Development Of Peptic Ulcer Disease Research Articles

Eradication of Helicobacter pylori Infection Reduces the Incidence of Peptic Ulcer Disease in Patients using Nonsteroidal Anti‐Inflammatory Drugs: A Meta‐Analysis

To investigate the association between use of nonsteroidal anti-inflammatory drugs (NSAID) and Helicobacter pylori infection, interactive effect of H. pylori infection and NSAID use on the development of peptic ulcer disease (PUD), and the effect of H. pylori eradication therapy on PUD development. We performed a systematic literature search in EMBASE and PubMed for relevant articles published in English between January 1989 and August 2010, with the following MeSH and/or key words: non-steroidal anti-inflammatory drugs, or NSAIDs, Helicobacter pylori, or H. pylori, peptic ulcer disease or PUD, and randomized-control study or clinical trial. The meta-analysis was conducted using the Review Manager 4.2.2. In the analysis of five studies, the pooled prevalence of H. pylori infection was 74.5% and 71.1% in NSAID users and non-NSAID users, respectively, (OR = 0.65; 95% CI: 0.35-1.20, p = .170). In the analysis of nine studies, the pooled prevalence of PUD in NSAID users was 31.2% and 17.9% in the presence and absence of H. pylori infection, respectively, (OR = 3.08; 95% CI: 1.26-7.55, p = .010). Moreover, in the analysis of seven studies, PUD developed in 6.4% and 11.8% of NSAID users with and without eradication therapy, respectively (OR = 0.50; 95% CI: 0.36-0.74, p < .001). The preventive effect of the eradication therapy was further revealed in NSAID-naive users (OR = 0.26; 95% CI: 0.14-0.49, p < .0001) and in the Asian population (OR = 0.30; 95% CI: 0.16-0.56, p < .001). NSAID use is not associated with H. pylori infection in patients with PUD. PUD is more common in H. pylori positive than in negative NSAID users. Moreover, H. pylori eradication therapy reduces PUD incidence in NSAID users, especially in naive users and in the Asian population.

Variations in Helicobacter pylori Cytotoxin-Associated Genes and Their Influence in Progression to Gastric Cancer: Implications for Prevention

Helicobacter pylori (HP) is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes) pathogenicity island (cagPAI), a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma) using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche) methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous) showed statistically significant differences (P<0.05), and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value = 2.07×10−6), and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations.

Different risk factors influence peptic ulcer disease development in a Brazilian population

To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients. From all 1466 consecutive dyspeptic patients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall χ² = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall χ² = 30.5, P < 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P < 0.0001) and intestinal metaplasia (OR = 1.0520, P < 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P < 0.0001) and with the incidence of DU (OR = 3.6077, P < 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P= 0.2863). In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metaplasia; and H. pylori of vacA m1 genotype for DU.

In Vivo Expression of Helicobacter pylori Virulence Genes in Patients with Gastritis, Ulcer, and Gastric Cancer

The best-studied Helicobacter pylori virulence factor associated with development of peptic ulcer disease or gastric cancer (GC) rather than asymptomatic nonatrophic gastritis (NAG) is the cag pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into host epithelial cells. Here we used real-time reverse transcription-PCR (RT-PCR) to measure the in vivo expression of genes on the cagPAI and of other virulence genes in patients with NAG, duodenal ulcer (DU), or GC. In vivo expression of H. pylori virulence genes was greater overall in gastric biopsy specimens of patients with GC than in those of patients with NAG or DU. However, since in vitro expression of cagA was not greater in H. pylori strains from patients with GC than in those from patients with NAG or DU, increased expression in GC in vivo is likely a result of environmental conditions in the gastric mucosa, though it may in turn cause more severe pathology. Increased expression of virulence genes in GC may represent a stress response to elevated pH or other environmental conditions in the stomach of patients with GC, which may be less hospitable to H. pylori colonization than the acidic environment in patients with NAG or DU.

Genotypic and Phenotypic Variation of Lewis Antigen Expression in Geographically Diverse Helicobacter pylori Isolates

Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and β-(1,3)galT loci in 113 H. pylori strains. Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.

