Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 78, Issue 2
Displaying 1-7 of 7 articles from this issue
  • Susumu OKABE, Masayuki KAWAKAMI
    1981 Volume 78 Issue 2 Pages 57-62
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    Antisecretory effects of ranitidine on secretagogue-stimulated gastric secretion in acute fistula rats were studied. Histamine 2HCl (8mg/kg/hr), pentagastrin (125μg/kg/hr) or carbachol (128μg/kg/hr) was continuously given i. v. by an infusion pump, through the tail vein to acute fistula rats. Gastric secretion was collected hourly for 5hr and analyzed for its components. Cimetidine was used as a reference drug. Both drugs were given ix. by a bolus injection in the tail vein 30min after the injection of each stimulant. Both ranitidine (1 and 10mg/kg) and cimetidine (10 and 60mg/kg) significantly (P<0.05) inhibited the histamine-stimulated gastric secretion (volume, acid and pepsin output) for 1 to 4hr. Both ranitidine (10mg/kg) and cimetidine (60mg/kg) significantly (P<0.05) inhibited the pentagastrin-stimulated gastric secretion for 2 to 3hr. Both ranitidine (10mg/kg) and cimetidine (10 and 60mg/kg) markedly inhibited the gastric acid secretion in response to carbachol. However, cimetidine (10 or 60mg/kg) significantly (P<0.05) stimulated the volume and pepsin output by carbachol. We conclude that ranitidine is about 6 times more potent than cimetidine for histamineor pentagastrin-stimulated gastric secretion and almost equal to cimetidine for carbachol-stimulated gastric acid output in rats.
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  • Hikaru NAGATOMI, Shigeo MITSUHIRO, Tadaatsu OGITA, Yutaka MIZUSHIMA
    1981 Volume 78 Issue 2 Pages 63-70
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    We studied the binding activities especially the binding to the cartilage of the specific antibodies, which were purified from a new therapeutic agent of osteo-arthrosis, Artroglobina using several tissue materials. A purified specific antibodies pre-adsorbed with the pig liver and muscle homogenates lost the binding activity to the pig heart but retained the specific activity to the pig cartilage. The same results were obtained with the tissues from the rat and the hen. It also had the same activity on human cartilage, and the adsorption with the cartilage from either pig or human led the complete loss of the binding activity to the human cartilage. Evidence of the specific activity of these purified specific antibodies to the human cartilage in vitro suggests that further studies are warranted as a similar specific binding reaction of Artroglobina to the cartilage, in situ may occur of patients with osteo-arthritis and who are being treated clinically.
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  • Hidetaka NARIKAWA, Reiko OYAMA, Shoichi HARIGAYA
    1981 Volume 78 Issue 2 Pages 71-78
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    As quaternary ammonium compounds are generally not absorbed from gastric mucosa, the direct action of these compounds on the gastric mucosa can be investigated by means of intragastric (oral) administration to pylorus ligated animals. Effects of timepidium bromide (TB), an anti-cholinergic quaternary ammonium compound, on gastric secretion of pylorus ligated rats were investigated. When TB (100mg/kg) was administered orally, the secretion volume of gastric juice decreased slightly, while the concentrations of free acid and pepsin in gastric juice decreased remarkably. When TB was administered intraduodenally (100mg/kg) or subcutaneously (10mg/kg), secretion of gastric juice and free acid was strongly inhibited, but the pepsin concentration in gastric juice was not influenced (i. d.) or slightly increased (s. c.). In the oral administration of various drugs such as atropine, hyoscine-N-butylbromide and oxethazaine (Ox), only Ox caused a decrease in pepsin concentration in gastric juice. Similar effects of TB on the pepsin concentration in the gastric juice were also observed in experiments using stomach perfused rats. TB has no effect on enzymatic activity ofpepsin in in vitro experiments. From these results, it is assumed that TB inhibits acid and pepsin secretion mainly by a direct action on the gastric mucosa.
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  • Tsutomu SUZUKI, Teiko KAWAI, Jiro UESUGI, Toshio YOSHII, Saizo YANAURA
    1981 Volume 78 Issue 2 Pages 79-90
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    We examined the quantitative evaluation of preference for morphine by assessing the conflict behavior between positive motivation and negative motivation. The apparatus consisted of a single runway in which both the usual diet and morphine-admixed food were placed. For access to the latter, the rats were compelled to pull heavy weights which were connected to their necks. During the forced trials (only morphine-admixed food was given) and the choice trials (rats could select either food), the preference rates gradually increased and then became stable at levels of 60%. After these trials, experiments on conflict behavior were performed using several different weights. Assessment of relation between the intensity of the dependence on the drug and the degree of weight showed a good correlation. We conclude that the preference for a drug can be quantitatively measured by means of assessing conflict behavior.
