Pylori-positive Chronic Gastritis Research Articles

Urinary metabolic profiles during Helicobacter pylori eradication in chronic gastritis.

Helicobacter pylori (H. pylori) infection is a major risk factor for chronic gastritis, affecting approximately half of the global population. H. pylori eradication is a popular treatment method for H. pylori-positive chronic gastritis, but its mechanism remains unclear. Urinary metabolomics has been used to elucidate the mechanisms of gastric disease treatment. However, no clinical study has been conducted on urinary metabolomics of chronic gastritis. To elucidate the urinary metabolic profiles during H. pylori eradication in patients with chronic gastritis. We applied LC-MS-based metabolomics and network pharmacology to investigate the relationships between urinary metabolites and H. pylori-positive chronic gastritis via a clinical follow-up study. Our study revealed the different urinary metabolic profiles of H. pylori-positive chronic gastritis before and after H. pylori eradication. The metabolites regulated by H. pylori eradication therapy include cis-aconitic acid, isocitric acid, citric acid, L-tyrosine, L-phenylalanine, L-tryptophan, and hippuric acid, which were involved in four metabolic pathways: (1) Phenylalanine metabolism; (2) phenylalanine, tyrosine, and tryptophan biosynthesis; (3) citrate cycle; and (4) glyoxylate and dicarboxylate metabolism. Integrated metabolomics and network pharmacology revealed that MPO, COMT, TPO, TH, EPX, CMA1, DDC, TPH1, and LPO were the key proteins involved in the biological progress of H. pylori eradication in chronic gastritis. Our research provides a new perspective for exploring the significance of urinary metabolites in evaluating the treatment and prognosis of H. pylori-positive chronic gastritis patients.

A Link Between Platelet-to-Lymphocyte Ratio and Helicobacter pylori Infection

Abstract Background: Gastritis is a progressive disease that evolves from a non-atrophic to an atrophic state and progresses through intestinal metaplasia, even leading to gastric cancer. Gastritis is defined by an inflammatory process of the mucosal lining of the stomach. Aim: We aimed to identify any association between Helicobacter pylori (H. pylori)-positive gastritis and simple inflammatory markers derived from a complete blood count such as the platelet-to-lymphocyte ratio (PLR). Material and Methods: We performed a retrospective case-control study in which we included patients who underwent an upper digestive endoscopy with biopsy between January 2019 and December 2020 and were diagnosed with gastritis. H. pylori status was determined from the histopathological examination, and complete blood count was performed from venous blood samples. The final study group included 125 patients with H. pylori-positive chronic gastritis, and the control group was made up by 207 patients without H. pylori infection. Results: We found a higher value of the PLR in H. pylori-positive patients than in the control group, but the difference was not significant statistically. Conclusions: PLR levels could be a predictor of inflammation in H. pylori infection, but an extensive study is needed to confirm this theory.

Investigation of Aryl Hydrocarbon Receptor, Zinc, and Vitamin B12 Levels in Chronic Gastritis with Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection is known as the most common cause of worldwide common chronic gastritis. Pathogenic mechanisms caused by H. pylori in diseases are still not fully understood. In addition, it has been reported that H. pylori can alter gene expressions in infected tissues and affect transcription factor activation. It is reported that aryl hydrocarbon receptor (AhR), which is a cytoplasmic transcription factor, functions in the immune system and plays a role in immune cells in barrier organs such as the gastrointestinal system, skin, and lungs. H. pylori infection affects the absorption of micronutrients such as trace elements, minerals, and vitamins by disrupting gastric secretion and acidification functions. Zinc (Zn) trace element is thought to be able to modulate the induction of AhR-responsive genes in endothelial cells. Although it is emphasized that trace elements are related with gastritis, relationship between Zn and AhR is not fully known, especially in chronic gastritis accompanied by H. pylori infection. In this study, serum levels of AhR, Zn, and AhR antagonist vitamin B12 were determined in chronic gastritis with H. pylori infection. Fifty volunteers diagnosed with H. pylori positive and negative chronic gastritis were included in this study. Collected from individuals participating were 5 ml of venous blood samples, and their serums were separated. AhR serum level of the study group was determined using enzyme-linked immunosorbent assay method. Zn concentrations in serum samples were measured using inductively coupled plasma atomic emission spectroscopy. When AhR and Zn serum levels were compared in H. pylori positive and negative chronic gastritis patients, it was found that AhR serum level of H. pyloripositive chronic gastritis patients increased but it was not statistically significant (p = 0.595). However it was determined Zn and B12 serum levels werestatistically significantly decreased (p < 0.001). This study has a crucial importance since to be the first one investigating relationship between serum AhR, Zn, and vitamin B12 levels in the pathogenesis of H. pylori gastritis in adults. Examination of AhR, Zn and B12 levels in H. pylori positive gastritis patients contributes to elucidating molecular mechanism of the disease.

