Gastric acid secretion of normal Japanese subjects in relation to Helicobacter pylori infection, aging, and gender

BACKGROUND: In Japan, where the incidence of gastric cancer is high, Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects. METHODS: The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-stimulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology. RESULTS: Mean EGT values were 3.9 +/- 1.5 mEq/10 min in H. pylori-negative men, 1.6 +/- 2.5 in H. pylori-positive men, 2.2 +/- 0.9 in H. pylori-negative women, and 1.5 +/- 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects. CONCLUSIONS: In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility of acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan.     

Two distinct types of cancer of different origin may be mixed in gastroesophageal junction adenocarcinomas in Japan: Evidence from direct evaluation of gastric acid secretion

Abstract

Background and aims. Barrett's esophageal cancer is usually included in gastroesophageal (GE) junction adenocarcinoma in Japanese people. No study on the pathogenesis of Barrett's esophageal cancer in comparison with GE junction adenocarcinoma other than Barrett's esophageal cancer has been reported in Japan. The aim of this study was to evaluate the clinical and pathological characteristics and gastric acid secretion of Barrett's esophageal cancer and GE junction adenocarcinoma other than Barrett's esophageal cancer in Japanese subjects. Material and methods. Twenty-three patients with Barrett's esophageal cancer and 23 patients with GE junction adenocarcinoma other than Barrett's esophageal cancer were enrolled in this study. We evaluated and compared them by assessing the Helicobactor pylori (HP) infection status and gastric acid secretion using the endoscopic gastrin test (EGT). Results. In the patients with Barrett's esophageal cancer, no significant difference was found in the mean EGT value between HP-positive and -negative patients, but in the patients with GE junction adenocarcinoma other than Barrett's esophageal cancer, the mean EGT value in HP-positive patients was significantly lower than that in HP-negative patients. Conclusion. Two distinct types of cancer of different origin may be mixed in GE junction adenocarcinomas. One is Barrett's esophageal cancer associated with high gastric acid secretion and reflux of gastric acid into the esophagus, the other is cancer resembling distal gastric cancer associated with gastric atrophy and low gastric acid secretion.     

Helicobacter pylori Infection Influences Tumor Growth of Human Gastric Carcinomas

Background: Helicobacter pylori infection is considered a risk factor for gastric carcinoma. However, the effect of eradication therapy in gastric carcinoma patients is not well known. The aim of this study was to investigate the relationship between H. pylori infection and tumor growth of gastric carcinoma. Methods: Fifty-one patients with gastric carcinoma participated in the study. Thirty-three were H. pylori-positive, 6 were H. pylori-negative, and 12 were diagnosed with gastric carcinoma after eradication of H. pylori. To investigate tumor growth of gastric carcinoma, cell proliferation and angiogenesis of the tumors were evaluated by immunohistochemical techniques using Ki-67 and CD34. Results: The Ki-67 labeling index was 47.9?±?2.6 (mean?±?s) in the H. pylori-positive group, 38.1?±?3.6 in the H. pylori-eradicated group, and 22.2?±?5.5 in the H. pylori-negative group. It was significantly lower in the H. pylori-eradicated and H. pylori-negative groups than in the H. pylori-positive one, and a significant difference was also found between the H. pylori-positive and H. pylori-eradicated groups. The microvessel counts were 62.5?±?3.0, 50.2?±?4.0, and 66.0?±?9.8 in the positive, eradicated, and negative groups, respectively. A significant difference was found between the H. pylori-positive and H. pylori-eradicated groups. Conclusion: Our results suggest that H. pylori infection is associated with cell proliferation, and its eradication may influence tumor vascularity of gastric carcinoma. Therefore, H. pylori eradication therapy may contribute to the suppression of tumor growth.     

‘Serological biopsy’ in first‐degree relatives of patients with gastric cancer affected by Helicobacter pylori infection

