Different dosage regimens of rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotype status.

Objective: For the treatment of gastroesophageal reflux disease, intragastric pH should be lower than 4.0 for no more than 4 hours a day (<16.7%).

Expression of the hepatic endothelin system in human cirrhotic livers.

It is considered that endothelin-1 participates in the development of liver cirrhosis and it has been recognized that every component of the endothelin system is upregulated in cirrhotic livers. However, the expression pattern of this system, including interaction between its components, is not fully understood in human livers. In this study, the expression pattern of the endothelin system was examined.

Unexpected mexiletine responses of a mutant cardiac Na+ channel implicate the selectivity filter as a structural determinant of antiarrhythmic drug access.

Gating properties of Na(+) channels are the critical determinants for the state-dependent block by class I antiarrhythmic drugs; however, recent site-directed mutagenesis studies have shown that the Na(+) channel selectivity filter region controls drug access to and dissociation from the binding site. To validate these observations, we have exploited a naturally occurring cardiac Na(+) channel mutation, S1710L, located next to the putative selectivity filter residue of domain 4, and evaluated the pharmacological properties to mexiletine using whole-cell, patch-clamp recordings. Consistent with the large negative shift of steady-state inactivation and the enhanced slow inactivation, the S1710L channel showed greater mexiletine tonic block than wild-type (WT) channel.

Three-dimensional microarray compared with PCR-single-strand conformation polymorphism analysis/DNA sequencing for mutation analysis of K-ras codons 12 and 13.

Background: We developed a rapid, precise, and accurate microarray-based method that uses a three-dimensional platform for detection of mutations.

Methods: We used the PamChip microarray to detect mutations in codons 12 and 13 of K-ras in 15 cell lines and 81 gastric or colorectal cancer tissues. Fluorescein isothiocyanate-labeled PCR products were analyzed with the microarray.

Alterations of endothelin-converting enzyme expression in early and advanced stages of human coronary atherosclerosis.

Endothelin-1 is a potent vasoconstrictor and exhibits a mitogenic activity on vascular smooth muscle cells (SMCs). Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin-1 processing. We studied the immunolocalization of ECE in human coronary atherosclerotic lesions with different disease stages.

Asymmetry in the perception of motion-in-depth.

We investigated the anisotropic responses between the detection of motion toward and motion away from the observers with expanding/contracting shaded circles. Our experiments followed visual search paradigm with two exceptions: (1) the stimulus presentation time was fixed for 300 ms and (2) the mean error rates were adopted as a dependent variable. In Experiment 1, targets and distractors were defined by expanding (or contracting) convex/concave circles.

Polymorphism of interleukin-1beta affects the eradication rates of Helicobacter pylori by triple therapy.

Background And Aims: Polymorphism in interleukin-1beta (IL-1beta) is associated with intragastric pH levels in Helicobacter pylori-positive subjects. Intragastric pH levels affect the activity of antibiotics against H. pylori in the stomach.

Pharmacogenomics of proton pump inhibitors.

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are metabolized by cytochrome P450 isoenzyme 2C19 (CYP2C19) in the liver. There are genetic differences that affect the activity of this enzyme. The genotypes of CYP2C19 are classified into three groups: homozygous extensive metabolizer (homEM), heterozygous extensive metabolizer (hetEM), and poor metabolizer (PM).

Effects of Western, Vegetarian, and Japanese dietary fat model diets with or without green tea extract on the plasma lipids and glucose, and liver lipids in mice. A long-term feeding experiment.

Background/aims: The purpose of this study was to investigate the long-term effects of three model diets containing different fats, with or without a small amount of green tea extract (GTE), on plasma lipids and glucose, and liver lipids in mice.

Methods: Male mice (2 months old) fed 10% fat diets with Western (W), Vegetarian (V), and Japanese (J) fat compositions with or without 0.03% GTE for 7 months.

Telomere shortening in human coronary artery diseases.

Background: Increased cell turnover in response to injury is considered to be important in the development of atherosclerotic plaques. Telomere shortening has been shown to be associated with cell turnover. We assessed the telomere length of human coronary endothelial cells to clarify whether there is a relationship between telomere shortening and coronary artery disease (CAD).

High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin.

Background/aims: Some patients are refractory to the usual triple therapy for eradication of Helicobacter pylori, consisting of a proton pump inhibitor, amoxicillin and clarithromycin, so there needs to be an alternative strategy for retreatment after failure to eradicate the infection.

Methodology: The study group comprised 17 H. pylori-positive patients who had failed to clear H.

Effect of dietary docosahexaenoic acid and catechins on maze behavior in mice.

Background/aims: Docosahexaenoic acid (DHA; 22:6 n-3) and catechins are food components that play an important role in maintaining human health. However, the effect of a simultaneous intake of DHA and catechins on brain function is unknown. The purpose of this study was to investigate the effect of DHA and catechins on maze behavior in mice.

Ceriporic acid C, a hexadecenylitaconate produced by a lignin-degrading fungus, Ceriporiopsis subvermispora.

A lignin-degrading basidiomycete, Ceriporiopsis subvermispora produces a series of alkyl- and alkenylitaconates (ceriporic acids). Previously, two alkylitaconic acids with tetradecyl and hexadecyl side chains were isolated and identified as 1-heptadecene-2,3-dicarboxylic acid (ceriporic acid A) and 1-nonadecene-2,3-dicarboxylic acid (ceriporic acid B). In the present study, one hexadecenylitaconate (ceriporic acid C) was isolated and its chemical structure was analyzed by glycolation and subsequent (1) trimethylsilation, or (2) acetalation with acetone and acetone-d6.

