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Neville W SPURLING, Ralph A HARCOURT, John J HYDE
1986 Volume 11 Issue 4 Pages
237-277
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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The effects of repeated oral administration of cefuroxime axetil, were assessed in Beagles. The test material, an ester, is hydrolysed following absorption from the intestine to yield the therapeutically active moiety, cefuroxime, together with acetic acid and acetaldehyde ; in this study cefuroxime and unhydrolysed cefuroxime axetil were detected in the blood. Cefuroxime axetil was administered twice daily during 27 weeks by gavage of aqueous, suspensions, total daily doses were equivalent to 100, 400 or 1600 mg cefuroxime/kg/day. Apart from three cases of intercurrent illness, unrelated to treatment, the dogs remained in good health. Effects observed in the 1600 mg/kg group included vomiting and slight suppression of body weight gain. Minor variations in haematological measurements included rather low haemoglobin levels, packed cell volumes and erythrocyte counts. Slightly smaller numbers of neutrophils were thought to reflect reduced demand on normal defensive mechanisms due to continued antibiotic treatment. Prolongation of prothrombin time and activated partial thromboplastin time is attributed to disturbance of the intestinal microbial flora and reduced synthesis of vitamin K, on which the dog is highly dependent. Cefuroxime does not have the N-methylthiotetrazole side chain thought to be responsible for inhibition by other cephalosporins of the vitamin K-dependent step in the synthesis of clotting factors. Variations in plasma chemistry included rather low levels of plasma protein. Electrophoresis showed this to be a generalized reduction; only gamma globulins were proportionally decreased and this finding, like the low neutrophil counts, is attributed to the protective action of the antibiotic. Minor metabolic adjustments to the compound are reflected in plasma levels of cholesterol and triglycerides. This spectrum of findings was seen only to a very limited extent in the 400 mg/kg group ; the 100 mg/kg group was, with very few exceptions, unaffected by the treatment. Macroscopic post mortem examination and microscopic examination of tissues revealed no treatment-related features indicative of toxicity. Cefuroxime axetil was thus shown to possess very little toxicity when administered repeatedly in large doses to Beagles. The lowest dose level in this study was ten times the proposed daily clinical dose in man.
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Takao HASHIMOTO, Kouichi TAKEUCHI, Setsuko OHNO, Setsuko KOMATSU
1986 Volume 11 Issue 4 Pages
279-291
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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We examined the effects of mitomycin C and aminopterin on ovulation in vivo and, fertilization, subsequent cleavage and implantation in slc-ICR female mice using methods of fertilization and culture in vitro. Chemicals were injected into mice at the MI (meiosis I) stage or 3 hours before the MI stage in order to examine their toxicity. Mitomycin C did not affect ovulation, but decreased the rate of fertilization. A high dose of mitomycin C (4 mg/kg) inhibited fertilization and the development of ova to the 2-cell stage. Aminopterin affected neither ovulation nor fertilization. At either the MII (meiosis II) stage or 3 hours before the MII stage, high doses (4 and 2 mg/kg) of mitomycin C arrested cleavage and implantation. The cleavage was blocked frequently between the 3-4 cell stage and the 5-8 cell stage. Aminopterin affected neither cleavage nor implantation.
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Kiyoshi MATSUMOTO, Akio USUI, Toshiaki OCHIAI, kiyoshi SEKITA, Yasushi ...
1986 Volume 11 Issue 4 Pages
293-301
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW=330±32g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments.
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Takashi HASEGAWA, Kazuo TSUJITA, Kazuo TAKAHASHI
1986 Volume 11 Issue 4 Pages
313-329
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Antigenicity of MY-5 1 16 was studied in the experimental animals and the following results were obtained. 1. MY-5 1 16 was shown to be non-immunogenic in rabbits, guinea pigs and mice when given alone As immunogen. 2. Protein conjugate of MY-5116 induced antibody of hapten specific antibody when using guinea pigs and mice as immunizing species. However, MY-5116 was shown to be not capable of reaction with anti MY-5116-OVA antibodies. 3. Guinea pigs had no skin contact sensitivity against MY-5116 examined by means of maximization test. In conclusion, MY-5116 lacks immunogenicity and eliciting antigenicity in this experimental conditions and this suggests that drug allergic response would either not occur or be minimal, if any, when MY-5116 is administered clinically.
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[in Japanese]
1986 Volume 11 Issue 4 Pages
352-357
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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[in Japanese]
1986 Volume 11 Issue 4 Pages
358-373
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Yoshifumi TANIMOTO, Kazuhiko MATSUNOTO
1986 Volume 11 Issue 4 Pages
395-397
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Mamoru NOMURA, Noriko TESHIMA, Masao YAMADA
1986 Volume 11 Issue 4 Pages
398-400
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Shuzo SUZUKI
1986 Volume 11 Issue 4 Pages
401-403
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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kazuhiko MATSUMOTO, Toyohiko MORINO, Hitomi HARA, keiko MOTOYAMA
1986 Volume 11 Issue 4 Pages
404-407
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Kunio NAKAYAMA, Toshio MATSUMOTO, Kyoji NODA, Fumihiro YAMAMOTO
1986 Volume 11 Issue 4 Pages
408-410
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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[in Japanese]
1986 Volume 11 Issue 4 Pages
411-413
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Hiroshi MORIOKA, Takayoshi KOBAYASHI
1986 Volume 11 Issue 4 Pages
414-417
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Isamu AKAIKE, Jiro ADACHI
1986 Volume 11 Issue 4 Pages
423-431
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Masanobu FUkUI, Toshinori FURUKAUA
1986 Volume 11 Issue 4 Pages
432-443
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Michihiro T. SUZUKI, Fumiaki CHO
1986 Volume 11 Issue 4 Pages
444-455
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Ryohei Hasegawa, Jun Kanno
1986 Volume 11 Issue 4 Pages
462-469
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Naochika MATSUNUMA, Tokuma YANAI
1986 Volume 11 Issue 4 Pages
470-476
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Hiroaki MIYAJIMA
1986 Volume 11 Issue 4 Pages
477-481
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Mitsutoshi Watanabe
1986 Volume 11 Issue 4 Pages
482-485
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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Kiyoshi IMAI
1986 Volume 11 Issue 4 Pages
486-492
Published: November 25, 1986
Released on J-STAGE: February 21, 2008
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