Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 98, Issue 6
Displaying 1-9 of 9 articles from this issue
  • Tomoko FUJII
    1991 Volume 98 Issue 6 Pages 419-434
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Increasing numbers of neurotoxins or therapeutic agents that have specific target cells or receptors can be used to assess the developmental correlation between the structure and function of various organs including the brain. Patients with chronic diseases are now able to maintain their social activities but still must be medicated for a long period of their life. This might increase the potential hazard of prenatal drug exposure in the progeny. Functional teratology is quite a new concept in neuroscience. Recent observations of our laboratory and those of others suggest that the sensitive period for functional teratology might encompass the whole stage of fetal life in animals and humans. The shortage of precise information on the developmental integration of the structure and function of the neurons with different properties is a problem to be solved for the further progress of developmental pharmacology and toxicology. Single exposures to drugs at a different stage during the gestational period of rats or mice might provide more useful information on the relationship between the lesioned area and related functional disorders manifested postnatally. This paper reviews recent advances in developmental neuropharmacology and functional neuroteratology including beneficial points of the short-term exposures to drugs.
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  • Shin-ichi MORISHITA, Masamichi SHOJI, Yasuhiro OGUNI, Chishio SUGIMOTO ...
    1991 Volume 98 Issue 6 Pages 435-442
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Pharmacological effects of Reiousan, a crude drug preparation consisting of bezoar and ginseng, on experimental cerebral ischemia and anoxia were studied. After administration of Reiousan, the survival time of mice subjected to hypobaric hypoxia and the gasping duration of isolated rat head tended to increase. Reiousan inhibited all the following: lipid peroxides production in rat brain homogenate, tissue swelling induced by the xanthine-xanthine oxidase system in rat brain cortical slices, rat brain swelling induced by freezing, lipid peroxides production in the rat brain after ligation of bilateral common carotid arteries, and lipid peroxides production in Mongolian gerbil brain after reperfusion following ligation of bilateral common carotid arteries. These effects may result from antioxidant activity of bilirubin, a constituent of bezoar.
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  • Shozo TAKAMURA, Junko YOSHIDA, Shiro SUZUKI
    1991 Volume 98 Issue 6 Pages 443-448
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Ehrlich ascites tumor cells (EAT) could not proliferate in a basal medium (BM) . L-Cysteine (L-CYS) added to BM in a concentration of 0.5 to 2 mM could promote the growth of EAT. At an usual concentration of L-CYS (1 mM), the growth-rate was 233% (n = 50) at 72 hr after EAT transplantation. A similar growth-rate was obtained when EAT was transplanted 24 hr after addition of L-CYS to BM, although the free SH content in L-CYS-added BM at this time decreased to the level of that in BM. S-Methyl and S-benzyl-L-cysteine showed no growth-promoting effect. The metabolic products of L-CYS (L-cysteine sulfinic acid, hypotaurine and taurine) showed a lower effect or none, but L-cystine showed the same activity as L-CYS. The EAT cultured in L-CYS-added BM was found to have an increased intracellular free SH and unchanged protein SH. These findings suggest that L-CYS added to BM is changed in a non-SH compound (possibly L-cystine) that is taken up into the cells and increases the intracellular free SH, resulting in the cell growth promotion.
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  • Tomoaki MIYAZAWA, Chie MURAYAMA, Hidehiko NAKAGAWA
    1991 Volume 98 Issue 6 Pages 449-456
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Lisuride is an ergot derivative with central dopaminergic (D2 agonistic) and serotonergic (5-HT1A agonistic) activity. The effect of lisuride on experimental cerebral infarction in rats was investigated. Cerebral infarction was induced by intracarotid infusion of a 50-μl mixture in which deformed and rigid red blood cells treated with hypertonic solution were contained. Lisuride or 0.9 % NaCl was administered subcutaneously 30 min before induction of cerebral infarction. Lisuride (0.01 mg/kg) not only prolonged the survival time of the animals but also suppressed cerebral edema, increase in the electrolytes content and histological damage in the brain. These results suggest that lisuride has a protective effect against cerebral infarction.
