Pathogenesis Of Peptic Ulcer Disease Research Articles

Molecular hydrogen in human breath: a new strategy for selectively diagnosing peptic ulcer disease, non-ulcerous dyspepsia and Helicobacter pylori infection

The gastric pathogen Helicobacter pylori utilizes molecular hydrogen (H2) as a respiratory substrate during colonization in the gastric mucosa. However, the link between molecular H2 and the pathogenesis of peptic-ulcer disease (PUD) and non-ulcerous dyspepsia (NUD) by the enzymatic activity of H. pylori still remains mostly unknown. Here we provide evidence that breath H2 excretion profiles are distinctly altered by the enzymatic activity of H. pylori for individuals with NUD and PUD. We subsequently unravelled the potential molecular mechanisms responsible for the alteration of H2 in exhaled breath in association with peptic ulcers, encompassing both gastric and duodenal ulcers, along with NUD. We also established that carbon-isotopic fractionations in the acid-mediated bacterial environment regulated by bacterial urease activity cannot discriminate the actual disease state i.e. whether it is peptic ulcer or NUD. However, our findings illuminate the unusual molecular H2 in breath that can track the precise evolution of PUD and NUD, even after the eradication of H. pylori infection. This deepens our understanding of the pathophysiology of PUD and NUD, reveals non-invasively the actual disease state in real-time and thus offers a novel and robust new-generation strategy for treating peptic-ulcer disease together with non-ulcer related complications even when the existing 13C-urea breath test (13C-UBT) fails to diagnose.

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.

Fluoroquinolone-based protocols for eradication of Helicobacter pylori.

Helicobacter pylori (H. pylori) is a widespread pathogen infecting about 40% of people living in urban areas and over 90% of people living in the developing regions of the world. H. pylori is well-documented as the main factor in the pathogenesis of peptic ulcer disease, chronic gastritis, and gastric malignancies such as cancer and mucosa-associated lymphoid tissue-lymphoma; hence, its eradication is strongly recommended. The Maastricht IV consensus, which focused on the management of H. pylori infection, set important new strategies in terms of treatment approaches, particularly with regards to first- and second-line treatment protocols and led to improved knowledge and understanding of H. pylori resistance to antibiotics. In recent years, various fluoroquinolone-based protocols, mainly including levofloxacin, have been proposed and effectively tested at all therapeutic lines for H. pylori eradication. The aim of the present paper is to review the scientific literature focused on the use of fluoroquinolones in eradicating H. pylori.

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.

Helicobacter pylori Susceptibility in the GWAS Era

Helicobacter pylori infection remains one of the most common chronic bacterial infections worldwide and is causally linked to the pathogenesis of peptic ulcer disease, gastric adenocarcinoma, and MALT (mucosa-associated lymphoid tissue) lymphoma.1 However, the majority of infected patients generally remain asymptomatic and never develop significant disease. Because of its wide prevalence and causal association with serious disease outcomes, this infection has deservedly commanded the attention and dedication of researchers across the globe.

Helicobacter pyloriInfection and Upper Gastrointestinal Disorders

It has been thirty years since the two Australians Robin Warren and Barry Marshall discovered Helicobacter pylori (H. pylori) in 1983 [1]. In order to fulfil the Koch's postulates, Marshall and Morris drank a solution which was a suspension of H. pylori. This produced gastritis from which the bacteria could be reisolated [2]. It will be interesting to see how the approach to treatment has progressed in these three decades after the discovery of the organism-based both on consensus guidelines and other research in this field. The changes in the consensus statements have been highlighted. The isolation of H. pylori from the gastric mucosa and the report of the organism's urease activity generated excitement especially when it was postulated by Marshall that these microorganisms could be the cause of gastritis and could be a dominant etiological factor in the pathogenesis of peptic ulcer disease (PUD). With the isolation of H. pylori, floodgates opened to a new era of discovery and understanding of gastroduodenal pathology. These results were a paradigm shift from the earlier belief that PUD disease was related to stress, lifestyle, and acid secretion based on the dictum of Schwarz “no acid no ulcer.” The early nineteen eighties when Warren and Marshall reported their findings coincided with omeprazole belonging to the group of proton pump inhibitors (PPIs) being introduced. This PPI was documented as a potent antisecretory agent which yielded very good results for ulcer healing and achieving a potential cure for patients with PUD when compared to the earlier drugs belonging to the group of H2 receptor antagonists. Hence there was lot of scepticism in the gastroenterology community world over to accept that PUD was the result of infection. However, it was found that patients with PUD continued to have remission of the disease even after cessation of antisecretory therapy.

