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Taishi Higashi, Haruki Tanaka, Ayumi Yoshimatsu, Haruna Ikeda, Kanako Arima, Masatoshi Honjo, Chihiro Iwamoto, Keiichi Motoyama, Hidetoshi Arima
The purpose of this study was to design cyclodextrin (CyD)-based pseudorotaxane-like supramolecular complexes with various isoprenoid compounds, such as reduced coenzyme Q10 (R-CoQ10), squalene, tocotrienol, and teprenone, and to evaluate their pharmaceutical properties. Squalene, tocotrienol, and teprenone formed precipitates with β-CyD and γ-CyD in aqueous solution, whereas R-CoQ10 formed precipitates with γ-CyD aqueous solution. The results of powder X-ray diffraction and (1)H-NMR analyses indicated that these precipitates are derived from pseudorotaxane-like supramolecular complexes...
2016: Chemical & Pharmaceutical Bulletin
Wakana Onuma, Susumu Tomono, Shinngo Miyamoto, Gen Fujii, Takahiro Hamoya, Kyoko Fujimoto, Noriyuki Miyoshi, Fumio Fukai, Keiji Wakabayashi, Michihiro Mutoh
This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity...
February 23, 2016: Oncotarget
Mitsuhiro Fujishiro, Kazuhide Higuchi, Mototsugu Kato, Yoshikazu Kinoshita, Ryuichi Iwakiri, Toshio Watanabe, Toshihisa Takeuchi, Nobuyuki Sugisaki, Yasushi Okada, Hisao Ogawa, Tetsuo Arakawa, Kazuma Fujimoto
A 24-week, double-blind, clinical trial of rabeprazole for the prevention of recurrent peptic ulcers caused by low-dose aspirin (LDA) has been reported, but trials for longer than 24 weeks have not been reported. The aim of this study is to assess the long-term efficacy and safety of rabeprazole for preventing peptic ulcer recurrence on LDA therapy. Eligible patients had a history of peptic ulcers on long-term LDA (81 or 100 mg/day) therapy. Patients with no recurrence of peptic ulcers at the end of the 24-week double-blind phase with rabeprazole (10- or 5-mg once daily) or teprenone (50 mg three times daily) entered the extension phase...
May 2015: Journal of Clinical Biochemistry and Nutrition
Koji Takeuchi, Shinichi Takayama, Erika Hashimoto, Misaki Itayama, Kikuko Amagase, Chitose Izuhara
BACKGROUND AND AIM: We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats. METHODS: Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate...
December 2014: Journal of Gastroenterology and Hepatology
Toshihisa Takeuchi, Kazuhiro Ota, Satoshi Harada, Yuichi Kojima, Takuya Inoue, Ryuichi Iwakiri, Yasuhisa Sakata, Kazuma Fujimoto, Tsuyoshi Fujita, Takeshi Azuma, Kazuhide Higuchi
BACKGROUND AND AIM: Proton-pump inhibitors are known to be effective in the treatment and prevention of ulcers related to low-dose aspirin (LDA), but few reports address H2 -receptor antagonists (H2RAs) and gastroprotective agents (GPs). This study was intended to compare the therapeutic effects of an H2RA and a GP against gastroduodenal mucosal injuries in patients taking LDA. METHODS: The subjects consisted of patients requiring continuous LDA treatment, in whom no peptic ulcer was found on endoscopy at enrollment...
December 2014: Journal of Gastroenterology and Hepatology
Wenxing Yang, Yosuke Tanaka, Miki Bundo, Nobutaka Hirokawa
Beta cell injury due to oxidative stress is a typical etiology of diabetes caused by nutritional excess, but its precise mechanism remains largely elusive. Here, we demonstrate that the microtubule motor KIF12 mediates an antioxidant cascade in beta cells as an intracellular target of excess fat intake or "lipotoxicity." KIF12 knockout mice suffer from hypoinsulinemic glucose intolerance due to increased beta cell oxidative stress. Using this model, we identified an antioxidant signaling cascade involving KIF12 as a scaffold for the transcription factor Sp1...