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  • Etsuko MAEDA, Toshio UEMATSU
    1991 Volume 98 Issue 6 Pages 457-466
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    The anti-pyretic activity of alminoprofen (AP), a non-steroidal anti-inflammatory agent, and its mode of action were investigated in conscious febrile rabbits. A fever was evoked by i.v. injection of lipopolysaccharide (LPS), intracisternal (i.c.) injection of leukocytic pyrogen (LP) or i.c. injection of arachidonic acid (AA). The amount of PGE2 or AP in the cerebrospinal fluid (CSF) after i.v. LPS was estimated using an RIA or HPLC method. AP (3 ?? 30 mg/kg, p.o.) dose-dependently inhibited the LPS (0.5 pg/kg, i.v.)-induced fever; AP, ibuprofen, indomethacin and pranoprofen had ED50 values of 9.64, 26.45, 4.41 and 11.91 mg/kg, p.o., respectively. PGE2 in the CSF was markedly increased during the elevation of body temperature after i.v. LPS (0.5 μg/kg). AP (30 mg/kg, p.o.) markedly inhibited the increase in PGE2 that was observed in the CSF during fever developed in response to i.v. LPS (0.5 μg/kg). The AP concentration in the CSF 2hr after AP (30 mg/kg, p.o.) was 2.86 × 10-6 (1.15 ?? 4.57 × 10-6) M, a concentration too low to inhibit PG synthesis. A dose-dependent fever was observed after i.c. LP (1 ?? 8 unit) or AA (10 ?? 100 pg). AP (30 mg/kg, p.o.) shifted the dose-response curves for the i.c. LP-induced fever to the right, but did not have any effect on the i.c. AA-induced fever. These results suggest that AP has a relatively potent anti-pyretic activity, and its mechanism of action involves competition with LP at a site in the CNS, but does not involve an inhibition of cyclooxygenase at a central site, which has been considered as an anti-pyretic mechanism of nonsteroidal anti-inflammatory drugs.
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  • Etsuko MAEDA, Toshio HUJIYOSHI, Toshio UEMATSU
    1991 Volume 98 Issue 6 Pages 467-474
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Effects of alminoprofen (AP), a non-steroidal anti-inflammatory agent, were investigated using several experimental gouty models. AP (3 ?? 30 mg/kg, p.o.) dose-dependently inhibited urate crystal-induced rat paw edema. AP (3 ?? 30 mg/kg, p.o.) inhibited the accumulation of exudate and decreased the total counts of leukocytes and the amount of PGE2 in a dose-dependent manner in sodium urate crystalinduced pleuritic rats. AP (0.3 ?? 10 mg/kg, p.o.) showed a dose-related analgesic activity on the pain response in sodium urate crystal-induced arthritic rats. AP (10-5 ?? 10-3M) inhibited the sodium urate crystal-induced β-glucuronidase release from guinea pig neutrophils at more than 10-4M. AP (10-5 ?? 10-3M) did not inhibit the sodium urate crystal-induced production of O2- from guinea-pig neutrophils. AP (10-6 ?? 10-4M) inhibited dose-dependently the chemotaxis of leukocytes induced by chemotactic factors from guinea pig neutrophils stimulated with sodium urate crystals. AP (10-6 ?? 10-4M) inhibited the sodium urate crystal-induced production of PGE2 from rat peritoneal leukocytes in a dose-related manner. These results suggest that AP has a potent anti-inflammatory and analgesic activity in sodium urate crystal-induced inflammations, and these effects are exerted through its combined inhibitions of PGE2 synthesis, leukocyte chemotaxis and lysosomal enzyme release.
