Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 97, Issue 5
Displaying 1-7 of 7 articles from this issue
  • Effects of FOY-305 on reflux esophagitis after total gastrectomy in rats
    Koumei KAMIYASU, Hiroshi AWATA, Shogo INOSHIRI, Akira DOI, Nagashige O ...
    1991 Volume 97 Issue 5 Pages 241-249
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    We investigated the effect of camostat mesilate (FOY-305), an oral protease inhibitor, on reflux esophagitis after total gastrectomy followed by an end-to-side esophago-jejunostomy (Billroth-II) in rats. Effects of FOY-305 were compared with those of sodium alginate (AL-Na) and cimetidine. On the basis that esophageal ulceration occurred from post-operative day 5 in this model, rodents were fed with special chows containing test drugs from day 2 for 5 or 12 days in order to examine the prophylactic effects (Exp. I) and from day 7 for two weeks in healing experiments (Exp. II). In Exp. I, FOY-305 significantly prevented esophageal ulceration on post-operative days 7 and 14. However, AL-Na significantly prevented esophageal ulceration on post-operative day 7 but not on day 14. In Exp. II, FOY-305 had a remarkable therapeutic effect on esophageal ulceration on day 21. Food intake and body weight of rodents in the FOY-305-treated group were higher than those in the control group. In pathohistological studies, FOY-305 elicited an inhibitory effect on ulceration and induced esophageal mucosal regeneration at the ulceration sites. In contrast, AL-Na and cimetidine did not have any significant therapeutic effect. These results suggest that FOY-305 is an effective agent for the treatment of reflux esophagitis after total gastrectomy.
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  • Analysis of mechanism in the pathogenesis of reflux esophagitis after total gastrectomy in rats
    Koumei KAMIYASU, Shogo INOSHIRI, Nagashige OMAWARI, Tadao OKEGAWA, Aki ...
    1991 Volume 97 Issue 5 Pages 251-257
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Esophagitis after total gastrectomy has been associated with biliary and pancreatic reflux into the esophagus. The purpose of this study is to clarify the effect of FOY 305 on these factors in the esophagitis. We initially produced esophagitis in rats with total gastrectomy followed by an end-to-side esophago-jejunostomy (Billroth II) . After treatment of FOY 305 on post-operative day 7 in this model, esophageal washout samples were analyzed for increases in activity of trypsin and total bile acid concentration. FOY-305 completely inhibited increases of trypsin activity in 2 and 4 hr, and it significantly (P < 0.05) reduced bile acid concentration in 4 hr after initiating treatment. In addition, we evaluated the injurious effect of trypsin and sodium taurocholate (Tc-Na) on isolated esophagi of rats by measuring released tyrosine in the medium and used it as an index of the degree of injury. Tc-Na (3-fold of enteral bile acid concentration) inflicted only a slight injurious effect with negligible tyrosine release increases, and it did not show synergistic action when concomitantly used with trypsin. However, trypsin clearly induced increased tyrosine release from the esophageal mucosa, and this effect was significantly (P<0.001) inhibited by FOY-305 (50 μM). These results indicate that trypsin is one of the important factors in the pathogenesis of reflux esophagitis after total gastrectomy, and FOY-305 exerts a therapeutic effect by eliciting an inhibitory action against trypsin activity.
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  • Hisatsugu MIYATA, Naoyuki HIRONAKA, Kiyoshi ANDO
    1991 Volume 97 Issue 5 Pages 259-266
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    In a 2-lever operant chamber situation for food reinforcement, the effects of nicotine, arecoline and physostigmine on delayed discrimination responses in rats treated with ethylcholine mustard aziridinium ion (AF64A) were investigated. AF64A at 6 nmol, i.c.v., decreased the percentage of correct choices (% CR) at the delay time of 4 sec, and this effect depended on the delay time. On the other hand, AF64A at the same dose shortened the latency (LAT: the period from the end of the delay time to the initiation of lever-pressing responses) at the delay time of 16 sec, but this effect didn't depend on the delay time. Nicotine at 0. 25 mg/kg, s.c., improved the decrease of % CR; and at 0.13 ?? 0.5 mg/kg, s.c., it shortened LAT at the delay time of 4 sec in rats treated with AF64A. Arecoline at 4 mg/kg, s.c., and physostigmine at 0.06 ?? 0.5 mg/kg, s.c., extended LAT, but both drugs showed no effects on % CR at the delay time of 4 sec in rats treated with AF64A. These results suggest that the present procedure might be useful for the evaluation of drug effects on memory in rats, and nicotine improved the delayed discrimination disruption induced by AF64A.
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  • Sadayoshi ONODERA, Masaichi YOSHINAGA, Kunizou TAKENAGA, Atsushi TOYOS ...