Ulcerogenic Helicobacter pylori Strains Isolated from Children: A Contribution to Get Insight into the Virulence of the Bacteria

Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA “on” status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors.

CYP2C19 Genetic Polymorphisms in Patients with Peptic Ulcer Disease and Nonulcer Dyspepsia in Thailand

Purpose: Recently, the CYP2C19 genotype has been found to be an important factor in peptic ulcer healing rate, H. pylori. eradication and has influences on the therapeutic efficacy of proton pump inhibitor. The aim of this study was to investigate CYP2C19 genotype status in patients with peptic ulcer disease and non-ulcer dyspepsia in Thailand. Methods: Clinical information, endoscopic findings and H. pylori infection of all patients were collected between January 2009 and April 2010 in Thammasat University Hospital, Thailand. The upper GI endoscopy was performed in all patients. Three antral biopsies were obtained, one for rapid urease test and culture, one for histopathology and another one for CYP2C19 study. Patients were regarded as H. pylori-positive if at least one of the examinations gave a positive result. The CYP2C19 genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: Total 121 patients were enrolled in this study including 61 males and 60 females with mean age of 51.3 years. There were 86 patients with non-ulcer dyspepsia and 36 patients with peptic ulcer disease. The prevalence of CYP2C19 genotype was 45/121 (37.2%) in RM, 65/121 (53.7%) in IM and 11/121 (9.1%) in PM. The prevalence of H. pylori infection was demonstrated in 77.8% in RM, 76.9% in IM and 63.7% in PM without statistical different between each group. However, the prevalence of peptic ulcer disease in CYP2C19 genotype RM and IM was significantly greater than those of genotype PM (29.5% vs 16.7%: P<0.05 and 29.2% vs 16.7%: P<0.05 respectively). Conclusion: CYP2C19 genotype IM was the most common genotype in Thailand followed by genotype RM and PM. Peptic ulcer disease has significant greater prevalence in CYP2C19 genotype RM and IM than those of genotype PM. CYP2C19 genotypes might play a role in the development of peptic ulcer disease and need further studies to clarify this relationship.

Quality of Life among Adult Patients with Peptic Ulcer in the City of Sulaimani

Objectives: To assess the quality of life for adult patients with peptic ulcers in the city of Sulaimani.Methodology: A descriptive study, using the assessment approach was conducted on patients with peptic ulcerdisease from January 12th, 2009 to September 30th, 2009. A purposive "non-probability" sample of (100) paƟents(males and females) with peptic ulcers who attended Kurdistan Center for Gastroenterology and Hepatology wereselected for the study. A questionnaire was adapted from the World Health Organization quality of life questionnaire(1998) for the purpose of the study. It is comprised of (3) parts that included sociodemographic characteristics form,medical history form and adult peptic ulcers patients' quality of life (QoL) questionnaire. A pilot study was carried outon (10) paƟents for the period of January 12th through January 28th, 2009 to determine the study quesƟonnaire'sreliability through the use of stability (test-retest method). A panel of (14) experts was involved in the determinationof the questionnaire's content validity. Data were analyzed through the application of the descriptive statistical dataanalysis approach (frequency, percentage, mean of scores) and inferential statistical data analysis approach (Pearsoncorrelation coefficient and chi-square).Results: The findings of the study indicated that quality of life was affected in physical domain and that age, gender,marital status, and monthly income had significant relationship with quality of life domains.Recommendations: The study recommends that young adults, particularly Individuals with blood group (O) should behighly aware from gastrointestinal (GI) symptoms and avoids risk factors for the development of peptic ulcer disease(PUD). Also, the study recommends providing health assurance and conducting further multi centers studies in orderto demonstrate the differences in QoL issues for PUD patients.

