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  • 1
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    Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis
    Wiley ; 2005
    In:  Alimentary Pharmacology and Therapeutics Vol. 21, No. 11 ( 2005-06), p. 1331-1339
    Details
    In: Alimentary Pharmacology and Therapeutics, Wiley, Vol. 21, No. 11 ( 2005-06), p. 1331-1339
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.2005.21.issue-11
    DOI: 10.1111/j.1365-2036.2005.02486.x
    Language: English
    Publisher: Wiley
    Publication Date: 2005
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  • 2
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    Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study)
    Wiley ; 2018
    In:  Neurogastroenterology & Motility Vol. 30, No. 7 ( 2018-07)
    Details
    In: Neurogastroenterology & Motility, Wiley, Vol. 30, No. 7 ( 2018-07)
    Abstract: Functional dyspepsia ( FD ), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo‐controlled, double‐blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. Methods FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single‐blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy ( OTE ). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders‐Symptom Severity Index ( PAGI ‐ SYM ), the Global Overall Symptom scale ( GOS ), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m‐ FSSG ), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale ( HADS ). Key Results Rikkunshito increased OTE compared to placebo at 8 weeks ( P  = .019). Rikkunshito improved upper gastrointestinal symptoms ( PAGI ‐ SYM , GOS , and m‐ FSSG ) at 8 weeks, especially postprandial fullness/early satiety ( P  = .015 and P  = .001) and bloating ( P  = .007 and P  = .002) of the PAGI ‐ SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks ( P  = .027) correlated with those of PAGI ‐ SYM ( r  = .302, P  = .001), GOS ( r  = .186, P  = .044), and m‐ FSSG ( r  = .462, P   〈  .001), postprandial fullness/early satiety ( r  = .226, P  = .014), dyspepsia ( r  = .215, P  = .019), and PDS ( r  = .221, P  = .016). Conclusion & inferences Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.
    Type of Medium: Online Resource
    ISSN: 1350-1925 , 1365-2982
    URL: Issue
    URL: Article
    DOI: 10.1111/nmo.2018.30.issue-7
    DOI: 10.1111/nmo.13319
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2008278-2
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  • 3
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    High molecular protein of Helicobacter pylori responsible for inhibition of ornithine decarboxylase activity of human gastric cultured cells
    Wiley ; 2002
    In:  Alimentary Pharmacology & Therapeutics Vol. 16, No. s2 ( 2002-04), p. 167-173
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 16, No. s2 ( 2002-04), p. 167-173
    Abstract: Ornithine decarboxylase (ODC), a rate‐limiting enzyme of polyamine biosynthesis, mediates epithelial cell proliferation and plays a critical role in the optimal repair of gastric mucosal damage. Several studies have shown that Helicobacter pylori inhibits the growth and proliferation of gastric cells in vitro . Aim: To test whether H. pylori extract affects ODC mRNA expression and its enzyme activity in gastric cells and to examine the partial characterization of the molecule responsible for this effect. Methods: Human gastric cells (MKN‐45) were used. Bacterial extracts from various E. coli or H. pylori strains, namely (1) cagA + , vacA + , CagA + , VacA + ; (2) cagA + , vacA + , CagA + VacA – ; or (3) cagA – , vacA + , CagA – , VacA – were added to the cells. Cell proliferation was assessed by [ 3 H]‐thymidine incorporation, viability by MTT assay and LDH release test, ODC enzyme activity by 14 CO 2 counts from L‐[1 14 C]ornithine, and ODC mRNA by Northern blotting. Results: H. pylori and E. coli extract did not affect viability of gastric cells. H. pylori extract, especially extracts containing a protein greater than 50 kDa, significantly inhibited proliferation and ODC activity of gastric cells while E. coli extract had no effect. Inhibition of ODC activity was found in extracts of all H. pylori strains, irrespective of CagA and VacA protein expression. Serum stimulation induces an increase in ODC mRNA while H. pylori extract did not affect ODC mRNA expression. Conclusion: High molecular weight (greater than 50 kDa) proteins of H. pylori extract without CagA or VacA protein inhibited proliferation and ODC activity of human gastric cells, but did not affect ODC mRNA expression, suggesting that inhibition of ODC activity is regulated at the post‐transcriptional level.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Article
    DOI: 10.1046/j.1365-2036.16.s2.20.x
    Language: English
    Publisher: Wiley
    Publication Date: 2002
