Lifestyle and dietary factors associated with serologically detected gastric atrophy in a Caucasian population in the GISTAR study.

OBJECTIVE: To identify dietary and lifestyle factors associated with decreased pepsinogen levels indicative of gastric atrophy. METHODS: Participants aged 40 to 64 from the "Multicentric randomized study of H. pylori eradication and pepsinogen testing for prevention of gastric cancer mortality (GISTAR study)" in Latvia tested for serum pepsinogen, as well as for Helicobacter pylori infection by 13 C-urea breath test or serology were included. Data on sex, age, education, employment, diet, smoking, alcohol and proton pump inhibitor use were obtained by survey and compared for participants with and without serologically detected gastric atrophy defined as pepsinogen I/pepsinogen II ≤ 2 and pepsinogen I ≤ 30 ng/mL. RESULTS: Of 3001 participants (median age 53, interquartile range, 11.0, 36.9% male) 52.8% had H. pylori and 7.7% had serologically detected gastric atrophy. In multivariate analysis, increasing age, consumption of alcohol, coffee, and onions were positively, while H. pylori , former smoking, pickled product and proton pump inhibitor use were inversely associated with gastric atrophy. Pepsinogen values were higher in smokers and those with H. pylori . Pepsinogen ratio was lower in those with H. pylori . When stratifying by H. pylori presence, significantly higher pepsinogen levels remained for smokers without H. pylori . CONCLUSION: Several dietary factors and smoking were associated with serologically detected gastric atrophy. Pepsinogen levels differed by smoking and H. pylori status, which may affect the serologic detection of gastric atrophy. There seems to be a complicated interaction between multiple factors. A prospective study including atrophy determined by both serology and histology is necessary.

Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oil (EO) is the main extract of patchouli and tangerine peel with antiinflammatory, antiulcer, and other functions. However, the efficacy and mechanism of the combination of EO from patchouli and tangerine peel against gastric ulcer (GU) are unclear. AIM OF THE STUDY: This study aims to reveal the protective effect of the combination of EO from patchouli and tangerine peel against GU in rats, as well as explore the optimal ratio and possible mechanism of EO in GU treatment. MATERIALS AND METHODS: The GU model is executed via water immersion and restraint stress. The repair effect of EO in different proportions on gastric mucosa injury and the effects on serum gastrin (GAS), pepsinogen C (PGC), prostaglandin E2 (PGE2), and 5-hydroxytryptamine in GU rats were observed. The optimal ratio obtained was used in the second part to set different dose groups for further experiment. The effects of the different EO doses on gastric mucosal ulcer formation and gastric acid secretion were evaluated. The morphology of chief and parietal cells were observed via transmission electron microscopy. The contents of GAS, PGC, substance P (SP), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), cholecystokinin (CCK), PGE2, and motilin (MTL) in serum in different groups were detected via enzyme-linked immunosorbent assay. Expressions of epidermal growth factor (EGF) and trefoil factor 2 (TFF2) protein in gastric tissues were detected via immunohistochemistry, and expressions of c-Jun N-terminal kinase (JNK), P53, Bcl-2-associated X protein (Bax), and Caspase-3 protein in gastric tissues were detected via western blotting. RESULTS: The EO from patchouli and tangerine peel at 1:2 ratio of compatibility significantly improved gastric mucosal injury, decreased serum GAS and PGC contents, and increased the PGE2 level in serum (p < 0.05). The mixture of EO from patchouli and tangerine peel (Mix-EO) can reduce the formation of gastric mucosal ulcers, reduce gastric mucosal injury, improve the expansion of the endoplasmic reticulum of the chief cells, repair mitochondrial damage, and inhibit the secretion of gastric acid by parietal cells. Mix-EO at 300 mg/kg can reduce the expression of serum GAS, PGC, SP, CCK, and cAMP/cGMP (p < 0.05 or 0.01); increase the expression of EGF and TFF2 protein in gastric tissues (p < 0.01); and inhibit the expression of JNK, p53, Bax, and Caspase-3 proteins (p < 0.01). CONCLUSION: The combination of EO from patchouli and tangerine peel can repair the gastric mucosal damage in GU rats and prevent the occurrence of ulcers by inhibiting the secretion of gastric acid, enhancing the defensive ability of gastric mucosa, and suppressing the apoptosis of gastric epithelial cells. Moreover, the optimal compatible ratio of patchouli and tangerine peel is 1:2.

Short term micronutrient-antioxidant supplementation has no impact on a serological marker of gastric atrophy in Zambian adults: retrospective analysis of a randomised controlled trial.

