Chise Kodaira

Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy.

Backgrounds and aims:  Eradication rates of Helicobacter pylori by a proton pump inhibitor‐based triple therapy depend on CYP2C19 genotype status. We investigated whether gastric acid inhibition during an eradication therapy would influence the eradication rates attained by the triple therapy.

Treatment strategy to eradicate Helicobacter pylori infection: impact of pharmacogenomics-based acid inhibition regimen and alternative antibiotics

The eradication rates of Helicobacter pylori by the triple therapy consisting of a proton pump inhibitor (PPI) and two antimicrobial agents are mainly influenced by bacterial susceptibility to antimicrobial agents and magnitude of acid inhibition during the treatment with a PPI. Acid inhibition during the treatment is affected by the dosing schemes of acid inhibitory drugs (i.e., PPI), genotypes of drug-metabolizing enzymes (i.e., CYP450 2C19), drug transporters (i.e., multi-drug resistant transporter-1) and inflammatory cytokines (i.e., IL-1β). Modification of dosing schedules of a PPI, such as frequent PPI dosing and concomitant dosing with a histamine 2-receptor antagonist, could overcome these genetics-related differences in therapeutic effectiveness. For attaining higher eradication rates, the tailored regimen based on the relevant pharmacogenomics is preferable.

Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori

Polymorphism in MDR1 is associated with variation in the plasma level of a proton pump inhibitor.

Resistance of Helicobacter pylori to quinolones and clarithromycin assessed by genetic testing in Japan

Background and Aim:  As bacterial resistance to clarithromycin limits the efficacy of clarithromycin‐based regimens for Helicobacter pylori infection, attention has turned to quinolone‐based rescue therapies. Resistance of H. pylori to both clarithromycin and quinolone can be predicted by genetic testing. Here, we used this approach to evaluate the prevalence of clarithromycin‐ and quinolone‐resistant strains of H. pylori in Japan.

Sitafloxacin-based third-line rescue regimens for Helicobacter pylori infection in Japan.

Quinolone‐based regimens have been used as the rescue for eradication of Helicobacter pylori. Sitafloxacin is known to have low minimum inhibitory concentration for H. pylori. Here, we compared two sitafloxacin‐based eradication regimens as rescue for the eradication of H. pylori.

Rabeprazole 10 mg q.d.s. decreases 24‐h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype

Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid‐related diseases.

[13C]-pantoprazole breath test to predict CYP2C19 phenotype and efficacy of a proton pump inhibitor, lansoprazole.

Background  13CO2 is produced on metabolism of 13C‐labelled‐pantoprazole ([13C]‐pantoprazole) by CYP2C19.

Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan

BackgroundMatrix metalloproteinases (MMPs) are a family of enzymes that degrade most macromolecules making up the extracellular matrix. MMPs are involved in not only the gastric mucosal inflammatory response but also the pathogenesis of Helicobacter pylori-associated diseases. In the renin-angiotensin system, chymase (CMA) is related to gastric carcinogenesis and angiogenesis in H. pylori-infected patients. We aimed to clarify the association of MMP-7-181 and CMA/B polymorphisms with susceptibility to gastric cancer and cancer progression in H. pylori-infected patients.MethodsWe assessed the MMP-7-181 and CMA/B polymorphisms in H. pylori-positive patients with gastric cancer (n = 160), gastric ulcer (n = 157), duodenal ulcer (n = 121), and H. pylori-positive gastritis alone as controls (n = 156).ResultsFor gastric cancer risk, the age-and sex-adjusted odds ratio (OR) of the MMP-7-181 G allele carrier relative to the A/A genotype was significantly increased [OR, 2.32; 95% confidence interval (CI), 1.24–4.35], especially in patients with noncardia cancer (OR, 2.31; 95% CI, 1.22–4.36) and those with clinical stage III or IV cancer (OR, 3.66; 95% CI, 1.54–8.73). Carriage of the CMA/B A allele was significantly associated with gastric cancer development (OR, 1.73; 95% CI, 1.10–2.71). Simultaneous carriage of both the MMP-7-181 G allele and the CMA/B A allele dramatically increased the gastric cancer risk (OR, 8.18; 95% CI, 2.79–23.93).ConclusionsIn Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. MMP-7-181 and CMA/B genotyping tests might be useful tools for screening for individuals with higher gastric cancer risk.

Esophageal mucosal injury with low-dose aspirin and its prevention by rabeprazole.

Aspirin is used widely as an antithrombotic drug for the prevention of cardiovascular and cerebrovascular events. Although aspirin increases the risk for gastrointestinal mucosal injury, the effect on esophageal mucosa is unclear. This study investigates whether aspirin induces esophageal mucosal injury and whether a proton‐pump inhibitor can prevent such injury in relation to CYP2C19 genotypes. Fifteen healthy Japanese volunteers are dosed for 7 days in a 5‐way randomly crossover trial: placebo, aspirin 100 mg, rabeprazole 10 mg, and aspirin 100 mg plus rabeprazole 10 mg either once daily or 4 times per day. All subjects undergo endoscopy and 24‐hour intragastric pH monitoring on day 7. With the aspirin regimen, esophageal mucosal disorders occur in 7 patients (46.7%) (5, grade M; 2, grade A). The median 24‐hour pH differs significantly among subjects who develop grade M or A gastroesophageal reflux disease and those who do not develop gastroesophageal reflux disease; the median pH in grade A gastroesophageal reflux disease is significantly lower (1.5 [range, 1.1–1.9]) than that in patients without gastroesophageal reflux disease (5.6 [range, 0.8–8.4], P = .04). Rabeprazole significantly inhibits acid secretion irrespective of CYP2C19 genotypes and decreases the incidence of aspirin‐related esophageal injury and symptoms according to increasing pH value. Aspirin induces esophageal mucosal injury in an acid‐dependent manner. Concomitant proton‐pump inhibitor therapy may prevent advanced effects of low‐dose aspirin.

Modified allele-specific primer–polymerase chain reaction method for analysis of susceptibility of Helicobacter pylori strains to clarithromycin

Background and Aim:  Most clarithromycin‐resistant strains of Helicobacter pylori have a mutation from adenine (A) to guanine (G) at position 2142 or 2143 of the 23S rRNA gene. Our aim in this study was to develop a polymerase chain reaction (PCR)‐based assay that could determine these mutations in a single reaction tube.