Effect of Helicobacter pylori infection on the expression of DNA mismatch repair protein

BACKGROUND: Helicobacer pylori infection is a major gastric cancer risk factor. Deficient DNA mismatch repair (MMR) caused by H. pylori may underlie microsatellite instability (MSI) in the gastric epithelium and may represent a major mechanism of mutation accumulation in the gastric mucosa during the early stages of H. pylori-associated gastric carcinogenesis. In this study, we examined the expression of DNA MMR protein (hMLH1 and hMSH2) in patients with chronic H. pylori infection before and after eradication of the infection. MATERIALS AND METHODS: Gastric tissue samples were collected from 60 patients with H. pylori gastritis and peptic ulcer disease before and after eradication of the infection. The DNA MMR protein expression (hMLH1 and hMSH2) was determined by immunohistochemical staining in 60 patients before and after H. pylori eradication. The percentage of epithelial cell nuclei and intensity of staining were then compared in gastric biopsies before and after eradication. RESULTS: The percentage of hMLH1 (76.60 +/- 20.27, 84.82 +/- 12.73, p=.01) and hMSH2 (82.36 +/- 12.86, 88.11 +/- 9.27, p<.05) positive epithelial cells significantly increased in 53 patients who became H. pylori-negative after eradication therapy. However, the intensity of hMLH1 and hMSH2 staining was not significantly different. In those 7 patients, who did not respond to the eradication therapy and were still H. pylori-positive, the percent positivity and intensity of hMLH1 and hMSH2 staining did not change. CONCLUSIONS: The expression of DNA MMR proteins increased in the gastric mucosa after H. pylori eradication, indicating that H. pylori gastritis may be associated with a reduced DNA MMR system during infection. The effect of H. pylori infection on MMR protein expression appears to be at least partially reversible after H. pylori eradication. These data suggest that H. pylori gastritis might lead to a deficiency of DNA MMR in gastric epithelium that may increase the risk of mutation accumulation in the gastric mucosa cells during chronic H. pylori infection.     

Gender Difference of Circulating Ghrelin and Leptin Concentrations in Chronic Helicobacter pylori Infection

Background:  Both ghrelin and leptin are important appetite hormones secreted from the stomach. We examined whether demographic background, Helicobacter pylori infection, or its related gastritis severity could be associated with circulating ghrelin and leptin levels.
Methods:  This study prospectively enrolled 341 dyspeptic patients (196 females, 145 males), who had received endoscopy to provide the gastric specimens over both antrum and corpus for histology reviewed by the updated Sydney's system. The fasting blood sample of each patient was obtained for total ghrelin and leptin analysis.
Results:  Without H. pylori infection, there were similar ghrelin levels between female and male patients. In the H. pylori -infected patients, the males had lower plasma ghrelin levels than females (1053 vs. 1419 pg/mL, p  < .001). Only in males, not in females, the H. pylori infection and its related acute and chronic inflammation scores were significantly associated with a lower ghrelin level ( p  ≤ .04). The multivariate regression disclosed that only the chronic inflammation score independently related to a lower ghrelin level. Only in males, the ghrelin levels ranked in a downward trend for the gastritis feature as with limited-gastritis, with antrum-predominant gastritis, and with corpus-gastritis (1236, 1101, and 977 pg/mL). Leptin level was not related to H. pylori -related gastritis, but positively related to body mass index.
Conclusion:  There should be a gender difference to circulating total ghrelin levels, but not leptin levels, in response to H. pylori infection and its related chronic gastritis.     

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 infection and eradication on gastric epithelial cell proliferation and apoptosis.

OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS: both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.     

Increased cell proliferation in chronic Helicobacter pylori positive gastritis and gastric carcinoma--correlation between immuno-histochemistry and Tv image cytometry.

BACKGOUND: Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium. METHODS: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58+/-15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n = 10), chronic gastritis without IM (n = 24), chronic gastritis with IM (n = 20), and gastric carcinoma (n = 16). Thirty-three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho- and densitometric parameters of each nuclei and 6 additional parameters of each smear. RESULTS: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3+/-13.05% prior to the eradication and it decreased to 55.8+/-23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in GL phase (r = -0.415) and S phase (r = 0.385), Integrated Optical Density mean (r = 0.598), density maximum (r'= 0.608), surface (r = 0.670), layers (r = 0.638), diameter minimum (r = 0.619), diameter maximum (r = 0.730) and perimeter (r = 0.501), respectively (p < 0.05). CONCLUSIONS: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.     