CORRECTION OF NITRIC OXIDE SYSTEM IN PATIENTS WITH HELICOBACTER PYLORI-ASSOCIATED CHRONIC GASTRITIS AND CONCOMITANT TYPE 2 DIABETES MELLITUS

The current data suggest that Helicobacter pylori infection and type 2 diabetes mellitus may affect the state of nitric oxide system, which significantly influences stomach functioning. The aim of the research was to study the state of nitric oxide system in patients with Helicobacter pylori-associated chronic gastritis and concomitant type 2 diabetes mellitus, and to investigate the potential of eupatilin in its correction. 172 patients with confirmed chronic gastritis were enrolled into the study. They were divided into 4 groups: І (n=71) included individuals with Helicobacter pylori-positive chronic gastritis and type 2 diabetes mellitus; ІІ (n=21) included patients with Helicobacter pylori-negative chronic gastritis and type 2 diabetes mellitus; ІІІ (n=48) included patients with Helicobacter pylori-positive chronic gastritis without type 2 diabetes mellitus; IV (n=32) was made up with individuals having Helicobacter pylori-negative chronic gastritis without type 2 diabetes mellitus. According to prescribed therapeutic schemes the patients of groups І and ІІІ were additionally subdivided into the following subgroups: groups I-A (n=35) and III-A (n=24) underwent anti-Helicobacter therapy, groups I-В (n=36) and III-B (n=24) were prescribed to receive anti-Helicobacter therapy and eupatilin. Anti-Helicobacter therapy included pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg bid for 10 days. The patients received Eupatilin as an active agent of Stilen preparation, which contains 0.48 – 1.44 mg of eupatilin, tid for 28 days. Nitrites content and activity of inducible and constitutional nitric oxide synthases were analyzed in blood serum before the treatment and on the 28th day after the therapy completed. The patients of group I before the treatment were found to have an increase of nitrites level in 1.4 times, inducible nitric oxide synthase in 1.5 times higher in comparison to the patients of group II. An activity of constitutional nitric oxide synthase in patients with chronic gastritis and type 2 diabetes mellitus was found to be decreased regardless the Helicobacter pylori-status in 2.3 and 2.7 times in comparison to the patients of groups III and IV respectively. Eupatilin prescription promoted Helicobacter therapy eradication and treatment outcomes through nitrites decrease in 1.5 times, reduction of inducible nitric oxide synthase activity in 1.2 times, and growth of constitutional nitric oxide synthase in1.2 times in patients of I-B group in comparison to group I-A. Combined anti-Helicobacter therapy with eupatilin promotes successful Helicobacter pylori eradication, which was 6.2% higher in patients of I-B group than in I-A group. Conclusions: Helicobacter pylori-associated chronic gastritis in patients with type 2 diabetes mellitus is followed by rise of nitrites, inducible nitric oxide synthase activity and simultaneous decline of constitutional nitric oxide synthase in blood serum. Eupatilin prescription as a component of integrated anti-Helicobacter therapy increases the efficacy of Helicobacter pylori eradication and improves the state of nitric oxide-system due to its anti-inflammatory, antioxidant and cytoprotective properties.

High rates of clarithromycin and levofloxacin resistance of Helicobacter pylori in patients with chronic gastritis in the south east area of Vietnam

BackgroundThe increasing rates of clarithromycin (CLR)- and levofloxacin (LVX)-resistant Helicobacter pylori are the main causes of the considerable decrease in the eradication rates of triple therapy and LVX-based regimens. The aims of this study were to determine the rates of CLR- and LVX-resistant H. pylori by the Epsilometer test and to assess the risk factors for this antibiotic resistance among patients with chronic gastritis in the south east area of Vietnam. MethodsGastric biopsy specimens were obtained from 153 patients with H. pylori-positive chronic gastritis for use in culture and in the Epsilometer test to determine CLR and LVX susceptibilities. ResultsThe rates of H. pylori resistance to CLR and LVX were 72.6% and 40.5%, respectively. Dual-resistant H. pylori (to both CLR and LVX) accounted for 30.7% of patients. The rates of high-level resistance to CLR and LVX were 18.9% and 83.9%, respectively. Multivariate analysis showed that age older than 30 years (odds ratio [OR] = 3.80, 95% confidence interval [CI] 1.61–8.97) and history of H. pylori treatment (OR = 8.72, 95% CI 1.90–39.91) were independent risk factors for CLR resistance, whereas only age older than 35 years (OR = 2.42, 95% CI 1.23–4.76) was an independent risk factor for LVX resistance. ConclusionsThese results revealed high rates of resistance of H. pylori to CLR and LVX in patients with chronic gastritis in the south east area of Vietnam. This suggests that CLR-based triple therapy should not be used for the eradication treatment of H. pylori, and LVX susceptibility testing of H. pylori strains should be performed before choosing alternative regimens.

