Comparison of acid inhibition with standard dosages of proton pump inhibitors in relation to CYP2C19 genotype in Japanese.

Introduction: The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power.

Methods: Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers.

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

Backgrounds: 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.

Luminescent material based on the [Eu(TTA)3(H2O)2] complex incorporated into modified silica particles for biological applications.

Amino-functionalized luminescent silica particles were investigated for use in immunoassays. The particles were prepared by the Stöber method where the [Eu(TTA)3(H2O)2] complex (TTA: 3-thenoyltrifluoroacetonate) was incorporated into silica particles during the hydrolysis and condensation of TEOS: tetraethylorthosilicate. Then, the amino groups were introduced in the particle surface using APTS: 3-aminopropyltriethoxisilane.

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.

Background: Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h.

Ability of rabeprazole to prevent gastric mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19 genotype.

Background & Aims: Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage.

Methods: Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days.

Impact of acid inhibition on esophageal mucosal injury induced by low-dose aspirin.

Background And Aim: Aspirin enjoys widespread use as an antithrombotic drug, but such ubiquity also increases the risk of gastrointestinal mucosal injury. Recent studies have shown that aspirin can also induce esophageal mucosal injury. We resolved to determine the intragastric pH value necessary to prevent aspirin-induced esophageal mucosal injury.

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.

Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy.

Aim: To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment.

Methods: We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ: 10 mg or 20 mg od, 20 mg bid, or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14.

Influence of different proton pump inhibitors on activity of cytochrome P450 assessed by [(13)C]-aminopyrine breath test.

Aminopyrine is metabolized by cytochrome P450 (CYP) in the liver. The investigators evaluated influences of different PPIs on CYP activity as assessed by the [(13)C]-aminopyrine breath test ([(13)C]-ABT). Subjects were 15 healthy volunteers with different CYP2C19 status (5 rapid metabolizers [RMs], 5 intermediate metabolizers [IMs], and 5 poor metabolizers [PMs]).

The dual therapy with 4 times daily dosing of rabeprazole and amoxicillin as the 3rd rescue regimen for eradication of H. pylori.

Backgrounds/aims: Most of patients who are refractory to usual standard eradication therapies for H. pylori infection have rapid metabolizer genotype of CYP2C19 and are infected with resistant strains to several antimicrobial agents. However, most of H.

[A case of eosinophilic gastroenteritis accompanied with fasciitis of the extremities].

We encountered a very rare case of eosinophilic gastroenteritis accompanied with fasciitis of the extremities. The patient was a 28-year-old woman with epigastralgia, eosinophilia plus leukocytosis, massive pleural effusion and ascites, and thickening of the walls of the intestine. Increase of the eosinophilic fraction in her ascites led to a diagnosis of eosinophilic gastroenteritis.

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen.

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.

Prospective study of daily low-dose nedaplatin and continuous 5-fluorouracil infusion combined with radiation for the treatment of esophageal squamous cell carcinoma.

Background: Protracted low-dose concurrent chemotherapy combined with radiation has been proposed for enhanced treatment results for esophageal cancer. We evaluated the efficacy and the toxicity of a novel regimen of daily low-dose nedaplatin (cis-diammine-glycolatoplatinum) and continuous infusion of 5-fluorouracil (5-FU) with radiation in patients with esophageal squamous cell carcinoma.

Methods: Between January 2003 and June 2008, 33 patients with clinical stage I to IVB esophageal squamous cell carcinoma were enrolled.

Relationship between low-dose aspirin-induced gastric mucosal injury and intragastric pH in healthy volunteers.

Background And Aims: Gastric acid plays an important role in the pathogenesis of gastric mucosal lesions. We investigated whether aspirin-induced gastric mucosal injury might have any association with the intragastric pH.

Materials And Methods: Fifteen healthy, Helicobacter pylori-negative volunteers randomly underwent the four different 7-day regimens: (1) aspirin 100 mg, (2) rabeprazole 10 mg, (3) aspirin 100 mg + rabeprazole 10 mg, and (4) aspirin 100 mg + rabeprazole 40 mg.

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

Background: (13)CO(2) is produced on metabolism of (13)C-labelled-pantoprazole ([(13)C]-pantoprazole) by CYP2C19.

Aim: To investigate whether the [(13)C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese.

Methods: We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping.

A case of small bowel adenocarcinoma in a patient with Crohn's disease detected by PET/CT and double-balloon enteroscopy.

Small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) is quite rare, difficult to diagnose without surgery, and has a poor prognosis. Here, we report a 48-year-old man with SBA and a 21-year history of CD who was diagnosed by a combination of positron emission tomography/computed tomography (PET/CT) and double-balloon enteroscopy (DBE). Since the age of 27 years, the patient had been treated for ileal CD and was referred to our hospital with persistent melena.

CYP2C19 genotype is associated with symptomatic recurrence of GERD during maintenance therapy with low-dose lansoprazole.

Background/aims: Maintenance therapy of gastroesophageal reflux disease (GERD) is usually performed with a low dose of a proton-pump inhibitor (PPI). Because PPIs are metabolized by CYP2C19 in the liver, we investigated whether a patient's CYP2C19 genotype was associated with symptomatic recurrence of GERD during maintenance therapy with a low dose of a PPI.

Methods: We enrolled 124 patients with erosive GERD whose esophageal mucosal breaks were endoscopically proven to be cured after treatment with lansoprazole 30 mg/day for 8 weeks.

Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects.

Background And Aims: The effect of multidrug resistance transporter gene 1 (MDR1) on the bioavailability and kinetics of several substrates has not yet been fully elucidated. We evaluated the influence of MDR1 C3435T polymorphism on the pharmacokinetics and pharmacodynamics of lansoprazole in Japanese subjects.

Methods: Fifteen healthy volunteers with the rapid extensive metabolizer genotype of CYP2C19 were classified into three MDR1 C3435T genotype groups: C/C (n = 5), C/T (n = 5), and T/T (n = 5).

[A case of elderly esophageal adenocarcinoma successfully treated with daily low-dose nedaplatin (CDGP) and continuous infusion of 5-FU combined with radiation].

We report an elderly patient with esophageal adenocarcinoma in whom a complete response (CR) was obtained by chemoradiotherapy using daily low-dose nedaplatin (CDGP) and continuous infusion of 5-FU. A 86-year-old man who had non-tuberculous mycobacterial infection was admitted for dysphagia, and diagnosed with Stage II A (T2N0M0) esophageal adenocarcinoma of the lower esophagus according to the TNM classification (sixth edition) of the International Union against Cancer (UICC). Chemoradiotherapy using daily low-dose CDGP and continuous infusion of 5- FU was performed, and thereafter one cycle of chemotherapy using CDGP and 5-FU was added.

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

Background: Matrix 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.

MDR1 C3435T polymorphism has no influence on developing Helicobacter pylori infection-related gastric cancer and peptic ulcer in Japanese.

Aims: P-glycoprotein, the gene product of multidrug-resistant transporter-1 (MDR1), confers multidrug resistance against antineoplastic agents but also affects the kinetic disposition of some drugs and carcinogens. MDR1 C3435T polymorphism influences the development of colon cancer and adult acute myeloid leukemia by the association with transporting carcinogen. The aim of this study was to clarify the association of MDR1 C3435T polymorphism with susceptibility to gastric cancer and peptic ulcers in patients with Japanese H.

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.