Background: Relatives of patients with gastric cancer are at increased risk of developing this disease, especially if they are infected by Helicobacter pylori. Moreover, H. pylori‐related atrophic gastritis and hypochlorhydria are well‐documented risk factors for noncardia gastric cancer. Serum pepsinogen I (sPGI) and II (sPGII) levels are low in this condition. The aim of our study was to assess by means of a ‘Gastropanel’ blood test, including sPGI, sPGII, gastrin‐17 (G‐17) and antibodies anti‐H. pylori (IgG‐Hp), both functional and morphological features of gastric mucosa in Hp?+?ve subjects with a family history of gastric cancer. Materials and Methods: Twenty‐five Hp?+?ve subjects consecutively referred to our department for gastrointestinal complaints, selected as first‐degree relatives of patients suffering from gastric cancer, were enrolled in the study and then matched for sex and age with 25 dyspeptic and Hp?+?ve subjects with no family history of gastric neoplasia. Blood samples were taken for determination of gastropanel in all patients; in addition, antibodies against CagA were analysed. Results: No statistically significant differences were detected zbetween the two groups as regards alcohol consumption, coffee intake and smoking habits. Mean sPGI levels in Group A (83.4?±?58.4 μg/L) were significantly lower than those in Group B (sPGI 159.5?±?80.6 μg/L; P?P?Conclusion: First‐degree relatives of patients with noncardia gastric cancer affected by H. pylori infection present lower sPGI and sPGII levels, possibly due to the increased frequency of atrophic lesions in these patients.     

Rebamipide, a Cytoprotective Drug, Increases Gastric Mucus Secretion in Human: Evaluations with Endoscopic Gastrin Test

We have previously developed a rapid, simple endoscopic method for evaluating gastrin-stimulated maximal acid output (the endoscopic gastrin test, EGT). In EGT, gastric fluid newly secreted over 10 min after gastrin stimulation is collected under direct endoscopic visualization. In this study, employing the EGT, we evaluated the effect of rebamipide, a cytoprotective anti-ulcer drug, on gastric mucus secretion. In ten Helicobacter pylori-negative healthy volunteers, gastric juice was collected by EGT prior to and after 4-week administration of rebamipide. The collected gastric juice was subjected to analysis for gastric mucus output. Total gastric mucin output was significantly increased by 53% by rebamipide administration from 3.2 ± 1.2 mg hexose/10 min to 4.9 ± 2.2 mg hexose/10 min (P < 0.01). Further analysis by ion-exchange chromatography revealed that rebamipide administration induced a specific increase in acidic mucin rich in sialic acid. Applying EGT, this study demonstrated that rebamipide administration increased gastric mucus secretion in human.     

Delay in gastric emptying in patients with chronic renal failure

Background: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). Delayed gastric emptying might be a possible pathophysiological mechanism. The aims of this study were to evaluate gastric emptying in patients with CRF and to correlate the findings with GI symptoms and evaluate the impact of Helicobacter pylori infection in CRF patients on gastric emptying. Methods: Thirty‐nine patients with CRF (17 F, 22 M) were compared with 131 healthy subjects (74 F, 57 M). A standardized breakfast was given with 20 spherical, radiopaque markers (ROMs). The emptying was followed by fluoroscopy after 4, 5 and 6?h. Gastric emptying was assessed by calculating the individual mean percentual gastric retention of markers, 4 to 6?h after the meal. The perceived severity of GI symptoms was assessed with a validated questionnaire. Because of gender differences in gastric emptying, men and women were compared separately and a percentile of 95 was chosen as the upper reference value. H. pylori infection was assessed using a serological method. Results: Delayed gastric emptying was found in 14 out of 39 (36%) of the CRF patients. There was no relationship between delayed gastric emptying and age, GI symptoms, H. pylori infection or underlying renal disease. However, a higher proportion of patients in peritoneal dialysis demonstrated delayed gastric emptying compared with predialytic patients (6 of 9 versus 2 of 13, P?=?0.026). Men with CRF had a higher gastric retention compared with healthy men (16.6 (0–63.3)% versus 0 (0–2.1)%, P?P?P?=?0.93), but 4 women with CRF had delayed gastric emptying (P?=?0.02). Eighteen of the CRF patients had GI symptoms (6 F, 12 M) and 21 were asymptomatic (11 F, 10 M). There was no difference in mean gastric retention in patients with CRF with and without GI symptoms (M: 13.3 (0–55.0)% versus 47.5 (5.0–65.0)%, P?=?0.51, F: 16.6 (0–63.3)% versus 13.3 (0–59.2)%, P?=?0.96). Gastric emptying in CRF patients with and without H. pylori infection showed no difference. Conclusions: Delayed gastric emptying is common in patients with chronic renal failure, particularly in men. The delay was not associated with the presence of GI symptoms, underlying renal disease or H. pylori infection. However, the dialytic status might have an impact on gastric emptying in patients with CRF.     

Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects

Background Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately. Methods The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown. Results In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r = 0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r = 0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion. Conclusions The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.     

Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men

Background

The gastric acid secretion level is an important determinant for the manifestation of the gastroesophageal reflux disease spectrum, finally leading to the development of esophageal adenocarcinoma (EAC). Although the incidence of EAC has remained low in Asia, understanding the recent trend in gastric acid secretion should be helpful in estimating future incidences of EAC in that area. We investigated the latest chronological change (1995–2014) in gastric acid secretion in normal Japanese patients.

Methods

A total of 307 asymptomatic Japanese men who attended the clinic for annual endoscopic checkups from 1995 to 2014 were enrolled in this analysis. Gastrin-stimulated gastric acid secretion was estimated with the endoscopic gastrin test. The association between gastric acid secretion and chronological period was assessed with a multivariate linear regression analysis.

Results

Overall gastric acid secretion gradually increased over the 20-year period in the entire cohort in the unadjusted analysis (p < 0.05). However, the apparent increase was largely related to the relative decreasing rate of H. pylori infection, which profoundly inhibited gastric acid secretion. Gastric acid secretion did not change over the 20-year period in H. pylori-negative subjects, and it showed only a mild increase during this period in H. pylori-positive subjects.

Conclusions

Considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over a 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Japanese population will differ from those in Western countries in the post-H. pylori era.

     

Chronic Atrophic Gastritis and Metachronous Gastric Cancer in Japanese Alcoholic Men With Esophageal Squamous Cell Carcinoma

Background: The risk of metachronous gastric cancer is high in Japanese with esophageal squamous cell carcinoma (SCC), especially in alcoholic men, suggesting a common background underlying the gastric and esophageal cancers. Methods: Endoscopic follow‐up ranging from 7 to 160 months (median, 47 months) after the initial diagnosis was performed in 99 Japanese gastric‐cancer‐free alcoholic men (56.8 ± 6.4 years) with esophageal SCC detected by an endoscopic screening examination. Chronic atrophic gastritis (CAG) assessed by the serum pepsinogen test and Helicobacter pylori status was compared between 90 of the 99 esophageal SCC cases and 180 age‐matched Japanese gastric‐ and esophageal‐cancer‐free alcoholic men. Results: The serum pepsinogen test showed a higher seroprevalence of severe CAG among the cases than among the age‐matched controls (35.4% vs. 14.2% for H. pylori‐seropositive, 71.4% vs. 7.7% for H. pylori‐indeterminate, and 17.1% vs. 9.8% for H. pylori‐negative, respectively; H. pylori status‐adjusted p = 0.0008), whereas their H. pylori status was similar. The accelerated progression of severe CAG observed in the Japanese alcoholic men with esophageal SCC suggests the existence of common mechanisms by which both esophageal SCC and H. pylori‐related severe CAG develop in this population. Metachronous gastric adenocarcinoma was diagnosed in 11 of the 99 gastric‐cancer‐free patients, and the cumulative rate of metachronous gastric cancer within 5 years was estimated to be 15% according to the Kaplan–Meier method. The age‐adjusted hazard ratios were 7.87 (95% confidence interval: 1.43 to 43.46) and 4.84 (1.16 to 20.21), respectively, in the patients with severe CAG in comparison with those without CAG and those without severe CAG. Inactive heterozygous aldehyde dehydrogenase‐2, a very strong risk factor for esophageal SCC in the alcoholics, was not associated with an increased risk of metachronous gastric cancer. Conclusions: Accelerated development of severe CAG at least partially explained the very high frequency of development of metachronous gastric cancer in this population.     

Does Antral Distension Inhibit Gastric Acid Secretion or Stimulate Bicarbonate Secretion in ‘Healthy’ Subjects?

The effects of a 150-ml antral balloon distension on pentagastrin-stimulated gastric acid secretion and bicarbonate secretion were studied in nine healthy subjects and eight duodenal ulcer (DU) patients. The gastric secretions were simultaneously measured, using a luminal perfusion and pH/PCO₂ measurements. Two of the healthy subjects and six of the DU patients were positive for Helicobacter pylori. When H. pylori-positive and -negative subjects were compared, basal gastric acid and bicarbonate outputs did not differ significantly. In H. pylori-infected subjects the bicarbonate transport increased by about 70% on pentagastrin stimulation. In the H. pylori-negat'we group pentagastrin had no effect on the bicarbonate secretion. Antral distension elicited a 30-35% inhibition of pentagastrin-stimulated gastric acid secretion in the group of H. pylori-negative subjects, whereas the acid secretory level remained essentially unchanged in the positive group. Bicarbonate secretion decreased transiently by the distension in the negative subjects, whereas a slight increase was observed in the infected group. We conclude that antral distension inhibits pentagastrin-stimulated gastric acid output in healthy H. pylori-negative subjects. Our results strongly suggest that the underlying mechanism is a direct inhibition of gastric parietal cell function and not an increased gastric bicarbonate secretion. Furthermore, the results indicate that this defective distension-induced acid inhibition may be correlated to H. pylori infection rather than to duodenal ulcer disease.     

Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients

Background Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Methods Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Results Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean?±?SD of hs-CRP among men and women were 2.85?±?2.84?mg/dl and 2.80?±?4.80?mg/dl (p?=?0.047) respectively. Mean?±?SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83?±?3.80?mg/dl, 3.52?±?5.1?mg/dl, 2.22?±?2.3?mg/dl and 5.3?±?5.04?mg/dl respectively. Relationship between hs-CRP and inflammation activities (p?p?p?Conclusion Although serum hs-CRP is not a specific biomarker for gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.     

Biphasic effects of H. pylori infection on low-dose aspirin-induced gastropathy depending on the gastric acid secretion level

Background

The association of Helicobacter pylori infection with aspirin-induced gastropathy is controversial. H. pylori infection exerts diverse effects on gastric acid secretion. In this study, the interaction between H. pylori infection and aspirin was investigated with reference to the individual gastric acid secretion level in H. pylori-positive subjects.

Methods

Ninety-three (81 men, mean age: 70?years) long-term low-dose aspirin takers were prospectively enrolled. H. pylori infection was evaluated by serum IgG antibody determination, and gastrin-stimulated acid output was assessed with the endoscopic gastrin test. H. pylori-positive aspirin-takers were classified into 2 subgroups (hyposecretors and non-hyposecretors). The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score; intensive aspirin-induced gastropathy was defined as a modified Lanza score of ??4. Multiple logistic regression analyses were used to adjust for potential confounders.

Results

With H. pylori-negative patients taken as the reference, H. pylori infection was found to be positively associated with intensive gastropathy among non-hyposecretors, with an odds ratio (OR) (95?% confidence interval [CI]) of 4.2 (1.1?C17.1), while the infection was negatively associated with gastropathy among hyposecretors, with an OR (95?% CI) of 0.3 (0.08?C0.9). Aspirin-induced gastropathy occurred preferentially in the antrum among H. pylori-positive non-hyposecretors, while it affected the fundus among H. pylori-positive hyposecretors.

Conclusion

The effect of H. pylori infection on the aspirin-induced gastropathy was biphasic depending on the individual gastric acid secretion level. In the presence of sufficient amounts of gastric acid, H. pylori infection and aspirin could synergistically damage gastric mucosal integrity, while in the absence of sufficient amounts of gastric acid, the synergistic effect could be completely counteracted and the infection could even suppress the aspirin-induced gastropathy.     

Dyspepsia and Helicobacter pylori in Japanese employees with and without ulcer history

In a Dutch working population, the apparent association between dyspeptic symptoms and Helicobacter pylori infection was found to be entirely due to subjects with an ulcer history. In general populations with a much higher prevalence of H. pylori infection and peptic ulcer disease, such as in Japan, the relationship between dyspepsia and H. pylori has yet to be clarified. A questionnaire on ulcer history and dyspeptic symptoms during the preceding 3 month period was obtained from apparently healthy Japanese employees who underwent a periodic medical examination. In addition, serum samples were analysed for anti-H. pylori IgG antibodies. A total of 196 men and 35 women, aged 23–71 years, participated in the study. Seven women (20%) and 49 men (25%) had a diagnosis of peptic ulcer disease. Among 41 subjects with verified duodenal (26) and/or gastric (17) ulcer, 95% were H. pylori positive while 32% had had frequent dyspeptic symptoms in the 3 months prior to the study (29% of the 35 men and 50% of the 6 women). Among the 147 men and 28 women without an ulcer history, the 3 month period prevalence of frequent dyspepsia was 14 and 32%, respectively. The rate of H. pylori positivity was 80% in non-ulcer dyspeptics and 68% in all other non-ulcer subjects (95% confidence intervals: 61–92 and 61–76%, respectively). Significant differences in symptoms between H. pylori positive and negative subjects could not be detected, neither in the whole population nor in the non-ulcer group. In conclusion, in this Japanese working population, no association was found between dyspeptic symptoms and H. pylori infection, irrespective of the inclusion of subjects with a peptic ulcer history.     