Su1781 Reactive Gastropathy and Correlation With Medications, Helicobacter pylori and Gastric Inflammation

INTRODUCTION: Studies show that single nucleotide polymorphisms (SNPs) in nonsteroidal anti-inflammatory drug (NSAID)-metabolising enzymes (mainly CYP2C9 & CYP2C8) may predispose NSAID-users to peptic ulcer disease (PUD) or upper gastrointestinal bleeding (UGIB). However, results to date have been inconclusive due to small sample sizes and different study designs. METHODS: We hypothesised that the eight closely-linked clinically important SNPs in the CYP2C family of genes, namely CYP2C8*3 (rs11572080 & rs10509681), CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 may predispose to PUD via impaired NSAID metabolism as well as other potentially important mechanisms such as metabolism of arachidonic acid (AA) and protonpump inhibitors (PPIs). Subjects endoscoped for suspected PUD/UGIB at 13 hospitals in the UK between 2005 and 2011 were recruited and interviewed using a structured questionnaire. Recruits were categorised as either NSAID-users (use within 2 weeks) or non-users (no use within 3 months). UGIB was defined as haematemesis, melaena or anaemia, and endoscopic stigmata of recent bleeding. H. pylori status was ascertained in most subjects. Following extraction of genomic DNA, genotyping was performed by KBioscience Ltd (UK). Logistic regression analysis was used to test for association between each SNP and risk of PUD/ UGIB. Interaction terms were introduced to determine whether any observed genetic effects were influenced by factors including type of NSAID, PPI use and gender. RESULTS: Overall,1246 white patients were recruited and categorised as follows: 485 (39%) PUD+/NSAID+; 357 (29%) PUD+/NSAID-; 125 (10%) PUD-/NSAID+; 280 (22%) PUD-/NSAID-. Seven SNPs were included in the final analysis (CYP2C19*3 was monomorphic and excluded). All SNPs were in Hardy-Weinberg equilibrium. Logistic regression analysis of cases (PUD+; n=842) and controls (PUD-; n=405), assuming an additive mode of inheritance at each SNP, showed that only CYP2C19*17 was significantly associated with PUD (p=0.006), with suggestion of an allele-dose effect, even on classifying cases as those using only CYP2C9/CYP2C8substrate NSAIDs (p=0.005). Post-hoc analysis showed no interaction between CYP2C19*17 and NSAID type, PPI use or gender. Subgroup analysis per ulcer type showed CYP2C19*17 was significantly associated with risk of gastric ulcers (p=0.02), whilst only rs11572080 was associated with risk of duodenal ulcers (p=0.04). No SNPs were associated with UGIB. CONCLUSION: Possession of CYP2C19*17 allele is associated with PUD, especially gastric ulcers, regardless of aetiology. We postulate that this could be through its effect on the metabolism of AA or other endogenous substances, leading to impairment of gastrointestinal mucosal defences. Further studies are needed to correlate the functional consequences of CYP2C19*17 in the pathogenesis of PUD.

PREVALENCE OF H. PYLORI

Background: Acid peptic disease is a world wide problem among all the age groups and both sexes. Duodenal ulcer is common as compared to gastric ulcer. Its prevalence being 4:1 in USA & UK and 5:1 in Pakistan1,2,3. Etiology of peptic ulcer is almost certainly multi-factorial. Basic paradigm for ulcer disease is the imbalance between the digestive activity of acid and pepsin and the protective mechanism in place toresist mucosal digestion. Over the past few years a new line of thought has been evolved after isolating spiral campylobacter like organism from antral biopsy specimens. H pylori is now considered to be an important if not the only causative agent of gastritis and peptic ulcer disease. The dictum; No acid – No ulcer summarized the pathogenesis of peptic ulcer disease but new dictum seems to be; No H.pylori -No ulcer4,5, as over90% of Duodenal ulcer and 70% of Gastric ulcer patients are infected byH.Pylori6. Aim of the study was to evaluate the prevalence of H.pylori among Duodenal ulcer patients at Faisalabad District and its suburbs. Study Design: Descriptive Study. Period: From Mar 2008 to Oct 2008. Materials and Methods: 50 patients (40 Males, 10 Females) belonging to Faisalabad District and surrounding areas with upper gastrointestinal symptoms of acid peptic disease and endoscopy proved duodenal ulcer were subjected to gastric antral mucosal biopsies for evaluation of the H.Pylori status with the help of unease test and histological examination of biopsy specimen. Results: Epigastric pain was the most frequent symptom 90%. (46 out of 50 patients). 92% showed evidence of H. pylori infection. Maximum incidence of H. pylori was recordedin age group IV (46—55 years). Maximum number of patients was skilled workers (35 out of 50) 70%. 80 % of the patients belonged to lower and middle class. Percentage of H.pylori positivity was 89.1 % and 84.34 %. Conclusions: Acceptance of contributory role and high prevalence rate of H.pylori instigates us for addition of antimicrobial treatment to the conventional treatment with H2 Blockers and PPIs which is cost effectiveand alter the course of the disease.