Effects of probiotics or broccoli supplementation on Helicobacter pylori eradication with standard clarithromycin-based triple therapy.

Background/AimsThe eradication failure rate of standard triple therapy (proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has increased owing to antibiotic resistance in Korea. We assessed whether Saccharomyces boulardii probiotic or broccoli sprout extract sulforaphane supplementation could increase the H. pylori eradication rate and/or reduce antibiotic-associated adverse events.MethodsA total of 217 patients with H. pylori-positive chronic gastritis or peptic ulcer disease were recruited. Clarithromycin resistance was assessed in all patients by testing for A2142G and A2143G point mutations in H. pylori 23S rRNA using a dual-priming polymerase chain reaction (PCR) oligonucleotide. Thirty-four patients (17.3%) were clarithromycin-resistant and were excluded from the study. Finally, 183 patients with infections not resistant to clarithromycin were randomly assigned to triple therapy only (group A, n = 61), triple therapy plus probiotics (group B, n = 61), or triple therapy plus sulforaphane (group C, n = 61) groups. CYP2C19 polymorphisms were examined at position G681A of exon 5 and G636A of exon 4 by PCR with restriction fragment length polymorphism (PCR-RFLP) analysis. H. pylori eradication was assessed by 13C-urea breath test 4 weeks after treatment completion.ResultsThe eradication rates were similar among the groups both in the intention-to-treat (A = 85.2%, B = 89.6%, and C = 81.6%) and per-protocol (A = 89.2%, B = 86.8%, and C = 96.3%) analyses. The frequencies of overall adverse events in the groups also did not differ (A vs. B: p = 0.574; A vs. C: p = 1.000).ConclusionsProbiotic or sulforaphane with triple therapy for H. pylori infection neither increased the eradication rate nor reduced the occurrence of adverse events.

Epidemiological characterization, genetic alterations of Helicobacter pylori infection in chronic gastric disorder and prognostic values of heterozygosity loss in chromosome 3p.

From the literature review, there seem to be no studies conducted on infection caused by Helicobacter pylori in patients with gastric MALT lymphoma in the KSA region. The present research is an attempt to understand the prevalence of patients infected with H. pylori in the selected region and the role of allelic imbalance of chromosome 3p regions to understand the clinical manifestations and features associated with MALT lymphomagenesis. The researcher analyzed the frequency of infection in patients from the region of Saudi Arabia by examining the data collected from hospitals and biopsy tissue samples as per the recommended protocol. The endoscopic diagnosis was performed to collect biopsy samples. Histology and AP-PCR DNA fingerprinting analyses were performed from the endoscopic gastric mucosal biopsies collected from patients with associated gastric MALT lymphoma. The existence of H. pylori was examined based on the results of gastric mucosal biopsies stained with hematoxylin-eosin (H&E) and Steiner's silver stains. MALT, MALT lymphoma tissue samples and H. pylori-positive chronic gastritis were examined for LOH at chromosome 3p24 using standard procedures and techniques. The findings of the paper revealed the H. pylori was found to be positive in 17% of the cases significantly high among the age group of 31-50years. Patients with MALT, MALT lymphoma, and H. pylori-associated gastritis presented features such as lymphocyte accumulation, vacuolation, Peyer's patch appearance, and lymphatic follicles. H. pylori were found to appear as a dense colored accumulated mass in the gastric epithelial layer. The findings from AP-PCR generated DNA fingerprints revealed intense band including two prominent bands in MALT lymphoma. Among other loci, 3p24 was the only one locus that showed high percentages of LOH as reported earlier in all cancer-related cases. The findings of this research paper empower the fact that allelic imbalances play a vital role in the development of MALT lymphoma. However, future researches should be conducted to identify the chromosome regions of the AP-PCR generated DNA fingerprints of human gastric MALT lymphoma in order to confirm this proposition.