Bile acid reflux and possible inhibition of Helicobacter pylori infection in subjects without gastric surgery

Bile acids are generally known to inhibit growth of Helicobacter pylori in vitro, but whether they do so in humans with no gastric surgery has been uncertain. The present study addresses this issue. Among healthy control subjects with preserved acid secretion, H. pylori-positive subjects were older and had lower gastric bile acid concentrations than H. pylori-negative subjects (P < 0.05). Among gastric ulcer patients with preserved acid secretion, H. pylori-positive patients had a higher basal acid output than H. pylori-negative patients (P < 0.05). Among H. pylori-positive subjects with preserved acid secretion, duodenal ulcer patients had a higher basal and maximum acid output than healthy control subjects (P < 0.01). In conclusion, gastric bile acids may suppress initial stages of H. pylori infection in subjects without gastric surgery. However gastric bile acids may have little effect on peptic ulcer disease, once H. pylori infection is established.     

Prevalence of low vitamin B12 and high homocysteine in serum in an elderly male population: association with atrophic gastritis and Helicobacter pylori infection

Background: Deficiency of vitamin B12 raises the serum and tissue levels of homocysteine. Atrophic corpus gastritis results in impaired secretion of intrinsic factor and may lead to malabsorption of vitamin B12 in the intestine. We examined how common an undiagnosed vitamin B12 deficiency is among elderly men in the general population and, in particular, how often this deficiency is related to atrophic corpus gastritis. Methods: The serum level of pepsinogen I (S‐PGI) was assayed in a population‐based sample of 12,252 men (age 51–65 years) from two cities in Finland. In this sample, all 635 men with S‐PGI?n?=?402) with S‐PGI?≥?50?μg/l. Serum levels of vitamin B12 (S‐B12), folate (S‐Fol), total homocysteine (S‐Hcy) and Helicobacter pylori antibodies (S‐HpAb) were assayed in all, or in large subsamples, of the men in Series A and C. Results: The men in Series A had significantly lower S‐B12 and S‐Fol levels than those in Series C. In Series A, 172 of 613 men tested (28%) had S‐B12?P?P??15?μmol/l was 27% in Series A and 15% in Series C (P?2 =?4.63). Among subjects with S‐B12?P?P?Conclusions: Low S‐B12 related to atrophic corpus gastritis is relatively common (prevalence 2.5%) among elderly males in the general population. An ongoing H. pylori infection occurs in three‐fourths of these cases.     

Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa

Background and Aim: Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line. Methods: IRX1 methylation was studied by methylation specific polymerase chain reaction (MSP) and bisulfate sequencing polymerase chain reaction (BSP) methods in gastric mucosa tissues from H. pylori‐positive chronic gastritis patients or H. pylori‐negative chronic gastritis patients. Promoter activity, methylation status and gene expressing level of IRX1 were evaluated by persistent infecting H. pylori on human gastric cells GES‐1 in vitro. Electron microscopy was used to observe the effect of H. pylori infection on GES‐1 gastric mucosa cells. Results: The methylation level of IRX1 promoter in H. pylori positive chronic gastritis and H. pylori negative chronic gastritis was 55.30% ± 13.17 versus 5.20% ± 6.31, respectively (P < 0.01). H. pylori infection stimulated increased microvillus, and mucous secretion on GES‐1 cells. Infection of H. pylori induced IRX1 promoter methylation and downregulation of the promoter activity as well as gene expression significantly. Conclusions: This study firstly demonstrated that H. pylori infection contributes to IRX1 promoter methylation on gastric mucosa.     

Effects of Cyclooxygenase-2 Inhibitor on Gastric Acid Secretion in Helicobacter pylori-infected C57BL/6 Mice