Helicobacter pylori VacA Induces Programmed Necrosis in Gastric Epithelial Cells

Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach and contributes to the development of peptic ulcer disease and gastric cancer. The secreted pore-forming toxin VacA is one of the major virulence factors of H. pylori. In the current study, we show that AZ-521 human gastric epithelial cells are highly susceptible to VacA-induced cell death. Wild-type VacA causes death of these cells, whereas mutant VacA proteins defective in membrane channel formation do not. Incubation of AZ-521 cells with wild-type VacA results in cell swelling, poly(ADP-ribose) polymerase (PARP) activation, decreased intracellular ATP concentration, and lactate dehydrogenase (LDH) release. VacA-induced death of these cells is a caspase-independent process that results in cellular release of histone-binding protein high mobility group box 1 (HMGB1), a proinflammatory protein. These features are consistent with the occurrence of cell death through a programmed necrosis pathway and suggest that VacA can be included among the growing number of bacterial pore-forming toxins that induce cell death through programmed necrosis. We propose that VacA augments H. pylori-induced mucosal inflammation in the human stomach by causing programmed necrosis of gastric epithelial cells and subsequent release of proinflammatory proteins and may thereby contribute to the pathogenesis of gastric cancer and peptic ulceration.

Helicobacter pylori and gastritis: Untangling a complex relationship 27 years on

Since its' introduction by Warren and Marshall 27 years ago, Helicobacter pylori (HP) has become the linchpin in our understanding of important gastric conditions including gastritis, intestinal metaplasia (IM), gastric/duodenal ulcers (GU/DU), Mucosal Associated Lymphoid Tumour (MALToma) and gastric cancer. Initially named Campylobacter pyloridis, it was re-named HP when biochemical and genetic characterization of the organism showed that it was not a member of the Campylobacter genus. The finding in 1983 was seminal. It is now recognized that HP is the most common chronic human bacterial infection and it is the most common cause of gastritis. It is strongly implicated in the development of peptic ulcer disease and gastric neoplasms. In the years since its' discovery, much headway has been made in the understanding of this ubiquitous organism that had remained elusive, with much work focused on eradication, in part driven by pharmaceutical research and development. Standard triple therapy emerged to eradicate HP. However, with the emergence of HP resistance, newer regimes have been put forth that include quadruple therapy, sequential therapy and a dizzying array of other combinations bent on eradicating HP. Much less is known about the natural history of HP, the different faces of HP internationally, HP eradication and its effect on gastritis, IM, GU/DU and gastric cancer. This review will address the changing face of HP in 2011.

Gastric cytoprotection 30 years after its discovery by André Robert: a personal perspective

It is generally accepted that the development of gastric mucosal injury and protection is a consequence of an imbalance between the existing aggressive and defensive factors in the gastric mucosa. The excess secretion of gastric acid and increased production of pepsin have been considered as the main etiological factors in the development of peptic ulcer diseases in humans. André Robert and his coworkers (Kalamazoo, Michigan, USA) identified a new pathway for the gastric mucosal protection against the gastric mucosal damage injury (e.g. from HCl, NaOH, NaCl, ethanol, or thermal injury) by small doses of prostaglandins (1-5 μg/kg given ig or sc), without presence of any gastric acid secretory properties in rats. This phenomenon was termed "gastric cytoprotection" (1979). The results of this basic research offered a lot of new possibilities to test this hypothesis in different experimental models under different experimental conditions, in both human healthy subjects as well as in patients with various gastrointestinal disorders (acute and chronic gastrointestinal inflammatory conditions in the stomach and intestines, as well as GI precancerous states, i.e., oesophageal, stomach, pancreatic, liver and colon cancers). An international symposium on "gastric cytoprotection: 30 years after André Robert's concept" was organized at Split (Croatia) on September 13, 2009, at which invited experts from China, Croatia, Italy, Japan, Poland, and USA gave presentations and discussed the studies performed in the field of cytoprotection between 1979 and 2009. This paper provides a short critical summary of this meeting in the context of an "official historic background" of the events underlying the discovery of "gastric cytoprotection" which originated from the pioneering work of André Robert.