The role of transferrin receptor in the Helicobacter pylori pathogenesis; L-ferritin as a novel marker for intestinal metaplasia

Helicobacter pylori growth requirements is a prerequisite to invade gastric epithelium and the process of injury to gastric cells will eventually lead to gastric cancer. The aim of this study is to investigate the effect of iron challenge on the expression of genes involved in iron homeostasis. The presence of Phosphoglucosamine mutase (glmM), cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) genes and mRNA expression of Iron Regulatory Protein 2 (IRP2), Transferrin Receptor (TFRC) and Ferritin Light Chain (FTL) genes in samples of 28 normal gastric mucosa, 33 chronic gastritis, 29 gastritis with intestinal metaplasia, 29 intestinal type adenocarcinoma patients were examined by real-time PCR. Immunohistochemistry was used to analyze cellular localization and protein levels. In the all H. pylori positive tissues, particularly in the basal regions of foveolar cells, TFRC was overexpressed (P < 0.05), and regardless of the H. pylori infection, FTL was overexpressed in all patient, exclusively in metaplastic glandular cells (P < 0.05). Furthermore, overexpression of IRP2 was associated with H. pylori positive chronic gastritis and intestinal metaplasia (P < 0.05). Our findings confirm the role of transferrin receptor in H. pylori attachment into the gastric mucosa to capture iron. Overexpression of FTL gene in metaplastic cells could be considered as a research background to investigate the role of this gene in the differentiation of gastric cells into intestinal metaplasia. In addition, this gene could be suggested as a diagnostic marker to be included among the other markers routinely performed by clinical diagnostic laboratories.

Characterisation of point mutations in domain V of the 23S rRNA gene of clinical Helicobacter pylori strains and clarithromycin-resistant phenotype in central Vietnam.

The prevalence of clarithromycin (CLR)-resistant Helicobacter pylori is increasing worldwide, including in Vietnam. The aims of this study were to determine point mutations in the 23S rRNA domain V of clinical H. pylori strains in central Vietnam, to estimate the prevalence of phenotypic CLR resistance and to assess the association between 23S rRNA domain V genotype and CLR-resistant phenotype. Sequencing of the 23S rRNA domain V of H. pylori strains from gastric biopsy specimens was performed for 185 patients with H. pylori-positive chronic gastritis, of which 104 samples were subjected to susceptibility testing to determine CLR resistance. A total of 24 types of point mutation were detected. A2143G and A2142G mutations were observed in 40.5% and 4.3%, respectively. New point mutations were detected (C2041T, C2083T, C2191T, G2220A, G2225A, G2240A, C2273T, T2276C, G2287A, C2399T, A2445G and C2622T). 23S rRNA domain V genotypes were diversified, with combinations of two or more point mutations as well as single point mutations. The rate of phenotypic CLR resistance was 53.8%, increasing from 40.4% in 2012-2014 to 70.2% in 2015-2017 (P=0.0045). A2143G and A2142G accounted for 89.3% of phenotypically CLR-resistant H. pylori isolates. A diversity of point mutations in the 23S rRNA domain V was observed in clinical H. pylori isolates. The rate of phenotypically CLR-resistant H. pylori is significantly increasing in central Vietnam. Further research is necessary to clarify the role of the combination of 23S rRNA domain V mutations in the molecular mechanism of CLR resistance.

Helicobacter pylori 23S rRNA gene mutations associated with clarithromycin resistance in chronic gastritis in Vietnam.

Data about the prevalence of the A2142C, A2142G, and A2143G mutations in 23S rRNA gene is still limited. The aim of this study was to determine the prevalence of these mutations in 23S rRNA gene of H. pylori vietnamese strains. One hundred and sixty-nine patients with H. pylori-positive chronic gastritis were examined. H. pylori was detected by rapid urease test and Polymerase chain reaction (PCR). Total DNA was extracted from gastric biopsy specimens. A2142C, A2142G, and A2143G mutations were detected by DNA sequencing and PCR-restriction fragment length polymorphism (PCR-RFLP). A2143G mutation was detected in 36.1% of samples, A2142G mutation in 3.6%, while A2142C mutation was not found in any case. The mixture of wild-type and mutation strains was found in 50% of specimens with A2142G, in 23% of specimens with A2143G mutation. There was no association of 23S rRNA gene point mutations with gender or age. However, an association between the heterogeneity of mutation and age was evidenced, with mean age of the group of pure A2143G higher than the group of wild-type/A2143G mixture, and rate of the wild-type/A2143G mixture higher in patients under 40 years of age. A2143G mutation was prominent, while A2142C mutation was not found in the 23S rRNA gene. PCR-RFLP has revealed a reliable assay allowing a rapid and cost-effective detection of clarithromycin-resistant strains. This is useful in countries as Vietnam with high prevalence of clarithromycin-resistance before choosing optimal therapy for H. pylori eradication.

