Helicobacter pylori-induced downregulation of the secretory leukocyte protease inhibitor (SLPI) in gastric epithelial cell lines and its functional relevance for H. pylori-mediated diseases

The secretory leukocyte protease inhibitor (SLPI) exerts antiproteolytic activity towards serine proteases, as well as anti-microbial and anti-inflammatory effects. To investigate its role in H. pylori-mediated diseases, SLPI expression was analyzed by RT-PCR, ELISA and immunohistochemistry in clinical samples and gastric tumor cell lines. Determination of the mucosal SLPI levels in 126 patients confirmed the previously reported downregulation of SLPI in H. pylori-infected patients. The lower SLPI levels in antral biopsies of H. pylori-positive subjects were associated with a 30-fold increase (p<0.01) in neutrophil elastase activity, and a significant negative correlation was demonstrated for both parameters (R=-0.63, p=0.0002). Eradication of the bacterium in a long-term study (5-7 years) led to a recovery of mucosal SLPI expression. In vitro experiments using four gastric tumor cell lines (AGS, MKN-28, MKN-45, NCI-N87) generally confirmed the clinical findings. While the co-incubation of these cell lines with H. pylori resulted in lower or unchanged SLPI protein levels, the corresponding SLPI mRNA amounts were upregulated by up to five-fold (p=0.006) in all cell lines. Taken together, these results indicate that the reduction in antral SLPI levels in H. pylori-infected subjects has a functional relevance for gastric mucosa and the H. pylori-induced decrease in SLPI is primarily regulated at the posttranslational level.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

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.     

Relationship between vitamin B12, folate and homocysteine levels and H. pylori infection in patients with functional dyspepsia: A cross-section study

ABSTRACT: BACKGROUND: H. pylori infection has been associated with many micronutrient deficiencies. There is a dearth of data from communities with nutritional deficiencies and high prevalence of H. pylori infection. The aim of this study was to determine the impact of H. pylori infection on serum levels of vitamin B12, folate and homocysteine in patients with functional dyspepsia (FD). METHODS: One hundred and thirty-two patients with FD undergoing gastroscopy were enrolled. The serum was analyzed for B12, folate and homocysteine levels before gastroscopy. H. pylori infection was diagnosed by histopathological examination of gastric biopsies and urea breath test. An independent sample t-test and the Mann-Whitney test were used to compare mean serum concentrations of biomarkers between H. pylori-positive and H. pylori-negative groups of patients. A Chi-square test was performed to assess the differences among proportions, while Spearman's rho was used for correlation analysis between levels of B12 and homocysteine. RESULTS: The mean age of the group was 40.3 +/- 11.5 (19-72) years. Folate deficiency was seen in 43 (34.6%), B12 deficiency in 30 (23.1%) and hyperhomocysteinemia in 60 (46.2%) patients. H. pylori was present in 80 (61.5%) patients with FD while it was absent in 50 (38.5%). Mean serum levels of B12, folate and homocysteine in the H. pylori-positive group of patients were not significantly different from the levels in the H. pylori-negative group (357 +/- 170 vs. 313 +/- 136 pg/mL; p = 0.13), (4.35 +/- 1.89 vs. 4.42 +/- 1.93 ng/mL; p = 0.84); (15.88 +/- 8.97 vs. 16.62 +/- 7.82 mumol/L; p = 0.24); respectively. B12 deficiency ([less than or equal to]200 pg/mL) was 23.8% in the H. pylori-positive patients versus 22.0% in the H. pylori-negative patients. Folate deficiency ([less than or equal to]3.5 ng/mL) was 33.8% in the H. pylori-positive group versus 36% in the H. pylori-negative group. Hyperhomocysteinemia (>15 mumol/L) was present in 46.2% of H. pylori-positive patients compared to 44% in the H. pylori-negative group. Correlation analysis indicated that serum B12 levels were inversely associated with serum levels of homocysteine in patients with FD (rho = 0.192; p = 0.028). CONCLUSIONS: This study demonstrated an inverse relationship between serum levels of B12 and homocysteine in patients with FD. Moreover, no impact of the presence of H. pylori was found on B12, folate and homocysteine levels in such patients.     