Effect of Smoking and Histological Gastritis Severity on the Rate of H. pylori Eradication with Omeprazole, Amoxicillin, and Clarithromycin

Background. The combination of omeprazole, amoxicillin, and clarithromycin is a common regimen against Helicobacter pylori. Several recent studies have shown that smoking, high intragastric acidity, and the degree of histological gastritis are associated with H. pylori eradication failure.
Materials and Methods. One hundred and thirty-seven H. pylori –positive patients were treated with a 1-week regimen composed of omeprazole, 20 mg once daily; amoxicillin, 500 mg; and clarithromycin, 200 mg thrice daily. Success of the treatment was evaluated by histology and the ¹³C-urea breath test at least 4 weeks after completion of therapy. Data about age, gender, alcohol intake, smoking habits, and previous proton pump inhibitor intake were collected in patient interviews. We evaluated fasting gastric pH and the degree of histological gastritis before eradication of H. pylori.
Results. The overall eradication of H. pylori at 4 weeks was successful in 98 of 137 patients (72%). On the multivariate analysis, a low grade of inflammation in the antrum ( p ≤ .01; 95% confidence interval [CI], 2.34–16.75), low grade of activity in the fundus ( p ≤ .05; 95% CI, 1.31–9.65), and smoking ( p ≤ .05; 95% CI, 1.27–6.82) were the significant independent factors predicting treatment failure.
Conclusions. These findings indicate that H. pylori eradication therapy with omeprazole, amoxicillin, and clarithromycin is less effective in patients who smoke and more effective in patients with high scores of antral inflammation and fundal activity at baseline biopsy.     

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.     

Increase of antigen-presenting cells in the gastric mucosa of Helicobacter pylori-infected children

BACKGROUND: Infection with Helicobacter pylori leads to an increase of T cells in the gastric mucosa of children. In contrast to peripheral blood, where monocytes are the most abundant antigen-presenting cells, CD14+ macrophages are very rare in infected gastric mucosa. We postulated that other types of antigen-presenting cells must be present in infected gastric mucosa. MATERIAL AND METHODS: Antral biopsies were obtained from 56 children. The cellular expression of major histocompatibility complex (MHC) class II molecules, CD1a/b, and CD23, which are involved in antigen presentation were analyzed by immunohistochemistry. In addition, T cells (CD4, CD8, CD25, and gamma/delta-TCR), B cells (anti-IgM), macrophages (CD14) and granulocytes (CD15) were quantified. RESULTS: Twenty-eight children were H. pylori-infected. Thirteen children were healthy, 15 had other gastric pathologies. T cells (p<.0001), B cells (p<.0001), CD23+ (p<.0001), and CD1a/b+ (p<.005) cells were significantly increased in the lamina propria of H. pylori-infected children, whereas macrophages were rare without significant differences among the groups. Within the epithelium, CD8+ T lymphocytes predominated clearly over CD4+ cells. H. pylori-negative children had only few MHC class II-positive cells within the gastric epithelium, whereas MHC class II antigens were strongly expressed on epithelial cells (p<.0001) of all H. pylori-infected children. CONCLUSION: Helicobacter pylori infection leads to an enhanced expression of antigen-presenting molecules together with a parallel rise of T cells in the lamina propria. This may represent an effort of the immune system to optimize local immune responses against H. pylori. We speculate that the epithelium participates in the initiation of a local immune response against H. pylori.     

Characteristics of Helicobacter pylori-induced gastritis and the effect of H. pylori eradication in patients with chronic idiopathic thrombocytopenic purpura