October 27, 2014: Developmental Cell
R Iwakiri, K Higuchi, M Kato, M Fujishiro, Y Kinoshita, T Watanabe, T Takeuchi, M Yamauchi, M Sanomura, H Nakagawa, N Sugisaki, Y Okada, H Ogawa, T Arakawa, K Fujimoto
BACKGROUND: 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...
October 2014: Alimentary Pharmacology & Therapeutics
Youki Ueda, Kyoko Mori, Shinya Satoh, Hiromichi Dansako, Masanori Ikeda, Nobuyuki Kato
Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although the sustained virologic response rate in the treatment of genotype 1 using new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has been improved by more than 70%, several severe side effects such as skin rash/ageusia and advanced anemia have become a problem. Under these circumstances, a new type of anti-HCV oral drug with few side effects is needed. Our recently developed HCV drug assay systems, including the HuH-7 cell line-derived OR6 and AH1R, and the Li23 cell line-derived ORL8 and ORL11, allow genome-length HCV RNAs (several strains of genotype 1b) encoding renilla luciferase to replicate efficiently...
May 2, 2014: Biochemical and Biophysical Research Communications
Sha Shi, Han Wang, Hui Gao, Zhen Li, Fei-Xue Chen, Xiu-li Zuo, Yan-qing Li
BACKGROUND AND AIMS: The intestinal epithelial barrier plays an important role in the pathogenesis of non-steroidal anti-inflammatory drug-induced enteropathy, and its disruption is often associated with increased cell shedding. The purpose of this report is to observe the gap density in indomethacin-induced small intestinal damage by confocal laser endomicroscopy (CLE) and to investigate the mechanisms involved in this process and how mucosal protectants improve intestinal epithelial barrier dysfunction...
July 2014: Digestive Diseases and Sciences
Weidong Zhao, Xiaoqin Zhong, Xinying Zhuang, Hongmei Ji, Xinxin Li, Anqing Li, Ruicai Wang, Jianyou Zhu, Yanqing Li
The aim of this study was to assess the effect of Helicobactor pylori (H. pylori) infection and drug therapy on functional dyspepsia (FD) symptoms and gastrointestinal eosinophil count. In this study, 215 continuous FD patients fulfilling Rome III criteria were enrolled. The patients were divided into a H. pylori-positive group and a H. pylori-negative group. The H. pylori-positive group was divided into H. pylori-eradicated and H. pylori-uneradicated groups following H. pylori-eradication treatment, and the H...
July 2013: Experimental and Therapeutic Medicine
Koji Takeuchi, Chitose Izuhara, Shinichi Takayama, Takumi Momode, Masahiro Kojo, Daisuke Hara, Kikuko Amagase
We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y₁₂ receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into the rat stomach, one from the esophagus and another through the pylorus via an incision in the duodenum. In the first model, the stomach was perfused with 25 mM ASA dissolved in 50 mM HCl using an infusion pump, and gastric bleeding was measured as the hemoglobin concentration in perfusate collected every 15 min...
2014: Current Pharmaceutical Design
Ling-Ling Zhu, Ling-Cheng Xu, Yan Chen, Quan Zhou, Su Zeng
AIM: To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal (GI) injury with combined protective medications. METHODS: A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital, School of Medicine, Zhejiang University. The hospital has 2300 beds and 2.5 million outpatient visits annually. Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011...
June 28, 2012: World Journal of Gastroenterology: WJG
Kouichi Sakurai, Akihito Nagahara, Kazuhiko Inoue, Junichi Akiyama, Katsuhiro Mabe, Junichi Suzuki, Yasuki Habu, Akihiro Araki, Tsuyoshi Suzuki, Katsuaki Satoh, Haruhiko Nagami, Ryosaku Harada, Nobuo Tano, Masayasu Kusaka, Yasuhiko Fujioka, Toshikatsu Fujimura, Nobuyuki Shigeto, Tsuneyo Oumi, Jun Miwa, Hiroto Miwa, Kazuma Fujimoto, Yoshikazu Kinoshita, Ken Haruma
BACKGROUND: In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms. METHODS: This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily)...