Helicobacter pylori-induced immunological responses in patients with duodenal ulcer and in patients with cardiomyopathies

The interaction between the bacteria and the host is a key factor determining the clinical consequences of H. pylori infection. The immune system plays an important role in either promoting or preventing the disease. The mucosal production of TNF-alpha, IL-6, IL-8 and IL-10 and the CagA status were investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antral mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). The local TNF-alpha, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of H. pylori-positive (58 of 100) healthy blood donors. In complementary studies focusing on extragastric disease, it was found that 57% of patients with ischaemic heart disease were seropositive as concerns H. pylori, and 91% of them had antibodies against human heat shock protein 60, too. This study suggests that, besides the bacterial virulence factor, the host response of an increased mucosal production of inflammatory cytokines can be relevant to the gastric pathophysiology in H. pylori-induced DU. At the same time, in ischaemic heart diseases the role of autoimmune processes induced by H. pylori cannot be excluded.     

Intrafamilial transmission of Helicobacter pylori among the population of endemic areas in Japan

BACKGROUND: Helicobacter pylori (H. pylori) infection is a worldwide phenomenon related to several gastrointestinal diseases. However, because many aspects concerning the route of transmission remain unclear, we performed this epidemiologic study to clarify the route of intrafamilial transmission of H. pylori. MATERIALS AND METHODS: A retrospective study was performed in three widely separate areas in Japan to investigate the prevalence of H. pylori infection. In 1993, 613 residents were tested as were 4136 in 2002, including 1447 family members of 625 families. Antibody to H. pylori (anti-H. pylori) was determined by enzyme-linked immunosorbent assay. RESULTS: In 2002, the age-adjusted anti-H. pylori prevalence in Hoshino Village (67.5%) was significantly higher than in Kasuya Town (55.0%) and in Ishigaki City (54.7%) (p < .0001, p = .0039, respectively). The age-adjusted anti-H. pylori prevalence of Ishigaki City significantly decreased from 1993 (68.4%) to 2002 (52.5%), showing an age cohort effect. However, the prevalence did not significantly differ in children aged 0-6 years of Ishigaki City between 1993 (9.6%) and 2002 (10.3%). A familial analysis in 2002 demonstrated that the prevalence of anti-H. pylori was significantly higher in children with anti-H. pylori-positive (21.6%, 22 of 102) than with -negative mothers (3.2%, 3 of 95) (p < .0001, by Mantel-Haenszel test), whereas there was no significant difference between children with anti-H. pylori-positive and -negative fathers. Moreover, the prevalence was significantly higher in wives with anti-H. pylori-positive (64.0%, 208 of 325) than with -negative husbands (46.5%, 80 of 172) (p = .0071, by Mantel-Haenszel test) and in husbands with anti-H. pylori-positive (72.2%, 208 of 288) than with -negative wives (56.0%, 117 of 209) (p = .0106, by Mantel-Haenszel test). CONCLUSIONS: In the last decade, H. pylori infection decreased in the general population of Japan by improvement of general hygiene conditions, but did not differ in young children, most likely because of mother-to-child transmission.     

Helicobacter pylori stimulates a mixed adaptive immune response with a strong T-regulatory component in human gastric mucosa

BACKGROUND: Host factors play an important role in the pathophysiology of Helicobacter pylori infection and development of gastritis and related disease. The established opinion is that the T-cell-mediated immune response to H. pylori infection is of Th1 type. Our earlier immune cell phenotype studies indicate a mixed Th1-Th2 profile of the effector cells. Therefore, an extensive adaptive and regulatory cytokine gene expression profile was conducted by quantitative real-time polymerase chain reaction (qPCR). MATERIALS AND METHODS: Biopsies from gastric mucosa of 91 patients diagnosed as H. pylori negative, H. pylori positive with gastritis, or H. pylori positive with peptic ulcer were obtained by endoscopy. Gene expressions of nine cytokines and CagA status were measured by qPCR. RESULTS: All cytokine genes showed higher expression levels in the presence of H. pylori when compared to H. pylori-negative samples (fold increase: IL8: x 11.2; IL12A: x 2.4; TNF-alpha: x 5.2; IFN-gamma: x 4.3; IL4: x 3.6; IL6: x 14.7; and IL10: x 6.7). Patients infected with CagA-positive strains had higher expression of IL1-beta and IL18 compared to patients infected with CagA-negative strains (x 1.6 for IL1-beta and x 2.0 for IL18). Patients with duodenal ulcer had a lower antral Th1/Th2 ratio than other H. pylori-positive patients. CONCLUSIONS: The cytokine profile of H. pylori-infected gastric mucosa shows a mixed Th1-Th2 profile. Furthermore, a high IL10 expression may indicate that also regulatory T cells play a role in the chronic phase of H. pylori infection.     

