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Takehisa Hanawa, Yayoi Kawano, Mitsutoshi Satoh
 Anticancer drug-induced stomatitis develops in 30% to 40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan. The "hospital formulation" is a customized medicine which hospital pharmacists prepare when doctors cannot carry out the medical therapy most suitable for a patient using commercial medicines. However, as the duties of pharmacists increase, use of the "hospital fomulation" decreases. Therefore, development of "hospital fomulations" based on individual evidence has a limit...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Man Hagiyama, Norikazu Yabuta, Daisuke Okuzaki, Takao Inoue, Yasutoshi Takashima, Ryuichiro Kimura, Aritoshi Ri, Akihiko Ito
Intraluminal pressure elevation can cause degenerative disorders, such as ileus and hydronephrosis, and the threshold is fairly low and constant, 20-30 cm H2 O. We previously devised a novel two-chamber culture system subjecting cells cultured on a semipermeable membrane to increased culture medium height (water pressure up to 60 cm H2 O). Here, we sought to determine how a continuous pressure load of ~30 cm H2 O affects proliferating epithelial cells with special interest in the link with cell morphology. We cultured several different cell lines using the low static pressure-loadable two-chamber system, and examined cell growth, cell cycle, and cell morphology...
2017: Frontiers in Physiology
Yayoi Kawano, Ayano Imamura, Tomoe Nakamura, Mio Akaishi, Mitsutoshi Satoh, Takehisa Hanawa
The stomatitis caused by anticancer agents and radiation therapy deteriorates patient QOL, potentially causing eating disorders as a result of pain. Although gargling and ointments can be used in the treatment of stomatitis, patients must spit out mouthwash after use, while ointment application requires a finger to be inserted into the oral cavity. In contrast, sprays eliminate these potential compliance problems. Therefore, we developed a stomatitis spray that remains on the oral mucosa. It has been reported that irsogladine maleate (IM) is effective against stomatitis via oral administration...
December 1, 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
Tomoo Nakagawa, Tatsuro Katsuno, Yoshiko Noguchi, Yasushi Mandai, Sayuri Yoshihama, Keiko Saito, Daisuke Maruoka, Tomoaki Matsumura, Makoto Arai, Osamu Yokosuka
Irsogladine maleate (2,4-diamino-6-[2,5-dichlorophenyl]-s-triazine maleate; IM), an anti-peptic ulcer drug, may have a protective effect on the gastrointestinal mucosa. This study investigated the effects of IM on spontaneous colitis in interleukin-10 gene-deficient (IL-10(-/-)) mice. Five-week-old IL-10(-/-) mice were fed a control diet or one containing 100 ppm of IM for 10 weeks. Colonic tissues were evaluated morphologically and histologically. J774A.1 murine monocyte/macrophage cells were incubated with IM after lipopolysaccharide stimulation...
2015: Biological & Pharmaceutical Bulletin
Yuichi Kojima, Toshihisa Takeuchi, Kazuhiro Ota, Satoshi Harada, Shoko Edogawa, Ken Narabayashi, Sadaharu Nouda, Toshihiko Okada, Kazuki Kakimoto, Takanori Kuramoto, Takuya Inoue, Kazuhide Higuchi
This study assessed time-course changes of the small intestinal lesions during long-term treatment with diclofenac sodium plus omeprazole and the effects of irsogladine on such lesions. Thirty two healthy volunteers were treated with diclofenac sodium (75 mg/day) plus omeprazole (10 mg/day) for 6 weeks, with irsogladine (4 mg/day) added from weeks 6 to 10 (Group A) or with diclofenac sodium plus irsogladine for 6 weeks (Group B). Five volunteers received diclofenac sodium plus omeprazole for 10 weeks (Group C)...
July 2015: Journal of Clinical Biochemistry and Nutrition
Takayoshi Suzuki, Masashi Matsushima, Aya Masui, Shingo Tsuda, Jin Imai, Jun Nakamura, Yoko Tsukune, Tetsufumi Uchida, Hiroki Yuhara, Muneki Igarashi, Jun Koike, Tetsuya Mine
AIM: To evaluate the efficacy of adding irsogladine maleate (IM) to proton-pump inhibitor (PPI) therapy in non-erosive reflux disease (NERD) treatment. METHODS: One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM (group I) or rabeprazole plus placebo (group P). The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and the short form (SF)-36 quality of life questionnaires after four weeks of treatment...
