| Co-Investigator(Kenkyū-buntansha) |
ARIMURA Yoshihiro The first Dept.of Internal Medicine, Kyorin University School of Medicine, Lectu, 医学部, 講師 (40222765)
YAMAKAWA Yoshio National Institute of Infectious Diseases, Biochemistry and Cell Biology, Head o, 細胞化学部, 室長 (50100102)
SUZUKI Kazuo National Institute of Infectious Diseases, Bioactive Molecules, Head of Laborato, 生物活性物質部, 室長 (20192130)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
1) The selection of model animals
Usually, MPO activity nor MPO-ANCA are detected in normal blood. However, both of them are detected at high level in rat plasma derived from anti-glomerulo basement membrane (GBM) antibody-induced-nephritis and adjuvant-induced-arthritis. GBM-induced-nephritis rat showed high protein urine, joint swelling was detected in paw injected adjuvant.
2) The evaluation of aseanostatin, i-14 : 0 on improvement of adjuvant-induced-arthritis
Oral administration (20 mg/kg), or intraperitoneal administration (30 mg/kg) was continued to adjuvant-induced-arthritis rat for 18 days. MPO-ANCA level decreased near the normal level. On the other hand, the degree of joint swelling, change of weight of thymus and spleen, biochemical change of serum were hardly affected by administration of aseanostatin. Intraperitoneal administration of aseanostatin appeared effective on improvement of inhibition of body weight decrease, leukocyte increase, paw swelling, bone destruction, howe
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ver, similar result was detected in the group injected only solvent for 18 days. This phenomenon could be explained by the reason that injection of intraperitoneal induce inflammation at the site, then anti-inflammatory effect may produce. As a result, treatment effect of aseanostatin may be weak. Since measurement of aseanostatin as a fatty acid could not establish, concentration of aseanostatin could not clear exactly, it may be low level in serum. Moreover, effect of aseanostatin on improvement of GBM-induced-nephritis will investigate.
Summary
1) MPO-ANCA titer increased in serum derived from adjuvant-induced-arthritis rat.
2) Administration of aseanostatin decreased MPO-ANCA titer near the normal level, however it's medical effect was not enough.
3) Since MPO-ANCA is one of indicator of neutrophil activation, decrease of MPO-ANCA titer could reflect reduction of risk of arthritis. However, condition of arthrits was hardly improvement.
4) Epitope analysis would need to clarify the relationship between induction of MPO-ANCA and arthritis. Less
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