Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 104, Issue 2
Displaying 1-7 of 7 articles from this issue
  • Hajime YASUHARA
    1994 Volume 104 Issue 2 Pages 67-78
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Ethnic difference is considered to be a major barrier in world-wide drug development. There seem to be many ethnic factors, genetic, environmental and cultural differences. There exists genetic polymorphism in drug metabolism especially for N-acetylation, debrisoquine hydroxylation and S-mephenytoin hydroxylation. The frequency of slow acetylator, poor metabolizer of debrisoquine and S-mephenytoin are 10 %, less than 1 % and 20 % in Japanese and 50 %, 10 % and 5 % in Caucasians respectively. Clinical responses and adverse effect of drugs are associated with these phenotypes. A retrospective study was conducted to determine whether inter-ethnic pharmacokinetic difference is larger than intra-ethnic variability. Individual pharmacokinetic parameters for most drugs were found to be extremely variable, but similarities of pharmacokinetic parameters were observed for Cmax, and AUC between Japanese and other races. The results suggest that intra-ethnic variability is larger than inter-ethnic difference. The knowledge of genetic polymorphisms must find its way into clinical practice in order to achieve rational drug therapy that is more effective and safer for the benefit of the patient.
    Download PDF (20893K)
  • Misao SUZUKI
    1994 Volume 104 Issue 2 Pages 79-84
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Transgenic mice are very useful for analyzing the functions of a gene either at the tissue level or at the whole body level. Here we describe the production of transgenic mice by the microinjection of DNA into the pronuclei of fertilized mouse eggs.
    Download PDF (8975K)
  • Masako GOTO, Mikio HAYASHI, Yoshiyuki SEYAMA, Saburo YAMASHITA
    1994 Volume 104 Issue 2 Pages 85-89
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    To clarify the anti-calcinosis actions of traditional Chinese medicine (Dai: Dai-saiko-to) and estradiol benzoate (E2), 7-week or retired (about 6-months-old) female rats were treated with Vit.D2 (1.75 × 105 I.U./kg b.w./day) for 4 days, and then were fed a basal diet containing Dai (at ten times the medical dose in humans) or were injected i.p. with E2 (at the medical dose in humans) for 6 weeks. The following results were obtained: 1) Dai did not improve Ca and P metabolism in experimental calcinosis of 7-week female rats; 2) in retired female rats, Dai decreased both P in the heart and the ratio of Ca to P in bone, similar to the treatment with E2. Dai, as well as E2, seemed to nomalize Ca and P metabolism disturbed by Vit.D2 treatment.
    Download PDF (9247K)
  • Hitoshi MATSUKURA, Makoto MASUDA, Aoi UCHIDA, Toshiro KAMISHIRO
    1994 Volume 104 Issue 2 Pages 91-100
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+, K+-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+, K+-ATPase activity, and their IC50 values were 31 μM and 24 μM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+, K+-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+, K+-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+, K+-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+, K+-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+, K+-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+, K+-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+, K+-ATPase activity to the same degree as the single administration.
    Download PDF (18054K)
  • Kuniko HARA, Yasuhiro AKIYAMA, Takashi TOMIUGA, Masatoshi KOBAYASHI, T ...
    1994 Volume 104 Issue 2 Pages 101-109
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    To evaluate whether the vitamin D3 level in the plasma influences the inhibitory effect of vitamin K2 on bone loss, vitamin K2 (25 mg/kg/day) was administered to ovariectomized (OVX) rats fed a diet containing vitamin D3 (V.D (+)) or a diet deficient in vitamin D3 (V.D (-)) . After 3 months of treatment, the plasma 25-OH-vitamin D3 (25-OH-D3) level in the V.D (-)-sham group was about 1/3 of that in the V.D (+)-sham group. The plasma calcium level and alkaline phosphatase activity were also significantly lower in the V.D (-)-sham group than in the V.D (+)-sham group. In the V.D (+) group, the plasma 25-OH-D3 level in the vitamin K2 group was about 1.5 times higher than that in the OVX-control group. Ovariectomy resulted in a significant decrease in bone density, bone mineral content (BMC) and bone mineral density (BMD) of femurs in both the V.D (+) and V.D (-) groups. In the V.D (-) group, vitamin K2 had no marked effect on the bone loss. In the V.D (+) group, the bone density and BMD in the mid portion of the femur were significantly increased by vitamin K2 treatment. These findings suggest that the effect of vitamin K2 on bone loss is affected by the vitamin D3 level in the plasma.
    Download PDF (15616K)
  • Jun KOJIMA, Kenjirou YAMANA
    1994 Volume 104 Issue 2 Pages 111-120
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Effects of oral administration of NIK-247 (9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta-[b]quinoline monohydrochloride monohydrate) and THA (9-amino-1, 2, 3, 4-tetrahydroacridine hydrochloride hydrate) on the EEG of normal and nucleus basalis magnocellularis (NBM) lesioned rats were examined. NIK-247 at 1mg /kg and 3 mg/kg did not show any effects on the EEG of normal rats, but NIK-247 at 10 mg/kg significantly lowered the total power of the cortical EEG in normal rats. THA at 3 mg/kg and 10 mg/kg also decreased the total power of cortical EEG in normal rats. In the NBM-lesioned rats, decreases of delta wave activity as well as the total power of cortical EEG were observed with both NIK-247 and THA at 3 mg/kg, respectively. The arousal effects of these two drugs were comparable to the effect of physostigmine, suggesting the central cholinergic effects of both NIK-247 and THA.
    Download PDF (16341K)
  • Hirokazu TANAKA, Yasuhiko KITOH, Noriko KITABAYASHI, Yumi MATSUMURA, H ...
    1994 Volume 104 Issue 2 Pages 121-131
    Published: 1994
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    We tried to develop a new delayed healing model of an open wound made on the dorsal skin of a rat by inducing malnutrition with restriction of food intake. We determined the effects of a newly introduced ointment gauze containing 5% lysozyme hydrochloride (M-1011G) on this model. Malnutrition characterized by a decrease in body weight and serum protein was produced by restricting the daily intake of commercially avail able food to 6 g for 2 weeks without liver disturbance and thereafter maintained with food intake of 12 g/day. Under these conditions, healing of the open wound made on the dorsal skin was prolonged, as compared with that of the wound made on a well-nourished animal. In this model, statistical studies showed that M-1011G was the most effective in accelerating the reduction of the wound area and shortening of the time required for the complete healing, among the following treatments: sterilized gauze alone, ointment gauze alone and 5% lysozyme hydrochloride-containing emulsified ointment. Histological findings showed that M-1011G greatly accelerated the granulation of this tissue which is essential for wound healing, probably due to stimulation of epidermization and regenerated granulation in the wound.
    Download PDF (33692K)
feedback
Top