Development Of Peptic Ulcer Disease Research Articles

Distinctive aspects of peptic ulcer disease, Dieulafoy's lesion, and Mallory-Weiss syndrome in patients with advanced alcoholic liver disease or cirrhosis.

To systematically review the data on distinctive aspects of peptic ulcer disease (PUD), Dieulafoy's lesion (DL), and Mallory-Weiss syndrome (MWS) in patients with advanced alcoholic liver disease (aALD), including alcoholic hepatitis or alcoholic cirrhosis. Computerized literature search performed via PubMed using the following medical subject heading terms and keywords: "alcoholic liver disease", "alcoholic hepatitis"," alcoholic cirrhosis", "cirrhosis", "liver disease", "upper gastrointestinal bleeding", "non-variceal upper gastrointestinal bleeding", "PUD", ''DL'', ''Mallory-Weiss tear", and "MWS''. While the majority of acute gastrointestinal (GI) bleeding with aALD is related to portal hypertension, about 30%-40% of acute GI bleeding in patients with aALD is unrelated to portal hypertension. Such bleeding constitutes an important complication of aALD because of its frequency, severity, and associated mortality. Patients with cirrhosis have a markedly increased risk of PUD, which further increases with the progression of cirrhosis. Patients with cirrhosis or aALD and peptic ulcer bleeding (PUB) have worse clinical outcomes than other patients with PUB, including uncontrolled bleeding, rebleeding, and mortality. Alcohol consumption, nonsteroidal anti-inflammatory drug use, and portal hypertension may have a pathogenic role in the development of PUD in patients with aALD. Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients. The frequency of bleeding from DL appears to be increased in patients with aALD. DL may be associated with an especially high mortality in these patients. MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism, and is associated with aALD. Patients with aALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics. Pre-endoscopic management of acute GI bleeding in patients with aALD unrelated to portal hypertension is similar to the management of aALD patients with GI bleeding from portal hypertension, because clinical distinction before endoscopy is difficult. Most patients require intensive care unit admission and attention to avoid over-transfusion, to correct electrolyte abnormalities and coagulopathies, and to administer antibiotic prophylaxis. Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal. Prompt endoscopy, after initial resuscitation, is essential to diagnose and appropriately treat these patients. Generally, the same endoscopic hemostatic techniques are used in patients bleeding from PUD, DL, or MWS in patients with aALD as in the general population. Nonvariceal upper GI bleeding in patients with aALD has clinically important differences from that in the general population without aALD, including: more frequent and more severe bleeding from PUD, DL, or MWS.

Depression and the Risk of Peptic Ulcer Disease: A Nationwide Population-Based Study.

The risk of peptic ulcer disease (PUD) among patients with depression has raised concern. This study determined the association between depression and the subsequent development of PUD using claims data.Patients newly diagnosed with depression in 2000 to 2010 were identified as depression cohort from the Taiwan National Health Insurance Research Database. The comparison cohort was randomly selected from subjects without depression, frequency matched by age and gender and diagnosis date, with a size 2-fold of the size of the depression cohort. The incidence of PUD was evaluated for both cohorts by the end of 2011. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of PUD using the Cox proportional hazards regression model.The depression cohort consisted of 23,536 subjects (129,751 person-years), and the comparison cohort consisted of 47,069 subjects (285,592 person-years). The incidence of PUD was 2-fold higher in the depression cohort than in the comparison cohort (33.2 vs 16.8 per 1000 person-years) with an age adjusted HR of 1.97 (95% CI = 1.89–2.06) or a multivariable adjusted HR of 1.35 (95% CI = 1.29–1.42).Depression might increase the risk of developing PUD. Prospective clinical studies of the relationship between depression and PUD are warranted.