BACKGROUND: The association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been reported widely. We investigated the prevalence of H. pylori infection, its virulence profile and the effectiveness of its eradication in patients with ITP. MATERIALS AND METHODS: Twenty patients with ITP, 20 with peptic ulcer (10 gastric ulcer (GU), 10 duodenal ulcer (DU)) and 20 with NUD were studied. The virulence profile of the strains was assessed by genotyping for cagA, vacA, iceA, and hpyIIIR/hrgA and by assaying for IL-8 and DNA fragmentation after incubation with AGS cells. Infected patients and two uninfected ITP patients received triple therapy and platelets were counted before and 1 month, 6 months, 1 year, and 2 years after eradication therapy. RESULTS: H. pylori infection was found in 17 ITP (85%), 20 ulcer (100%) and 13 NUD (65%) patients. Biopsies and strains were collected from five ITP, 20 ulcer and 13 NUD patients. The ITP patients had a pangastritis or corpus-predominant gastritis pattern. All H. pylori isolates, from ITP, ulcer and NUD patients, were cagA(+) and vacA s1/m1, and did not differ in levels of IL-8 induction or DNA fragmentation. Fifteen ITP (88%) and 17 ulcer (85%) patients had successful eradication of H. pylori. Ten of these 15 (67%) H. pylori-eradicated ITP patients had platelet recovery. There was no significant change in platelet count in the two ITP patients in whom eradication failed or in the two originally H. pylori-uninfected ITP patients, or in the treated ulcer patients. Age at onset of ITP was the main determinant of platelet recovery: 100% of patients diagnosed after the age of 60 recovered compared with only 22% of those diagnosed before 50. CONCLUSIONS: H. pylori-infected ITP patients have a corpus-predominant pattern of gastritis but the virulence profile of their strains does not differ from that of ulcer or NUD patients. Eradication of H. pylori infection is a good therapeutic option for some patients with chronic ITP, especially for those who develop ITP in older age.     

幽门螺杆菌感染促进胃炎儿童胃粘膜细胞的增殖

本研究旨在探讨幽门螺杆菌感染对小儿慢性胃炎患者细胞增殖的影响,使用内镜检查消化不良患者的上消化道症状,使用改良的Giemsa染色检测胃粘膜活组织中幽门螺杆菌,用苏木精/曙红和改良的吉姆萨染色活组织,并通过光学显微镜研究染色后胃粘膜样品组织病理学变化,RT-PCR检测各组胃粘膜细胞中调控细胞凋亡的Bcl-2、Bcl-xl、Bax和PCNA的mRNA表达,提取胃粘膜细胞蛋白质,利用蛋白质免疫印迹分析蛋白质浓度。组织化学染色结果表明,与对照相比,患有胃炎和幽门杆菌感染后的胃炎患者胃粘膜细胞明显增加,且幽门螺杆菌感染后细胞增殖更显著(p<0.05);幽门螺杆菌感染后Bcl-2和Bcl-xl,PCNA在患者体内表达显著上调(p<0.05),而细胞促凋亡因子Bax基因在胃炎患者感染幽门螺杆菌后被显著下调(p<0.05),蛋白免疫印迹分析Bcl-2,Bcl-xl,Bax和PCNA蛋白表达趋势与基因表达一致,说明结果可靠。幽门螺杆菌感染会显著提高慢性胃炎儿童患者胃粘膜细胞的增殖。     

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.     

Eradication of Helicobacter pylori and resolution of gastritis in the gastric mucosa of IL-10-deficient mice

BACKGROUND: Helicobacter pylori has been shown to induce pronounced gastric inflammation in the absence of interleukin-10 (IL-10) by 6 weeks post inoculation. The ability of IL-10(-/-) mice to eradicate H. pylori has not been demonstrated, possibly due to early sacrifice. Therefore, the long-term effect of enhanced gastritis on H. pylori colonization was determined in IL-10(-/-) mice. METHODS: C57BL/6 and IL-10(-/-) mice were infected with H. pylori and assessed for the degree of gastritis, bacterial load, and in vitro T-cell recall response at 4 and 16 weeks of infection. RESULTS: Infection of IL-10(-/-) mice resulted in significantly more severe gastritis than wild-type control mice and eradication of H. pylori by 4 weeks post inoculation. By 16 weeks, the level of gastritis in IL-10(-/-) was reduced to the levels observed in wild-type mice. Splenocytes from IL-10(-/-) mice were prone to produce significantly greater amounts of IFN-gamma than wild-type mice when stimulated with bacterial antigens. CONCLUSIONS: These results indicate that the host is capable of spontaneously eradicating H. pylori from the gastric mucosa when inflammation is elevated beyond the chronic inflammation induced in wild-type mice, and that the gastritis dissipates following bacterial eradication. Additionally, these data provide support for a model of gastrointestinal immunity in which naturally occurring IL-10-producing regulatory T cells modulate the host response to gastrointestinal bacteria.     