Clarithromycin resistance and female gender affect Helicobacter pylori eradication failure in chronic gastritis.

Background/AimsThe eradication rate of the first-line triple therapy (a proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has gradually decreased in Korea. We evaluated whether clinical parameters, clarithromycin resistance, and CYP2C19 genotype can affect the eradication failure.MethodsA total of 203 patients with H. pylori-positive chronic gastritis were consecutively enrolled. They received clarithromycin-based triple therapy for 7 days. A clarithromycin resistance test was performed by detection of A2142G and A2143G point mutations in H. pylori 23S rRNA. The CYP2C19 genotype was examined for polymorphism G681A of exon 5 and G636A of exon 4 by polymerase chain reaction with restriction fragment length polymorphism. Eradication was assessed by a 13C-urea breath test 4 weeks after treatment.ResultsOf 203 patients, 190 completed the study. The eradication rate was 64.0% according to intention-to-treat analysis and 68.4% by per-protocol analysis. CYP2C19 genotypes were identified as follows: 75 poor metabolizers, 75 intermediate metabolizers, and 40 rapid metabolizers. Nonetheless, this polymorphism was not significantly associated with eradication failure (p = 0.682). Clarithromycin resistance was detected in 33/190 patients (17.4%), and their eradication rate was zero. Clarithromycin resistance (odds ratio [OR], 19.13; 95% confidence interval [CI], 9.35 to 35.09) and female gender (OR, 1.73; 95% CI, 1.15 to 4.25) were significantly associated with eradication failure. The other clinical parameters such as age, cigarette smoking, alcohol intake, the body mass index, hypertension, and diabetes were not significantly associated with eradication.ConclusionsClarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.

STUDY ON POINT MUTATIONS AT POSITIONS 2132 AND 2143 IN 23S RRNA GENE OF HELICOBACTER PYLORI AMONG PATIENTS WITH CHRONIC GASTRITIS

Background: Clarithromycin resistance in Helicobacter pylori has been found to be associated with point mutations at positions 2142 and 2143 in 23SrRNA gene. The aims of this study were: (1) to determine the rates of point mutations A2143G, A2142G and A2142C in 23SrRNA gene of H. pylori among patients with chronic gastritis by PCR-RFLP technique; and (2) to assessthe association between these mutations and some clinical, endoscopic and histopathological characteristics of chronic gastritis. Patients and methods: two hundreds and twenty six patients with H. pylori-positive chronic gastritis were determined A2143G, A2142G and A2142C mutations by PCR-RFLP technique with DNA extracted from endoscopic biopsy specimens of gastric mucosa. Results: The rate of point mutations at positions 2142 and 2143 in 23S rRNA gene of H. pylori was 35.4% in total, the A2143G and A2142G mutationsaccounted for 92.5% and 7.5% of all point mutations, respectively. No A2142C mutation was found. These mutations were not associated with age, gender,distribution of gastritis, and the presence of atrophic gastritis. The rate of A2143G mutation in groups with and without a history of clarithromycin treatment were 44.9% and 24.8%, respectively (p = 0,0065). The A2142G mutation was associated with intestinal metaplasia and/or dysplasia. Conclusion: The point mutations at positions 2142 and 2143 in 23S rRNA gene were found at a high rate in H. pylori strains amongpatients with chronic gastritis, with the absolute predominance of A2143G mutation. The A2143G mutation was associated with a history of clarithromycin treatment. Key words: 23S rRNA gene, Helicobacter pylori, A2143G, A2142G, A2142C mutation, clarithromycin resistance, chronic gastritis.

Inverse Association Between Helicobacter pylori Gastritis and Microscopic Colitis.

