GC/MS-based differential metabolic profiling of human peptic ulcer disease to study Helicobacter pylori-induced metabolic perturbations

Helicobacter pylori infection has been significantly linked to Peptic Ulcer Disease and Gastric Cancer.Metabolomic fingerprinting may offer a principal way of early diagnosis and to understand the molecular mechanism of H.pylori-induced pathogenicity.The rationale of the study is to explore the underlying distinct metabolic mechanisms of H.pylori-induced PUD and to identify potential biomarkers for disease diagnosis and associated risks using Gas chromatography/mass spectrometry.GC/MS-based analytical method was used to compare metabolic profiles of healthy controls(N=20)and peptic ulcer patients(N=45).Acquired metabolomic data were analyzed by constructing a diagnostic model using principal component analysis and a non-parametric two-tailed paired Wilcoxon analysis to identify disease-specific metabolic biomarkers.A total of 75 low-molecular-weight endogenous metabolites were detected during comparative metabolomic analysis of PUD vs.healthy gut tissues,among which 16 metabolites are being proposed to be diagnostic markers of Human PUD.Perturbations related to amino acids,carbohydrates,fatty acids,organic acids,and sterol metabolism were significantly revealed during this differential metabolomic profiling.Results convincingly suggest that metabolic profiles can contribute immensely in early diagnosis of the disease and understanding molecular mechanisms of disease progression for predicting novel drug targets for prophylactic and anaphylactic measures.

Clinical characteristics of Helicobacter pylori-negative drugnegative peptic ulcer bleeding

AIM:To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori(H.pylori)-negative and drug-negative]peptic ulcer bleeding(PUB).METHODS:A consecutive series of patients who experienced PUB between 2006 and 2012 was retrospectively analyzed.A total of 232 patients were enrolled in this study.The patients were divided into four groups according to the etiologies of PUB:idiopathic,H.pylori-associated,drug-induced and combined(H.pylori-associated and drug-induced)types.We compared the clinical characteristics and outcomes between the groups.When the silver stain or rapid urease tests were H.pylori-negative,we obtained an additional biopsy specimen by endoscopic re-examination and performed an H.pylori antibody test 6-8 wk after the initial endoscopic examination.For a diagnosis of idiopathic PUB,a negative result of an H.pylori antibody test was confirmed.In all cases,re-bleeding was confirmed by endoscopic examination.For the risk assessment,the Blatchford and the Rockall scores were calculated for all patients.RESULTS:For PUB,the frequency of H.pylori infection was 59.5%(138/232),whereas the frequency of idiopathic cases was 8.6%(20/232).When idiopathic PUB was compared to H.pylori-associated PUB,the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis during the hospital stay(30%vs 7.4%,P = 0.02).When idiopathic PUB was compared to drug-induced PUB,the patients in the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis upon admission(30%vs 2.7%,P < 0.01).When drug-induced PUB was compared to H.pylori-associated PUB,the patients in the drug-induced PUB were older(68.49 ± 14.76 years vs 47.83 ± 15.15 years,P< 0.01) and showed a higher proportion of gastric ulcer(77%vs 49%,P < 0.01).However,the Blatchford and the Rockall scores were not significantly different between the two groups.Among the patients who experienced drug-induced PUB,no significant differences were found with respect to clinical characteristics,irrespective of H.pylori infection.CONCLUSION:Idiopathic PUB has unique clinical characteristics such as re-bleeding after initial hemostasis upon admission.Therefore,these patients need to undergo close surveillance upon admission.

Optimal initiation of Helicobacter pylori eradication in patients with peptic ulcer bleeding