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  • 4
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    Comparison of the effects of rebamipide with those of cimetidine on chronic gastritis associated with Helicobacter pylori in Mongolian gerbils
    Wiley ; 2003
    In:  Alimentary Pharmacology & Therapeutics Vol. 18, No. s1 ( 2003-07), p. 1-7
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 18, No. s1 ( 2003-07), p. 1-7
    Abstract: Background and Aims : The effects of rebamipide on chronic gastritis associated with Helicobacter pylori have not been well‐defined. We compared these effects of rebamipide with those of cimetidine in Mongolian gerbils infected with H. pylori . Methods : Mongolian gerbils with or without H. pylori were divided into 10 groups 6 weeks after inoculation and fed diets containing a drug (rebamipide or cimetidine) or control diet. All animals were sacrificed 4 weeks after grouping. Their stomachs were examined for histology, colonization by H. pylori , myeloperoxidase activity (myeloperoxidase), production of neutrophil chemokine (CINC/KC) and tumour necrosis factor‐α (TNF‐α), and serum gastrin levels. Results :  H. pylori colonized all of the inoculated animals. Neither rebamipide nor cimetidine decreased myeloperoxidase activity, but each reduced wet stomach weight in H. pylori ‐infected animals. The amount of increase in CINC/KC and TNF‐α in gastric tissue caused by H. pylori infection was decreased by treatment with rebamipide or cimetidine. H. pylori infection increased serum gastrin levels, and this increase was significantly enhanced by cimetidine but not rebamipide. Conclusions : Rebamipide may improve H. pylori ‐infected chronic gastritis by preventing the production of inflammatory cytokines and chemokines, as does cimetidine, but may be preferable to cimetidine for long‐term administration for treatment of H. pylori ‐infected chronic gastritis due to its effect on serum gastrin levels.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Article
    DOI: 10.1046/j.1365-2036.18.s1.18.x
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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  • 5
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    Effects of rebamipide, a gastro‐protective drug on the Helicobacter pylori status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double‐blind placebo‐controlled multicentre trial
    Wiley ; 2003
    In:  Alimentary Pharmacology & Therapeutics Vol. 18, No. s1 ( 2003-07), p. 146-152
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 18, No. s1 ( 2003-07), p. 146-152
    Abstract: Aims : To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro‐mucosal inflammation after eradication. Methods : Two hundred and six H. pylori ‐positive patients with active gastric ulcer underwent 8‐week based therapy (OA) consisting of 2‐week amoxicillin with omeprazole and subsequent 6‐week omeprazole. They randomly received either rebamipide (OA‐R) or placebo (OA‐P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically. Results : Per Protocol Set analysis showed no significant difference in eradication rate between OA‐R (64.6%; 95% confidence interval, 54.3–75.0%) and OA‐P (67.9%; 95% CI, 57.6–78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement ( P  = 0.017) in inflammation scores in OA‐R (1.84 ± 0.41) compared with that in OA‐P (2.02 ± 0.39) after 16‐weeks of treatment. This suppressive effect on inflammation was observed even in the OA‐R patients unsuccessfully eradicated. Conclusion : Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Article
    DOI: 10.1046/j.1365-2036.18.s1.20.x
    Language: English
    Publisher: Wiley
    Publication Date: 2003
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  • 6
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    Increased expression of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats
    Wiley ; 2002
    In:  Alimentary Pharmacology & Therapeutics Vol. 16, No. s2 ( 2002-04), p. 52-58
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 16, No. s2 ( 2002-04), p. 52-58
    Abstract: Epidermal growth factor (EGF), which binds to EGF receptors (EGF‐R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF‐R expression is present and confined to the basal layer. Aim: To examine histological changes in and dynamics of EGF‐R expression during healing after acid reflux oesophagitis in a rat model. Methods: Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF‐R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF‐R mRNA and protein by RT–PCR and Western blotting or immunohistochemistry. Results: Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 ± 3.09 μm in controls to 142.73 ± 11.59 μm ( P  〈  0.001) in ligated rats, as well as elongation of papillae and basal cell hyperplasia. The number of BrdU‐positive cells among basal cells on day 14 was significantly increased from 7.1 ± 0.8/field in controls to 30.9 ± 3.0/field in ligated rats. Expression of EGF‐R mRNA and protein was significantly increased on day 14 and most basal cells were immunohistochemically positive in both BrdU and EGF‐R staining. Conclusion: Acid reflux‐induced oesophageal injury caused basal cell hyperplasia with an increase in cell proliferation and EGF‐R expression. Activation of EGF‐R gene and protein in response to acid reflux‐induced injury may facilitate mucosal healing. These results suggest that epidermal growth factor receptors play a crucial role in healing after acid reflux oesophagitis in rats.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Article