Reconstitution of Helicobacter pylori VacA toxin from purified components.

Helicobacter pylori VacA is a pore-forming toxin that causes multiple alterations in human cells and contributes to the pathogenesis of peptic ulcer disease and gastric cancer. The toxin is secreted by H. pylori as an 88 kDa monomer (p88) consisting of two domains (p33 and p55). While an X-ray crystal structure for p55 exists and p88 oligomers have been visualized by cryo-electron microscopy, a detailed analysis of p33 has been hindered by an inability to purify this domain in an active form. In this study, we expressed and purified a recombinant form of p33 under denaturing conditions and optimized conditions for the refolding of the soluble protein. We show that refolded p33 can be added to purified p55 in trans to cause vacuolation of HeLa cells and inhibition of IL-2 production by Jurkat cells, effects identical to those produced by the p88 toxin from H. pylori. The p33 protein markedly enhances the cell binding properties of p55. Size exclusion chromatography experiments suggest that p33 and p55 assemble into a complex consistent with the size of a p88 monomer. Electron microscopy of these p33/p55 complexes reveals small rod-shaped structures that can convert to oligomeric flower-shaped structures in the presence of detergent. We propose that the oligomerization observed in these experiments mimics the process by which VacA oligomerizes when in contact with membranes of host cells.

The role of an aggressive factor in peptic ulcer disease (pud)

The stomach is the expanded part of the digestive tract between the esophagus and the small intestine. It acts as a reservoir and has chief function in enzymatic digestion. Several types of glands provide different types of secretions in the alimentary tract most of which act as lubricant and to protect the stomach mucosa from excoriation.The pathophysiology of peptic ulcer disease (PUD) is often described as an imbalance between aggressive factors and mucosal protective mechanisms. Helicobacter pylori, a gram-negative organism that has been identified as a potential causative agent in the pathogenesis of peptic ulcer disease, which is diagnosed by invasive or non-invasivemethods. Three classes of drugs have been shown to have a direct effect on Helicobacter pylori: antibiotics, bismuth salts, and proton pump inhibitors. Because Helicobacter pylori is difficult to eradicate, most treatment regimes combine agents from two or even all three of these cases. In all of them, patients with active peptic disease shouldalso receive a total of 6 weeks of acid suppression with an H2-receptor antagonist. The discovery of Helicobacter pylori as a gastrointestinal pathogen has had a profound effect on current concepts of the pathogenesis and treatment of peptic ulcer disease. Key words: peptic ulcer disease, Helicobacter pylori, H2-receptor antagonist, pathophysiology

In Situ Expression of cagA and Risk of Gastroduodenal Disease in Helicobacter pylori–infected Children

Gastroduodenal disease is more common among adults and children with cagA+ Helicobacter pylori infection, but disease severity varies among those infected with cagA+ strains. We examined whether cagA in situ expression can predict disease manifestations among H pylori-infected children. Fifty-one children were selected from 805 patients with abdominal symptoms who underwent esophagogastroduodenoscopy with gastric biopsies. Endoscopic and histologic gastritis were scored and H pylori colonization was quantified by Genta stain and in situ hybridization expression of 16S rRNA and cagA. Endoscopy was either normal (n = 14) or demonstrated nodularity (n = 18), gastric ulcer (n = 8) or duodenal ulcer (n = 11). H pylori was present in 7, 18, 6, and 10 children, respectively. Expression of 16S rRNA and cagA were significantly higher in children with ulcer compared with normal children. The fraction of H pylori bacteria expressing cagA in situ was higher in children with ulcer compared to those with endoscopic nodularity (P < 0.05). Thus, cagA in situ expression is increased in H pylori-infected children with peptic ulcers and may play a role in the pathogenesis of peptic ulcer disease during childhood. Determination of in situ expression of cagA complements traditional isolation and in vitro testing of single-colony isolates.