A Matched Case-control Study of the Association between Low-dose Aspirin and Peptic Ulcers in Patients without a History of Peptic Ulcers

Background: Long-term administration of low-dose aspirin (LDA) is associated with greater risk of adverse events, including gastro duodenal ulcers. This study aimed to assess the risk factors and efficacy of medications to prevent the development of peptic ulcer disease in Japanese patients without prior history of peptic ulceration. Methods: We conducted a matched case-control study using esophagogastroduodenoscopy records collected from January through December 2010. We enrolled 219 consecutive outpatients receiving LDA (100 mg) and 219 ageand sex-matched controls who did not receive LDA and did not have a prior history of peptic ulcer. Clinical parameters, reason for endoscopy, and endoscopic findings were analyzed. Results: A significantly higher number of patients receiving LDA compared to those not receiving LDA were diagnosed endoscopically with peptic ulceration (20 [9.1%] vs. 7 [3.2%]; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.26−7.35; p=0.016). Multiple logistic regression analysis identified male sex, abdominal symptoms, and non-steroidal anti-inflammatory drug (NSAID) and LDA use and PPI use as risk and protective factors, respectively, for peptic ulcer (OR, 4.7, 95% CI, 1.28−17.64, p=0.020; OR, 2.5, 95% CI, 1.01−6.12, p=0.047; OR, 6.8, 95% CI, 1.72−26.40, p=0.006; OR, 9.72; 95% CI, 2.64−35.72, p=0.006; and OR, 0.1, 95% CI, 0.04−0.57, p=0.006, respectively). Conclusion: LDA and NSAID use increases the risk of peptic ulcer even in patients without peptic ulcer history; proton pump inhibitors reduce the risk of developing gastric or duodenal ulcers. These results may help identify patients who require interventions for the prevention of NSAIDor LDA-induced peptic ulcers.

The distribution of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 genes of Helicobacter pylori in China.

BackgroundThe plasticity region of Helicobacter pylori (H. pylori) is a large chromosomal segment containing strain-specific genes. The prevalence of the plasticity region genes of the H. pylori strains in China remains unknown. The aim of this study was to examine the status of these genes and to assess the relationship between the genes and the diseases caused by H. pylori infection.MethodsA total of 141 strains were isolated from patients with chronic active gastritis (CAG), peptic ulcer disease (PUD) and gastric carcinoma (GC). The prevalence of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 was determined using PCR, and the results were analyzed using the chi-squared test.ResultsThe prevalence rates of jhp0940, jhp0945, jhp0947, jhp0949 and jhp0951 in the H. pylori strains were 42.55, 51.06, 20.57, 56.03 and 63.12 %, respectively. The prevalence rates of jhp0940 were similar in the isolates from the CAG, PUD and GC patients, and there was no association between the jhp0940 status and any of the diseases. In contrast, the prevalence rates of jhp0945, jhp0947, jhp0949 and jhp0951 were significantly higher in the PUD and GC isolates than in the CAG isolates (p < 0.01). A univariate analysis showed that jhp0945, jhp0947, jhp0949 and jhp0951 increased the risk of PUD, while only jhp0951 was significantly associated with PUD in the multivariate analysis (p = 0.0149). The jhp0945-positive isolates were significantly associated with an increased risk for GC (p = 0.0097).ConclusionThe plasticity region genes are widely distributed in Chinese patients, and a high prevalence of these genes occurs in more serious diseases. Therefore, jhp0951 status is an independent factor associated with the development of PUD, and jhp0945 may predict the future development of GC in patients with CAG and is considered to be the best candidate disease marker for H. pylori-related diseases.

Effects of the CYP2C19 genetic polymorphism on gastritis, peptic ulcer disease, peptic ulcer bleeding and gastric cancer.

