. Eradication of H. pylori rapidly decreases basal acid secretion and gastrin-releasing, peptide-stimulated acid secretion. There are now reports that maximally-stimulated acid secretion, a measure of the parietal cell mass, falls significantly six and 12 months after eradication of H. pylori from duodenal ulcer patients. This might be due to withdrawal of the trophic effect of gastrin. However H. pylori can also decrease gastric acid secretion, both through the mechanisms described in Dr. Cave''s paper and by causing gastric mucosal atrophy with loss of parietal cells. The net effect on acid presumably depends on which mechanism predominates. The processes involved may be crucial determinants of clinical outcome. For example, infection with little atrophy and high acid secretion is associated with duodenal ulcers, while infection with atrophy and low acid secretion increases the risk of gastric cancer of the intestinal-type.     

Helicobacter pylori modulation of gastric acid

Helicobacter pylori plays major causative roles in peptic ulcer disease and gastric cancer. Elevated acid secretion in patients with duodenal ulcers (DUs) contributes to duodenal injury, and diminished acid secretion in patients with gastric cancer allows carcinogen-producing bacteria to colonize the stomach. Eradication of H. pylori normalizes acid secretion both in hyper-secreting DU patients and hypo-secreting relatives of gastric cancer patients. Therefore, we and others have asked how H. pylori causes these disparate changes in acid secretion. H. pylori gastritis more or less restricted to the gastric antrum in DU patients is associated with increased acid secretion. This is probably because gastritis increases release of the antral acid-stimulating hormone gastrin and diminished mucosal expression of the inhibitory peptide somatostatin. Bacterial products and inflammatory cytokines including TNFalpha may cause these changes in endocrine function. Gastritis involving the gastric corpus tends to diminish acid secretion, probably because bacterial products and cytokines including IL-1 inhibit parietal cells. Pharmacological inhibition of acid secretion increases corpus gastritis in H. pylori-infected subjects, so it is envisaged that gastric hypo-secretion of any cause might become self-perpetuating. H. pylori-associated mucosal atrophy will also contribute to acid hypo-secretion and is more likely in when the diet is high in salt or lacking in antioxidant vitamins. Data on gastric acid secretion in patients with esophagitis are limited but suggest that acid secretion is normal or slightly diminished. Nevertheless, H. pylori infection may be relevant to the management of esophagitis because: (i) H. pylori infection increases the pH-elevating effect of acid inhibiting drugs; (ii) proton pump inhibitors may increase the tendency of H. pylori to cause atrophic gastritis; and (iii) successful eradication of H. pylori is reported to increase the likelihood of esophagitis developing in patients who had DU disease. Points (ii) and (iii) remain controversial and more work is clearly required to elucidate the relationship between H. pylori, acid secretion, gastric mucosa atrophy and esophagitis.     

Long-term effects of Helicobacter pylori infection on acid and pepsin secretion.

Chronic Helicobacter pylori infection causes a slight postprandial hypergastinemia, generally referred to as exaggerated or inappropriate gastrin release. This can be ablated by eradication of this infective agent. The expectations that this would further unravel the mysteries of the pathogenesis of peptic ulcer disease have not been fulfilled. It is now well established that of conventional acid secretory patterns such as basal acid secretion, maximum gastrin-stimulated acid secretion, and of sensitivity of the parietal cell to gastrin, only basal acid is modified by chronic H. pylori colonization. This particularly relates to basal secretion in duodenal ulcer patients, as basal secretion of otherwise healthy, chronically H. pylori-infected subjects appears to be affected in only a small proportion of subjects. It is of particular interest, however, that chronic H. pylori infection supplies a solid explanation why acid inhibitory pathways are deficient in duodenal ulcer disease, since this is reversible following H. pylori eradication as demonstrated by elegant studies with gastrin-releasing, peptide-stimulated acid secretion. Furthermore, it has gradually become apparent that exaggerated gastrin response is probably no more than an innocent bystander of chronic H. pylori infection. Paradoxically, in a small subset of patients, hypo-or anacidity accompanying chronic H. pylori infection can be reverted by H. pylori eradication, for currently unknown reasons.     

Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal ulcer patients--evaluation of 24-h pH monitoring.

