| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
1) In the present clinical study, the effects of plasma circulating inflammatory cytokines, plasma NOx levels and soluble Fas on acute lung injury and other organ failure were investigated in fifteen septic shock patients; seven patients were survivor and the other eight were nonsurvivor. The average PaO2/FIO2 ratio in nonsurvivors was lower than that in survivors (108±28 vs. 177±37; mean ±SD). Although plasma average Nox levels and sFas concentrations in nonsurvivors were much higher than those in survivors (Nox; 112.4±27.4 vs. 68.5 ±30.3 micro M/L, sFas; 3.3 ±1.2 vs. 1.4 ±0.5 U/ml), no correlation was found between PaO2/FIO2 ratio and Plasma Nox or sFas concentrations. In the present animal investigation, plasma inflammatory cytokines, plasma Nox levels, sFas and Fas expression in lung and liver tissues were investigated in cecal ligation and puncture (CLP) and liver ischemic reperfusion (I/R) rats. Although plasma levels of NOx in CLP rats were higher than those of I/R rats (33.5±2.
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8 vs. 26.2±1.9 micro M/L), these values were considered minimal. Plasma sFas concentrations in CLP rats were lower than that in I/R rats. The expression of 66 kilodalton molecular weight Fas with Western blot in the lungs and the livers of CLP rats were less than that in I/R rats.
The results of this clinical study and animal investigation suggest that a slightly elevated plasma Nox level has no effect on onset of acute lung injury and that apoptosis has only a slight effect on sepsis related lung injury in patients with sepsis but has some important effects on I/R related liver injury.
2) Next, diamine oxidase (DAO) activity, IL-6, IL-8, IL-10 and sFas were measured in 14 septic patients with hyperbilirubinemia. The average total and direct bilirubin levels were 7.8±1.0mg/dl and 5.l±0.6mg/dl. The average IL-6, IL-8 and IL-10 were 146.8±35.3pg/ml, 120.6±14.4pg/ml and 197.5±43.5pg/ml, respectively. The average sFas level was 5.2±0.8ng/ml. Significant correlations were found in total birilubin value and sFas concentrations, IL-6/IL-10 and in DAO levels and sFas, IL-6/10 ratio.
These results of this clinical study suggests that the increased plasma DAO level showed ischemic change in the gut and hyperbirirubinemia correlated to hypercytokinemia or apoptosis. But effects of gut lavage on hyperbirilubinemia could not be proven in this study, because only 4 patients with informed consent of this study were treated with hole gut lavage. Less
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