The CYP2C19 genotype has been found to be an important factor for peptic ulcer healing and H. pylori eradication, influencing the efficacy of proton pump inhibitors (PPIs) and the pathogenesis of gastric cancer. The aim of this study was to investigate clinical correlations of the CYP2C19 genotype in patients with gastritis, peptic ulcer disease (PUD), peptic ulcer bleeding (PUB) and gastric cancer in Thailand. Clinical information, endoscopic findings and H. pylori infection status of patients were assessed between May 2012 and November 2014 in Thammasat University Hospital, Thailand. Upper GI endoscopy was performed for all patients. Five milliliters of blood were collected for H. pylori serological diagnosis and CYP2C19 study. CYP2C19 genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) and classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). A total of 202 patients were enrolled including 114 with gastritis, 36 with PUD, 50 with PUB and 2 with gastric cancer. Prevalence of CYP2C19 genotype was 82/202 (40.6%) in RM, 99/202 (49%) in IM and 21/202 (10.4%) in PM. Overall H. pylori infection was 138/202 patients (68.3%). H. pylori infection was demonstrated in 72% in RM genotype, 69.7% in IM genotype and 47.6% in PM genotype. Both gastric cancer patients had the IM genotype. In PUB patients, the prevalence of genotype RM (56%) was highest followed by IM (32%) and PM(12%). Furthermore, the prevalence of genotype RM in PUB was significantly greater than gastritis patients (56% vs 36%: p=0.016; OR=2.3, 95%CI=1.1-4.7). CYP2C19 genotype IM was the most common genotype whereas genotype RM was the most common in PUB patients. All gastric cancer patients had genotype IM. The CYP2C19 genotype RM might be play role in development of PUD and PUB. Further study in different population is necessary to verify clinical usefulness of CYP2C19 genotyping in development of these upper GI diseases.

Are probiotics useful in Helicobacter pylori eradication?

Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects.

Association of cytokine gene polymorphisms in peptic ulcer development in the Bashkortostan Republic

Peptic ulcer disease (PUD) is a chronic disease based on recurrent gastric or duodenal ulcers. Association analysis of common polymorphisms of the cytokines genes IL1B (rs1143634), IL1RN (rs71941886), IL8 (rs4073), IL10 (rs1800872), and TNFA (rs1800629) was conducted in 254 patients with gastric ulcer or duodenal ulcer and in 277 unrelated healthy individuals from the Bashkortostan Republic. Associations of the rs1143634C allele and the C/C genotype of the IL1B gene with PUD in ethnic Bashkirs have been revealed. The frequency of the rs4073A/A genotype of the IL8 gene was significantly higher in the control group as compared to patients infected with H. pylori. Our results confirm the significant role of rs1143634 of the IL1B gene in PUD development.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: old question new insights.

Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians.

Association of polymorphisms in virulence factor of Helicobacter pylori and gastroduodenal diseases in South Korea

Clinical outcomes of Helicobacter pylori (HP) infection have been shown to be dependent on the variability of virulence factors. The aim of this study was to evaluate the prevalence of each virulence factor and the association between polymorphisms of the virulence factors of HP, and the clinical outcome of gastroduodenal diseases in South Korea. Four hundred one HP colonies were analyzed (75 colonies from 45 controls; 71 colonies from 39 benign gastric ulcer [BGU] patients; 102 colonies from 54 duodenal ulcer [DU] patients; 121 colonies from 77 stomach cancer patients; and 32 colonies from 25 dysplasia patients). Polymerase chain reaction amplifications for vacA, cagA, iceA, oipA, and dupA were performed using DNA extract from HP isolates cultured from mucosal biopsy specimens. dupA was regarded as positive when all of jph0718, jph0719, and dupA were positive. Most colonies were composed of vacA s1 (100.0%), i1 (100.0%) and m1 (92.9%), cagA-positive (87.2%), iceA1 (95.8%), oipA-positive (91.2%), and dupA-negative (52.0%) genotypes. dupA was more frequently expressed in BGU (81.3%), DU (74.7%), and dysplasia (41.7%) than control (16.7%) (P < 0.001). Infection by dupA-positive HP showed an increased risk of BGU (odds ratio 33.06, 95% confidence interval 11.91-91.79) and DU (odds ratio 15.60, 95% confidence interval 6.49-37.49). HP infection in South Koreans appears to be closely related to highly virulent strains (vacA s1/i1/m1, cagA(+), iceA1(+), and oipA(+)), except dupA. dupA has an intimate association with the development of peptic ulcer diseases.