Inflammatory bowel disease is known to be inversely associated with Helicobacter pylori infection of the upper gastrointestinal tract. We hypothesized that a similar inverse association also applied to microscopic colitis. The associations between microscopic colitis and presence of H. pylori-positive chronic active gastritis (CAG), H. pylori-negative CAG, intestinal metaplasia, or gastric atrophy were expressed as odds ratios with their 95% confidence intervals. Multivariate logistic regression analyses were used to adjust these associations for sex, age, percentage residents per ZIP code with white, black, Hispanic, or Asian ethnicity, percentage with college education, average housing values, annual income, and population size of individual ZIP codes. H. pylori-positive CAG was less common among patients with than without microscopic colitis (odds ratio = 0.61; 95% confidence interval, 0.52-0.70). Intestinal metaplasia also occurred less frequently among patients with than without microscopic colitis (0.75, 0.65-0.86). These inverse associations remained unaffected by adjustments for parameters of ethnicity and socioeconomic status. In contradistinction with H. pylori-positive CAG, H. pylori-negative CAG was more common in patients with than without microscopic colitis (1.54, 1.17-1.97). H. pylori infection and microscopic colitis are inversely associated. This observation is consistent with similar inverse associations found between H. pylori and inflammatory bowel disease. These relationships may provide clues about the yet unknown etiology of microscopic colitis.

Clinical observation on ilaprazole containing ten-day standard quadruple therapy and sequential therapy in the treatment of two hundred cases of chronic gastritis with Helicobacter pylori infection

Objective To investigate the clinical efficacy of ilaprazole and bismuth combined ten-day standard quadruple therapy and sequential therapy in the treatment of patients with Helicobacter pylori （H .pylori）infected chronic gastritis.Methods A total of 200 patients with H .pylori-positive chronic gastritis diagnosed by gastroendoscopy examination and rapid urease test （RUT）were randomly divided into standard quadruple therapy group and sequential therapy group,100 cases in each group.One group received ilaprazole,bismuth,amoxicillin-clavulanatepotassium and ofloxacin 10-day standard quadruple therapy, and the other group received ilaprazole, amoxicillin-clavulanatepotassium, ofloxacin and furazolidone 10-day sequential therapy.In four to six weeks after the therapy,the condition of H .pylori eradication was detected by a 14 C-urea breath test.The improvement of clinical symptoms and adverse effects were also observed. Normal distributed and variance homogenized measurement data were compared by t test,while unordered categorical data were analyzed by chi-square test and the exact probability method,and categorical data were compared by two independent sample rank sum test.Results The per-protocol analysis values of H .pylori eradication rates of the standard quadruple therapy group and the sequential therapy group were 88.54%（85/96）and 87.23%（82/94）,respectively,while the intention-to-treat analysis values were 85 .00%（85/100）and 82.00%（82/100 ）,respectively.The effective rates of symptomatic relief of upper abdominal pain,acid regurgitation,heart burning in the standard quadruple therapy group and the sequential therapy group were 95 .83%（92/96）and 95 .74%（90/94）,respectively. The incidence of adverse effects which weve very mild was 6.25 % （6/96 ） and 7.44% （7/94 ）, respectively.There was no statistically significant difference in the above three factors between the two groups （all P 〉0.05）.Conclusions Ilaprazole and bismuth combined 10-day standard quadruple therapy and sequential therapy in the treatment of patients with H .pylori positive chronic gastritis both achieves high rates of H .pylori eradication and symptom relief with mild adverse effects. Key words: Ilaprazole; Standard quadruple regimen; Sequential regimen; Helicobacter pylori; Eradication

Helicobacter pylori infection and administration of non-steroidal anti-inflammatory drugs down-regulate the expression of gastrokine-1 in gastric mucosa

Gastrokine-1 is a novel protein that plays an important role in the maintenance of the integrity of the gastric mucosa. However, whether Helicobacter pylori infection and non-steroidal anti-inflammatory drugs, which are known to cause gastric mucosal injuries, affect gastrokine-1 expression in the gastric mucosa is unknown. The aim of the present study was to determine gastric mucosal expression of gastrokine-1 in patients with Helicobacter pylori infection or long-term non-steroidal anti-inflammatory drug administration. A total of 40 patients with functional dyspepsia (20 with Helicobacter pylori-negative chronic gastritis, and 20 with Helicobacter pylori-positive chronic gastritis), and 37 Helicobacter pylori-negative long-term non-steroidal anti-inflammatory drug users (26 with aspirin, 11 with selective cyclooxygenase-2 inhibitors) were selected. In addition, 20 Helicobacter pylori-negative healthy volunteers were recruited as controls. All subjects underwent endoscopies with biopsies taken from the antrum and the sites with lesions. Gastric mucosal changes were detected endoscopically and histologically, and gastrokine-1 protein expression in the antral mucosa was analyzed by immunohistochemistry. Expression of gastrokine-1 protein was decreased in Helicobacter pylori-positive chronic gastritis compared with Helicobacter pylori-negative subjects and the healthy controls. Similarly, gastrokine-1 expression in non-steroidal anti-inflammatory drug users was also decreased, compared with the healthy controls, but there was no significant difference in gastrokine-1 expression between the aspirin group and selective cyclooxygenase-2 inhibitor group. Moreover, gastrokine-1 expression levels tended to be associated with the severity of chronic gastritis. Both Helicobacter pylori infection and long-term non-steroidal anti-inflammatory drug administration downregulate gastrokine-1 expression in the gastric mucosa, which may contribute to the gastric mucosal injuries induced by these two factors.