It is accepted that eradication of Helicobacter pylori leads to healing of chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence in duodenal ulcer (DU) patients. However, it is not entirely known whether the eradication of the bacteria normalizes gastric acid secretion and abolishes dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the intragastric acidity and dyspeptic complaints before, and 3 months after, eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric pH was measured by 24-h continuous intraluminal recording, serum gastrin measurements and Congo-red tests were also performed. Dyspeptic complaints and antacid consumptions were recorded in diary cards, antisecretory therapy was not allowed after the cessation of eradication therapy. Endoscopy, H. pylori status and Congo-red tests were controlled at the 6th and 12th week, while pH measurements and serum gastrin tests were performed at inclusion and 3 months later. Three patients dropped out and in 14 out of the remaining subjects healing of DUs and successful eradication was achieved by the 6th and 12th week controls. The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not changing significantly by the 3-month controls (from 1.9+/-0.5 to 1.8+/-0.4 and from 52.6+/-5.5% to 58.6+/-5%, respectively). Similarly, no significant changes were observed in serum gastrin levels and dyspeptic symptom scores (from 72+/-7 pg/ml to 56.7+/-8 pg/ml and from 2.69+/-0.4 to 1.26+/-0.3, respectively). The antacid consumption was almost stable when compared with the pre- and post-eradication periods. It was concluded that despite successful H. pylori eradication and healing of DU, intragastric acidity does not change significantly at least 3 months after the therapy. The persisting dyspeptic symptoms and the need for antacid consumption suggest that some healed ulcer patients require antisecretory therapy in the post-eradication period.     

Effect of Helicobacter pylori eradication on extent of duodenal gastric metaplasia and grade of gastritis

The extent of the regression of duodenal gastric metaplasia (DGM) after the eradication of Helicobacter pylori infection is controversial. Therefore, we decided to assess the degree of DGM before, sex weeks and one year after H. pylori eradication. 105 consecutive Helicobacter pylori positive patients with endoscopically proven duodenal ulcer, with DGM and Helicobacter pylori infection were recruited for this study. The diagnosis of Helicobacter pylori infection was based on CLO-test and histology, and DGM was assessed on four bulb biopsies taken before, sex weeks and one year after Helicobacter pylori eradication. Histological assessment of Helicobacter pylori associated gastritis was performed according to the Sydney classification. Follow up study on 98 patients before, six weeks and one year after the eradication of Helicobacter pylori showed that the mean extent of DGM did not change significantly after eradication and did not differ when compared with 14 patients with persisting infection. Our results show that the inflammatory process related to Helicobacter pylori does not play the main role in the development of DGM.     

Hypergastrinemia increases gastric epithelial susceptibility to apoptosis

Plasma concentrations of the hormone gastrin are elevated by Helicobacter pylori infection and by gastric atrophy. It has previously been proposed that gastrin acts as a cofactor during gastric carcinogenesis and hypergastrinemic transgenic INS-GAS mice are prone to developing gastric adenocarcinoma, particularly following H. pylori infection. We hypothesised that the increased risk of carcinogenesis in these animals may partly result from altered susceptibility of gastric epithelial cells to undergo apoptosis. Gastric corpus apoptosis was significantly increased 48 h after 12Gy gamma-radiation in mice rendered hypergastrinemic by transgenic (INS-GAS) or pharmacological (omeprazole treatment of FVB/N mice) methods and in both cases the effects were inhibited by the CCK-2 receptor antagonist YM022. However, no alteration in susceptibility to gamma-radiation-induced gastric epithelial apoptosis was observed in mice overexpressing progastrin or glycine-extended gastrin. Apoptosis was also significantly increased in gastric corpus biopsies obtained from H. pylori-infected humans with moderate degrees of hypergastrinemia. We conclude that hypergastrinemia specifically renders cells within the gastric corpus epithelium more susceptible to induction of apoptosis by radiation or H. pylori. Altered susceptibility to apoptosis may therefore be one factor predisposing to gastric carcinogenesis in INS-GAS mice and similar mechanisms may also be involved in humans.     

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children

Background. Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal‐stimulated gastrin in relation to H. pylori infection among pediatric patients. Materials and Methods. Thirty‐six children aged 10–17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2–3 months after H. pylori eradication. Meal‐stimulated serum gastrin response was assessed before and 12 months after eradication. Results. H. pylori gastritis was typically antrum‐predominant. Acid secretion was greater in H. pylori‐positive patients with duodenal ulcer than in gastritis‐only patients or controls [mean ± standard error (SE): 6.56 ± 1.4, 3.11 ± 0.4 and 2.65 ± 0.2 mEq/10 minutes, respectively; p < .001]. Stimulated acid secretion was higher in H. pylori‐positive boys than girls (5.0 ± 0.8 vs. 2.51 ± 0.4 mEq/10 minutes, respectively; p < .05). Stimulated acid secretion pre‐ and post‐H. pylori eradication was similar (5.47 ± 0.8 vs. 4.67 ± 0.9 mEq/10 minutes, respectively; p = .21). Increased basal and meal‐stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p < .001 and peak from 544 to 133 pg/ml, p < .05). Conclusions. H. pylori infection in children is associated with a marked but reversible increase in meal‐stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.     