E-cadherin gene promoter hypermethylation in H. pylori-induced enlarged fold gastritis

BACKGROUND: Promoter hypermethylation of E-cadherin plays an important role on gastric carcinogenesis. We have previously reported that the odds ratio for gastric carcinoma and the prevalence of diffuse-type early gastric carcinoma in Helicobacter pylori-induced enlarged fold gastritis increased with increasing fold width. Thus, we examined E-cadherin methylation in gastric mucosa from H. pylori-induced enlarged fold gastritis before and after H. pylori eradication. Moreover, we analyzed the mechanism of H. pylori infection-induced E-cadherin hypermethylation. MATERIALS AND METHODS: Twenty-three H. pylori-positive patients with enlarged folds, 18 H. pylori-positive and seven H. pylori-negative patients without enlarged folds, were involved in the study. E-cadherin promoter methylation was studied using quantitative methylation-specific polymerase chain reaction. We investigated methylation percentage and DNA methyltransferase activity in gastric cancer cell lines treated with EGF, TNFalpha, and MG132. RESULTS: E-cadherin methylation percentage of the gastric antral and body mucosa in H. pylori-positive patients with enlarged folds was much greater than that in both H. pylori-positive and -negative patients without enlarged folds. After H. pylori eradication, the methylation percentage in six patients with enlarged fold gastritis decreased significantly from 15.6 +/- 3.9 to 8.8 +/- 2.2 (p < .05). Moreover, the methylation was induced by TNFalpha, MG132, and EGF treatment, and DNA methyltransferase activity was induced by EGF treatment in MKN-1 cells. CONCLUSIONS: Our findings suggest that the hypermethylation of E-cadherin promoter might be involved in the process of gastric carcinoma through the specialized factors in H. pylori-induced enlarged fold gastritis.     

Reactive Nitrogen Species Mediate DNA Damage in Helicobacter pylori-Infected Gastric Mucosa

Background:  Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori . 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells.
Methods:  Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori -positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system.
Results:  In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa ( p  = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG ( p  = .004 and .007, respectively).
Conclusions:  Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori -induced DNA damage in gastric mucosa.     

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.     

Strategy for eliminating gastric cancer in Japan

A study conducted by the Japan Gast Study Group showed that eradication of Helicobacter pylori reduced the risk of gastric cancer by about one-third. However, it did not completely prevent the onset of latent gastric cancer among those at high risk (i.e., with atrophic gastritis). To prevent deaths from gastric cancer, it is necessary to eradicate H. pylori infection. We propose a program of risk stratification based on the presence of H. pylori infection with or without atrophic gastritis followed by targeted interventions. Those at no risk for gastric cancer (no H. pylori, no atrophic gastritis) need no therapy or follow-up. Those at low risk (H. pylori infected, nonatrophic gastritis) need only H. pylori eradication therapy. The smaller groups at high or very high risk need eradication and cancer surveillance. We estimated the costs and the benefits of this strategy. Gastric cancer screening by simultaneous measurement of serum pepsinogen and H. pylori antibody combined with eradication of H. pylori in all individuals at risk would initially increase national healthcare expenditure, but this would be offset by markedly reducing the cost of treating gastric cancer. The proposed strategy should prevent about 150,000 deaths from gastric cancer during the 5 years after its adoption. If the loss caused by these deaths is also taken into account, the economic effect of this strategy becomes enormous. It would probably reduce the incidence of gastric cancer by more than 80-90% within 10 years. The Japanese government should take the initiative to implement this strategy as soon as possible.     

Serological responses of FldA and small-molecular-weight proteins of Helicobacter pylori: correlation with the presence of the gastric MALT tissue

PURPOSE: We tested whether the serological response to Flavodoxin-A (FldA) protein and anti-Helicobacter pylori immunoblots correlated to the degree of mucosaassociated lymphoid tissue (MALT) in the stomach. METHODS: Eighty H. pyloni-infected patients with different degrees of MALT in the stomach were investigated with serum sampling and endoscopy on enrolment, the 2nd and the 12th months after anti-H. pylori therapy. All sera were tested for the anti-FldA protein and anti-H. pylon immunoblots, including 19.5, 26.5, 30, 35, 89, and 116 KDa (CagA). Regression of follicular gastritis was assessed by histology. RESULTS: Patients with dense lymphoid follicles had higher prevalence rates of anti-FldA protein, 19.5, 26.5, and 30 KDa antibodies of H. pylori (p < .05). Histologic downgrade of MALT was observed in 25% (10/40) of patients in the 2nd month and in 60% (23/38) in the 12th month after H. pylori therapy. After H. pylori eradication, the patients with MALT and dense lymphoid follicles had significantly negative seroconversions of 19.5, 26.5, 30, and 35 KDa antibodies (p < .05), but not of CagA and FldA. CONCLUSION: Patients with gastric MALT and dense lymphoid follicles had different anti-H. pylori serological responses to those with scanty or an absence of lymphoid follicles. The negative seroconversion of the smaller-molecular-weight proteins, but not CagA and FldA, may correlate with the regression of MALT by H. pylori eradication.     

