Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 76, Issue 2
Displaying 1-8 of 8 articles from this issue
  • Masaki TAKAHASHI, Yoshio AIZAWA
    1980 Volume 76 Issue 2 Pages 93-97
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Effects of intra-uterine or tail vein administration of prostaglandin (PG) F on hormone levels in ovaries were studied. Adult Wistar rats weighing 150-180 g were used. PGF was injected into the uterine lumen (100 ng/rat) and tail vein (200 ng/0.1 ml) of estrus rats, respectively, and intra-uterine administration of PGF was given to hypophysectomized rats. Variation in the levels of ovarian steroids (estradiol, progesterone, 20a-hydroxypregn-4-en-3-one (20α-OH-P)) were studied. The amount of PGF injected into rats was minute compared with that of the usual PGF injection (μg/0.1 ml). Before start of the experiments, the levels of ovarian steroids of adult rats in all stages of estrous were measured. Each of the three steroids showed a maximum level at the time of proestrus. When PGF was administered into the uterine lumen and tail vein of rats, the level of estradiol increased gradually, while that of progesterone and 20α-OH-P decreased sharply at 10 min (p<0.05) after administration. On the other hand, when PGF was given into the uterine lumen of hypophysectomized rats, the reverse pattern was seen, that is, estradiol decreased, whereas progesterone and 20α-OH-P gradually increased. Thus, the intrauterine administration of PGF does have an effect on levels of ovarian steroids.
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  • Kentaro KOGI, Satoshi CHIDA, Tetsuo KIMURA, Teruo SAITO
    1980 Volume 76 Issue 2 Pages 99-107
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Oral administration of isosorbide dinitrate (ISDN), 1 ?? 2 mg/kg, resulted in a dose-dependent decrease in the pulse pressure by reducing the systolic pressure and slightly elevating the diastolic pressure in conscious dogs. Therefore, this system was employed to evaluate the effectiveness of the sustained-release ISDN tablet as compared with that of the standard tablet. Four standard tablets (20 mg of ISDN) given in a single dose significantly decreased the pulse pressure, which became lowest at 2 hr after administration and returned to the near original level at 6 hr. On the other hand, with four sustained-release tablets (80 mg of ISDN) 4 hr was required to produce a maximum decrease, and at 10 hr, the pulse pressure was still much lower than the original level. The plasma concentration of ISDN was measured by a gas chromatographic method. The time course of the plasma concentration of ISDN after administration of each preparation was correlated with that of the decrease in pulse pressure. This suggests that the system employed is useful in evaluating the bioavailability of various preparations of organic nitrates (ISDN). In addition, these data demonstrate that the sustained-release formulation of ISDN possesses a prolonged pharmacological effect.
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  • Kenji ONODERA, Shinobu SAKURADA, Ryuichiro ANDO, Norio TAKAHASHI, Take ...
    1980 Volume 76 Issue 2 Pages 109-115
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Male Wistar rats, 35-days-old, maintained on a thiamine deficient diet for 30 days showed marked growth inhibition and a heart rate less than 70% of that of control rats. We examined the effect of thiamine deficiency on the action of drugs effecting the central nervous system at this period. In thiamine deficient rats treated with chloral hydrate 200 mg/kg, ketamine 100 mg/kg, sodium pentobarbital 50 mg/kg, and hexobarbital 100 mg/kg, the sleeping time increased. Pretreatment with 15 mg/kg of the metabolic enzymes inhibitor, SKF-525A, 30 min prior to the hexobarbital administration resulted in prolongation of sleeping time in all groups. The thiamine deficient rats slept almost 3.5 times longer than did the control group. Pretreatment with 100 mg/kg of the metabolic enzyme inducer, sodium phenobarbital, 48 hours prior to hexobarbital treatment resulted in decreased sleeping time in all groups, as compared with only hexobarbital treatment. In the thiamine deficient rats, the catalepsy and ptosis induced by the i.p. administration of tetrabenazine 50 mg/kg was reduced even when the control and pair-fed groups responded to this drug at the drug peak time. The spontaneous neuronal activity of lateral hypothalamus was most sensitive to the administration of 5-hydroxytryptophan in thiamine deficient rats.