Helicobacter felis and Helicobacter bizzozeronii induce gastric parietal cell loss in Mongolian gerbils

Non-pylori helicobacter infections are associated with gastritis, gastric ulcers and MALT lymphomas in man. Approximately 50% of these are caused by helicobacters commonly found in dogs and cats, including Helicobacter felis, Helicobacter bizzozeronii and H. salomonis. In contrast to Helicobacter pylori, the virulence mechanisms of these species are unknown. In this study the virulence of H. felis, H. bizzozeronii and H. salomonis was investigated in Mongolian gerbils. Female SPF gerbils were inoculated intragastrically with H. felis, H. bizzozeronii or H. salomonis and sacrificed 3 weeks later. Fundus and antrum samples were taken for bacterial detection by PCR. A longitudinal strip covering all stomach regions was taken for histology. Gastric colonization, inflammation, apoptosis, loss of parietal cells and cell proliferation were assessed. Controls and H. salomonis inoculated gerbils were negative in PCR. H. felis and H. bizzozeronii inoculated animals were positive. H. felis inoculated animals showed loss of parietal cells extending from the limiting ridge into the fundus. A high cell proliferation rate was noticed in the mucosal area devoid of parietal cells. A dense band of apoptotic cells and large numbers of Helicobacter bacteria were seen at the transition zone between affected and normal parietal cells. In H. bizzozeronii infected gerbils, this was less pronounced. Focal apoptotic loss of gastric epithelial cells was spatially associated with the presence of bacteria especially in H. felis and to a lesser extent in H. bizzozeronii infected gerbils. This loss of cells may lead to intestinal metaplasia.     

Chronic Helicobacter pylori infection results in gastric hypoacidity and hypergastrinemia in wild-type mice but vagally induced hypersecretion in gastrin-deficient mice

Helicobacter pylori infection is a causal factor of gastric cancer (which is associated with low gastric acid secretion) or duodenal ulcer (high acid secretion). Parietal cells and ECL cells in the stomach are controlled by gastrin, which plays a crucial role in the regulation of acid secretion. The present study was undertaken to identify a possible role of gastrin in determining the different responses of the parietal cells and ECL cells to chronic H. pylori infection. Wild-type (C57BL/6J) gastrin(+/+) mice and gastrin(-/-) knockout mice, generated through targeted gene disruption and backcrossed eight times to C57BL/6J, were infected with H. pylori for 9 months. The acid output was measured 4 h after pylorus ligation (known to cause vagal excitation). The gastric mucosa was examined by immunocytochemistry with antisera to alpha-subunit of H+/K(+)-ATPase for the parietal cells, and to histamine and vesicle monoamine transporter-2 for the ECL cells, and by quantitative electron microscopy. In infected gastrin(+/+) mice, the acid output and the percentage of secreting parietal cells (freely fed state) were 20-30% of the values in uninfected controls, while the density and ultrastructure of parietal cells were normal. The infected mice had hypergastrinemia and displayed hypertrophy and hyperplasia of ECL cells. Although uninfected gastrin(-/-) mice had lower the acid output than uninfected gastrin(+/+) mice, there was a higher acid output (approximately 3 times) in infected gastrin(-/-) mice than their uninfected homologues. The numbers of parietal cells and ECL cells remained unchanged in infected gastrin(-/-) mice. In conclusion, chronic H. pylori infection results to impaired parietal-cell function (acid hyposecretion), hypergastrinemia and hyperplasia of ECL cells in wild-type mice but leads to vagally induced hypersecretion in gastrin-deficient mice.     

Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. METHODS: We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.     