Involvement of Helicobacter pylori infection and impaired glucose metabolism in the increase of brachial-ankle pulse wave velocity

BACKGROUND: The role of Helicobacter pylori in the pathogenesis of atherosclerosis remains controversial. The present study was designed to elucidate the pathogenic role of H. pylori in the early stages of atherosclerosis by measurement of brachial-ankle pulse wave velocity (baPWV) in relation to glucose metabolism. MATERIALS AND METHODS: baPWV level, anti-H. pylori antibody, fasting blood glucose (FBG), and glycosylated hemoglobin A1c (HbA1c) and other conventional risk factors for cardiovascular diseases were measured in 947 subjects who attended their annual medical check-up. RESULTS: Multiple regression analyses indicated that age, gender (male), body mass index, FBG, systolic blood pressure, and smoking habits were each independently related to baPWV values. In younger subjects (30-49 years), H. pylori seropositivity was significantly correlated with an increase of baPWV levels (r = 0.100, p = .0445). baPWV values in the H. pylori-positive subjects with impaired glucose metabolism (IG: FBG >or= 110 mg/dL and/or HbA1c >or= 5.9%) were significantly greater than those in the H. pylori-negative subjects with IG (p = .0078). Furthermore, H. pylori-positive subjects with IG were at higher risk for increase of baPWV, in younger (r = 0.203, p < .0001) as well as in older subjects (50-69 years, r = 0.099, p = .0009). CONCLUSIONS: These results suggest that H. pylori seropositivity is a potential risk factor for increased baPWV levels, and that H. pylori infection accelerates the effect of IG on an increase of baPWV, especially in younger subjects. Thus, the possible interaction between H. pylori infection and IG may contribute to the early development of atherosclerosis.     

Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR) was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR) = 5.72, 95% confidence interval (CI) = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31). Patients with gastric cancer (21/21, 100%, p = 0.006) or peptic ulcers (20/21, 95%, p = 0.02) were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%). In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.     

Apoptosis in Helicobacter pylori gastritis is related to cagA status

BACKGROUND: Helicobacter pylori infection increases gastric epithelial cell apoptosis; however, the influence of cagA status is still controversial. We aimed to investigate if cagA status is related to apoptosis in H. pylori gastritis at different anatomic sites of the gastric mucosa. MATERIALS AND METHODS: We studied by immunohistochemistry (streptavidin-biotin method) pro-apoptotic (Bax and Bak) and antiapoptotic (Bcl-2 and Bcl-x) proteins expression, scored from 0 to 4, in gastric biopsies, at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 50 patients with H. pylori gastritis (22 males, 28 females, median age 40 years) and eight non-infected patients (6 males, median age 39.6 years). H. pylori and cagA status were determined by polymerase chain reaction. RESULTS: Apoptotic proteins were expressed in a granular pattern, in the cytoplasm of foveolar cells; Bax and Bak expression was higher than Bcl-2 and Bcl-x in most cases and was significantly higher in patients infected by cagA-positive strains than in those infected by cagA-negative strains (p = .001). Bak expression was higher at the lesser curvature (antrum and incisura) than in the other regions (p = .002) and was correlated with atrophy. Anti-apoptotic proteins were significantly more expressed at the antral lesser curvature than in the other regions of the stomach (Bcl-2: p = .02; Bcl-x: p < .001). CONCLUSIONS: Infection with cagA-positive strains is significantly associated with overexpression of pro-apoptotic proteins in the gastric mucosa, mainly at the antral lesser curvature, which may have a role on atrophy development. Anti-apoptotic proteins were also overexpressed at the lesser curvature, which may occur to keep epithelial cell turnover or might be related to malignant transformation.     

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.     