    1991 Volume 97 Issue 5 Pages 267-276
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Cernitin pollen extract (CN-009), extract from several pollen species, has been used for urinary dysfunction. As its mode of action has not been clarified, we investigated the action of CN-009 on the isolated bladder smooth muscles of rats, guinea pigs and cats and the intravesical pressure in female rats. CN-009 contracted isolated detrusor muscles of rats, guinea pigs and cats in a concentrationdependent manner. In the guinea pig detrusor muscle, the contractile effect of CN-009 was depressed by atropine, diphenhydramine and increased by cimetidine. In the rat detrusor muscle, the CN-009-induced contraction was depressed by atropine. In adult rats (11 ?? 23 weeks old) and aged rats (2 years old), CN-009 showed a dose-dependent increase of intravesical pressure to the same extent in spite of the fact that the aged rats had a lower responsiveness to acetylcholine. In adult rats, the CN-009-induced increase of intravesical pressure was reduced completely by atropine and partly reduced by phentolamine and guanethidine. Three weeks consecutive oral administration of CN-009 tended to increase the basal intravesical pressure and tended to elevate the isoproterenol-induced decrease and serotonininduced increase in the intravesical pressure. These results suggest that CN-009 contracts the detrusor muscle, a process that is mainly mediated by muscarinic receptor activation. The contraction induced by CN-009 of detrusor muscle causes the increase of intravesical pressure.
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  • Masahiko KAGOSHIMA, Noriko TOMOMATSU, Tetsuko FUKUDA, Hiroshi MIKASHIM ...
    1991 Volume 97 Issue 5 Pages 277-286
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    We investigated the effects of Y 20811 on chemical mediator-induced bronchoconstriction and the release of chemical mediators into lung perfusion fluid during arachidonic acid (AA) -induced bronchoconstriction in guinea pigs. Y-20811(0.01 ?? 1 mg/kg, i.v.), like acetylsalicylic acid or indomethacin, dose-dependently suppressed arachidonic acid and LTD4-induced bronchoconstriction, and it (1 mg/kg, i.v.) also inhibited PAF-induced bronchoconstriction in guinea pigs. However, at a dose of 1 mg/kg, i.v., it was inactive against the bronchoconstriction induced by histamine, serotonin and acetylcholine in guinea pigs. Y-20811 (0.3 ?? 10 mg/kg) administered orally also prevented the LTD4-induced bronchoconstriction in a dose-dependent manner. This protective effect of Y-20811 (10 mg/kg, p.o.) persisted for at least 24 hr. Y-20811 (10 mg/kg, p.o.) also inhibited antigen-induced bronchoconstriction in guinea pigs passively sensitized with anti-ovalbumin guinea pig serum and pretreated with mepyramine. In the perfused and ventilated guinea pig lungs, Y-20811 inhibited AA-induced bronchoconstriction, decreased the release of TXA2 (estimated as TXB2) and increased the release of PGE2 into the perfused lung fluid, significantly (TXB2 and PGE2 were measured by HPLC). Therefore, Y-20811 suppressed various stimulant-induced bronchoconstrictions through the decrease of TXA2 production and the increase of PGE2 production. Thus, Y-20811 should prove useful as an antiasthmatic drug.
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  • Ryuichi HOSHINO, Masatoyo KAGOSHIMA, Hideyo SHIMADA
    1991 Volume 97 Issue 5 Pages 287-296
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    We examined the antisecretory and antiulcer activities of NIK-228 in rats. Male Wistar rats (200 to 250 g) were used under 24 to 48 hr fasted (without water) conditions. NIK-228 and famotidine were administered orally 1 hr before pylorus ligation, stress or each ulceration inducer. Both NIK-228 (10 to 100 mg/kg) and famotidine (0.3 to 3 mg/kg) dose-dependently inhibited gastric secretion in pylorus ligated rats. Water-immersion stress-, indomethacin or pylorus ligation (Shay) -induced gastric ulcers were dose-dependently inhibited by NIK-228 (10 to 100 mg/kg), but only water-immersion stress and indomethacin induced ulcers were dose-dependently inhibited by famotidine ( 0.03 to 3 mg/kg). Ethanol and 0.6N HCl-induced gastric lesions were remarkably inhibited by NIK-228 (ED50 = 2.7 and 5.6 mg/kg), but tended to be inhibited also by famotidine (0.3 to 3 mg/kg). Cysteamine-induced duodenal ulcer was inhibited significantly by NIK-228 (30, 100 mg/kg) or famotidine (3 mg/kg). NIK-228 may produce its antiulcer effects via antisecretory and cytoprotective effects. These results suggest that NIK-228 has antisecretory and antiulcer activities.
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  • Izumi KONDO
    1991 Volume 97 Issue 5 Pages 297-306
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    To understand the function of the periodontal ligament as a tooth support, stress-strain curves obtained from the transverse section of the mesial root of the rat mandibular first molar were analyzed following administration of BAPN, known as an inhibitor of collagen cross-linking. An experimental group of rats took drinking water containing 0.2% of BAPN ad libitum for 20 days. Radiographs of the transverse section of the molar root were processed by an image analyzer. Mechanical testing was performed by pushing the tooth out of the surrounding alveolar bone at a loading speed of 7 mm/min in an extrusive direction. Doses of BAPN ranged from 19 to 29 mg/100 g bw/day during the experimental period. By the analysis of stress-strain curves, it was found that the maximum shear stress, the elastic stiffness and the failure strain energy density decreased respectively to 42, 43 and 43 percent of the control values following administration of BAPN. However BAPN did not cause a significant change in the maximum strain. It is supposed that the changes in the mechanical properties of the ligament were caused by the inhibition of cross-linking of periodontal collagen fibers.
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