Neurosis and genetic theory of etiology and pathogenesis of ulcer disease

Based on the analysis of literature data and our own research, we have developed the original concept of etiology and pathogenesis of peptic ulcer disease. An analysis of the literature shows that none of the theories of pathogenesis of peptic ulcer disease does not cover the full diversity of the involved functions and their shifts, which lead to the development of ulcers in the stomach and the duodenum. Our neurogenic-genetic theory of etiology and pathogenesis of gastric ulcer and duodenal ulcer very best explains the cause-and-effect relationships in the patient peptic ulcer, allowing options for predominance in one or the other case factors of neurosis or genetic factors. However, it is clear that the only other: combination of neurogenic factor with genetically modified reactivity of gastroduodenal system (the presence of the target organ) cause the chronicity of the sores. The theory of peptic ulcer disease related to psychosomatic pathologies allows us to develop effective schema therapy, including drugs with psychocorrective action. On the basis of our theory of the role of Helicobacter pylori infection is treated as a pathogenetic factor in the development of peptic ulcer disease.

Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers

BackgroundLong-term administration of low-dose aspirin (LDA) is associated with a greater risk of adverse events, including gastroduodenal ulcers. The purpose of this study was to identify the risk factors for and assess the role of medication use in the development of peptic ulcer disease in Japanese patients with no history of peptic ulcers.MethodsConsecutive outpatients receiving LDA (75 mg/day) who underwent esophagogastroduodenoscopy between January and December 2010 were enrolled. Clinical parameters, peptic ulcer history, concomitant drugs, the presence of Helicobacter pylori infection, reason for endoscopy, and endoscopic findings were analysed.ResultsOf 226 total patients, 14 (6.2%) were endoscopically diagnosed with peptic ulcer. Age, sex, current smoking status, current alcohol consumption, endoscopic gastric mucosal atrophy, and abdominal symptoms were not significantly associated with peptic ulcers. Diabetes mellitus was more frequent (42.9% vs. 16.5%; P = 0.024) in patients with peptic ulcers than in those without peptic ulcers. Using multiple logistic regression analysis, co-treatment with anticoagulants or proton pump inhibitors (PPIs) was significantly associated with increased and decreased risk for peptic ulcer, respectively (odds ratio [OR], 5.88; 95% confidence interval [CI], 1.19 − 28.99; P = 0.03 and OR, 0.13; 95% CI, 0.02 − 0.73; P = 0.02, respectively). Co-treatment with additional antiplatelet agents, H2-receptor antagonists, angiotensin II Type 1 receptor blockers, angiotensin-converting enzyme inhibitor, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, or nonsteroidal anti-inflammatory drugs was not associated with peptic ulcer development.ConclusionThe use of PPIs reduces the risk of developing gastric or duodenal ulcers in Japanese patients taking LDA without pre-existing gastroduodenal ulcers. However, this risk is significantly increased in both patients ingesting anticoagulants and patients with diabetes. These results may help identify patients who require intensive prophylaxis against aspirin-induced peptic ulcers.

Low Prevalence of Helicobacter pylori Infection in IBD Patients from a Predominantly African/Caribbean Urban Center

Purpose:Helicobacter pylori (HP) is a gram negative bacterium which can survive the harsh acidic environment of the human stomach, infecting 50% of people. In developing countries, this value can be up to 90%. HP infection is associated with the development of peptic ulcer disease, gastric cancer, and MALT lymphoma. Risk factors include lower socioeconomic status, overcrowding, poor hygiene, and living in a developing country. Published rates of HP infection in the Caribbean ranges from 55%-70%. HP detection can include histologic testing of the endoscopic biopsy specimens or fecal antigen. The latter is often also used to document HP eradication after therapy or to monitor progression in the presence of continued symptoms. Patients with inflammatory bowel disease (IBD) have lower HP infection rates than the rest of the population. In fact, some studies believe HP infection may be protective in the yet to be determined factors that are causative of IBD. A recent study demonstrated that the presence of HP was inversely associated with IBD, ulcerative colitis (UC), Crohn's disease (CD), and indeterminate colitis. A recent meta-analysis reported IBD populations having a HP prevalence of 27.1% and control populations with 40.9%. However, this impact in underserved urban areas, is not well-described. The aim of our study was to determine the prevalence of HP in an urban population of Afro-Caribbean patients with IBD. Methods: IBD patients (N=347) were identified by ICD-9 coding and were retrospectively evaluated for the presence of HP by positive histology. A control group was determined by a database of patients with abdominal symptoms (N=321). Both groups were compared for HP status and demographic data. The IBD group was evaluated on the basis of UC and CD. Results: The IBD cohort comprised a group with an average age 45 years, 86% black, 62% UC, 31% CD, and 7% indeterminate colitis. The control group was an older cohort at 59 years, and 67% black. The IBD group was found to have an HP prevalence of 3.4%, as compared to 10.3% in our control group. Both these values are significantly lower than those reported in the literature, but consistent with the finding of lower HP rates in IBD patients. The control group was evaluated from a database of N=321 patients seen from 2009-2012. The average age was 59 years. 67% were black, 24% Afro-Caribbean. HP status was determined using biopsy or by HP stool antigen as a surrogate. Conclusion: These findings report a lower HP prevalence in both groups in this urban Afro-Caribbean population, as compared to those expected to be found in a U.S. cohort or either IBD (3.4%) or non-IBD (10.3%) populations. However, the lower HP prevalence, as compared to the control group, is consistent with recent literature.