BACKGROUND: Gastric cancer is a major contributor to cancer deaths in Zambia but, as elsewhere, no preventive strategies have been identified. We set out to investigate the possibility of reducing gastric atrophy, a premalignant lesion, using micronutrient-antioxidant supplementation. METHODS: We analysed 215 archival samples from a randomised controlled trial of micronutrient-antioxidant supplementation carried out from 2003 to 2006. Participants were randomised to receive either the supplement or placebo and had been taking the allocated intervention for a mean of 18 (range 14-27) months when the samples used in this study were taken. We used low pepsinogen 1 to 2 (PEP1:2) ratio as a surrogate marker of gastric atrophy. A PEP 1:2 ratio of less than three was considered low. HIV serology, age, nutritional status, smoking, alcohol intake and gastric pH were also analysed. Ethical approval was obtained from the University of Zambia Biomedical Research Ethics Committee (011-04-12). The randomized trial was registered (ISRCTN31173864). RESULTS: The overall prevalence of low PEP 1:2 ratio was 15/215 (7%) and it did not differ between the placebo (8/103, 7.8%) and micronutrient groups (7/112, 6.3%; HR 1.24; 95% CI 0.47-3.3; P = 0.79). The presence of low PEP 1:2 ratio was not influenced by HIV infection (HR 1.07; 95% CI 0.37-3.2; P =0.89) or nutritional status but it inversely correlated with gastric pH (Spearman's rho = -0.34; P = 0.0001). Age above 40 years was associated with atrophy, but neither alcohol nor smoking had any influence. CONCLUSION: Short term micronutrient supplementation does not have any impact on PEP 1:2 ratio, a serological marker of gastric atrophy. PEP 1:2 ratio inversely correlates with gastric pH.

Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy.

AIM: The association of motilin, ghrelin, leptin, gastrin, pepsinogen (PG) I and II with cancer chemotherapy-associated dyspepsia syndrome (CADS) was investigated in 35 patients with breast cancer receiving first cycle of 5-fluorouracil, cyclophosphamide, epirubicin (FEC60) chemotherapy. PATIENTS AND METHODS: The onset of dyspeptic symptoms on days 3 and 10 after chemotherapy identified patients with and without CADS. Gastrointestinal symptoms were scored with the Gastrointestinal Symptom Scoring Rate (GSRS) questionnaire. Gastrointestinal peptides were evaluated by enzyme-linked immunosorbent assay. RESULTS: Twenty-one patients (60%) had CADS. The area under the curve (AUC) of ghrelin was higher, whereas that of PGI, PGII and motilin were lower in patients with CADS compared to those without. In patients with CADS, the AUC of PGI and PGII negatively correlated with the GSRS indigestion cluster. CONCLUSION: Impairment of gastrointestinal motility suggested by low motilin concentrations and mucosal damage mirrored by an increase of ghrelin seem to be involved in the onset of CADS in patients during chemotherapy for breast cancer.

No association of coffee consumption with gastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive reflux disease: a cross-sectional study of 8,013 healthy subjects in Japan.

Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.

Sitafloxacin resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a third-line regimen in Japan.

The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of ≤1 µg/mL against all 100 H. pylori isolates, and the MIC(90) (MIC for 90% of the organisms) of STX was 5 log(2) dilutions lower than that of levofloxacin (LVX). The MIC(50) (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 µg/mL and was significantly lower than that of LVX (8 µg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy [rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100mg b.i.d. for 7 days]. The eradication rate was 75% using intention-to-treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy.

Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis.

OBJECTIVES: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). METHODS: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. RESULTS: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. CONCLUSIONS: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

The effect of 5-year vitamin C supplementation on serum pepsinogen level and Helicobacter pylori infection.

We conducted a population-based, double-blind, randomized controlled trial to examine the effect of vitamin C supplementation on serum pepsinogen (PG) level, Helicobacter pylori (H. pylori ) infection, and cytotoxin-associated gene A (Cag A) status. Subjects aged 40 to 69 years living in one village in Akita prefecture, a high-risk area for gastric cancer in Japan, were recruited through annual health check-up programs. Among 635 subjects diagnosed as having chronic gastritis on the basis of serum PG levels, after excluding ineligible cases, 439 subjects were assigned to one of four groups using a 2 x 2 factorial design (0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C). However, based on the results from two beta-carotene trials in the United States, we discontinued beta-carotene (vitamin C supplementation was continued). Finally, 120 subjects in the low-dose group (vitamin C 50 mg), and 124 subjects in the high-dose group (vitamin C 500 mg) completed the 5-year supplementation. The difference in the change of PGI/II ratio between baseline and after 5-year follow up was statistically significant between the intervention groups among those who completed the supplementation: - 0.25 for the low-dose group and - 0.13 for the high-dose group (P = 0.046). To conclude, vitamin C supplementation may protect against progression of gastric mucosal atrophy.

Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first-line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery.

OBJECTIVES: Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin-deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency. DESIGN: Clinical study of consecutive patients. SETTING: The catchment area of Sahlgrenska University Hospital, Göteborg. SUBJECTS: A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery. INTERVENTIONS: Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin. MAIN OUTCOME MEASURES: Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin. RESULTS: About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests. CONCLUSIONS: Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.