Helicobacter pylori and Non-malignant Diseases

It is well known that Helicobacter pylori infection is associated with many nonmalignant disorders such as gastritis, peptic ulcer, gastroesophageal reflux disease (GERD), gastric polyp, nonsteroidal anti-inflammatory drug (NSAID)/aspirin-induced gastric injury, and functional dyspepsia. In 2008, interesting articles on the association of H. pylori infection with these disorders were presented, some of which intended to reveal the mechanisms of inter-individual differences in response to H. pylori infection, and have demonstrated that genetic differences in host and bacterial factors as well as environmental factors account for these differences. A decline in the occurrence of peptic ulcer related to H. pylori was confirmed. An inverse relationship between H. pylori infection and GERD was also confirmed but the impact of gastric atrophy on the prevention of GERD remained debatable. For NSAID-induced gastric injury, eradication of H. pylori infection has been recommended. During this year, eradication of H. pylori infection was recommended for patients treated with antiplatelet therapy as well as aspirin and NSAID. It was also reported that for patients with functional dyspepsia, eradication of H. pylori offers a modest but significant benefit.     

Resolution of gastrointestinal protein loss after Helicobacter pylori eradication in a patient with hypertrophic lymphocytic gastritis

BACKGROUND: Lymphocytic gastritis is a rare condition found in approximately 1% of dyspeptic patients. An association with Helicobacter pylori infection has been described. Hypertrophic lymphocytic gastritis is a rare cause of gastrointestinal protein loss. Here, we describe a patient with hypertrophic lymphocytic gastritis, in whom gastrointestinal protein loss resolved completely following H. pylori eradication. CASE REPORT: A 38-year old obese man without gastrointestinal symptoms showed a markedly decreased serum protein (53 g/l, normal 66-85 g/l), a decreased serum albumin (33 g/l, normal 35-52 g/l) and decreased serum immunoglobulin G and immunoglobulin M levels. A renal cause for protein loss was excluded, liver function was normal. Endoscopy of the upper gastrointestinal tract revealed enlarged rigid gastric folds, and an H. pylori-associated lymphocytic gastritis. 99mTc-labelled albumin scintigraphy showed an increased activity in the upper left abdomen compatible with protein secretion in the stomach, and tracer pooling in the upper small bowel. Push enteroscopy with histology demonstrated a normal upper small bowel. Two months after eradication therapy, cure of H. pylori infection was documented and serum protein (71 g/l) and albumin (41 g/l) had returned to normal, while lymphocytic gastritis was still present. One year after eradication therapy endoscopy of the upper gastrointestinal tract and histology and laboratory values were normal. CONCLUSION: Protein-losing gastropathy caused by H. pylori-associated hypertrophic lymphocytic gastritis can be cured solely by H. pylori eradication therapy.     

Effect of Helicobacter pylori Eradication on Incidence of Gastric Cancer in Human and Animal Models: Underlying Biochemical and Molecular Events

Background:  Gastric cancer remains one of the most common cancers worldwide. A strong association exists between Helicobacter pylori infection and the risk of developing noncardia gastric cancer. H. pylori eradication by antibiotic treatment is regarded as a primary chemoprevention strategy to reduce gastric cancer incidence.
Aim:  To analyze the efficacy of H. pylori eradication in preventing gastric cancer in human and animal models, and to discuss whether biochemical, genetic, and epigenetic changes associated with H. pylori infection are reversible after curing the infection.
Results:  Several intervention trials have indicated that in some patients, H. pylori eradication leads to regression and prevents the progression of precancerous lesions. The eradication therapy reduces gastric cancer incidence in patients without any precancerous lesions at the baseline and is most effective before the development of atrophic gastritis. A few recent intervention studies in Japan have demonstrated significant prophylactic effects of eradication therapy on the development of gastric cancer, suggesting the use of eradication therapy in high-risk populations as a gastric cancer reduction strategy. However, gastric cancer may still develop despite successful eradication therapy. Studies in animal models have confirmed the use of eradication therapy at an early point of infection to prevent gastric cancer development.
Conclusion:  H. pylori eradication may not completely abolish the risk of gastric cancer. However, eradication therapy may be used in high-risk populations to reduce gastric cancer incidence. It can reverse many biochemical, genetic, and epigenetic changes that H. pylori infection induces in the stomach.