April 28, 2015: World Journal of Gastroenterology: WJG
Ryo Miyata, Kazuaki Nomura, Takuya Kakuki, Ken-Ichi Takano, Takayuki Kohno, Takumi Konno, Norimasa Sawada, Tetsuo Himi, Takashi Kojima
The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA...
April 2015: Journal of Membrane Biology
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
I J Savitri, K Ouhara, T Fujita, M Kajiya, T Miyagawa, M Kittaka, M Yamakawa, H Shiba, H Kurihara
BACKGROUND AND OBJECTIVE: Periodontitis is an infectious disease caused by an interaction between the host and periodontopathogenic bacteria. Regulating the immune response in human gingival epithelial cells (HGEC) may contribute to the prevention of periodontitis. Irsogladine maleate (IM) has previously been shown to regulate inflammation and the cell-cell junctional barrier in HGEC. In addition to these functions, control of bacterial recognition is important for preventing inflammation in periodontal tissue...
August 2015: Journal of Periodontal Research
Yoshihiro Isomura, Yutaka Yamaji, Atsuo Yamada, Yoshitaka Watanabe, Hirobumi Suzuki, Yuka Kobayashi, Shuntaro Yoshida, Hirotsugu Watabe, Yoshihiro Hirata, Haruhiko Yoshida, Kazuhiko Koike
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause a high frequency of mucosal injuries in the small intestine. However, no reliable intervention, other than cessation of NSAIDs, has been established. OBJECTIVE: To evaluate whether irsogladine maleate reduces these injuries while continuing NSAID therapy. DESIGN: Prospective, interventional, endoscopist-blinded, randomized, controlled trial (RCT). SETTING: University hospital...
July 2014: Gastrointestinal Endoscopy
Hiroshi Satoh, Kikuko Amagase, Koji Takeuchi
Antisecretory drugs such as histamine H₂-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for the treatment of this complication. We examined the effects of mucosal protective agents (MPAs) (misoprostol, irsogladine, and rebamipide) and mucin of porcine stomach on diclofenac-induced intestinal lesions and the exacerbation of the lesions by ranitidine or omeprazole...
February 2014: Journal of Pharmacology and Experimental Therapeutics
M Sagawa, J Shibuya, S Takahashi, C Endo, M Abiko, H Suzuki, Y Matsumura, T Sakuma, N Sato, H Deguchi, Y Nakamura, T Hasumi, T Kondo
AIM: Although angiogenesis plays an important role in the invasion and metastasis of solid tumors, very few anti-angiogenetic drugs have been developed. Reexamining the anti-angiogenetic effects of existing drugs such as Thalidomide is another possible strategy for drug discovery. Irsogladine maleate (IM) is a drug invented to treat gastric ulcers; however, several reports have shown that IM also exerts anti-angiogenetic effects in vitro, in vivo and in humans. In order to elucidate whether treatment with IM would improve the prognoses of patients with resected lung cancer, we conducted a randomized trial...
December 2013: Minerva Chirurgica
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
Takanori Kuramoto, Eiji Umegaki, Sadaharu Nouda, Ken Narabayashi, Yuichi Kojima, Yukiko Yoda, Kumi Ishida, Ken Kawakami, Yosuke Abe, Toshihisa Takeuchi, Takuya Inoue, Mitsuyuki Murano, Satoshi Tokioka, Kazuhide Higuchi
BACKGROUND: Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects. METHODS: Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days...
