|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1992 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1991 : ¥1,100,000 (Direct Cost : ¥1,100,000)
1). We have demonstrated that vitamin D_3 stimulates the production of prostacyclin by vascular smooth muscle cells. As the mechanism involved, we have further shown that 1,25-dihydroxyvitamin D_3 induces the expression of cyclooxygenase mRNA. The data suggest that vitamin D_3 could be an anti-atherosclerotic agent.
2). Using 22-oxa-1,25-dihyroxyvitamin D_3, an analog of vitamin D_3, we have shown that this action of vitamin D_3 is not due to an increase in Ca^<2+> in vivo and in vitro (Life Sci.,51:1105-1112,1992).
3). The polyol pathway is implicated in the pathogenesis of chronic diabetic complications. We have extracted a potent aldose reductase inhibitor from Kampo medicine and identified it as isoliquiritigenin, whose potency is equivalent to ONO-2235. We also found that this substance has an anti-platelet action (Eur.J.Pharmacol., 212: 87-92, 1992).
4). In relation to the polyol pathway, we have demonstrated that aldose reductase mRNA is induced at the physiological concentration of glucose in calf pulmonary artery endothelial cells. This finding probably indicates the correlation between activation of the polyol pathway and reduction of prostacyclin synthesis by endothelial cells, suggesting that elevation of blood glucose could be a trigger for atherosclerosis via the polyol pathway (Diabetologia 35: 730-734, 1992).
5). We have further found an important role of cyclic AMP in diabetic neuropathy (J. Clin. Endocrinol. Metab., 74: 393-398, 1992).