Impact of diabetes mellitus on worsening of the left ventricular ejection fraction in exercise-gated 201Tl myocardial single photon emission computed tomography in patients with coronary artery disease.

It remains uncertain whether factors other than the severity of coronary artery disease (CAD) are associated with the worsening of the left ventricular ejection fraction (LVEF) by exercise. In the present study the impact of coronary risk factors on the worsening of LVEF by exercise was investigated in 391 patients with known or suspected CAD using exercise-gated (201)Tl scanning to calculate the LVEF. Significant worsening of the LVEF by exercise was defined as >4.

Identification of cardiac sarcoidosis with (13)N-NH(3)/(18)F-FDG PET.

Unlabelled: To our knowledge, no study investigating the usefulness of cardiac PET for detection of myocardial involvement of sarcoidosis is available. We investigated whether (13)N-NH(3)/(18)F-FDG PET could identify cardiac involvement in patients with sarcoidosis.

Methods: Seventeen patients with cardiac sarcoidosis underwent cardiac (13)N-NH(3)/(18)F-FDG PET under fasting condition.

Analysis of molecular interactions in heat-induced aggregation of a non-inhibitory serpin ovalbumin using a molecular chaperone.

Aggregation occurs through hydrophobic interactions when a polypeptide chain refolds in non-native states or when genetic variants of biologically active proteins assume inappropriate conformations, as observed in the case of dysfunctional serpins. Here, using the molecular chaperone BiP from bovine liver microsomes, we characterized the hydrophobic nature of the peptide segment which is considered to be a site required for aggregation among a non-inhibitory serpin ovalbumin in a heat-denatured state. Screening of the peptide scan for binding of BiP showed that BiP-binding sites are mostly buried in the folded ovalbumin.

Differential expression of cornified cell envelope precursors in normal skin, intraorally transplanted skin and normal oral mucosa.

Background: Skin flaps have routinely been used as substitutes for oral mucosa after extensive resection of oral tissues. However, it remains unknown how the transplanted skin flaps perform as a host defence in the new environment of the oral cavity.

Objectives: To evaluate the expression of cornified cell envelope (CCE) precursors in pretransplanted (normal) skin, intraorally transplanted skin and normal oral mucosa, because CCEs are highly responsible for a protective barrier in each type of epithelium.

High susceptibility of nullizygous p53 knockout mice to colorectal tumor induction by 1,2-dimethylhydrazine.

Purpose: The susceptibility of male p53 nullizygote (-/-), heterozygote (+/-), and wild-type (+/+) mice to 1,2-dimethylhydrazine (DMH) induction of colon carcinogenesis was investigated.

Methods: In a preliminary short-term experiment, male mice of three genotypes were given s.c.

Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori.

Current regimens for the eradication of Helicobacter pylori consist of a proton pump inhibitor (PPI) plus one or two antibacterial agents, such as amoxicillin (AMPC), clarithromycin (CAM) or metronidazole (MNZ). PPIs are mainly metabolized by S-mephenytoin 4'-hydroxylase (CYP2C19) in the liver. The polymorphism of CYP2C19 is associated with the pharmacokinetics and pharmacodynamics of PPIs.

New lignan glycosides from Chinese medicinal plant, Sinopodophillum emodi.

Two new podophillotoxin glucosides, L-picropodophillotpxin 7'-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside) (2) and L-picropodophillotpxin 7'-O-beta-D-glucopyranoside (3), were isolated from Chinese medicinal plant, Sinopodophillum emodi, together with 4 known compounds, podophillotoxin (1), podorhizol 4'-O-beta-D-glucopyranoside (4), deoxypodophillotoxin (5), and dehydropodophillotoxin (6). The structures of 2 and 3 were finally determined by the extensive decouping and nuclear Overhauser effect (NOE) experiments in NMR spectra and circular dichroism (CD) spectra. Compound 2 is the second example of podophillotoxin diglucoside, and both the first one and 2 were isolated from S.

[Clinical significance of faecal calprotectin levels in patients with ulcerative colitis].

Aims: To assess the clinical significance of faecal calprotectin levels (a neutrophil protein) in patients with ulcerative colitis (UC).

Methods: 25 patients with UC provided stool samples for calprotectin assay and the amount of calprotectin was related to UC disease activity index in each patient. Of 25 patients 4 with prednisolone refractory UC received 10 granulocyte and monocyte adsorption apheresis (GMCAP) sessions of 60 minutes duration, flow rate 30 mL per minute for 10 consecutive weeks.

Enhanced expression of endothelin-A receptor in human transplant renal arteriosclerosis.

Transplant renal arteriosclerosis (TRA), characterized by concentric neointimal thickening, is one of the major causes of chronic rejection in human kidney transplantation. Endothelin-1 is known to be a powerful vasoconstrictor and a vascular smooth muscle cell mitogen. Previous experimental studies have shown that endothelin-A receptor (ET(A) receptor) is expressed selectively in vascular smooth muscle cells, and is the major mediator of endothelin-1-induced effects.

Proliferative activity of canine mast cell tumours evaluated by bromodeoxyuridine incorporation and Ki-67 expression.

The proliferative activity of 91 canine mast cell tumours was assessed on the basis of the Ki-67 positive index (Ki-67 PI) and mitotic index (MI) and, in 15 cases, also by the labelling index of bromodeoxyuridine (BrdU; an analogue of tritiated thymidine) incorporated in vivo into S-phase cells. BrdU and Ki-67 were detected immunohistochemically. The tumours were graded histologically (I, II or III).