The effects of hexasulfobutylated C 60 (FC 4 S) on (1) coronary occlusion/reperfusion and (2) isolated aortic ring preparation of rats were studied in vivo and in vitro. In the in vivo studies, FC 4 S (1-10 µg/kg, iv) reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation during the coronary artery occlusion phase and the reperfusion phase. FC 4 S increased nitric oxide (NO) and decreased lactate dehydrogenase in plasma during the period of cardiac ischemia and reperfusion. In animals subjected to 4 h of coronary occlusion, pretreatment with FC 4 S (10 µg/kg, iv) reduced the cardiac infarct zone (expressed as percent of area at risk) from 39.7 ± 4.8% to 11.3 ± 4.1 %. Mortality during cardiac ischemia and reperfusion was completely prevented after injection of FC 4 S (10 µg/Kg iv). In the isolated endothelium-containing aortic ring preparation, phenylephrine (PE) elicited contractions and FC 4 S elicited a significant relaxing effect on PE-precontracted aortic rings. This relaxing effect of FC 4 S was reduced by pretreatment with N(G)-nitro-L-arginine methyl ester (1 mM), a blocker of NO synthase. It is concluded that FC 4 S may be useful as a potential cardioprotective agent for cardiac ischemia and reperfusion. The beneficial effect of FC 4 S may be partly correlated with its antioxidant property and also by the upregulation of NO production and vasodilation effects. Drug Dev. Res. 53:244-253, 2001.

Taiwan operates a unique no‐fault compensation‐based scheme for injuries caused by medication use. This article describes the operation of the Taiwan Drug Relief Foundation and some results since the Taiwan Drug Hazard Relief Act was enacted in 2000. We also briefly review similar no‐fault compensation systems in Germany, Japan, New Zealand and Nordic countries. The existence of these schemes provides timely relief and compensation to victims by avoiding the otherwise lengthy court process; however, medication safety education and applied pharmacogenomic and pharmacoepidemiological research are future aspirations to proactively address and prevent drug‐induced injuries.

The effects of hexasulfobutylated C₆₀ (FC₄S) and monomalonic acid C₆₀ (MMA C₆₀), the fullerene C₆₀ derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C₆₀ (10 µmol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C₆₀ (10 µmol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC₄S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC₄S (10 µmol/l). In the denuded aortic rings, FC₄S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC₄S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 µmol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC₄S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium.

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