| Project/Area Number |
11470238
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Chiba University |
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Principal Investigator |
HIRASAWA Hiroyuki Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (80114320)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANISHI Kazuya Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (80272326)
SHIGA Hidetoshi Chiba University, University Hospital Lecturer, 医学部・附属病院, 講師 (20282478)
ODA Shigeto Chiba University, Graduate School of Medicine, Assistant Professor, 医学部, 助教授 (90204205)
NAKAMURA Masataka Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (30315436)
MATSUDA Ken-ichi Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (60282480)
菅井 桂雄 千葉大学, 医学部, 助教授 (10187627)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | SIRS / multiple organ failure / cytokine / hypercytokinemia / apoptosis / cytokine modulation / apoptosis modulation / アポトーシスモデュレーション |
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| Research Abstract |
Inflammatory cytokines have been implicated as a key mediator playing an important role in the pathophysiology of multiple organ failure (MOF). This study was undertaken to evaluate the removal of cytokines from the circulation with continuous hemodiafiltration (CHDF) using polymethyl methacrylate membrane (PMMA-CHDF) and the efficacy of PMMA-CHDF in the treatment of sepsis or other critical conditions through such removal of causative mediators. In this study, we found that clearance of cytokines with PMMA-CHDF positively correlates with pre-CHDF blood levels of cytokine : the higher the blood level, the greater the clearance. Furthermore, our data showed that the blood levels of cytokines were significantly decreased with PMMA-CHDF. As for the clinical benefits of cytokine removal, there were positive correlation between changes in blood levels of cytokines with PMMA-CHDF and changes in cellular injury score in MOF patients. In acute respiratory distress syndrome (ARDS), there was a significant and positive correlation between the degree of decrease in blood levels of cytokines and the degree of improvement in respiratory index (RI). Thus these data clearly demonstrated that cytokine removal with PMMA-CHDF was clinically relevant in the critically ill. On the other hand, spontaneous and cytokine-induced apoptosis of circulating polymorphonuclear leukocyte (PMN) wewe greatly decreased in critical conditions such as sepsis and MOF. In contrast, the inhibited circulating PMN apoptosis could lead to be amplified systemic inflammation and organ injury. Therefore, we evaluated whether the removal of cytokines with PMMA-CHDF can modulates circulating PMN apoptosis or not. We investigated the relation between blood levels of cytokines and circulating PMN apoptosis with PMMA-CHDF in organ failure patients. We found that there was a correlation between the degree of decrease in blood levels of interleukin-6 and the degree of improvement in circulating PMN apoptosis.
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