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  • Evaluation of anti-rheumatic action
    Hajime FUJIMURA, Yasuzo HIRAMATSU, Yohei TAMURA, Masayoshi YANAGIHARA, ...
    1980 Volume 76 Issue 2 Pages 117-129
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Oral administration of 2-mercapto-2-methylpropanoyl-L-cysteine (SA 96), a newly synthesized sulfhydryl compound, showed protective and curative effects on adjuvant-induced arthritis in rats similarly to those seen with D-penicillamine (D-PA). However, the effects of these compounds were not dose-dependent, and the maximum effects of SA96 were observed at 10 mg/kg/day. On the contrary, SA96 and D-PA had little effect on the various acute and subacute inflammatory responses induced in rat and mice. Formation of hemolytic plaque forming cells in the spleen of mice immunized with 5×108 sheep red blood cells was potentiated by the oral administration of both compounds. These stimulatory effects of SA96 and D-PA on the humoral immune responses were also not dose-dependent, and the maximum effects of SA96 were observed with 10 mg /kg/day, as in the case of adjuvant-induced arthritis in rats. In in vitro experiments, the inactivation of rheumatoid factor and the inhibition of collagenase and bone alkaline phosphatase activities were observed with both compounds, but these effects of SA96 were more potent than those of D-PA. As there is a similarity in the pharmacological profiles of SA96 and D-PA, SA96 may prove to be clinically effective for rheumatoid arthritis.
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  • Shoichi MATSUMURA, Eiichi MORISHIGE, Osamu UNO, Motohiko UEDA
    1980 Volume 76 Issue 2 Pages 131-141
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Cardiovascular effects of dobutamine (DOB), isoproterenol (Iso), and dopamine (DA) were compared in Beagle dogs weighing 6.8 to 11.6 kg under experimental shock produced by ligation of the left coronary arteries and intravenous administration of hexamethonium-Br (10 mg/kg). Intravenous infusion of DOB (1 ?? 20μg/kg/min) dose-dependently improved the hemodynamic state of shock by increasing left ventricular dp/dt (LVdp/dt), cardiac output (CO), and blood pressure. These improvements were also observed with the infusion of DA (20 ?? 40hg/kg/min). However, the improvement with Iso (0.01 ?? 0.2μg/kg/min) was incomplete because of the marked fall of total peripheral resistance. Both DOB and DA increased the venous return, pressure in the inferior vanae cavae, and pressure difference between venous pressure and left ventricular end diastolic pressure. It was presumed that these effects were related to the stimulation of the a receptor in the venous system, in addition to the marked positive inotropic effects by DOB or DA. Iso increased significantly only the venous return. Although increases of coronary flow with DOB and DA are probably mainly due to an increase of myocardial oxygen consumption, the increase of coronary perfusion pressure also may contribute to the increase of coronary flow. As a result, myocardial oxygen balance was improved with DOB or DA. α stimulation in the venous system as well as β1 stimulation apparently contributes to improvement of the deteriorated hemodynamic state, in experimental shock, as induced in dogs.