Seropositivity to Helicobacter pylori heat shock protein 60 is strongly associated with intensity of chronic inflammation, particularly in antrum mucosa: an extension of an 18-year follow-up study of chronic gastritis in Saaremaa, Estonia

Helicobacter pylori is a cause of chronic gastritis and leads to development of atrophy in some cases. There is evidence that the heat shock protein 60 (HSP60) of H. pylori is involved in induction of chronic inflammation. Seroprevalence of IgG antibodies to H. pylori HSP60 in an adult cohort from Saaremaa, Estonia (68 persons, median age 57 years), with a high prevalence of antibodies to cell surface proteins of H. pylori (92%) and a well characterized dynamics of chronic gastritis in an 18-year follow-up study, was tested using purified H. pylori HSP60 at a concentration of 1 microg ml(-1) with ELISA. The state of the gastric mucosa and the presence of H. pylori in histological sections in the samples of 1979 and 1997 were assessed in accordance with the Sydney system. Seropositivity for H. pylori HSP60 was 65%. Immunological response to H. pylori HSP60 is associated with the morphological presence of H. pylori in the antrum and corpus (P=0.01) and is strongly correlated with the grade of chronic inflammation, particularly in the antrum mucosa (r=0.34; P=0.003; OR=5.97 (95% CI 1.21-29.3)), but is not associated with development of atrophy during 18 years of follow-up, or with the activity of gastritis. This finding supports the evidence that immunological response to H. pylori HSP60 may play a role in triggering of the inflammatory process in the gastric mucosa.     

Analysis of morphological variables and arterialization in the differential diagnosis of hepatic nodules in explanted cirrhotic livers

Background

The aim of this study was to investigate the relationship between mast cell density, histological severity of gastritis, and presence of Helicobacter pylori (H. pylori) in the antral mucosa of pediatric patients.

Methods

The study included 352 (192 male and 160 female, < 14 years old) patients. All cases underwent endoscopy, and biopsies were obtained for histopathological examination and evaluation of Helicobacter pylori. All biopsies were evaluated according to the Sydney system and mast cell density in the antral mucosa was analyzed by Giemsa stain. Spearman's correlation test was used to determine the relationship between mast cell density and other histopathological parameters. The comparison of mast cell density between H. pylori positive and negative groups was analyzed by Mann Whitney U test.

Results

Mast cell density was 12.6 ± 0.87 in 0.25 mm² (0–81). Means of severity of gastric inflammation in H. pylori-positive and negative patients were 1.7 ± 0.6 and 0.6 ± 0.7, respectively, which was statistically significant (p = 0.0001). Mast cell density was not correlated with presence and degree of inflammation, activity, presence and score of H. pylori in the antrum (p > 0.05). There was no significant correlation between mast cell density and allergy.

Discussion

We concluded that there may be some other ways for contribution of mast cells in pathologic processes involving gastrointestinal tract in children.     

Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.     

Cardiovascular autonomic response to food ingestion in patients with gastritis: a comparison between Helicobacter pylori-positive and -negative patients

BACKGROUND: Feeding evokes a cardiovascular response associated to an increased sympathetic drive. The role of the parasympathetic component in this regard is less clear. Improvement of postprandial vasovagal complaints after Helicobacter pylori eradication in three cases led us to assess autonomic response to feeding in H. pylori-positive patients in search for an exacerbated parasympathetic response. MATERIAL AND METHODS: Patients with mild or moderate chronic histologic gastritis were studied. Subjects with the same diagnosis but testing negative for H. pylori were used as controls. Noninvasive cardiovascular tests were applied before and after feeding. RESULTS: On sympathetic tests, standing postprandial blood pressure was lower than preprandially in 5/12 H. pylori-positive patients and in 0/9 controls, p = .045. Resting postprandial BP on handgrip test was significantly lower than preprandially only in H. pylori-positive patients (71 +/- 8 versus 76 +/- 6 mmHg, p = .0068). Regarding parasympathetic tests, the 4-s unloaded exercise revealed greater initial heart rate response to unloaded cycling after feeding than preprandially again only in H. pylori-positive patients (1.40 +/- 0.20 versus 1.33 +/- 0.17, p = .0195). On tests influenced by both branches of the autonomic system, a difference was seen in the chronotropic response to handgrip. Postprandial heart rate on effort of H. pylori-positive patients was not higher than preprandially in contrast to controls [intervals between 2 consecutive R waves on electrocardiogram (R-R intervals) of 666 +/- 39 versus 685 +/- 62 ms, p = .0195], suggesting blunted sympathetic activation in the former. CONCLUSION: Supporting the observations that motivate the study, our findings indicate blunted sympathetic reactivity and exacerbated vagal response to feeding in H. pylori-positive patients.     

Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation

BACKGROUND: Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. METHODS: Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. RESULTS: H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). CONCLUSIONS: The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.     

Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). Nitrotyrosine was determined by ECL Western blotting. It was additionally investigated whether the tissue levels of the cytokines correlated with the peripheral cytokine levels, and the CagA status of the patients. The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. There was a negative correlation between the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy specimens, considerable nitrotyrosine production was detected by ECL Western blotting. There was no significant difference in peripheral TNF-a and IL-6 production between the DU patients and healthy blood donors (n = 100; 58% of whom were also H. pylori-positive). Only the in vitro IL-8-producing capacity was higher in the peripheral blood of the DU group after ex vivo induction with H. pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This study suggests that besides the bacterial virulence factor, the host response, with an increased mucosal production of inflammatory cytokines and reactive oxygen and nitrogen species could be relevant to the gastric pathophysiology in H. pylori-induced DU. There is no generalized cytokine overproduction in these DU patients, but the moderate increase in in vitro IL-8 production might be of pathophysiological importance.     

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.     

Atrophic Changes of Gastric Mucosa Are Caused by Helicobacter pylori Infection Rather Than Aging: Studies in Asymptomatic Japanese Adults

Background. The current study was designed to evaluate the effect of aging and Helicobacter pylori infection on the gastric mucosa in asymptomatic Japanese adults.
Materials and Methods. Eighty-five asymptomatic healthy adults were recruited from a health-screening center in Sapporo. All subjects underwent endoscopy and gastric biopsy, and serum was obtained for IgG antibodies to H. pylori , serum gastrin, and pepsinogen levels.
Results. The prevalence of atrophic change of the gastric mucosa assessed by pathological findings increased with age (49% in the 30- to 39-year-old group compared to 89% in those 60 years and older, p < .001). The frequency of intestinal metaplasia also increased with age (38% in the 30- to 39-year-old group compared to 82% in those 60 years and older, p < .001). In contrast, the frequency of atrophic gastritis and intestinal metaplasia was extremely low in the H. pylori seronegative group regardless of age. Mean serum gastrin level in H. pylori -positive adults was significantly greater than in those who were H. pylori -negative (114.3 ± 11.2 compared to 65.8 ± 6.5 pg/ml, p < .03). The serum pepsinogen I-II ratio was significantly lower in those with H. pylori infection than in those without (3.1 compared to 6.6, p < .0001).
Conclusions. These results suggest that the chronological changes in the gastric mucosa in Japanese individuals are either entirely related to H. pylori infection or the process is greatly accelerated by H. pylori infection.     

Is Antrum or Corpus the Best Site for Culture of Helicobacter pylori?

Background Isolating Helicobacter pylori on culture media and performing antibiotic susceptibility testing is potentially the most useful tool for guiding antibiotic therapy, especially when antimicrobial resistance is suspected. The aim of this study was to determine whether the yield of H. pylori culture was related to the site from which the gastric specimen was obtained either before or after therapy.
Methods. Gastric mucosal biopsies from the antrum and the corpus of the stomach were cultured. H. pylori status was determined by histological assessment using the Genta stain.
Results. Fifty-two patients with documented H. pylori infection were studied: Twenty-three were tested before antibiotic therapy and 29 after therapy had failed. In 47 patients (90%), both antral and corpus culture specimens were positive. In 5 patients (10%), only one site was positive, with three false-negative antral and two false negative corpus cultures. The overall sensitivity of culture in detecting H. pylori infection was 95% (95% confidence interval = 89–98%) and was not significantly different for the antrum or corpus, either before or after therapy.
Conclusion. Culture of gastric biopsies from either the antrum or the corpus has an excellent diagnostic yield even in patients who failed antimicrobial therapy.