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  • Sadao NAKAYAMA, Mitsuaki SAKASHITA, Tadasuke NISHIMURA, Kohji SAKAMOTO
    1981 Volume 78 Issue 2 Pages 91-107
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    Experimental hyperlipemia induced by a high cholesterol diet (HCD) in male Sprague-Dawley rats was investigated by measuring lipid levels in serum, liver and aorta. Four old rats were fed a laboratory chow diet containing 0.5, 1.0 and 2.0% of cholesterol, for 6 weeks. Serum total lipid (TL) and total cholesterol (TC) in 1.0% HCD were markedly increased and reached peaks by feeding HCD for 18 to 21 days. Although the degree of increase in serum TL and TC was similar in both 0.5 and 2.0% HCD groups, these levels decreased more rapidly in the former and more slowly in the latter, after the levels had been reached a peak. The serum free cholesterol level reached a peak in those fed 0.5% HCD for 12 days and those fed 1.0% HCD for 21 days, but the subsequent reduction was smaller in extent as compared with serum TL and TC. Serum phospholipid (PL) level reached a peak in those fed both 0.5 and 1.0% HCD groups for 12 days and this level was maintained until 42 days in the 1.0% HCD group. Serum triglyceride (TG) levels increased during the fast half of the experimental period, but decreased in the second half, with no significant difference between the 0.5 and 1.0% HCD groups. Cholesterol in high density lipoprotein (HDL-C) decreased in rats on the HCD and there was a tendency toward reversion to normal levels from the 4th week in the group on the 2.0% diet, however, a continual decrease occurred in the 0.5 and 1.0% groups. The change in phospholipid in HDL (HDL-PL) was similar to that of HDL-C in both the 0.5 and 1.0% HCD groups. In liver lipids, TL and TC were markedly increased by HCD, but TG increased at first and then decreased as did serum TG. Liver PL decreased by 0.5 and 1.0% HCD groups. In aorta lipids, TL and TC decreased. As a remarkable increase in serum lipids and decrease in HDL-C and HDL-PL were continuous in the 1.0% HCD in comparison with 0.5 or 2.0% HCD, 1.0% HCD appears to be the most suitable experimental model of hyperlipemia in rats. In addition, it is considered that 0.5% HCD is suitable for investigation of the effect of a drug for a relatively short period of treatment.
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  • Hikaru NAGATOMI, Shigeo MITSUHIRO, Tadaatsu OGITA, Yutaka MIZUSHIMA
    1981 Volume 78 Issue 2 Pages 109-115
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    The absorption of and specific antibody formation to Artroglobina (: AG, β and γ-globulin fractions of anticartilage-antiparathyroid immune serum from the horse) administered into the rectum were studied in rats and guinea-pigs, and immunological tests in the “Phase I Study” were carried out using serum from volunteers. 1) When the radio-labelled AG (125I-AG) was administered into the rat rectum, the plasma level of 125I reached the maximum (3.1% of the total dosage) at 2 hour later and 0.3 per cent of the total dosage retained the reactivity with the anti Fab antibody. 2) Gel diffusion and PCA tests gave positive reactions in the sera after the second administration of AG in a dose of 20mg/kg, corresponding to 40 times the clinical dose, with a certain interval after the first treatment. From the results, it was confirmed that rectally-administered AG induces mainly IgG or IgE antibody formation, in the rat. 3) The administration of AG through the rectum did not induce the systemic anaphylaxic reaction in the guinea-pigs which had been administered AG into the rectum. The intravenous challenge, however, resulted in a positive anaphylaxis reaction in animals treated with AG rectally. This indicates the sensitization of the animal with AG by the rectal administration. 4) The specific antibody responses, immune complexes and complement values did not change in the sera of volunteers given AG which consisted of alternating cycles of twelve days of treatment with one suppository daily, and twelve days without treatment, in a clinical dose of 25mg. Nevertheless, AG must be carefully prescribed as higher doses given to experimental animals induced adverse immunological effects.
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  • Hiroyoshi NISHI, Akira ISHIBASHI, Daijiro HORII
    1981 Volume 78 Issue 2 Pages 117-126
    Published: 1981
    Released on J-STAGE: July 30, 2010
    JOURNAL FREE ACCESS
    The effects of intravenous administration of suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol], (MY 103) on cerebral venous outflow (VOF), blood gases, cerebral metabolic rate of oxygen (CMRO2) and other hemodynamic parameters were studied and effects compared to those of cinnarizine and papaverine, in gallamine immobilized dogs. MY 103 and papaverine at doses 0.1_??_1.0mg/kg, i. v. caused significant increases in VOF by 6.1_??_38.3% and 12.1_??_26.1%, respectively. The changes in VOF persisted for 1.4min and 0.5min in mean following 1.0mg/kg, i. v. of MY 103 and papaverine, respectively. Cinnarizine also increased VOF by 10.0 and 18.7% at doses 0.3 and 1.0mg/kg, i. v.. The duration of VOF changes by cinnarizine 1.0mg/kg, i. v., 2.4min (mean), was longer than the duration seen with the same dose of MY 103 or papaverine. Mean blood pressure (MBP) decreased dose dependently with these drugs and consequently the cerebral vascular resistance (CVR) decreased by 8.6_??_40.2% with MY 103, 13.6_??_25.0% with cinnarizine and 16.1_??_39.5% with papaverine administration, respectively. MY 103 and papaverine at a dose of 1.0mg/kg, i. v. did not affect pH, Pco2 and Po2 in arterial blood, but these two drugs did show a tendency to lower Pco2 and elevate Po2 in cerebral venous blood. CMRO2 was not significantly affected by MY 103 or papaverine. It is suggested that cerebral vasodilation may be the mechanism for VOF increase following MY 103 administration.
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