Comparison of constitutive and inducible levels of expression of peroxisomal beta-oxidation and catalase genes in liver and extrahepatic tissues of rat.

Previous studies from our laboratories have shown that carcinogenic peroxisome proliferators significantly increase the mRNA levels of peroxisomal beta-oxidation genes in the rat liver by enhancing the transcriptional activity. Because of a good correlation between the inducibility of peroxisome proliferation and carcinogenicity of this class of xenobiotics, we proposed that sustained induction of peroxisomal beta-oxidation system and the resultant oxidative stress form the basis for carcinogenesis. Since this concept implies that tumors should develop only in tissues which display maximal peroxisome proliferation, we have now assessed the degree to which catalase and the three beta-oxidation genes are expressed in liver and 12 extrahepatic tissues of adult rats fed for 2 weeks a diet containing 0.025% ciprofibrate (w/w), a peroxisome proliferator. In the ciprofibrate-treated rats, the levels of catalase mRNA increased to less than 2-fold in liver, kidney, intestine, and heart, but no change was detected in other tissues. The mRNA levels of the three genes of beta-oxidation system in the liver of adult rats treated with ciprofibrate increased greater than 20-fold. In contrast, in the kidney, small intestine, and heart the increases in the mRNA levels of all three beta-oxidation genes were small and varied from 2- to 4-fold following ciprofibrate treatment. Ciprofibrate did not significantly increase the levels of these mRNAs in the other nine tissues. These results correlated well with the levels of peroxisomal beta-oxidation activity, peroxisome volume density, and the immunologically quantified proteins in various tissues. These results provide evidence for the presence of beta-oxidation enzymes in peroxisomes of many tissues of rat and for tissue (cell)-specific differences in the inducibility of mRNAs of these beta-oxidation genes. The marked inducibility of beta-oxidation genes in liver and subsequent development of liver tumors support the hypothesis that tumors develop in tissues that show inducibility of peroxisome proliferation vis a vis beta-oxidation system following exposure to peroxisome proliferators.

Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin.

AIM: To investigate the effect of different proton pump inhibitors, S-mephenytoin 4'-hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori. METHODS: One hundred and eighty-seven H. pylori-infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated. RESULTS: The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) and lansoprazole-amoxicillin-clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention-to-treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin-resistant strains was significantly lower than that for clarithromycin-sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin-sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726). CONCLUSIONS: The success of the 1-week proton pump inhibitor-amoxicillin-clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole-based therapy, and the rabeprazole-based regimen has an advantage especially in extensive metabolizers.

[Cost-effectiveness of the treatment of reflux esophagitis: proton pump inhibitor versus histamine-2-receptor antagonist].

Gastroesophageal reflux disease(GERD) is a common condition and acid-suppressing agents are the mainstays of treatment. A clinical decision analysis comparing a proton pump inhibitor(PPI), lansoprazole and a histamine H2-receptor antagonist (H2RA), ranitidine for the treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The PPI was consistently superior to the H2RA with regard to both clinical effectiveness and cost-effectiveness. Prescription of PPIs for a one-month period would further enhance the cost-effectiveness of PPI treatment. The PPI first strategy is the preferred therapeutic approach for medical treatment of reflux esophagitis. We also recommend that prescription of PPIs for a one-month period be approved by the Japanese health insurance scheme.

[The clinical evaluation of structured questionnaire for reflux esophagitis].

Reflux esophagitis is suspected on clinical grounds and confirmed by a variety of endoscopical, roentgenological and physiological investigations, which are obviously inapplicable to an epidemiological survey. Questionnaire for the diagnosis of reflux disease(QUEST) can reduce bias introduced by observer variability, is practical, inexpensive, and noninvasive. QUEST also has good sensitivity and specificity for reflux esophagitis, so it's one of the useful diagnostic tools for reflux esophagitis. It, however, needs to be modified for the diagnosis of gastroesophageal reflux disease (GERD). Questionnaires to measure Quality of Life(QOL) quantitatively can be applied to the assessment of the severity of diseases or drug efficacy, and they are useful especially for the evaluation of endoscopy-negative GERD.