| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Research Abstract |
Thrombotic diseases are increasing recently. Among the various dsisease states, thrombotic episodes have been known to associate frequently with nephrotic syndrome which is characterized by hyperlipidemia and hypoalbuminemia. However, mechanism by which thrombus can be formed in this syndrome remains to be clarified. To elucidate the mechanism of thrombus formation under hypoalbuminemia and hyperlipidemia, coagulation and fibrinolytic states were characterized in Nagase analbuminemia rats (NAR) which reveals the patological condtions similar to nephrotic syndrome; i.e.analubuminemia and hyperlipidemia.
1. Anti human facotor Xa (FXa) activity was found in plasma of nar and Sprague-Dawrey rats (SDR), the value of which was found to be 2-3 times higher in nar than that in SDR. Although the plasma component responsible for the anti human F-Xa activity has not yet been fully identified, alpha2-macroglobulin may be possibly one of good candidates. Plasma levels of antithrombin III (at III) an
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d alpha2-plasmin inhibitor were higher in NAR than those in SDR.
2. When endotoxin was administered to NAR and SDR, mortality was significantly higher in NAR than that in SDR (30 % vs 0 %, respectively). Based on the findings of the changes in coagulation and fibrinolysis of these experimental DIC animals, severer DIC was induced in NAR than in SDR.
3. When thrombus was induced in the small mesenteric artery of rats by inserting the microglass pipette, thrombus was formed within 4-5 min of insertion in both animals. Thrombus thus formed gradually grew up in its size to dissociate from the glasspipette and vascular wall and flew away into circulation. Thrombus was disappeared in such a way within 3-4 min of the thrombus formation in SDR, whereas thrombus was disappeared at 12-15 min of the formation in NAR and the maximum size of thrombus was 3 times bigger in NAR than that in SDR.
These findings suggested that NAR might be sensitive to the stimuli causing to the thrombus formation and , thus, hypoalbuminemia and hyperlipidemia per se might be the risk factors for the thrombus formation. Less
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