AIM:To evaluate when Helicobacter pylori(H.pylori)eradication therapy(ET)should be started in patients with peptic ulcer bleeding(PUB).METHODS:Clinical data concerning adults hospitalizedwith PUB were retrospectively collected and analyzed.Age,sex,type and stage of peptic ulcer,whether endoscopic therapy was performed or not,methods of H.pylori detection,duration of hospitalization,and specialty of the attending physician were investigated.Factors influencing the confirmation of H.pylori infection prior to discharge were determined using multiple logistic regression analysis.The H.pylori eradication rates of patients who received ET during hospitalization and those who commenced ET as outpatients were compared.RESULTS:A total of 232 patients with PUB were evaluated for H.pylori infection by histology and/or rapid urease testing.Of these patients,53.7%(127/232)had confirmed results of H.pylori infection prior to discharge.In multivariate analysis,duration of hospitalization and ulcer stage were factors independently influencing whether H.pylori infection was confirmed before or after discharge.Among the patients discharged before confirmation of H.pylori infection,13.3%(14/105)were lost to follow-up.Among the patients found to be H.pylori-positive after discharge,41.4%(12/29)did not receive ET.There was no significant difference in the H.pylori eradication rate between patients who received ET during hospitalization a n d t h o s e w h o c o m m e n c e d E T a s o u t p a t i e n t s[intention-to-treat:68.8%(53/77)vs 60%(12/20),P=0.594;per-protocol:82.8%(53/64)vs 80%(12/15),P=0.723].CONCLUSION:Because many patients with PUB who were discharged before H.pylori infection status was confirmed lost an opportunity to receive ET,we should confirm H.pylori infection and start ET prior to discharge.

High rate of Helicobacter pylori reinfection in Lithuanianpeptic ulcer patients

AIM: To evaluate the frequency of Helicobacter pylori(H. pylori) reinfection in peptic ulcer patients during 9 years after H. pylori eradication.METHODS: We invited 117 peptic ulcer patients in whom eradication of H. pylori was confirmed 1 year after eradication treatment both by histology and by rapid urease test. In total, 57 patients were available for the study procedures: 34(59.6%) male, 23(40.4%) female; mean age 52.3 ± 13.0 years. There were 45(78.9%) patients with duodenal ulcer and 12(21.1%) with gastric ulcer. H. pylori was diagnosed by a rapid urease test and histology if endoscopy was performed. If endoscopy was refused, H. pylori was diagnosed by the C14-urea breath test and serology. H. pylori was established if at least one of the tests was positive.RESULTS: The mean follow-up was 8.9 ± 1.0 years(range, 6-12). H. pylori was established in 15 patients. In 2 H. pylori-negative patients, H. pylori was established during the follow-up period and eradicated. Therefore, we consider that reinfection occurred in 17 patients. In the per protocol analysis, reinfection was established in 17 of 57(29.8%; 95%CI: 19.2-42.2) patients during the follow-up period. The annual rate of infection was 3.36%. If all non-responders were considered H. pylori-negative, reinfection would be 14.5%(17/117), the annual ratebeing 1.63%. The mean age of patients with reinfection was 51.8 ± 14.0 years, and without reinfection was 52.5 ± 13.0 years, P > 0.05; the mean body mass index of patients with reinfection was 27.2 ± 4.1 kg/m2, and without reinfection was 25.7 ± 4.2 kg/m2, P > 0.05. There were no differences in the reinfection rates according the location of the peptic ulcer, the eradication regimen used, and smoking status.CONCLUSION: The reinfection rate of H. pylori is relatively high in Lithuania and probably related to the high prevalence of H. pylori, what may reflect differences in the socioeconomic status between Western and Eastern European countries.

Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer

AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori -infected populations. METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this metaanalysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries. CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.

Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer?

AIM:To investigate the effects of Helicobacter pylori (H pylori)eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer. METHODS:A multicenter prospective cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture,Japan.The study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication(eradication group)or conventional antacid therapy(non-eradication group).Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and questionnaire surveys,as well as Yamagata Prefectural Cancer Registry data,and was compared between the two groups and by results of H pylori therapy.RESULTS:A total of 4133 patients aged between 13 and 91 years(mean 52.9 years)were registered,and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 years.The sex-and age-adjusted incidence ratio of gastric cancer in the eradication group, as compared with the non-eradication group,was 0.58 (95%CI:0.28-1.19)and ratios by follow-up period(<1 year,1-3 years,>3 years)were 1.16(0.27-5.00),0.50 (0.17-1.49),and 0.34(0.09-1.28),respectively.Longer follow-up tended to be associated with better prevention of gastric cancer,although not to a significant extent.No significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy(32/2451 patients,1.31%)and those with treatment failure(11/639 patients,1.72%).Among patients with duodenal ulcer,which is known to be more prevalent in younger individuals,the incidence of gastric cancer was significantly less in those with successful eradication therapy(2/845 patients,0.24%)than in those with treatment failure(3/216 patients,1.39%). CONCLUSION:H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer.

Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers

AIM:To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori(H.pylori)-associated,non-steroidal inflammatory drug(NSAID)-associated and idiopathic-gastric ulcers.METHODS:We studied a cohort of randomly selected patients with H.pylori(group 1,n=30),NSAID(group 2,n=18),combined H.pylori and NSAID associated gastric ulcers(group 3,n=24),and patients with idiopathic gastric ulcers(group 4,n=20).Immunohistochemistry for MUC1,MUC4,MUC17,and staining for Erythrina cristagalli agglutinin and Sambucus nigra agglutinin(SNA)lectins was performed on sections from the ulcer margins.RESULTS:Staining intensity of MUC17 was higher in H.pylori ulcers(group 1)than in idiopathic ulcers(group4),11.05±3.67 vs 6.93±4.00 for foveola cells,and10.29±4.67 vs 8.00±3.48 for gland cells,respectively(P<0.0001).In contrast,MUC1 expression was higher in group 4 compared group 1,9.89±4.17 vs 2.93±5.13 in foveola cells and 7.63±4.60 vs 2.57±4.50 for glands,respectively(P<0.0001).SNA lectin staining was increased in group 4,in parallel to elevated MUC1expression,indicating more abundantα2-6 sialylation in that group.CONCLUSION:Cytoplasmic MUC17 staining was sig-nificantly decreased in the cases with idiopathic ulcer.The opposite was observed for both MUC1 and SNA lectin.This observation may reflect important pathogenic mechanisms,since different mucins with altered sialylation patterns may differ in their protection efficiency against acid and pepsin.

Effects of killing Helicobacter pylori quadruple therapy on peptic ulcer: A randomized double-blind clinical trial

AIM: To study the therapeutic efficacy of a Chinese and Western integrated regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated peptic ulcers(PU).METHODS: With prospective and double-blind controlled method, seventy-five active PU patients with H pylori infection were randomized to receive one of the following three regimens: (1) new triple therapy (group A:lansoprazole 30 mg qd, plus clarithromycin 250 mg bid,plus amoxycillin 500 mg tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3)placebo(group C: gastropine 3 tablets bid for 4 wk).H pylori eradication and ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The patients were followed up for 5 years.RESULTS: Both the healing rate of PU and H pylori eradication rate in group B were significantly higher than those in group C (100% and 96.4% vs 20% and 0%,respectively, P＜0.005), but there was no significant difference compared to those in group A (88% and92%, P＞0.05). The healing quality of ulcer in group B was superior to that in groups C and A (P＜0.05). The recurrence rate of PU in group B (4%) was lower than that in group A (10%) and group C (100%, P＜0.01).CONCLUSION: Killing Helicobacter pylori quadruple therapy can not only promote the eradication of H pylori and healing quality of ulcer but also reduce recurrence rate of ulcer.

Mucosal polymerase chain reaction for diagnosing Helicobacter pylori infection in patients with bleeding peptic ulcers