Multiple‐antibiotic‐resistant Helicobacter pylori infection eradicated with a tailor‐made quadruple therapy

In 2008, a 44-year-old woman with mild epigastralgia diagnosed as having Helicobacter pylori-positive chronic gastritis without peptic ulcer underwent eradication therapy with lansoprazole (LPZ), amoxicillin (AMPC) and clarithromycin (CAM) for 7 days, but it failed, so treatment with rabeprazole, AMPC, and metronidazole (MNZ) for another 7 days was given, but it also failed. She was then prescribed a modified, 14-day sequential therapy of LPZ and AMPC with an increased dose of CAM followed by MNZ supplement, but the infection was still not eradicated. The H. pylori was cultured and examined for antibiotic susceptibility with the agar dilution method and was found to be resistant to CAM, MNZ, and levofloxacin, and non-sensitive to AMPC, namely multiple-antibiotic-resistant, although sensitive to minocycline. The CYP2C19 genotype of the patient was an extensive metabolizer (G681A: G/A, G636A: G/G). In 2010, she gave informed consent for a 14-day, tailor-made, modified classical (or modified high-dose PPI + AMPC) quadruple therapy comprising 30 mg LPZ, 500 mg AMPC and 500 mg bismuth subnitrate, qid, and 100 mg minocycline, bid. Two months later, her urea breath test was negative. Histology and bacterial culture were still negative 1 year after the therapy. She did not have any adverse events during or after the novel therapy, nor did she feel any further epigastralgia.

Helicobacter pylori induces promoter hypermethylation and downregulates gene expression of IRX1 transcription factor on human gastric mucosa

Gene silence of IRX1 tumor suppressor by promoter CpG methylation combined with loss of heterozygosity (LOH) has been identified in human gastric cancer. This study investigated the association between methylation of IRX1 and Helicobacter pylori infection in gastric mucosa tissues and cell line. IRX1 methylation was studied by methylation specific polymerase chain reaction (MSP) and bisulfate sequencing polymerase chain reaction (BSP) methods in gastric mucosa tissues from H. pylori-positive chronic gastritis patients or H. pylori-negative chronic gastritis patients. Promoter activity, methylation status and gene expressing level of IRX1 were evaluated by persistent infecting H. pylori on human gastric cells GES-1 in vitro. Electron microscopy was used to observe the effect of H. pylori infection on GES-1 gastric mucosa cells. The methylation level of IRX1 promoter in H. pylori positive chronic gastritis and H. pylori negative chronic gastritis was 55.30%±13.17 versus 5.20%±6.31, respectively (P<0.01). H. pylori infection stimulated increased microvillus, and mucous secretion on GES-1 cells. Infection of H. pylori induced IRX1 promoter methylation and downregulation of the promoter activity as well as gene expression significantly. This study firstly demonstrated that H. pylori infection contributes to IRX1 promoter methylation on gastric mucosa.

Capsaicin-sensitive afferentation represents an indifferent defensive pathway from eradication in patients withH. pylorigastritis