“A surviving myth” – corticosteroids are still considered ulcerogenic by a majority of physicians

Objective. Evidence does not support an association between systemic corticosteroid use and the development of peptic ulcer disease (PUD) and prophylactic anti-ulcer therapy is not routinely indicated. The aim was to find out the opinion of physicians in the Czech Republic on corticosteroid-induced ulcers. Materials and methods. A questionnaire-based study targeting 360 physicians of different specialties (100 from Gastroenterology, 100 from General Practice, 80 from Pneumology/Immunology, and 80 from Neurology/Neurosurgery). Results. Eighty-two percent of the physicians considered corticosteroids ulcerogenic, 7.5% of the responders considered them ulcerogenic only in patients with a family history of PUD, and 10.3% of the physicians considered corticosteroids non-ulcerogenic. Seventy-five percent of the responders would administer concomitant antisecretory treatment. Sixty-seven percent of the physicians thought that PUD was a frequent complication of corticosteroid therapy. If the ulcerogenic potential of ibuprophene, diclofenac, and prednisone was a subject of the physicians' judgment, a majority (40.5%) considered prednisone to be the most ulcerogenic substance. Thirty percent of gastroenterologists (vs. 1.9% of others; p < 0.001) did not consider corticosteroids to be ulcerogenic; 27.4% (vs. 4.3%; p < 0.01) would not administer an antisecretory prophylaxis routinely. Conclusions. Although there is no evidence showing an association between PUD and the use of corticosteroids, a majority of physicians consider corticosteroids gastrotoxic. This applies, to a lesser extent, to gastroenterologists. Action should be taken to explode the myth about the gastrotoxicity of corticosteroids and to minimize useless expenses on concomitant prophylaxis.

Clinical Relevance and Diversity of Two Homologous Genes Encoding Glycosyltransferases in Helicobacter pylori

Helicobacter pylori is known to be a major cause of peptic ulceration. The jhp0562 gene, encoding a glycosyltransferase involved in the synthesis of the lipopolysaccharide, was associated with peptic ulcer disease (PUD) in children. The beta-(1,3)-galactosyltransferase [beta-(1,3)GalT] gene (jhp0563), involved in Lewis (Le) antigen expression, is highly similar to jhp0562. The clinical significance and diversity of both genes were examined by PCR and sequencing of clinical strains (n = 117) isolated from children with PUD (n = 57) and nonulcer dyspepsia (NUD; n = 60). The prevalence of the jhp0562 gene was significantly higher in strains with a more-virulent profile (strains positive for the cag pathogenicity island [PAI], vacA sl allele, babA, homB, phase-variable gene oipA "on" [i.e., functional], and hopQ I allele). The distribution of genotypes according to clinical outcome showed that the presence of jhp0562 represented one of the greatest risks for the development of PUD. Moreover, the triple-positive genotype for the cag PAI, jhp0562, and homB provided the best discriminatory model for distinguishing PUD and NUD outcomes in children. Sequence and in vitro expression analyses of jhp0562 showed the presence of a complete open reading frame, while the beta-(1,3)GalT gene was shown to be a phase-variable gene. The regular presence of jhp0562 in strains with a truncated beta-(1,3)GalT gene suggests that jhp0562 may also be implicated in the regulation of Le antigen expression. Overall, the results of this study suggest that the jhp0562 gene is of great clinical relevance, being a useful comarker for severe H. pylori-related disease and contributing to host adaptation.

Helicobacter pylori detection in gastric biopsies, saliva and dental plaque of Brazilian dyspeptic patients

Helicobacter pylori is an important human pathogen that causes chronic gastritis and is associated with the development of peptic ulcer disease and gastric malignancies. The oral cavity has been implicated as a potential H. pylori reservoir and may therefore be involved in the reinfection of the stomach, which can sometimes occur following treatment of an H. pylori infection. The objectives of this paper were (i) to determine the presence of H. pylori in the oral cavity and (ii) to examine the relationship between oral H. pylori and subsequent gastritis. Gastric biopsies, saliva samples and dental plaques were obtained from 78 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori using polymerase chain reaction and Southern blotting methods. Persons with gastritis were frequently positive for H. pylori in their stomachs (p < 0.0001) and there was a statistically significant correlation between the presence of H. pylori in gastric biopsies and the oral cavity (p < 0.0001). Our results suggest a relationship between gastric infection and the presence of this bacterium in the oral cavity. Despite this, H. pylori were present in the oral cavity with variable distribution between saliva and dental plaques, suggesting the existence of a reservoir for the species and a potential association with gastric reinfection.