Prevalence and Association of Helicobacter pylori in Downtown Brooklynʼs Minority Population

Purpose:Helicobacter pylori (H. pylori) infection is a pandemic disease; about 70% of the developing world population and 40% of the U.S. population harbor this bacteria as per the CDC. H. pylori has been implicated in the development of peptic ulcer disease and less frequently, gastric malignancy, namely adenocarcinoma and lymphoma of the gastric-mucosa-associated lymphoid tissue. Due to the serious consequences of this common infection and the lack of studies addressing H. pylori prevalence among minority patients, we aimed to investigate the prevalence of this infection in a downtown Brooklyn population. One of the most diverse urban populations in the country. Methods: Charts of all adult patients who underwent upper endoscopy with biopsy at our medical center in two years period were reviewed. Data about demographics, endoscopic, and histological findings were collected and analyzed. The presence of H. pylori infection was based on the immunohistopathological analysis of the biopsy samples. SAS software was used for statistical analysis. Results: Our cohort included 970 patients (37% males and 63% females). African Americans and Hispanics represented 52.5% and 28.3% of the study population, respectively. The prevalence of H. pylori was 24.64%. There was no association found between H. pylori prevalence and age, race, or sex (P 0.16, P 0.52, and P 0.87, respectively). Peptic ulcer disease was found in 11.5 % of our cohort which was significantly associated with H. pylori (16.3% vs 9.9% in non-infected patients, P 0.007). Gastric intestinal metaplasia (in 11.6% of the patients) was also associated with H. pylori infection (18.4% vs 9.4% in non-infected patients, P 0.0002). Conclusion:H. pylori prevalence among the downtown Brooklyn population is lower than the national average reported by CDC and even lower than any North American population reported in the literature. The environmental, bacteriological and host factors behind these findings need to be evaluated.