2012: BMC Gastroenterology
S Takayama, C Izuhara, N Yamada, S Yamanaka, E Hashimoto, S Kaneko, K Takeuchi
We set up a new model of gastric bleeding induced by the luminal perfusion of aspirin (ASA) in rats pretreated with clopidogrel under conditions where acid secretion is stimulated, and examined the effect of antiulcer drugs on the bleeding. Under urethane anesthesia, acid secretion was stimulated by i.v. infusion of histamine (8 mg/kg/h), and two catheters were inserted into the stomach, one from the esophagus and another from the duodenum. The stomach was perfused with 25 mM ASA at a rate of 0.1 ml/min using an infusion pump, and gastric bleeding was measured as hemoglobin concentration in the perfusate collected every 15 min...
February 2012: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Jin-Sup Shin, Udo Abah
A best evidence topic in cardiac surgery was written according to a structured protocol. We address whether routine pharmacological stress ulcer prophylaxis is of benefit for patients undergoing cardiac surgery. One hundred and fifty-six papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group, study type, relevant outcomes and results of these papers were tabulated. The results show that the incidence of stress ulcers following cardiac surgery is low (0...
May 2012: Interactive Cardiovascular and Thoracic Surgery
H Satoh, K Takeuchi
Recent advances in endoscopic techniques such as capsule endoscopy have revealed that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) often cause mucosal lesions not only in the upper gastrointestinal tract, but also in the small intestine in humans. Gastric and duodenal lesions caused by NSAIDs can be treated with anti-secretory agents such as proton pump inhibitors or histamine H2-receptor antagonists; however, these drugs are ineffective in treating NSAID-induced lesions in the small intestine...
2012: Current Medicinal Chemistry
Michio Hongo, Shigeru Harasawa, Tetsuya Mine, Iwao Sasaki, Kei Matsueda, Motoyasu Kusano, Nobuyoshi Hanyu, Koji Nakada, Chikashi Shibata
BACKGROUND AND AIM: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD. METHODS: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled...
January 2012: Journal of Gastroenterology and Hepatology
Masanori Ikeda, Yoshinari Kawai, Kyoko Mori, Masahiko Yano, Ken-ichi Abe, Go Nishimura, Hiromichi Dansako, Yasuo Ariumi, Takaji Wakita, Kazuhide Yamamoto, Nobuyuki Kato
BACKGROUND: Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication. Furthermore, recent reports revealed that the statins are associated with a reduced risk of hepatocellular carcinoma and lower portal pressure in patients with cirrhosis. The statins exhibited anti-HCV activity by inhibiting geranylgeranylation of host proteins essential for HCV RNA replication. Geranylgeranyl pyrophosphate (GGPP) is a substrate for geranylgeranyltransferase...
July 2011: Liver International: Official Journal of the International Association for the Study of the Liver
Shi-Yang Ma, Li-Shou Xiong, Yu-Gang Dong, Xiu-Yan Yang, Xiu-Ren Gao, Jian-Gui He, Liu-Qin Liang, Yi Cui, Min-Hu Chen
OBJECTIVE: To evaluate the side effects of non-steroidal anti-inflammatory drugs (NSAID) on gastric mucosa, and to study the preventive effects of teprenone in patients. METHODS: 108 patients taking NSAID for more than 3 months with no infection of helicobacter pylori (Hp) were collected. All patients were screened by endoscopy and their upper gastrointestinal symptoms were evaluated. Then, 16 patients with ulcers were excluded and 92 patients were randomly divided into intervention group with teprenone and control group...
April 28, 2009: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Qinxin Song, Aidong Wen, Li Ding, Li Dai, Lin Yang, Xiemin Qi
A sensitive HPLC-APCI-MS method for the determination of vitamin K(1) (VK-1) in human plasma was established. Target ions at [M+H](+)m/z 451.5 for VK-1 and [M+H](+)m/z 331.4 for the I.S. (teprenone). Calibration curve was linear over the range of 0.3-1,000 ng/ml. The lower limit of quantification was 0.3 ng/ml. The intra- and inter-batch variability values were less than 8% and 15%, respectively. The C(max) was 210.1+/-86.7 ng/ml while the elimination half-life (t(1/2)) was 8.8+/-1.7h and time to the C(max) was 5...
November 15, 2008: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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