Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 111, Issue 5
Displaying 1-6 of 6 articles from this issue
  • Satoru TAKAHASHI, Susumu OKABE
    1998 Volume 111 Issue 5 Pages 289-296
    Published: May 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Small animal models for Helicobacter pylori (H. pylori) infection have been widely examined and developed. Recently, the novel laboratory strain (the Sydney strain) of H. pylori, having a high ability to colonize the gastric mucosa of normal mice, was established. In the mice infected with the Sydney strain, chronic gastritis slowly develops, progressing to severe atrophy. The Sydney strain may become the standard one for experimental research. On the other hand, mice expressing Leb antigen were genetically produced. H. pylori well colonizes the gastric mucosa of the transgenic mice, but the gastric pathology remains unclear. However, formation of gastric ulcers has not been observed in mice. In contrast, H. pylori chronically infects Mongolian gerbils and causes severe gastritis and gastric ulcers. The H. pylori-induced gastric ulcers do not heal spontaneously, but are cured by drugs. To examine H. pylori colonization in the gastric mucosa and eradication of the bacteria, mouse models are satisfactory. However, in the case of studies on H. pylori-associated gastric pathology, the Mongolian gerbil model is better. Although these models have both merits and demerits, they are useful for elucidation of the pathogenesis of H. pylori-associated diseases and for development of drugs and therapies.
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  • Kazunao KONDO
    1998 Volume 111 Issue 5 Pages 297-301
    Published: May 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    We have established a novel photochemical model of intimal thickening in the rat femoral artery. The endothelium was injured by the photochemical reaction between rose bengal and green light, which was followed by thrombotic occlusion, vascular smooth muscle cells (VSMC) migration and proliferation. The neointima was formed by proliferated VSMC and the extracellular matrix, reaching to maximal thickness within 3 weeks after the endothelial injury. Using this model, we have investigated the effect of several anti-proliferative drugs, anti-allergic drugs, angiotensin converting enzyme inhibitors, prostaglandin E1, anti-thrombotics, or leukotrienes receptor antagonists, on intimal thickening. This model has two major advantages in comparison with other methods: one is that the media is free from mechanical stress, and the model is expected to represent pathological changes close to clinical atherosclerosis. Another advantage is that this method is also applicable to small animals such as mice, including transgenic mice. These advantages are very helpful for investigating the mechanism of atherogenesis.
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  • Kouichirou WADA, Yoshinori KAMISAKI
    1998 Volume 111 Issue 5 Pages 303-308
    Published: May 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    A new gastric ulcer model was developed by the ischemia-reperfusion procedure in rats. The ischemiareperfusion was produced by clamping the celiac artery and subsequent removal of the clamp. Until 36 hr after the ischemia, erosive lesions were observed in the gastric glands. However, 48 and 72 hr after the ischemia, gastric ulcers involving damage of muscularis mucosae were observed. Seven days after the ischemia, the injured areas were covered with regenerated mucosa. This model may be useful for investigating the mechanisms of pathogenesis of gastric ulcer and to evaluate efficacy of drugs.
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  • Hiroshi TAKAGI, Mizuo TAKASHIMA, S.Y. LIOU
    1998 Volume 111 Issue 5 Pages 309-316
    Published: May 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    KB-2796, a novel calcium channel blocker, is under development as an anti-migraine drug. We examined its effects on spreading depression (SD) in rat hippocampal slices as compared with those of flunarizine, dimetotiazine and sumatriptan. Extracellular recording was made from the CA1 subfield. An SD, followed by a series of spontaneous SDs, was induced by a brief period of hypoxia (40-60 sec). The latency of initiated SD and the interval between the initiated and subsequent spontaneous SDs were examined. KB-2796 significantly prolonged both latency and interval in a concentration-dependent manner (10-10-10-8 M). KB-2796 was about 1, 000 and 10 times more potent than flunarizine in prolonging the latency and interval, respectively. However, dimetotiazine and sumatriptan did not show any activity at 10-7 and 10-6 M. The effect of KB-2796 on SD may be due to their calcium channel blocking effects.
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  • Maki KAWASAKI, Isami KIMURA, Akihiko MATSUDA, Mikiko KATAOKA, Yukifumi ...
    1998 Volume 111 Issue 5 Pages 317-325
    Published: May 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    In this study, we attempted to confirm the assessment system of incidence of angialgia and thrombophlebitis by evaluating the influence of test solutions on the vascular permeability by intradermal injection into rat skin, and following results were obtained: 1) Dimensions of dye leakage in the rat skin were not increased by injection of one commercially available preparation (solution 1), but increased significantly by injection of a preparation (solution 2) that had induced a high incidence of angialgia in a clinical study. 2) Dimensions of the dye leakage increased significantly by injection of glucose solutions with about four degrees of osmolality ratio. 3) In the injection of acetate buffers with different titratable acidity, dimensions of the dye leakage increased depending on titratable acidity. 4) Solution 1 was adjusted to pH 4.43 with L-lactate, acetic acid or HCl, and then these solutions were intradermally injected to rats. The influence on dimensions of the dye leakage was in the following order of strength: acetic acid >> L-lactate > HCl. These results suggest that the vascular permeability by intradermal injection into rat skin is influenced by osmolality, pH, titratable acidity and composition of test solutions. Therefore, this system using the vascular permeability reaction in rat skin may be useful for evaluation of angialgia and thrombophlebitis incidence.
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  • Masamitsu TANAKA, Reiko NATSUKI
    1998 Volume 111 Issue 5 Pages 327-336
    Published: May 01, 1998
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    The inhibitory effect of ethanol absorption by zinc cysteine (Cys-Zn) and zinc acetylcysteine (ACys-Zn) were studied in mice. The mice orally received Cys-Zn, ACys-Zn, Cys or Zn acetate, and after 1 hr, 14C-ethanol was given orally or intraperitoneally (i.p.). At various times, blood was drawn from the tail vein and 14C-radioactivities determined. Cys-Zn and ACys-Zn inhibited the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, but Cys and Zn acetate caused no changes as compared to the control. Cys-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The levels of 14C-radioactivity and zinc in the gastrointestinal tract after oral administration (adm) of Cys-Zn and 14C-ethanol were significantly higher than those of the control for 7 hr. At 72 hr after adm, the urinary and fectal excretions of 14C-radioactivity were low when Cys-Zn was given at the dose of 5.0% or 0.5%. The excretion of 14C-radioactivity through expiration in both cys-Zn and control mice was about 28% of the dose at 5 hr after adm. Distributions of 14C-radioactivities in other organs of Cys-Zn treated mice were lower then those of the control. In the vitro study, Cys-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in the 9, 000 g supernatant of the small intestine. The results suggest that zinc complex shows a long-term adhesive and permeable action on the gastrointestinal tract in mice, and this inhibited ethanol absorption.
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