    DOI: 10.1046/j.1365-2036.16.s2.29.x
    Language: English
    Publisher: Wiley
    Publication Date: 2002
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  • 7
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    Telaprevir impairs renal function and increases blood ribavirin concentration during telaprevir/pegylated interferon/ribavirin therapy for chronic hepatitis C
    Wiley ; 2014
    In:  Journal of Viral Hepatitis Vol. 21, No. 5 ( 2014-05), p. 341-347
    Details
    In: Journal of Viral Hepatitis, Wiley, Vol. 21, No. 5 ( 2014-05), p. 341-347
    Abstract: We aimed to examine the relationship between renal dysfunction and anaemia that may develop during combination therapy involving pegylated interferon, ribavirin and telaprevir (PEG‐IFN/RBV/TVR) for the treatment of chronic hepatitis C. Sixty‐eight patients with genotype 1b high viral loads were treated with PEG‐IFN/RBV/TVR. Peg‐IFN and RBV doses were administered according to body weight. TVR was prescribed at 2250 mg/day for 44 patients and at 1500 mg/day for 24 patients who had low haemoglobin level ( 〈 12 g/dL). When anaemia had developed, the RBV dose was decreased. The serum TVR concentration at day 8 was measured, and the serum RBV concentration was measured serially. The estimated glomerular filtration rate ( eGFR ) was estimated to assess renal function. At week 1, serum TVR concentration was not correlated with a decrease in eGFR ; however, the TVR dose, on a weight basis (mg/kg), and eGFR were correlated ( r  = 0.2691; P  = 0.0265). Moreover, there was a negative correlation between eGFR and RBV serum concentration ( r  = −0.3694; P  = 0.0025), and the serum RBV concentration and decrease in the haemoglobin were significantly correlated from week 1 to week 8. In triple therapy, the TVR dose per weight is correlated with a decline in renal function. Thus, the serum concentration of RBV increases, with a concomitant decrease in haemoglobin. It is important to adjust the doses of TVR and RBV to avoid excessive serum RBV levels and the development of severe anaemia, to achieve a good clinical effect.
    Type of Medium: Online Resource
    ISSN: 1352-0504 , 1365-2893
    URL: Issue
    URL: Article
    DOI: 10.1111/jvh.2014.21.issue-5
    DOI: 10.1111/jvh.12162
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2007924-2
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  • 8
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    Basophil infiltration in eosinophilic oesophagitis and proton pump inhibitor‐responsive oesophageal eosinophilia
    Wiley ; 2015
    In:  Alimentary Pharmacology & Therapeutics Vol. 41, No. 8 ( 2015-04), p. 776-784
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 41, No. 8 ( 2015-04), p. 776-784
    Abstract: The features of proton pump inhibitor‐responsive oesophageal eosinophilia ( PPI ‐ REE ) are similar to those of eosinophilic oesophagitis (EoE), but PPI ‐ REE demonstrates symptomatic and histological responses to PPI therapy. Several studies have shown that basophils play a crucial role in the pathogenesis of allergic diseases. Aim To identify and compare basophil infiltration in the oesophageal epithelium in patients with EoE, PPI ‐ REE , gastroesophageal reflux disease ( GERD ) and normal oesophagus (controls). Methods Biopsy specimens from 43 patients, including 12 with EoE, 11 with PPI ‐ REE , 10 with GERD and 10 normal oesophagus, were analysed. Immunohistochemistry was performed to quantify the number of basophils and mast cells in the oesophageal epithelium. Double immunofluorescence staining for thymic stromal lymphopoietin ( TSLP ) and basophils was performed. Patients with EoE were treated with swallowed fluticasone. Results There were no differences in clinical, endoscopic or histological features between patients with EoE and PPI ‐ REE . There were more basophils and mast cells in patients with EoE and PPI ‐ REE than in patients with GERD and control subjects. Basophil infiltration of the oesophageal epithelium in patients with EoE was higher than that in patients with PPI ‐ REE (3.6 ± 2.8 per high power field vs. 1.2 ± 0.9 per high power field respectively; P  = 0.02); however, there was no significant difference in mast cell infiltration between the two groups. TSLP was highly expressed in the oesophageal epithelium in areas infiltrated by basophils. Steroid therapy significantly decreased intraepithelial basophils in patients with EoE. Conclusion Basophils may play an important role in the pathogenesis of eosinophilic oesophagitis.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.2015.41.issue-8