AIM: Helicobacter pylori(Hpylori) has been linked to chronic gastritis, peptic ulcers, gastric cancer and MALT-lymphoma.Conventional invasive tests are less sensitive than noninvasive tests in diagnosing H pylori infection in patients with bleeding peptic ulcers. Polymerase chain reaction is a sensitive and accurate method for diagnosing H pylori infection. The aim of this study was to evaluate the diagnostic role of mucosal polymerase chain reaction for H pylori infection in patients with bleeding peptic ulcers.METHODS: In patients with bleeding, non-bleeding peptic ulcers and chronic gastritis, we checked rapid urease test,histology, bacterial culture and mucosal polymerase chain reaction for detecting H pylori infection. Positive H pylori infection was defined as positive culture or both a positive histology and a positive rapid urease test. For mucosal polymerase chain reaction of Hpylori, we checked vacA (s1a, s1b, s1c, s2, m1, m1T, m2),iceA1,iceA2 and cag A.RESULTS: Between October 2000 and April 2002, 88 patients with bleeding peptic ulcers (males/females: 60/28, gastric ulcers/duodenal ulcers: 55/33), 81 patients with non-bleeding peptic ulcers (males/females: 54/27, gastric ulcers/duodenal ulcers: 45/36) and 37 patients with chronic gastritis (males/females: 24/13) were enrolled in this study. In patients with bleeding peptic ulcers, non-bleeding peptic ulcers and chronic gastritis, 45 patients (51%), 71 patients (88%)and 20 patients (54%) respectively were found to have positive H pylori infection (P＜0.001). In patients with bleeding peptic ulcers, non-bleeding peptic ulcers and chronic gastritis, polymerase chain reaction for H pylori infection was positive in 54 patients (61%), 70 patients (86%) and 20 patients (54%) respectively (P＜0.001). The sensitivity,positive predictive value and diagnostic accuracy of mucosal polymerase reaction for Hpylori infection were significantly lower in patients with bleeding peptic ulcers (84%, 79%and 81%) than in patients with non-bleeding peptic ulcers (99%, 99% and 98%) (P＜0.001, P＜0.01 and P＜0.001respectively). The sensitivity, negative predictive value and diagnostic accuracy of mucosal polymerase reaction for H pylori were significantly lower in patients with bleeding peptic ulcers (84%, 83% and 81%) than in patients with chronic gastritis (100%, 100% and 100%) (P= 0.02, P= 0.02and P = 0.001).CONCLUSION: Mucosal polymerase chain reaction for detecting H pylori infection is not reliable in patients with bleeding peptic ulcers.

One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the treatment of Helicobacter pylori infection in Brazilian patients with peptic ulcer

AIM: To assess the efficacy and safety of ranitidine bismuth citrate plus clarithromycin given for 1 wk in Brazilian patients with peptic ulcer.METHODS: One hundred and twenty patients with peptic ulcer were randomized in two treatment groups: (1) 1-wk regimen consisting of ranitidine bismuth citrate 400 mg b.i.d. with clarithromycin 500 mg b.i.d. or (2) 2-wk regimen of the same treatment. Eradication of the infection was considered when both the histologic examination and the urease test were negative for the infection 3 mo after treatment.RESULTS: By intention to treat analysis, Helicobacter pylori (H pylori) was eradicated in 73% and 76% of patients, respectively treated for 1 or 2 wk (P＞0.05). By per protocol analysis, the eradication rates were 80% and 83%,respectively, in patients treated for 1 or 2 wk (P＞0.05). Nine patients (8.2%) reported minor side effects. CONCLUSION: One-week therapy with ranitidine bismuth citrate and clarithromycin is safe, well tolerated and effective for treatment of H pylori infection, andappears to be comparable to the 2-wk regimen in terms of efficacy.

Accuracy of Helicobacter pylori serology in two peptic ulcer populations and in healthy controls

AIM: To estimate the test characteristics of Heli- cobacter pylori (Hpylori) serology and of C14-urea breath test (C14-UBT) in two different peptic ulcer populations and in community controls. Second, the aim was to explore the association between the level of H pylori IgG antibodies and severity of inflammation as to active peptic ulceration in the same populations. METHODS: Vagotomized (n= 83), medically treated peptic ulcer patients (n=73) and one reference group of community controls (n=88) were gastroscoped. H pylori status was determined by histology, bacterial growth, C14-UBT and serology. Based on the updated Sydney System, cumulative scores from biopsies from the prepyloruos, incisura angularis, corpus and fundus were calculated. RESULTS: The prevalence of H pylori infection varied from 70% to 79%. The C14-UBT had high accuracycompared to the serology test. The sensitivity of the serology test was good, but the specificity was low (41%-71%). The association between H pylori IgG antibodies and scores of gastric mucosal inflammation and current or previous peptic ulcer were weak. CONCLUSION: The accuracy of C14-UBT to diagnose H pylori infection was good, and the clinical utility of a negative H pylori serology test was substantial, while the gain in clinical information of a positive test was meagre. Positive H pylori titres could not distinguish between subjects with or those without active peptic ulceration.