Mechanistic insights into H. pylori pathogenesis and host response

Event Abstract Back to Event Mechanistic insights into H. pylori pathogenesis and host response Bow Ho1* 1 Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Helicobacter pylori is a Gram negative bacterial gastric pathogen that infects ~50% of the world’s population with some progressing to gastric cancer. The indelible link between Helicobacter pylori and severe gastric diseases coupled with the emergence of multiple-antibiotic resistant H. pylori and the high prevalence of gastric cancer necessitate urgent attention. Furthermore, the mechanistic action of pathogenesis has not been firmly established. Among the known pathogenic factors of H. pylori reported, cytotoxin associated gene A (CagA), an oncoprotein, has been cited to induce inflammatory response in host cells and cause disruption of gastric epithelial cell-cell tight junctions. We report here a surface localized heat shock protein that effects the cytoskeleton rearrangement of cells independently, and exacerbates disruption of cell-cell tight junctions through its interaction with CagA. This protein is found in all strains of H. pylori analysed, and that it aids the bacteria in colonizing BALB/c mice. The dynamics of interaction between heat shock protein and CagA intrabacterially, as well as between the bacterial pathogen and the host in the course of H. pylori pathogenesis will be discussed. Acknowledgements This work was supported by Grant No. R182000180213. References Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, et al. (2003) Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 300: 1430-1434. Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, et al. (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci U S A 90: 5791-5795. Du RJ, Ho B (2003) Surface localized Heat Shock Protein 20 (HslV) of Helicobacter pylori. Helicobacter 8: 257-267. Gong M, Ling SS, Lui SY, Yeoh KG, Ho B (2010) Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease. Gastroenterology 139: 564-573. Hatakeyama M (2008) Saga of CagA in Helicobacter pylori pathogenesis. Curr Opin Microbiol 11: 30-37. Kwok T, Zabler D, Urman S, Rohde M, Hartig R, et al. (2007) Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449: 862-866. Murata-Kamiya N, Kurashima Y, Teishikata Y, Yamahashi Y, Saito Y, et al. (2007) Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells. Oncogene 26: 4617-4626. Keywords: Helicobacter pylori, CagA, Cell-cell junction disruption, Heat Shock Protein 20, Pathogenesis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Ho B (2013). Mechanistic insights into H. pylori pathogenesis and host response. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00478 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Apr 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Bow Ho, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, michob@nus.edu.sg Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bow Ho Google Bow Ho Google Scholar Bow Ho PubMed Bow Ho Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Helicobacter pyloriγ-glutamyl transpeptidase: A formidable virulence factor

Helicobacter pylori (H. pylori) produce an enzyme known as γ-glutamyl transpeptidase (HpGGT) that is highly conserved and common to all strains. HpGGT has been gaining increasing attention as an important virulence factor of the bacterium, having been demonstrated to be an important colonization factor in several animal models and has also recently been strongly associated with the development of peptic ulcer disease. From the results of various independent researcher groups, it is clear that HpGGT acts through several pathways to damage gastric epithelial cells including the induction of apoptosis and cell cycle arrest, production of reactive oxygen species leading to DNA damage, promotion of inflammation by increasing cyclooxygenase-2 and interleukin-8 expression, and upregulation of heparin-binding epidermal growth factor-like growth factor resulting in cell survival and proliferation. In addition, the potential role of HpGGT in promoting gastric carcinogenesis will also be discussed in this review. Apart from affecting the gastric epithelium, HpGGT also has immunomodulatory actions on host immune cells where it displays an antiproliferative effect on T cells by inducing cell cycle arrest and also works with other H. pylori virulence factors to skew dendritic cells towards a tolerogenic phenotype, possibly contributing to the persistence of the pathogen in the gastric mucosa.

Helicobacter pylori: molecular detection of vacA gene and vacuolating activity in human gastric adenocarcinoma cells.

Helicobacter pylori strains secrete a vacuolating cytotoxin (VacA), plays an important role for the development of peptic ulcer disease and gastro-duodenal diseases. vacA gene is responsible to regulate the activity of the vacuolating cytotoxin. The objective of this study was molecular detection of vacA gene and observes the vacuolating activity on human gastric adenocarcinoma (AGS) cells. H. pylori vacA gene was determined by polymerase chain reaction. Vacuolation activity of VacA toxin in broth culture filtrates was assessed in AGS cells and quantified by neutral uptake assay. Different concentration dosages of VacA and incubation time were used in the measurement of the vacuolating activity on AGS cells. The results showed that VacA toxin could stimulate vacuolating activity on AGS cells with minimum concentration 1.0 μg/ml from both of s1m1 and s1m2 alleles (vacA gene). The toxin produced optimal reaction at 5.0 μg/ml with significant differences observed between the alleles. The results also showed that both alleles commenced the vacuolating activity at the minimum of 3 hr incubation time, and the activity showed in time-dependent manner. Optimal concentration of VacA toxin (s1m1 allele) causes more interaction with AGS cell producing more vacuolating activities. Time-dependent vaculation of both alleles might allow H. pylori for persistent infection without rapid destruction of gastric cells might promote gastro-duodenal diseases. The study provided us better understanding of the pathogenesis of the diseases associated with H. pylori infection which is an emerging problem in developing countries.