Urea, fluorofamide, and omeprazole treatments alter helicobacter colonization in the mouse gastric mucosa

BACKGROUND: Helicobacter pylori is a causative agent of gastric and duodenal ulcers and gastric cancer. Its urease enzyme allows survival in acid conditions and drives bacterial intracellular metabolism. We aimed to investigate the role of urease in determining the intragastric distribution of Helicobacter species in vivo. MATERIALS AND METHODS: The C57BL/6 mouse model of gastritis was used for infection with Helicobacter felis (CS1) or H. pylori (SS1). Urease-modulating compounds urea and/or fluorofamide (urease inhibitor) were administered to mice over 7 days. Concurrent gastric acid inhibition by omeprazole was also examined. Bacterial distribution in the antrum, body, antrum/body, and body/cardia transitional zones was graded "blindly" by histologic evaluation. Bacterial colony counts on corresponding tissue were also conducted. RESULTS: Urease inhibition by fluorofamide decreased H. pylori survival in most gastric regions (p < .05); however, there were no marked changes to H. felis colonization after this treatment. There was a consistent trend for decreased antral colonization, and an increase in antrum/body transitional zone and body colonization with excess 5% or 6% (w/v) urea treatment. Significant reductions of both Helicobacter species were observed with the co-treatment of urea and fluorofamide (p < .05). Collateral treatment with omeprazole did not alter H. pylori colonization patterns caused by urea/fluorofamide. CONCLUSIONS: Urease perturbations affect colonization patterns of Helicobacter species. Combined urea and fluorofamide treatment reduced the density of both Helicobacter species in our infection model.     

Influence of oral Helicobacter pylori on the success of eradication therapy against gastric Helicobacter pylori

Background. The goal of this study was to see whether Helicobacter pylori ( H. pylori ) in the oral cavity might adversely affect the outcome of eradication therapy for gastric H. pylori.
Materials and Methods. Forty-seven patients (36 males, 11 females) with gastric H. pylori infection were enrolled in this study. Gastric H. pylori infection was confirmed by both immunohistological staining with anti- H. pylori antibody and bacterial culture of biopsy specimens. The therapeutic regimen consisted of 30 mg/day lansoprazole, 750 mg/day metronidazole, and 400 mg/day clarithromycin administered for 2 weeks. A fragment of the H. pylori urease gene was amplified by nested PCR for DNA extracted from saliva and dental plaque from the same patients. We examined the correlation between the gastric eradication success rate and the prevalence of H. pylori in the oral cavity as determined by PCR before and after the eradication therapy.
Results. The eradication success rate was significantly lower in the oral H. pylori -positive cases (12/23, 52.1%) than in the negative cases (22/24, 91.6%) at 4 weeks after the therapy (p = .0028). Two years later, only 16 of the 23 (69.5%) oral H. pylori -positive cases were disease-free, as compared to 23 of the 24 (95.8%) oral H. pylori -negative cases (p = .018).
Conclusions. H. pylori in the oral cavity affected the outcome of eradication therapy and was associated with a recurrence of gastric infection. We recommend that oral H. pylori should be examined by nested PCR and, if positive, should be considered a causal factor in refractory or recurrent cases.     

Effects of dexamethasone and FK506 on Helicobacter pylori-induced gastritis and bacterial viability in Mongolian gerbils.

FK506 and dexamethasone were used to investigate whether or not immunosuppression affects H. pylori colonization and gastric mucosal damage induced by Helicobacter pylori in Mongolian gerbils. Two weeks after H. pylori infection, FK506 and dexamethasone or vehicle alone were subcutaneously administered once daily for the following 2 weeks. FK506 or vehicle alone was administered subcutaneously once daily for 5 weeks (1 week before and 4 weeks after infection). In H. pylori-infected animals for 4 weeks, hemorrhagic erosions and inflammatory responses (neutrophil infiltration and lymphoid follicle formation) were induced in gastric mucosa at an incidence of 100%. Both FK506 and dexamethasone administered for 2 weeks markedly reduced such mucosal changes. In these animals, H. pylori viability in the stomach was significantly elevated. FK506 administered for 5 weeks also significantly inhibited the hemorrhagic erosions, edema and neutrophil infiltration in the stomach. H. pylori viability was slightly elevated as compared with the control. It was concluded that the host immune responses might play dual roles both by deteriorating gastritis induced by H. pylori and by protecting against H. pylori infection in its early stage.     