Background: Helicobacter pylori-associated body gastritis inhibits gastric acid secretion. The aim of this study was to determine the effects of H. pylori infection on gastric acid secretion and further determine whether cyclooxygenase-2 was involved. Methods: C57BL/6 mice (n = 40) were inoculated with the Sydney strain of H. pylori. Control mice (n = 40) were treated with vehicle only. Half of the infected and control mice were fed an experimental diet containing etodolac (10 mg/kg/day) from 1 week after inoculation until the end of the experiment. Before, 12 and 24 weeks after inoculation, the gastric acid secretion, prostaglandin E2 (PGE₂) levels in the gastric mucosa, and gastritis scores according to the updated Sydney system were determined. Immunohistochemical staining of COX-2 protein was also performed. Results: No significant changes in gastric acid secretion, gastritis scores or PGE2 levels in the gastric mucosa were observed in uninfected groups with or without etodolac treatment during the study period. In the H. pylori-infected group without etodolac treatment, gastric acid secretion was significantly decreased with increases in PGE₂ levels in the gastric mucosa 24 weeks after inoculation compared with the controls. Gastritis score for activity was significantly higher, and strong staining for COX-2 protein was observed in the H. pylori-infected group. In the H. pylori-infected group with etodolac treatment, PGE₂ in the gastric mucosa was decreased and acid secretion was restored to the same level as in the control group. Conclusion: One of the mechanisms by which H. pylori infection inhibits gastric acid secretion is increased release of PGE₂ produced by COX-2, which is induced by H. pylori infection.     

Serum Anti-Helicobacter pylori IgG Antibody Titer in H. pylori-negative Cases with a Different Gastric Mucosal Atrophy Status

Objective This retrospective study was performed to investigate the anti-Helicobacter pylori IgG antibody serum titers in H. pylori-negative subjects with different degrees of gastric mucosal atrophy including C0 grade atrophy. Methods The absence of H. pylori infection was determined based on both negative serum anti-H. pylori IgG antibody test findings and no endoscopic evidence of that infection. Cases negative for the antibody and with positive endoscopic findings of H. pylori infection were defined as H. pylori-positive. The serum anti-H. pylori IgG antibody titers were analyzed in H. pylori-negative (n=1,087), -positive (n=69), and post-eradicated (n=278) subjects. Results The serum antibody titer in subjects with H. pylori-positive endoscopy findings was significantly higher than that in H. pylori-negative subjects, even when the serum titer indicated a negative result. In addition, the anti-H. pylori IgG antibody serum titer was higher in H. pylori-negative subjects with a greater degree of gastric mucosal atrophy. In a comparison between H. pylori-negative C0 and C1 gastric mucosal atrophy cases, the antibody serum titer in those classified as C0 was significantly lower. An analysis of H. pylori post-eradicated cases showed that the serum antibody titer decreased over time after successful eradication. Conclusion The disappearance of H. pylori infection in H. pylori-negative individuals may occur later in those with a greater degree of gastric mucosal atrophy. The serum antibody titer difference between the H. pylori-negative C0 and C1 groups might have been caused by the differences in distribution between H. pylori-uninfected subjects and those in whom the infection had disappeared, thus additional investigation is needed to clarify the significance of gastric mucosal classification including the C0 grade.     

Anti‐CagA and anti‐VacA antibodies in Helicobacter pylori‐infected patients with and without peptic ulcer disease in Serbia and Montenegro

Background: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori‐positive dyspeptic patients in Serbia and Montenegro. Methods: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49?±?15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti‐IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non‐ulcer dyspepsia (NUD) in the remaining 142 patients. Results: 129 (74.6%) patients were H. pylori‐positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P?P?Conclusions: In Serbia and Montenegro there is high seroprevalence of CagA‐positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA‐positive strains are more closely related to peptic ulcer disease.     

Helicobacter pylori independent chronological change in gastric acid secretion in the Japanese

Background—Gastric acid secretion in Japanesesubjects decreases with aging. One of the possible causative mechanismsof this attenuated acid secretion is speculated to be aHelicobacter pylori induced chronic gastritis. Theinfection rate of this microorganism has decreased recently in Japan.
Aims—To investigate whether gastric acidsecretion has altered over the past 20 years, and if so, what theinfluence of H pylori infection might be in the Japanese population.
Subjects and methods—Gastric acid secretion, serumgastrin and pepsinogen I and II concentrations, and Hpylori infection were determined in 110 Japanese subjects inboth the 1970s and 1990s.
Results—Basal acid output as well as maximal acidoutput have greatly increased over the past 20 years, not only inindividuals with H pylori infection but also in thosewithout infection. Furthermore, subjects with H pyloriinfection tended to show decreased gastric acid secretion in comparisonwith those without infection, particularly in geriatric subjects. Therewas a positive correlation between gastric acid secretion and serumpepsinogen I concentrations.
Conclusions—In Japan, both basal andstimulated gastric acid secretion have increased over the past 20 years; some unknown factors other than the decrease in Hpylori infection may play an important role in this phenomenon.

Keywords:gastric acid; Helicobacter pylori; aging; gastrin