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  • Masami TANAKA
    1991 Volume 98 Issue 6 Pages 475-481
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    To elucidate the action mechanisms of the IUD, I examined the relationships between ovarian steroid levels and contraceptive mechanisms in IUD-inserted rats. Female Wistar rats, 59-61 days old, were used and a polyethylene tube was into the bilateral uterine horns. Half of animals were injected with 1 mg indomethacin at the 30th and 31st days after the operation. All animals were decapitated at 1 hr after the 2nd injection. The presence of the IUD significantly increased the uterine weights due to the hypertrophy of the uterine wall, and it significantly increased ovarian testosterone and tended to increase ovarian estradiol and the estradiol/progesterone ratio. However, administration of indomethacin did not reduce these increased levels back to the levels of sham-operated rats. These results indicate that the presence of the IUD increased ovarian testosterone and estradiol, disturbing the balance between estrogen and progestin, with estrogen becoming dominant. It seems that these changes bring about the delay of fertilized egg development and disrupts the development of proper conditions for implantation, so that implantation of the fertilized egg on the endometrium is inhibited. Furthermore, this study suggests that the changes of the ovarian steroid levels in IUD-inserted rats may involve the participation of unknown uterine factors but not prostaglandins.
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  • Shigeru OSHIO, Tsunetada YAZAKI, Takashi UMEDA, Satoru OZAKI, Isao OHK ...
    1991 Volume 98 Issue 6 Pages 483-490
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    Experimental testicular dysfunction were produced by X-ray irradiation to the testes in mice. Mecobalamin (CH3-B12) was orally administered at a daily dose of 0.01, 0.1 or 1 mg/kg six times a week for 8 weeks from the next day after the irradiation. The control mice received physiological saline in the same manner. On 4th and 6th-week after the irradiation, the weights of testes and epididymides were decreased, although those of the body and accessory sex glands (seminal vesicle, coagulating gland and prostate) were nearly equal to those of non-irradiated mice. At the same time, the diameter of seminiferous tubules decreased and sperm parameters (sperm count, sperm motility and sperm abnormality) deteriorated. When CH3-B12 (1 mg/kg) was administered, the diameter of seminiferous tubules increased and sperm parameters improved as compared to those of the control. The results indicate that CH3-B12 improved the experimental testicular dysfunction in mice induced by the irradiation. These results suggest that CH3-B12 might accelerate testicular function.
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  • Naomi MACHIDA
    1991 Volume 98 Issue 6 Pages 491-501
    Published: 1991
    Released on J-STAGE: February 13, 2007
    JOURNAL FREE ACCESS
    The tracheal strip-chain preparations taken from immature (< 2 weeks old) and mature (> 16 weeks old) guinea pigs were used to study the cooling effects of bathing temperature on cholinergicallymediated contractions. In the tracheal muscles from immature animals, cooling of the bathing temperature from 37°C to 20°C augmented both the contractions induced by electrical stimulation (0.05 ?? 2 Hz, 0.6 msec, 150 mA) of intramural cholinergic nerves and contractions in response to acetylcholine (0.01 ?? 3 μM), while the cooling inhibited the carbachol (0.01 ?? 3 μM) -induced contractions. The pretreatment of the tissue with physostigmine (0.05 μM) also augmented both contractions induced by cholinergic nerve stimulation and those in response to acetylcholine (0.01 ?? 3 μM), but the cooling did not produce further augmentation of the responses. On the other hand, the tracheal muscles from mature animals showed a reduced contraction in response to cholinergic nerve stimulation by cooling, although the response was potentiated by the physostigmine pretreatment. Histochemical distributions of acetylcholinesterase activities were more marked in the tracheal muscles of immature guinea pigs than in mature ones. From these results, we conclude that increased responsiveness by cooling of the isolated immature guinea pig tracheal muscle to cholinergic nerve stimulation or exogenous acetylcholine may involve the decrease of intramural acetylcholinesterase activities which might be decreased age-dependently.
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