Helicobacter pylori infection and peptic ulcer disease in cirrhotic patients:An updated meta-analysis

BACKGROUND Peptic ulcer(PU)is more prevalent in patients with liver cirrhosis.The role of Helicobacter pylori(H.pylori)infection in the pathogenesis of PU in patients with cirrhosis is still not elucidated.AIM To perform a meta-analysis on the prevalence of H.pylori infection and PU and their association in liver cirrhosis patients.METHODS We searched PubMed,EMBASE,Web of Science,Cochrane,CNKI,Wangfang,and CQVIP databases from inception to July 10,2020.Odds ratio(OR)and 95%confidence interval(CI)were pooled using a random-effects model.The statistical heterogeneity among studies(I2-index),subgroup analyses,regression analysis,sensitivity analysis,and the possibility of publication bias were assessed.RESULTS A total of 14 studies(13 cross-sectional studies;1 cohort study)involving 2775 individuals(611 cases with PU and 2164 controls)were included in our metaanalysis.The prevalence of PU in patients with cirrhosis was 22%.The prevalence of H.pylori infection was 65.6%in cirrhotic patients with PU,and 52.5%in those without.The pooled overall OR was 1.73(95%CI:1.16-2.56,I2=66.2%,P<0.001,Z=2.7,Pz<0.05).We did not find the cause of heterogeneity in the subgroup analyses and meta-regression analysis except for one study.Funnel plot did not show significant publication bias.The results of Begg’s test and Egger’s test indicated no evidence of substantial publication bias(P_(Begg)=0.732,P_(Egger)=0.557).CONCLUSION There is a weakly positive association between H.pylori infection and PU in patients with liver cirrhosis.It is suggested that H.pylori infection may play a role in the pathogenesis of PU in liver cirrhotic patients.

Helicobacter Pylori Infections in Peptic Ulcer Perforations: A Retrospective Analysis in Two Referral Hospitals in Douala, Cameroon

Background: Perforations are major complications of peptic ulcer disease and surgical emergencies with important mortality and morbidity. Helicobacter pylori (H. pylori) has been identified as one of the commonest factors associated with peptic ulcer disease. However, little is known about its implication in cases of perforations in Cameroon. We aimed to determine the frequency of Helicobacter pylori infections in cases of perforated peptic ulcers, describe clinical features and outcomes of these cases in Cameroon. Method: A hospital-based retrospective cross-sectional study was conducted through the review of patients’ records admitted for peptic ulcer perforations in Laquintinie and Douala General Hospitals over a period of 5 years (January 2014 - December 2018). We defined H. pylori infection as;positive result on tissue biopsy at time of surgery. We used SPSS version 23.0 to analyse data and set an alpha value at P = 0.05. Results: We reviewed 115 cases of peptic ulcer perforation, with a mean age of 40 years and sex ratio (M:F) of 5:1. All patients underwent emergency laparotomy, 48 (41%) cases had a biopsy report and the prevalence of H. pylori infection in these cases was 47.9 %. Smoking, alcohol consumption and Non-Steroidal Anti-inflammatory Drugs (NSAIDs) use, were not associated with peptic ulcer perforation. The morbidity was at 43.7% and mortality at 14%. Mortality was increasing with a higher Mannheim Peritonitis Index score (OR: 23.51, 95% CI: 4.197 - 143.003, P-value: 0.000). Conclusion: We observed a high prevalence of H. pylori infection in patients with peptic ulcer perforations. We recommend systematic H. pylori screening in cases of perforations and that larger studies should be carried out to evaluate the association of H. pylori infection with peptic ulcer perforation in Sub-Saharan Africa.

Helicobacter pylori infection in bleeding peptic ulcer patients after non-steroidal antiinflammatory drug consumption

AIM:To establish the prevalence of Helicobacter pylori (H. pylori ) infection in patients with a bleeding peptic ulcer after consumption of non-steroidal antiinflamma- tory drugs (NSAIDs). METHODS:A very early upper endoscopy was performed to find the source of upper gastrointestinal bleeding and to take biopsy specimens for analysis of H. pylori infection by the rapid urease (CLO) test, histological examination, and bacterial culture. IgG anti-CagA were also sought. The gold standard for identifying H. pylori infection was positive culture of biopsy specimens or contemporary positivity of the CLO test and the presence of H. pylori on tissue sections. RESULTS:Eighty patients, 61 males (76.3%), mean age 61.2 ± 15.9 years, were consecutively enrolled. Forty-seven (58.8%) patients occasionally consumed NSAIDs, while 33 (41.3%) were on chronic treatment with low-dose aspirin (LD ASA). Forty-four (55.0%) patients were considered infected by H. pylori . The infection rate was not different between patients who occasionally or chronically consumed NSAIDs. The culture of biopsy specimens had a sensitivity of 86.4% and a specificity of 100%; corresponding figures for histological analysis were 65.9% and 77.8%, for the CLO test were 68.2% and 75%, for the combined use of histology and the CLO test were 56.8% and 100%, and for IgG anti-CagA were 90% and 98%. The highest accuracy (92.5%) was obtained with the culture of biopsy specimens.CONCLUSION:Patients with a bleeding peptic ulcer after NSAID/LD ASA consumption frequently have H. pylori infection. Biopsy specimen culture after an early upper gastrointestinal tract endoscopy seems the most efficient test to detect this infection.