Helicobacter pylori Infection and Peptic Ulcer Disease in Patients with Liver Cirrhosis

Background/AimsWe investigated the prevalence and relationship of peptic ulcer disease and Helicobacter pylori infection to liver cirrhosis.MethodsWe examined 288 patients with liver cirrhosis, 322 patients with non-ulcer dyspepsia, and 339 patients with peptic ulcer disease. Rapid urease test and Wright-Giemsa staining were used for diagnosis of H. pylori infection.ResultsThe prevalence of peptic ulcer disease in patients with cirrhosis was 24.3%. The prevalence of peptic ulcer disease in patients with cirrhosis divided into Child-Pugh classes A, B, and C was 22.3%, 21.0%, and 31.3%, respectively (p>0.05). The prevalence of H. pylori infection in the patients with cirrhosis, non-ulcer dyspepsia, and peptic ulcer without chronic liver disease were 35.1%, 62.4%, and 73.7%, respectively (p<0.001). The prevalence of H. pylori infection did not differ depending on whether there was peptic ulcer (35.6%) or not (34.9%) in patients with liver cirrhosis (p>0.05). The prevalence of H. pylori infection in patients with hepatitis virus-related liver cirrhosis and in the patients with alcohol-related liver cirrhosis was 42.5% and 22.0%, respectively (p<0.001). The prevalence of H. pylori infection in patients with Child-Pugh classes A, B, and C liver cirrhosis was 51.5%, 30.5%, and 20.0%, respectively (p<0.001).ConclusionsFactors other than H. pylori may be involved in the pathogenesis of peptic ulcer disease in the setting of liver cirrhosis.

Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain

Helicobacter pylori VacA, a pore-forming toxin secreted by an autotransporter pathway, causes multiple alterations in human cells, contributes to the pathogenesis of peptic ulcer disease and gastric cancer, and is a candidate antigen for inclusion in an H. pylori vaccine. Here, we present a 2.4-A crystal structure of the VacA p55 domain, which has an important role in mediating VacA binding to host cells. The structure is predominantly a right-handed parallel beta-helix, a feature that is characteristic of autotransporter passenger domains but unique among known bacterial protein toxins. Notable features of VacA p55 include disruptions in beta-sheet contacts that result in five beta-helix subdomains and a C-terminal domain that contains a disulfide bond. Analysis of VacA protein sequences from unrelated H. pylori strains, including m1 and m2 forms of VacA, allows us to identify structural features of the VacA surface that may be important for interactions with host receptors. Docking of the p55 structure into a 19-A cryo-EM map of a VacA dodecamer allows us to propose a model for how VacA monomers assemble into oligomeric structures capable of membrane channel formation.

Recurrence of peptic ulcer in uraemic and non‐uraemic patients after Helicobacter pylori eradication: a 2‐year study

The role of Helicobacter pylori in the pathogenesis of peptic ulcer disease in patients with uraemia remains unclear. To evaluate the long-term effect of H. pylori eradication in these patients. Uraemic and non-uraemic patients with peptic ulcer were enrolled in this study. Patients having history of non-steroidal anti-inflammatory drugs use or cardiovascular disease that need aspirin use were excluded. After confirmation of H. pylori infection, they received a triple therapy and were followed up for 2 years. Between September 1999 and December 2005, 34 patients (41%) of the end-stage renal disease [H. pylori (+) group] and 67 (84%) of the non-uraemic patients with peptic ulcer disease (PU group) received anti-H. pylori therapy. After triple therapy, 32 (94%) from the end-stage renal disease group and 64 (96%) from the peptic ulcer group obtained successful eradication. During the 2-year follow-up, three patients in the end-stage renal disease group were excluded because of the presence of cardiovascular disease and aspirin use in two cases and died of heart failure in one case; two patients in peptic ulcer group refused follow-up. Finally, 29 uraemic and 62 non-uraemic patients had achieved the follow-up. Recurrence of peptic ulcer was more in the end-stage renal disease group than in the peptic ulcer group with intention-to-treat analysis (eight of 32, 25% vs. two of 64, 3%, P = 0.001, OR: 10.0, 95% CI: 1.979-50.540) or per-protocol analysis (eight of 29, 28% vs. two of 62, 3%, P < 0.001, OR: 11.4, 95% CI: 2.245-58.168). Peptic ulcer recurrence after H. pylori eradication is higher in end-stage renal disease patients with peptic ulcer than in peptic ulcer patients without renal disease. Factors aside from H. pylori play an important role in peptic ulcer recurrence in end-stage renal disease patients.