To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H. pylori) positive chronic gastritis before and after eradication. Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H. pylori positive chronic gastritis (n = 18) before and after eradication. Traditional gastric mucosal histology (and Warthin-Starry silver impregnation) and special histochemical examinations were carried out. Immunohistochemistry for capsaicin receptor (TRVP1), calcitonin gene-related peptide (CGRP) and substance P (SP) were carried out by the labeled polymer immunohistological method (Lab Vision Co., USA) using polyclonal rabbit and rat monoclonal antibodies (Abcam Ltd., UK). Eradication treatment was successful in 16 patients (89%). Seven patients (7/18, 39%) remained with moderate complaints, meanwhile 11 patients (11/28, 61%) had no complaints. At histological evaluation, normal gastric mucosa was detected in 4 patients after eradication treatment (4/18, 22%), and moderate chronic gastritis could be seen in 14 (14/18, 78%) patients. Positive immuno-staining for capsaicin receptor was seen in 35% (7/20) of controls, 89% (16/18, P < 0.001) in patients before and 72% (13/18, P < 0.03) after eradication. CGRP was positive in 40% (8/20) of controls, and in 100% (18/18, P < 0.001) of patients before and in 100% (18/18, P < 0.001) after eradication. The immune-staining of gastric mucosa for substance-P was positive in 25% (5/20) of healthy controls, and in 5.5% (3/18, P > 0.05) of patients before and in 0% of patients (0/18, P > 0.05) after H. pylori eradication. Distibution of TRVP1 and CGRP is altered during the development of H. pylori positive chronic gastritis. The immune-staining for TRVP1, CGRP and SP rwemained unchanged before and after H. pylori eradication treatment. The capsaicin-sensitive afferentation is an independent from the eradication treatment. The 6 wk time period might not be enough time for the restituion of chronic H. pylori positive chronic gastritis. The H. pylori infection might not represent the main pathological factor in the development of chronic gastritis.

Reduced secretion of epidermal growth factor in duodenal ulcer patients with Helicobacter pylori infection.

To investigate the concentration changes of epidermal growth factor (EGF) in duodenal ulcer patients with Helicobacter pylori (H. pylori) infection. Immunoreactive concentration of somatostatin, gastrin and epidermal growth factor of gastric and saliva juice in healthy volunteers, and chronic gastritis and duodenal ulcer patients with H. pylori infection were measured by radioimmunoassay. Gastrin concentration of gastric juice in H. pylori-positive chronic gastritis (P > 0.05) and duodenal ulcer patients (P < 0.01) was higher than that of healthy volunteers (P < 0.05), whereas som atostatin concentration of gastric juice in chronic gastritis (P < 0.05) and duodenal ulcer patients (P < 0.01) was lower than that in healthy volunteers. Furthermore, EGF levels of gastric and saliva juice in duodenal ulcer patients with H. pylori infection (n = 10, 272.0 ng/L ± 96.3 ng/L and 8.3 ng/L ± 2.4 ng/L, respectively) were significantly lower than that in healthy volunteers (n = 12, 405.6 ng/L ± 35.6 ng/mL and 22.0 ng/L ± 17.0 ng/L, respectively) and in H. pylori-positive chronic gastritis patients (n = 25, 423.0 ng/L ± 104.0 ng/L and 22.0 ng/L ± 11.1 ng/L, respectively (P < 0.05). A lower secretion of EGF may be a causative factor in the pathogenesis of H. pylori-positive duodenal ulcer.

Influence of CYP2C19 functional polymorphism on Helicobacter pylori eradication

Proton pump inhibitors are mainly metabolized by cytochrome P450 2C19 in the liver. Recently, some studies have shown that the acid suppressing effect of proton pump inhibitors are influenced by a functional polymorphism of cytochrome P450 2C19. The aim of the present study was to investigate the effect of cytochrome P450 2C19 polymorphism on Helicobacter pylori eradication in patients who received proton pump inhibitors based triple therapy. We determined the incidence of cytochrome P450 2C19 genotypes and the effect of cytochrome P450 2C19 genotypes on Helicobacter pylori eradication rates in 105 patients with Helicobacter pylori-positive chronic gastritis. Upper endoscopic procedure and gastric biopsies were performed in all patients. Helicobacter pylori was demonstrated histologically. Lansoprazole, amoxicillin and clarithromycin twice a day for 14 days were prescribed for those found to be infected with Helicobacter pylori. More than one month after the medication, a 13C urea breath test was conducted to examine the success or failure of the eradication treatment. Cytochrome P450 2C19 polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. The genotypes of cytochrome P450 2C19 were classified into the three groups, as rapid extensive metabolizer, intermediate metabolizer and poor metabolizer. In our patient population, the frequencies of rapid extensive metabolizer, intermediate metabolizer and poor metabolizer were 72%, 23% and 5%, respectively. The eradication rate was 70.0% for rapid extensive metabolizer, 92% for intermediate metabolizer and 80% for poor metabolizer. The eradication rate was highest in intermediate metabolizer patients. The present study confirmed the low eradication rate for rapid extensive metabolizer. Our findings provide evidence that the cytochrome P450 2C19 genotype is useful to predict the success of treatment. For the rapid extensive metabolizer group, alternative regimens can be tried to increase the Helicobacter pylori eradication rates.