Detection of non-pylori Helicobacter species in "Helicobacter heilmannii"-infected humans

BACKGROUND: A small proportion of patients suffering from chronic active gastritis are diagnosed with gastric Helicobacter species other than Helicobacter pylori. Circumstantial evidence has suggested that these bacteria, also referred to as "Helicobacter heilmannii"-like organisms (HHLO), may be transmitted through animals. The isolation of a Helicobacter bizzozeronii strain from a human patient confirmed this hypothesis. It was the aim of the present study to assess the presence of animal Helicobacter species and H. pylori in humans infected with HHLO, as diagnosed by histology. METHODS: Paraffin-embedded gastric biopsy specimens of 108 HHLO-infected patients (42 women and 66 men) from three clinical centers were screened for the presence of animal gastric Helicobacter species by polymerase chain reaction (PCR), using assays targeting the 16S rDNA region of the three known canine and feline helicobacters (H. bizzozeronii, H. salomonis and H. felis), "Candidatus H. suis", and "Candidatus H. bovis". In addition, the presence of H. pylori was evaluated by multiplex PCR analysis. RESULTS: In 63.4% of the stomachs (64/101) classification of the Helicobacter infection into the above mentioned groups was achieved. Non-pylori Helicobacter species commonly colonizing the stomachs of cats and dogs were found in 48.5% (49/101) of the patients. Fourteen (13.9%) samples tested positive for "Candidatus H. suis", and "Candidatus H. bovis" was demonstrated in 1 (0.9%) patient. The presence of H. pylori was established in 13 patients (12.9%). Eleven stomachs (10.9%) were infected with at least two different Helicobacter species. CONCLUSIONS: This study identifies animal Helicobacter species in the stomach of a large series of HHLO-infected patients, which may have clinical implications in a subset of patients with gastric disease.     

Effects of estradiol and progesterone on gastric mucosal response to early Helicobacter pylori infection in female gerbils

BACKGROUND: Gender differences have been shown regarding the changes in the inflammatory response, gastrin secretion, and gastric acidity during Helicobacter pylori infection. Aim: To investigate the role of estradiol and progesterone in the changes of the gastric mucosa induced by H. pylori during the early stage of infection in female gerbils. MATERIALS AND METHODS: Thirty-three adult ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after infection they were treated with low and high doses of estradiol (50 and 250 microg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle. Non-ovariectomized infected gerbils were used as control. Gerbils were euthanized after 6 weeks of infection. Histologic evaluation, immunohistochemical detection of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two-sided p = .05 was considered significant. RESULTS: Estradiol-treated groups showed more intense and extended acute and follicular gastritis compared to the vehicle group, whereas progesterone-treated groups presented less gastritis than the other groups. Proliferation and apoptosis indexes were significantly lower in the vehicle group when compared with those of the control; both indexes were increased in the high-dose estradiol and progesterone groups as compared with those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle and progesterone groups. The high-dose progesterone group showed a significant reduction in the number of gastrin cells. CONCLUSIONS: Estradiol and progesterone participate in the gastric mucosal response to early H. pylori infection in gerbils.     

The influence of cholecystokinin on gastric myoelectrical activity in duodenal ulcer following Helicobacter pylori eradication--an electrogastrographic study.

Cholecystokinin (CCK) plays an important role in the regulation of postprandial gastric motor activity which was found to be abnormal in duodenal ulcer patients. This study was designed to compare the influence of CCK on gastric myoelectrical function in duodenal ulcer patients and healthy controls. Fifteen patients with active duodenal ulcer and Helicobacterpylori (H. pylori) infection and 15 healthy controls were included into this study. Electrogastrography (EGG) was performed before and 4 weeks after the eradication of H. pylori in ulcer patients and in healthy controls. We compared EGG parameters in the fasting and postprandial period and during intravenous infusion of caerulein, an analog of CCK with or without addition of loxiglumide, a specific CCK-1 receptor antagonist. The amplitude of fasting EGG in duodenal ulcer patients was similar to that in control subjects and was not affected by H. pylori eradication. In contrast, the amplitude of postprandial EGG was markedly increased in duodenal ulcer patients when compared to that in healthy controls and it was significantly reduced following the eradication of H. pylori. The blockade of CCK-1 receptors with loxiglumide in healthy controls or H. pylori eradicated ulcer patients significantly enhanced postprandial EGG amplitude almost to the level observed in the infected duodenal ulcer patients, but failed to affect this amplitude in ulcer patients. Exogenous caerulein, an analog of CCK, failed to affect EGG amplitude in duodenal ulcer patients with H. pylori infection, but it reduced significantly EGG amplitude in these patients after H. pylori eradication and in control subjects. This inhibitory effect of caerulein in H. pylori negative ulcer patients and healthy controls was abolished by the addition of loxiglumide. Ulcer patients showed significant dysrhythmia with tachygastria up to 20% of the recording time both under basal conditions and postprandially and H. pylori eradication was followed by a significant decrease in tachygastria to about 5%, the value being similar to that in healthy controls. We conclude that the amplitude and frequency of gastric myoelectrical activity are enhanced in duodenal ulcer patients and impaired in response to CCK but these changes can be normalized by successful H. pylori eradication.     