Managing peptic ulcer and gastroesophageal reflux disease in elderly Chinese patients &amp;ndash; focus on esomeprazole

Peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD) are not uncommon in elderly patients. Clinical presentations of these acid-related disorders may be atypical in the geriatric population. Older individuals are at increased risk for poor outcomes in complicated PUD and for development of GERD complications. Multiple risk factors (eg, Helicobacter pylori [HP], use of nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin) contribute to the development of PUD. Recent data has shown that HP-negative, NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk of recurrent ulcer bleeding and mortality. Effective management of PUD in the geriatric population relies on identification and modification of treatable risk factors. Elderly patients with GERD often require long-term acid suppressive therapy. Proton pump inhibitors (PPI) including esomeprazole are effective in the treatment of reflux esophagitis, maintenance of GERD symptomatic control, and management of PUD as well as its complications. Potential safety concerns of long-term PPI use have been reported in the literature. Clinicians should balance the risks and benefits before committing elderly patients to long-term PPI therapy.

Infection with Helicobacter pylori strains carrying babA2 and cagA is associated with an increased risk of peptic ulcer disease development in Iraq

Background and study aimSeveral genes of Helicobacter pylori, such as vacA, cagA, iceA and babA, have been reported to significantly increase the risk of gastrointestinal diseases. The aim of this study was to study the relationship between H. pylori virulence factors and clinical outcomes and identify the independent markers of peptic ulcer disease in Iraq. Patients and methodsDNA was extracted from specimens taken from 154 unselected H. Pylori positive Iraqi patients. Genotyping was performed by the polymerase chain reaction (PCR), using specific primers for cagA, vacA (s, m), iceA and babA2 genes. ResultsA total of 56 (82%) peptic ulcer disease (PUD) patients carried cagA+ strains, significantly more than the 56 (65%) non-ulcer disease (NUD) patients (p=0.017). The difference in the prevalence of babA2 positivity was significant between patients with NUD (33.7%) and PUD (58.8%) (p=0.002). In addition, babA2 was associated as an independent factor, with PUD (p=0.005; odds ratio (OR)=0.4; confidence interval (CI)=0.18–0.68) followed by cagA (p=0.05; OR=0.4; CI=0.18–0.85). Forty-five isolates (29%) were typed as ‘triple positive’ strains, and their presence was significantly associated with PUD (p=0.001). ConclusionThe cagA and babA2 genotypes might be considered as useful markers for PUD patients. However, iceA1 and iceA2 seem not to be good markers for the disease. The presence of H. pylori strains with triple-positive status is of high clinical relevance to H. pylori-associated diseases.

Su1780 CYP2C19*17 Gain of Function Mutation is Associated With the Development of Peptic Ulcer Disease

Su1780 CYP2C19*17 Gain of Function Mutation is Associated With the Development of Peptic Ulcer Disease

Prevalence of Helicobacter pylori infection among dyspepsia patients in Ibadan, South West Nigeria

Helicobacter pylori infection is typically acquired shortly after birth in both low and high-income regions of the world and once the infection is established, it commonly persists life long unless treated. This infection has been identified as an important risk factor for the development of peptic ulcer disease and is probably the most important cause of relapse in those previously treated for peptic ulcer disease. The aim of this study was to determine the prevalence of H. pylori infection in patients with peptic ulcer disease at the University College Hospital (UCH) Ibadan; South West Nigeria. Fifty-two (52) patients who had symptoms of dyspepsia were recruited for the study and each of them went through endoscopy. Forty-three (43) (82.7%) of the patients were diagnosed with peptic ulcer disease while nine (9) (17.3%) patients were diagnosed normal. The presence of H. pylori was determined using culture and Urease Breath Test (UBT). The culture result showed that thirty-five (35) (81.4%) of the patients diagnosed with peptic ulcer disease had H. pylori infection also, eight (8) (88.9%) of the normal patients were culture positive for H. pylori. The UBT result showed that 65.1% of the diagnosed peptic ulcer patients were positive for H. pylori, also 55.6% of the normal patients were found UBT positive for H. pylori. In all, H. pylori infection is very common among dyspepsia patients and the organism is closely associated with the disease in South West Nigeria. Key words: Helicobacter pylori, dyspepsia, urea breath test, South West Nigeria.