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  • Kenji ONODERA, Kensuke KISARA, Haruo OKABE, Yasumi OGURA
    1980 Volume 76 Issue 2 Pages 143-152
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Using male rats fed a thiamine deficient diet from the age of 35-days, an investigation was made of the effects on testicular tissue after 30 days of thiamine deficiency. It was found that : 1) In the thiamine deficient group, the seminiferous tubuli of rats having erections had atrophied and there was a decrease in the number of primary spermatocytes and spermatogonium, but a moderate increase in the number of sertoli cells. Furthermore, spermatids and spermia were rarely seen in tubuli which contained multinuclear giant cells. In the group of rats not having erections, moderate interstitial edema was seen and there was notable degeneration and reduction in the number of primary spermatocytes and spermatogonium. 2) In the group injected with thiamine hydrochloride after 21 days of thiamine deficient feeding, moderate interstitial edema was seen and the seminiferous tubuli were atrophic. 3) In the pair-fed group, there was a marked edema of interstitial tissue and an atrophy of seminiferous tubulus. 4) With regard to the effects of thiamine deficiency on the polyamine contents of the testicles, there was a marked decrease in spermidine content on the 12th day of feeding and a marked increase of spermine content on the 30th day. The spermidine/spermine ratio, which is high during periods of active cell differentiation and proliferation, was found to be significantly decreased in the thiamine deficient animals on both the 12th and 30th days of thiamine deficiency. Thus, it was clarified that thiamine deficiency causes disturbances in cell differentiation and proliferation in rat testes.
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  • Teruo KUDO
    1980 Volume 76 Issue 2 Pages 153-167
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Salivary flow and amylase secretion induced by substance P(SP) administered intraventricularly were considerably less than that by SP given intravenously (i.v.). Salivary flow induced by SP (i.v.) was partially inhibited by baclofen, atropine, d-tubocurarine, alcuronium, phenylephrine and PGE2, while it was enhanced by arachidonic acid and indomethacin. Salivary amylase secretion induced by SP given i.v. was enhanced markedly by isoproterenol, phenoxybenzamine, phentolamine and No. 865-123 (an adrenergic neuron blocking agent), and moderately by baclofen, PGE2 and arachidonic acid, while it was not influenced by propranolol. The enhancements of amylase secretion by adrenergic α-blockers were completely inhibited by propranolol. The in vitro examination using rat brain synaptosomes showed that SP promoted markedly the synthesis of PGs, especially of PGE2. These results suggest that the SP-receptor has a nicotinic receptor-like property and may be closely related to adrenergic α-receptors situated postsynaptically and presynaptically and to postsynaptic PGE2-receptors. From these results, it is concluded that SP-induced salivary flow and amylase secretion are modulated by the promotion of PGs synthesis in the autonomic nervous system.
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  • Relationship between the onset of motor incoordination and mercury contents in the brain
    Eijiro TAGASHIRA, Tomoko URANO, Saizo YANAURA
    1980 Volume 76 Issue 2 Pages 169-177
    Published: 1980
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Mice were given one or repeated administrations of methylmercury chloride (MMC) in an attempt to determine the sexual differences as related to toxic signs, particularly, motor incoordination and the period to evolvement of toxicity. Male and female mice were given 50.6 mg/kg of MMC (about equal to the LD50 in female mice) orally only once, and changes in general behavior and mortality were observed for the following 13 days. Another group of male and female mice was fed food containing 50 and 100 ppm of MMC for 30 days, respectively. The rotarod performance test was carried out daily during the application period, to compare the onset stages of toxic signs and motor incoordination between the groups. The mercury content of the brain was measured at 1-to 2-day intervals during the application period. When the animals were given MMC only once, the males began to die at 3 days, 7/8 of the group dying by the 7th day, while the females began to die at 8 days, with 5/8 of the group dying thereafter: there was thus an obvious sexual difference in the toxicity. When the animals were given MMC admixed with food, however, the females proved more sensitive to the compound both in onset and severity of toxic signs. The onset was seen in the females at the stage when they had ingested about half the amount of the toxic food ingested by the males. The onset and the period in days to the onset of suppressed rotarod performance both in the groups on 50 and 100 ppm were correlated to the daily intake of MMC, the total MMC intake to the onset in the 2 groups being similar. The accumulation of mercury in the brain increased linearly in both groups, with the MMC content of the brain at the onset was about 20 μg Hg per g of brain (on the wet basis), i.e., about twice that of the human brain. The mercury content in the brain of the female mice tended to reach the toxicity threshold earlier than that in the brain of the males.
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