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

BACKGROUND: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. AIM: This study was performed to investigate whether H. pylori-affected gastric mucosal MMP-2 and MMP-9 levels are reversible by successful treatment of the infection. PATIENTS AND METHODS: Fifty-eight patients with H. pylori-associated gastritis were treated with a combination regimen of acid inhibitory therapy and antibiotics for 14 days. The levels and isoforms of MMP-2 and MMP-9 were measured by semiquantitative gelatin-zymography, bioactivity assay and enzyme-linked immunosorbent assay in gastric mucosal biopsy homogenates. RESULTS: Latent, active, and total MMP-9 levels decreased consistently and significantly by successful H. pylori eradication, in antrum as well as corpus mucosa, compared with those prior to treatment, irrespective of the therapy regimen used. The elevated levels remained unchanged, however, when treatment failed. MMP-2 levels did not show major alterations after H. pylori therapy. CONCLUSION: Elevated MMP-9 levels in H. pylori-infected gastric mucosa are reversible by eradication of the infection. No major changes in mucosal MMP-2 levels were observed by H. pylori eradication.     

Experimental Helicobacter felis infection in transgenic mice expressing human group IIA phospholipase A2

BACKGROUND: Both various virulence factors of Helicobacter pylori and host factors influence the clinical outcome of H. pylori infection. In animal experiments with Helicobacter felis, large variations in the severity of disease have been observed between different mouse strains infected with a single isolate of H. felis. C57BL/6 J mouse strain that lacks the expression of group IIA phospholipase A2 has been shown to develop more severe gastric inflammation than other mouse strains. Thus, group IIA phospholipase A2 has been suggested to play a role in regulating inflammation in gastric mucosa. The aim of this study was to examine the possible role of group IIA phospholipase A2 in experimental Helicobacter infection. MATERIALS AND METHODS: Transgenic mice expressing human group IIA phospholipase A2 and their group IIA phospholipase A2 deficient nontransgenic C57BL/6 J littermates were infected with H. felis. The mice were killed 3, 8, and 19 weeks after inoculation of bacteria to determine the histopathological changes in gastric mucosa. RESULTS: The infected mice developed chronic inflammation in gastric mucosa. We found no differences in the colonization of bacteria between transgenic and nontransgenic mice. At 3 and 8 weeks, no difference was found in the severity of inflammation between the two groups. Nineteen weeks after the administration of bacteria the inflammation was more marked in nontransgenic than transgenic mice. Group IIA phospholipase A2 was expressed by in situ hybridization in the neck cells of the glandular stomach in transgenic mice. CONCLUSIONS: The results of the present study suggest that the endogenous expression of group IIA phospholipase A2 diminishes chronic inflammation in gastric mucosa in experimental H. felis infection in mice.     

Helicobacter felis infection causes an acute iron deficiency in nonpregnant and pregnant mice

BACKGROUND: The role of Helicobacter pylori infection in iron deficiency during pregnancy is limited. The aim of the present study was to assess the relationship between Helicobacter infection and levels of iron stores in pregnant mice. MATERIALS AND METHODS: Female C57BL/6 mice were either inoculated with 10(8) H. pylori, Helicobacter felis or water. In the nonpregnant study, 15 mice from each group were sacrificed after 4 and 20 weeks of infection. In the pregnancy study, after 6 weeks of infection all female mice were mated and approximately 2 weeks after mating, half of the pregnant mice (n = 9/group) from each group were sacrificed. The remaining mice were allowed to give birth, and approximately 4 weeks after birth, mice were asphyxiated with CO2, followed by heart puncture, and killed by cervical dislocation. Serum ferritin and iron were determined with a micro-particle enzyme immunoassay method and by a timed-endpoint method. RESULTS: Serum iron levels in mice infected with H. felis were significantly (p < .05) lowered compared to control (24%) and H. pylori (27%)-infected mice at 4 weeks of infection. Serum iron in the control, H. pylori and H. felis groups were significantly (p < .05) elevated at 20 weeks by 39, 26 and 77%, respectively, compared to 4 weeks of infection. H. felis-infected mice had a significantly (p < .05) decreased serum ferritin level during pregnancy (61%) compared to H. pylori-infected mice. CONCLUSION: These results suggest that H. felis but not H. pylori infection causes an acute iron deficiency in normal and pregnant mice.