Can Soluble Triggering Receptor Expressed on Myeloid Cells (sTREM-1) Be Considered an Anti-Inflammatory Mediator in the Pathogenesis of Peptic Ulcer Disease?

Soluble triggering receptor expressed on myeloid cells (sTREM-1) is a novel mediator involved in the pathogenesis of peptic ulcer disease. To investigate the potential role of sTREM-1 in the anti-inflammatory response in chronic gastritis, sTREM-1 was compared with other anti-inflammatory mediators of gastritis. Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1, interleukin (IL)-8, and IL-10 were estimated by enzyme immunoassays. Median sTREM-1 in patient controls and in patients with peptic ulcer disease was 3.91 and 44.27 pg/ml, respectively (P=0.006). Respective values of IL-8 were 1856.97 and 2030.66 pg/ml (P=0.023); those of IL-10 were 16.92 and 18.43 pg/ml (NS). The odds ratio for the presence of peptic ulcer in the event of a concentration of sTREM-1 higher than 15 pg/ml was 23.22 (95% CI, 2.58-208.62; P=0.002). A positive correlation was found between the ratios of IL-8/sTREM-1 and IL-8/IL-10 (r (s), + 0.365; P=0.021). In conclusion, sTREM-1 is an independent factor for the generation of peptic ulcer disease and might behave as an anti-inflammatory mediator in chronic gastritis.

Mucosal Plug in the Etiology of Peptic Ulcer Disease

The pathogenesis of duodenal ulcer begins at a site remote from the acid-pepsin pool. It is usually located a little farther away from the pylorus but within the first part of the duodenum, known as the duodenal cap. The etiological factors involved in the infliction of a particular site with duodenal ulceration have been highlighted in a recent study [1]. The famous dictum stated by Schwartz 90 years ago was “No acid, no ulcer” [2]. This has never been disputed since, but what was never defined in that phrase was how a particular site away from the pylorus could be inflicted with acid injury and how this injury could be limited to a few millimeters within the duodenal bulb if the acid had traversed through the pyloric sphincter? These pertinent issues are dealt with in this study. In recent studies, Helicobacter pylori, by contrast, has been implicated as one of the etiological factors in the pathogenesis of peptic ulcer disease [3], but why such bacterial injury inflicts a particular site when the bacteria are present diffusely in the antrum and the duodenum is not understood. This could occur if the particular site were exclusively isolated from the rest of the duodenum and were exclusively exposed to bacterial colonization, but that is not possible. Hence, the development of an ulcer at a particular site must be governed by intrinsic factors.

Helicobacter pylori culture and antimicrobial resistance in Iran

Helicobacter pylori is considered as an important etiologic factor in pathogenesis of peptic ulcer disease, chronic gastritis and gastric cancer. To eradicate this micro-organism, numerous regimens containing various antimicrobial agents have been suggested. However, H pylori antimicrobial resistance is a leading factor to treatment failure and recurrence of the disease. The aim of the study was to evaluate the prevalence of H pylori resistance to metronidazole, clarithromycin, tetracycline, amoxicillin, erythromycin and furazolidone in authors pediatric patients. Antral biopsy of all pediatric patients with negative history of receiving anti-H pylori regimen and endoscopic findings of nodular gastritis or peptic ulcer without previous history of NSAID consumption, burning and trauma were performed for H pylori histology, urease test and culture. All positive cultures were tested for antimicrobial susceptibility. Twenty four patients (14 male and 10 female) between 3.5 and 14 years of age were culture positive. 54.16% of the isolates were resistant to metronidazole, 8.33% to amoxicillin, 4.16% to erythromycin and 4.16% to clarithromycin. None of authors patients were resistant to tetracycline and furazolidone. H. pylori antimicrobial resistance could be a major contributor to failure of H pylori eradication. Continuous prospective surveillance of H. Pylori is essential. Moreover, culture and antimicrobial susceptibility test is recommended for resistant cases after the first failure to therapy.