Helicobacter pylori γ-Glutamyl Transpeptidase Is a Pathogenic Factor in the Development of Peptic Ulcer Disease

gamma-Glutamyl transpeptidase (GGT) has been reported to be a virulence factor of Helicobacter pylori associated with bacterial colonization and cell apoptosis. But its mechanism of pathogenesis is not firmly established. This study aims to examine its role in H pylori-mediated infection. Various H pylori isogenic mutants were constructed by a polymerase chain reaction (PCR) approach. H pylori native GGT protein (HP-nGGT) was purified with ion-exchange and gel-filtration chromatography. Generation of H2O2 was measured with fluorimetric analysis, whereas nuclear factor-kappaB (NF-kappaB) activation was determined by luciferase assay and Western blot. Cytokine production was examined by enzyme-linked immunoabsorbent assay and real-time PCR. DNA damage was assessed with comet assay and flow cytometry. The GGT activity of 98 H pylori isolates was analyzed by an enzymatic assay. Purified HP-nGGT generated H2O2 in primary gastric epithelial cells and AGS gastric cancer cells, resulting in the activation of NF-kappaB and up-regulation of interleukin-8 (IL-8) production. In addition, HP-nGGT caused an increase in the level of 8-OH-dG, indicative of oxidative DNA damage. In contrast, Deltaggt showed significantly reduced levels of H2O2 generation, IL-8 production, and DNA damage in cells compared with the wild type (P<.05). The clinical importance of GGT was indicated by significantly higher (P<.001) activity in H pylori isolates obtained from patients with peptic ulcer disease (n=54) than isolates from patients with nonulcer dyspepsia (n=44). Our findings provide evidence that GGT is a pathogenic factor associated with H pylori-induced peptic ulcer disease.

Risk Factors for Development and Recurrence of Peptic Ulcer Disease

Peptic ulcer disease (PUD) is one of the common gastrointestinal diseases, and its medical management has been developed so much that the incidence of its serious complications, such as bleeding and perforation, are declining significantly. Its prevalence in Korea is not definitely decreased, probably due to increasing proportion of elderly patients and their rising usage of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin. This study was conducted to identify the risk factors for development and recurrence of peptic ulcer disease in Korea. From 2003 to 2008, upper gastrointestinal endoscopy and detailed personal questionnaires were performed for patients who visited Department of Gastroenterology at Seoul National University Bundang Hospital. In total, 475 PUD patients and 335 non-ulcer dyspepsia patients were included. The results of questionnaires and repeated upper gastrointestinal endoscopy at initial diagnosis time and follow-up periods were analyzed. Multivariable analysis showed that male, H. pylori infection, NSAIDs use and smoking were risk factors for the development of PUD. The use of proton pump inhibitors (PPIs) and H2 receptor antagonists has significantly reduced the risk of PUD in patients who had taken NSAIDs and/or aspirin. H. pylori infection was found as the only risk factor for the recurrence of PUD. For the old patients who are taking drugs, such as NSAIDs and aspirin, concomitant use of PPIs or H2 receptor antagonists should be considered to protect from the development of PUD. H. pylori eradication has been confirmed again to be essential for the treatment of PUD patients infected with H. pylori.

A Changing Gastric Environment Leads to Adaptation of Lipopolysaccharide Variants in Helicobacter pylori Populations during Colonization

The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG) with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS) decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression.

Peptic ulcer disease and helicobacter pylori infection at kano, nigeria.

Background. Helicobacter pylori 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 Helicobacter pylori infection in patients with peptic ulcer disease at the Aminu Kano Teaching Hospital (AKTH), Kano, North-Western Nigeria.Methods. The study was cross sectional and conducted between December 2004 and May 2006. Consecutive patients with endoscopic diagnosis of peptic ulcer disease at the Endoscopy Unit of Aminu Kano Teaching Hospital, Kano were recruited. Other patients who had endoscopy within the study period for dyspepsia but with normal endoscopic findings were recruited as controls. Three gastric antral and two body biopsies were taken from each patient, and histological evaluation for presence of Helicobacter pylori was done using haematoxilin/eosin and modified Giemsa stains.Results. The Prevalence of Helicobacter pylori infectionin all the study subjects was found to be 81%. Helicobacter pylori were found present in 93.3% of patients with peptic ulcer disease. Presence of H. pylori infection in patients with duodenal ulcer and gastric ulcer were 95.8% and 90.9% respectively. However 80% of those with normal endoscopic findings also had Helicobacter pylori infection.Conclusion. Helicobacter pylori infection is very common among patients with peptic ulcer disease in Kano Nigeria. Patients with non-ulcer dyspepsia also have, to a lesser extent a high prevalence of Helicobacter pylori infection.