2013: BMC Gastroenterology
Nobuhiko Hayashi, Joseph George, Hisakazu Shiroeda, Takashi Saito, Nobuyuki Toshikuni, Mutsumi Tsuchishima, Tomiyasu Arisawa, Mikihiro Tsutsumi
BACKGROUND AND AIM: Aphthous stomatitis is one of the adverse effects associated with interferon (IFN) that forces dose reduction of IFN and there is no established therapy. This study was aimed to investigate whether irsogladine maleate, which enhances the functions of intercellular communication through the gap junctions, is effective for the treatment of aphthous stomatitis developed in hepatitis C virus (HCV) patients on pegylated-interferon (PEG-IFN) and ribavirin. METHODS: Nineteen patients with HCV were treated with PEG-IFN and ribavirin for 48 weeks...
June 2013: Journal of Gastroenterology and Hepatology
Tsuyoshi Miyagawa, Tsuyoshi Fujita, Kazuhisa Ouhara, Shinji Matsuda, Mikihito Kajiya, Kouichi Hayashida, Haruka Imai, Tetsuya Yoshimoto, Tomoyuki Iwata, Hideki Shiba, Yoshimitsu Abiko, Hidemi Kurihara
Periodontitis is an infectious inflammatory disease. Our previous studies have revealed that irsogladine maleate (IM) regulates intercellular junctional function and chemokine secretion in gingival epithelium, resulting in the suppression of the onset of periodontal disease in a rat model. Therefore, it is plausible that IM is a promising preventive remedy for periodontal disease. In this study, to gain a better understanding of IM in gingival epithelial cells, we employed a DNA microarray analysis. More specifically, human gingival epithelial cells (HGEC) were exposed to Aggregatibacter actinomycetemcomitans (A...
February 2013: International Immunopharmacology
M Nomura, M Kamata, H Kojima, K Hayashi, S Sawada
BACKGROUND: Oral mucositis is one of the most common side-effects of 5-fluorouracil (5-FU)-based chemotherapy. The objective of this study was to evaluate the effects of irsogladine maleate (IM) on fluorouracil-induced oral mucositis through a double-blind, placebo controlled trial. PATIENTS AND METHODS: Patients (N = 66) were randomly assigned to receive either placebo or IM (4 mg/day for 14 consecutive days). The incidence and maximum severity of fluorouracil-induced oral mucositis and safety of the irsogladine dosing regimen were evaluated...
April 2013: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Hana Yamaguchi, Kenji Suzuki, Masaki Nagata, Tomoyuki Kawase, Vijayakumar Sukumaran, Rajarajan A Thandavarayan, Yusuke Kawauchi, Junji Yokoyama, Masayuki Tomita, Hiroshi Kawachi, Kenichi Watanabe, Hiroyuki Yoneyama, Hitoshi Asakura, Ritsuo Takagi
Intestinal fibrosis is a common and severe complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). To investigate the therapeutic approach to intestinal fibrosis, we have developed a mouse model of intestinal fibrosis by administering dextran sulfate sodium (DSS) and examining the effects of irsogladine maleate (IM) [2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate], which has been widely used as an antiulcer drug for gastric mucosa in Japan, on DDS-induced chronic colitis. In this experimental colitis lesion, several pathognomonic changes were found: increased deposition of collagen, increased number of profibrogenic mesenchymal cells such as fibroblasts (vimentin(+), α-SMA(-)) and myofibroblasts (vimentin(+), α-SMA(+)) in both mucosa and submucosa of the colon with infiltrating inflammatory cells, and increased mRNA expressions of collagen type I, transforming growth factor (TGF)-β, matrix metalloproteinase (MMP)-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1...
June 2012: Medical Molecular Morphology
Michiyo Akagi, Kikuko Amagase, Toshiko Murakami, Koji Takeuchi
Irsogladine, a mucosal protective drug, was developed in Japan for the treatment of peptic ulcer disease and acute gastritis. This drug is superior to gefarnate, the same therapeutic category drug, in a randomized, controlled and double-blind clinical study in 1987. The mechanisms of irsogladine's actions are apparently different from those of antisecretory drugs. Irsogladine increases intracellular cyclic adenosine 3',5'-monophosphate content via non-selective inhibition of phosphodiesterase isozymes and exhibits gastric cytoprotection partly mediated by endogenous nitric oxide...
2013: Current Pharmaceutical Design
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