    DOI: 10.1111/apt.13141
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 9
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    Randomised clinical trial: prevention of recurrence of peptic ulcers by rabeprazole in patients taking low‐dose aspirin
    Wiley ; 2014
    In:  Alimentary Pharmacology & Therapeutics Vol. 40, No. 7 ( 2014-10), p. 780-795
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 40, No. 7 ( 2014-10), p. 780-795
    Abstract: Few studies have evaluated the effects of rabeprazole on low‐dose aspirin ( LDA )‐induced gastroduodenal injuries. Aim To conduct a randomised, double‐blind, triple‐dummy, active‐controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose–response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long‐term LDA therapy. Methods Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long‐term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. Results Among 472 randomised subjects, 452 subjects ( n  = 151, 150, 151, respectively) constituted the full analysis set. The cumulative recurrence rates of peptic ulcers over 24 weeks in the 10‐ and 5‐mg rabeprazole groups were 1.4% and 2.8%, respectively, both of which were significantly lower than that in the teprenone group (21.7%). The cumulative occurrence rate of bleeding ulcers over 24 weeks in the teprenone group was 4.6%, while bleeding ulcers were not observed in the 10‐ or 5‐mg rabeprazole groups. Rabeprazole was well tolerated at both doses. Conclusion Rabeprazole prevents the recurrence of peptic ulcers with no evidence of a major dose–response effect in subjects on low‐dose aspirin therapy.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.2014.40.issue-7
    DOI: 10.1111/apt.12907
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 10
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    Correlation of MAP kinases with COX‐2 induction differs between MKN45 and HT29 cells
    Wiley ; 2004
    In:  Alimentary Pharmacology & Therapeutics Vol. 20, No. s1 ( 2004-07), p. 143-150
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 20, No. s1 ( 2004-07), p. 143-150
    Abstract: Background : Mitogen‐activated protein (MAP) kinases, including extracellular signal‐regulated kinases (ERK),c‐Jun NH 2 ‐terminal kinases (JNK) and p38 MAP kinase (p38 MAPK) are important intermediates of the signal‐transduction pathway from the cell surface to the nucleus. Expression of cyclooxygenase (COX)‐2, associated with proliferation, apoptosis or both of gastrointestinal cancer cells, is mediated through MAP kinase families. However, the correlation between respective MAP kinase signals and COX‐2 in the proliferation of gastric and colon cancer cells has not been well elucidated. Aim : We examined the effect of selective inhibitors of MAP kinases and COX‐2 on serum‐induced proliferation of gastric (MKN45) and colon (HT29) cancer cells. Methods : After 24‐h serum starvation, cancer cells were stimulated with 2% serum and COX‐2 inhibitors (NS398 10 µmol/L, or etodolac 100 µmol/L) or 1 h after preincubation with inhibitors for ERK (PD98059 20 µmol/L) or p38 MAPK (SB203580 10 µmol/L). Phosphorylated MAP kinases and COX‐2 protein were evaluated by Western blotting, and the proliferation of cancer cells was estimated by 3 H‐thymidine incorporation. Transcription factors nuclear factor‐κB and CREB were assayed by an electorophoretic mobility shift assay. Results : Serum increased the proliferation of MKN45 and HT29 cells by 280% and 200%, respectively, compared with the control levels (100%). In both cancer cells, phosphorylated MAP kinases were increased within 30 min after stimulation. PD98059 and SB203580 inhibited the serum‐induced proliferation of MKN45 by 21% and 51% and of HT29 by 81% and 69%, respectively. NS398 and etodolac inhibited the proliferation of HT29 by 21% and 41%, respectively, but not that of MKN45. PD98059 and SB203580 also suppressed serum‐induced expression of COX‐2 protein in HT29 cells. In addition to the activation of MAP kinases and COX‐2, activities of nuclear factor‐κB and CREB were also increased during HT29 cell proliferation. Conclusions : These results suggest that the correlation of MAP kinases with COX‐2 induction for cell proliferation differs between MKN45 and HT29 cells.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.2004.20.issue-s1
    DOI: 10.1111/j.1365-2036.2004.01986.x
    Language: English
    Publisher: Wiley
    Publication Date: 2004
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