Effect of a Specific Cyclooxygenase-Gene Polymorphism (A-842G/C50T) on the Occurrence of Peptic Ulcer Hemorrhage

Cyclooxygenases (COX) catalyze the conversion of arachidonic acid to prostaglandins (PGs). COX-inhibiting drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), increase the risk for peptic ulcer disease. As a corollary, COX gene polymorphisms could be important in the pathogenesis of peptic ulcer disease because these affect prostaglandin formation and impair its protective effect at the level of the gastric mucosa. This study was designed to investigate the association between the functional single-nucleotide polymorphism, A-842G/C50T, in the COX-1 gene and peptic ulcer bleeding. We obtained DNA samples from 106 patients who underwent upper gastrointestinal endoscopy because of bleeding peptic ulcer disease and from 88 healthy control subjects. Genetic polymorphism in A-842G/C50T was determined by PCR followed by restriction-fragment-length-polymorphism analysis. Adjusted logistic regression analysis was performed to evaluate the associations. Risk factors associated with peptic ulcer bleeding were male gender (odds ratio, 4.78; 95% confidence interval, 2.6-8.8) and NSAID/aspirin-use (odds ratio, 38.39; 95% confidence interval, 14.2-103.6). The A-842G/C50T heterozygote was less frequent in peptic ulcer bleeding (n = 7) compared with healthy control subjects (n = 11). The adjusted risk for peptic ulcer bleeding among individuals who were heterozygote for the A-842G/C50T polymorphism was 0.75 (range, 0.19-3.01) compared with wild type. The COX-1 A-842G/C50T SNP does not influence the risk for developing peptic ulcer bleeding.

Random Mutagenesis of Helicobacter pylori vacA To Identify Amino Acids Essential for Vacuolating Cytotoxic Activity

VacA is a secreted toxin that plays a role in Helicobacter pylori colonization of the stomach and may contribute to the pathogenesis of peptic ulcer disease and gastric cancer. In this study, we analyzed a library of plasmids expressing randomly mutated forms of recombinant VacA and identified 10 mutant VacA proteins that lacked vacuolating cytotoxic activity when added to HeLa cells. The mutations included six single amino acid substitutions within an amino-terminal hydrophobic region and four substitutions outside the amino-terminal hydrophobic region. All 10 mutations mapped within the p33 domain of VacA. By introducing mutations into the H. pylori chromosomal vacA gene, we showed that secreted mutant toxins containing V21L, S25L, G121R, or S246L mutations bound to cells and were internalized but had defects in vacuolating activity. In planar lipid bilayer and membrane depolarization assays, VacA proteins containing V21L and S25L mutations were defective in formation of anion-selective membrane channels, whereas proteins containing G121R or S246L mutations retained channel-forming capacity. These are the first point mutations outside the amino-terminal hydrophobic region that are known to abrogate vacuolating toxin activity. In addition, these are the first examples of mutant VacA proteins that have defects in vacuolating activity despite exhibiting channel activities similar to those of wild-type VacA.

Soluble triggering receptor expressed on myeloid cells (sTREM-1): a new mediator involved in the pathogenesis of peptic ulcer disease

Triggering receptor expressed on myeloid cells (TREM-1) is a promoter of cytokine production triggered by microbial components. To investigate the significance of its soluble counterpart, sTREM-1, for the pathogenesis of peptic ulcer disease, sTREM-1 was compared with the proinflammatory mediators and the pathology score of gastritis. Forty patients with dyspepsia were enrolled: 20 with peptic ulcer and 20 controls without any macroscopic abnormalities. All patients were examined by endoscopy; gastric juice was aspirated and biopsy specimens were collected from the antrum and corpus of the stomach. sTREM-1 was estimated by a hand-made enzyme immunoassay. Interleukin-8 was estimated by enzyme-linked immunosorbent assay and lipid peroxidation, indexed by malondialdehyde, by the thiobarbituric assay, after passage through a high-performance liquid chromatography system. The median (+/-SE) of sTREM-1 of controls and patients with ulcer was 3.91+/-0.57 and 44.27+/-241.55 RU, respectively (P=0.006). The median (+/-SE) of interleukin-8 of controls and patients with ulcer was 1802.97+/-122.10 and 2030.66+/-64.44 pg/ml, respectively (P=0.023). sTREM-1 was positively correlated with the density of neutrophil and mononuclear infiltration scores and the total Sydney score (P=0.029, 0.043 and 0.041, respectively). sTREM-1 was positively correlated with interleukin-8 (P=0.042). sTREM-1 might be an independent factor involving with the peptic ulcerative inflammatory process that is positively correlated with histopathological abnormalities of gastritis.