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.

Polymorphism of -765G > C COX-2 is a risk factor for gastric adenocarcinoma and peptic ulcer disease in addition to H pylori infection:A study from northern India

AIM: To investigate -765G > C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and non- ulcer dyspepsia (NUD). METHODS: We enrolled 348 adult patients (62 gastric adenocarcinoma, 45 PUD and 241 NUD) undergoing upper gastrointestinal endoscopy at two referral centers between September, 2002 and May, 2007. H pylori infection was diagnosed when any of the four tests (RUT, culture, histopathology and PCR) were positive. Genotyping for -765G > C polymorphism of COX-2 was performed by PCR-RFLP analysis. RESULTS: Frequency of C carrier had significantassociation with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P < 0.001, odds ratio (OR) 8.20; 95% confidence interval (95% CI), 4.08-16.47] and PUD (77.4% vs 31.1%, P < 0.001; OR 8.04; 95% CI, 3.25-19.90). Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with (OR 7.83; 95% CI 3.09-19.85) and without H pylori infection (OR 7.06; 95% CI, 2.61-19.09). Patients with C carrier and H pylori infection had significant risk for the development of PUD (P < 0.001; OR 5.65; 95% CI, 2.07-15.34). CONCLUSION: -765G > C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H pylori infection might be useful in predicting the risk of PUD.

Effect of Banxia Xiexin decoction on Helicobacter pylori-related peptic ulcers and its possible mechanism via the TGF-β/Smad signaling pathway

OBJECTIVE: To investigate the effect of Banxia Xiexin decoction(BXD) on Helicobacter pylori(Hp)-related peptic ulcers(PUs) and the possible mecha-nism underlying BXD actions via the transforming growth factor-β/small mothers against decapentaplegic(TGF-β/Smad) signaling pathway.METHODS: PU patients with cold-heat complex syndrome were randomly assigned to groups that received Chinese or Western medicines with 20 patients in each group. Serum was collected after 7 d of treatment. The healthy group included 20 individuals. Gastric mucosal epithelial cell line GES-1 was cultured in vitro and randomly divided into the following seven groups: control, model, healthy,Western Medicine, prior treatment, low dosage,and high dosage. After 72 h of treatment with the corresponding serum, the m RNA and protein expression levels of TGF-β1, Smad3, and Smad7 were measured by reverse transcription quantitative polymerase chain reaction and western blotting, respectively.RESULTS: The m RNA expression levels of TGF-β1 and Smad3 in GES-1 cells were increased after Hp introduction, and these increased levels were reduced by the BXD-containing serum. The protein levels of p-Smad3, but not TGF-β1 or Smad3, were significantly increased in Hp-treated GES-1 cells,and treatment with the BXD-containing serum markedly decreased the protein levels. Smad7 expression was significantly enhanced following treatment with the BXD-containing serum at transcriptional and protein levels in a dose-dependent manner.CONCLUSION: BXD regulates the TGF-β/Smad signaling pathway by inhibiting the expression of TGF-β1 and Smad3, and increasing the expression of Smad7.

Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer

Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2<Abstract>Pro-inflammatory cytokines are produced in the gastric mucosa by inflammatory cells activated by chronic Helicobacter pylori (H. pylori) infection. Polymorphisms of these cytokine genes are associated with individual differences in gastric mucosal cytokine mRNA level, which result in differences in gastric mucosal inflammation, acid inhibition and gastroduodenal disease risk in response to H. pylori infection. Although polymorphisms of interleukin (IL)-1B, IL-1RN and TNF-A have been reported to relate well with gastric cancer and peptic ulcer risk, those of IL-2, IL-4, IL-6 and IL-8 genes are unclear. In combined analyses using data from previous stud- ies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among popula- tions. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo- denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations..02, 1.31-3.10). In peptic ulcer development, IL-2-330 G and IL-4-590 T allele carriers had a significantly decreased risk (0.37, 0.27-0.50 and 0.58, 0.34-0.99, respectively). Moreover, IL-2, IL-4, IL-6 and IL-8 gene genotypes prevalence differs among populations. The inflammatory cytokine gene polymorphisms (e.g. IL-4 -590 and IL-6 -572 for gastric cancer, and IL-4-590, IL-6-572 and IL-8-251 for peptic ulcer) have a more potent influence on development of gastroduo-denal diseases in Western than East Asian populations. These cytokine gene polymorphisms, as well as those of IL-1B, IL-1RN and TNF-A, may be used to identify groups at higher risk of gastric cancer and peptic ulcer, and those suitable for their prevention by H. pylori eradication therapy in Western populations.

Clinical significance of Helicobacter pylori cagA and iceA genotype status

AIM:To study the presence of Helicobacter pylori(H.pylori) virulence factors and clinical outcome in H.pylori infected patients.METHODS:A prospective analysis of ninety nine H.pylori-positive patients who underwent endoscopy in our Endoscopy suite were included in this study.DNA was isolated from antral biopsy samples and the presence of cagA,iceA,and iceA2 genotypes were determined by polymerase chain reaction and a reverse hybridization technique.Screening for H.pylori infection was performed in all patients using the rapid urease test(CLO-Test).RESULTS:From a total of 326 patients who underwent endoscopy for upper gastrointestinal symptoms,99 patients were determined to be H.pylori-positive.Peptic ulceration was seen in 33 patients(33%).The main virulence strain observed in this cohort was the cagA gene isolated in 43 patients.cagA was associated with peptic ulcer pathology in 39.5%(17/43) and in 28%(16/56) of non-ulcer patients.IceA1 was present in 29 patients(29%) and iceA2 in 15 patients(15%).Ulcer pathology was seen in 39%(11/29) of patients with iceA1,while 31%(22/70) had normal findings.The corresponding values for iceA2 were 33%(5/15) and 33%(28/84),respectively.CONCLUSION:Virulence factors were not common in our cohort.The incidence of factors cagA,iceA1 and iceA2 were very low although variations were noted in different ethnic groups.

Zinc carnosine-based modified bismuth quadruple therapy vs standard triple therapy for Helicobacter pylori eradication: A randomized controlled study

BACKGROUND Helicobacter pylori(H.pylori)infection is a worldwide problem with increasing burden on the health sector due to its increasing rate of resistance.The conventional triple therapy(TT)is becoming obsolete with a high failure rate of eradication,necessitating the need for better alternatives or regimens.AIM To investigate H.pylori eradication rate of TT vs modified bismuth quadruple therapy.METHODS Ninety-two patients with dyspepsia symptoms and positive ^(13)C-urea breath test were randomly assigned to two groups.The first group(control group)was treated for 14 d using standard TT protocol:Esomeprazole(40 mg twice daily),amoxicillin(1 g twice daily)and clarithromycin(500 mg twice daily).On the other hand,the second group was prescribed a 10-d course of modified bismuth quadruple therapy fortified with zinc carnosine:TT in addition to bismuth subcitrate(240 mg twice daily)and zinc carnosine(75 mg twice daily).A repeated 13C-urea breath test was done 4 wk after the completion of the eradication therapy.RESULTS Among the 92 subjects,67.4%were males and 32.6%were females.There were no differences in demographic characteristics(age,body mass index,smoking history,previous antibiotics use and ethnicity)between the modified bismuth quadruple therapy group and TT group.The eradication rate was higher[93.5%(43/46)]in the modified bismuth quadruple therapy group compared to 69.6%(32/46)in the standard TT group(P=0.003).Of the tested predictor variables,only nationality,smoking and therapy type were statistically significant.Besides dizziness,which was recorded in modified bismuth quadruple therapy group,there were no significant differences in side effects between the two groups.CONCLUSION Ten days of modified bismuth quadruple therapy fortified with zinc carnosine is superior to 14 d of conventional TT in eradicating H.pylori infection,with no additional significant adverse events.