| Project/Area Number |
11672273
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
FUJIMURA Akio Jichi Medical school Clinical Pharmacolgy Professor, 医学部, 教授 (90156901)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Yoshikazu Kitazato Research Institute, Division of Bacteriology, Chief, 基礎研究所・細菌研究室, 室長 (20195126)
TSURUOKA Shu-ich Jichi Medical school Clinical Pharmacolgy, Assistant Professor, 医学部, 助手 (50285798)
SUGIMOTO Koh-ichi Jichi Medical school Clinical Pharmacolgy, Associate Professor, 医学部, 講師 (90244491)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | E-coli O157 / verotoxin / lipopoly saccharide / renal damage / neutrophil / O-157 / 抗好中球抗体 / 腎障害 / IL6 / 時間薬理 |
|---|
| Research Abstract |
Lipopolysaccharide (LPS) and verotoxin-2 (VT2) are involved in the Escherichia coli O-157-induced renal damage. However, pathophysiologic profiles are not fully evaluated after an injection of each agent. This study was undertaken to address this issue.
1. Chronotoxicity of LPS in rats
LPS (5 mg/kg) was injected intravenously to Wistar rats at 9:00 or 21:00, and organ damages were evaluated. The degree of organ damages in the 21:00 trial were significantly greater than those in the 9:00 trial. The elevation in serum interleukin-6 (IL-6), an inflammatory cytokine, was greater and its synthesis in organs was more enhanced in the 21:00 trial. These data indicate that the toxicity of LPS depends on its dosing time, probably through the time-dependent difference in the IL-6 response.
2. Preventive effect of anti-neutrophil antibody against the VT_2-induced organ damage in mice.
VT_2 (100 ng) was injected intraperitoneally to C57BL/6 mice with and without the co-administration of anti-neutrophil mouse antibody at 0 and 24 hours following VT_2. After the injection of VT_2 alone, plasma neutrophil remarkably elevated and all animals died within 5 days after the VT_2 injection. Death rate was significantly reduced in mice with the anti-neutrophil antibody. These data suggest that neutrophil plays some role in the VT_2-induced organ damage.
|