Relationship Between Helicobacter pylori BabA and BabB Status with Other Virulence Factors and Their Correlation with Disease Outcome in Iran

Objectives: Helicobacter pylori (Hp) is an important human pathogen associated with gastrointestinal diseases such as gastritis, peptic ulcer disease (PUD) and gastric cancer. A number of pathogenic factors have been described for this bacterium, and some of them have been proposed as predictive markers of the clinical outcomes. However, with the exception of the cag and vacA status, there is no global consensus regarding the role of the other introduced virulence factors. Therefore, the aim of this study was to investigate the status of Hp strains regarding the Hp babA and babB (blood group antigen binding) adhesins and assess any existing association between the status of these genes and clinical outcomes in Iranian patients. Methods: Hp virulence genes were amplified by means of gene-specific polymerase chain reaction in clinical isolates of Hp from 72 Iranian patients (16 GC, 12 PUD, 44 NUD patients). Results: Eleven categories of genotypes were identified with the following frequencies: Group1: A+B+/cagA+/s1(38.0%); Group2: A+B+/cag+/s2(2.8%); Group3: A+B+/cag-/s1(1.4%); Group4: A+B-/cag+/s1(7%); Group5: A+B-/cag+/s2(2.8%); Group6: A-B+/cag+/s1(22.5%); Group7: A-B+/cag+/s2(14.1%); Group8: A-B+/cag-/s1(1.4%); Group9: A-B+/cag-/s2(4.2%); Group10: A-B-/cag+/s1(2.8%); Group11: A-B-/cag+/s2(2.8%). Frequency of Group1 in GC, NUD and PUD patients is 75%, 27.3% and 27.3% respectively and Group7 is prevalent in 36.4% of PUD patients. babA prevalence in GC, NUD and PUD patients was 75%, 47.7% and 33.3% and babB prevalence was 93.8%, 77.3% and 91.7% respectively. 75% of Hp isolates were babA/babB double positive in GC patients. Conclusion: Frequency of babB is higher among Iranian GC and PUD cases but babA frequency is limited to GC cases. Infecting strains from Groups 1 and 7 were found to be associated with GC and PUD respectively. Co-presence of cagA, s1vacA, babA and babB may work synergistically in exacerbating the resulting inflammation which may create grounds for development of intestinal metaplasia and eventually GC, whereas co-existence of cagA, s2vacA, babB may cause susceptibility to PUD development. In GC cases presence of babA/babB double positive are significantly prevalent (p = 0.044). Application of this analysis on additional samples will allow for a more concrete conclusion.

Involvement of the Helicobacter pylori plasticity region and cag pathogenicity island genes in the development of gastroduodenal diseases

Infection by Helicobacter pylori is associated with the development of several gastroduodenal diseases, including gastritis, peptic ulcer disease (gastric ulcers and duodenal ulcers), and gastric adenocarcinoma. Although a number of putative virulence factors have been reported for H. pylori, there are conflicting results regarding their association with specific H. pylori-related diseases. In this work, we investigated the presence of virB11 and cagT, located in the left half of the cag pathogenicity island (cagPAI), and the jhp917-jhp918 sequences, components of the dupA gene located in the plasticity zone of H. pylori, in Brazilian isolates of H. pylori. We also examined the association between these genes and H. pylori-related gastritis, peptic ulcer disease, and gastric and duodenal ulcers in an attempt to identify a gene marker for clinical outcomes related to infection by H. pylori. The cagT gene was associated with peptic ulcer disease and gastric ulcers, whereas the virB11 gene was detected in nearly all of the samples. The dupA gene was not associated with duodenal ulcers or any gastroduodenal disease here analyzed. These results suggest that cagT could be a useful prognostic marker for the development of peptic ulcer disease in the state of São Paulo, Brazil. They also indicate that cagT is associated with greater virulence and peptic ulceration, and that this gene is an essential component of the type IV secretion system of H. pylori.