Pathology: Granulocyte colony-stimulating factor has no adverse effects on atherosclerotic lesions in high cholesterol-fed miniature swine

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  • TAKAI Hirotake
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • MIYOSHI Akio
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • YAMAZAKI Masaki
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • ADACHI Kenji
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • KATAGIRI Kouichi
    Chugai Research Institute for Medical Science, Inc.
  • ARAKAWA Hitoshi
    Chugai Research Institute for Medical Science, Inc.
  • KATSUYAMA Kiyoka
    Chugai Research Institute for Medical Science, Inc.
  • ITO Tsuneo
    Chugai Research Institute for Medical Science, Inc.
  • FUJII Etsuko
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • HAYASHI Shuji
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • KATO Atsuhiko
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.
  • SUZUKI Masami
    Department of Safety Assessment, Fuji Gotemba Research Laboratory, Chugai Pharmaceutical Co., Ltd.

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タイトル別名
  • Granulocyte Colony-Stimulating Factor Has No Adverse Effects on Atherosclerotic Lesions in High Cholesterol-Fed Miniature Swine

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Granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize peripheral blood stem cells, and expected to restore cardiac function for patients with coronary artery diseases as a consequence of progression of atherosclerosis. Safety issues related to the administration of G-CSF to these patients, however, are still under study. The animal model for atherosclerosis was produced by feeding miniature swine a high-cholesterol diet for 3 months. G-CSF (5 or 10 μg/kg/day) was given to the animal model by daily subcutaneous injections for 10 days and 20 main arteries were evaluated pathologically. In addition, the general toxicological effects were studied on clinical signs, body weight, hematology, blood chemistry and pathology. In the G-CSF-treated groups, a variety of changes related to the major pharmacological activity of G-CSF including an increase in white blood cell (WBC) counts were observed. In many arteries, atherosclerotic lesions similar to Type I-V of the proposed classification by the American Heart Association were observed. No effects of the G-CSF treatment were seen on the histopathological findings, incidence, severity or distribution of atherosclerotic lesions. In addition, no infiltration of neutrophils to the lesions was observed. These findings suggest that the administration of G-CSF causes neither exacerbation or modification of atherosclerotic lesions nor adverse changes despite that a sufficient increase in WBC counts could be achieved in the peripheral blood.<br>

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