Ulutin O N, Balkuv-Ulutin S, Ugur M S, Ulutin T, Ozsoy Y, Cizmeci G
Haemostasis and Thrombosis Research Center, Cerrahpasa Medical School, Istanbul University, Turkey.
Adv Exp Med Biol. 1990;281:429-38. doi: 10.1007/978-1-4615-3806-6_46.
Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human.
去纤苷是一种脱氧多聚核糖核苷酸，已发现它可调节内皮细胞功能，使组织型纤溶酶原激活物（t-PA）增加，纤溶酶原激活物抑制剂（PAI）水平降低，同时前列环素（PGI2）生成增加。此外，它可提高人体血小板环磷酸腺苷（c-AMP）水平，减少丙二醛（MDA）和血栓素B2（TXB2）的形成。在体外实验以及大鼠端端吻合术中，去纤苷可抑制血小板聚集形成。所以，去纤苷可抑制血小板的激活。在动物实验中，除了蛋白C和S水平升高外，还观察到肝素的协同作用。在动物模型中已观察到强大的抗血栓作用。该药物在深静脉血栓形成（DVT）、周围闭塞性血管疾病（POVD）、中风和血栓栓塞病例中具有有益作用。通过其作用方式可以说，与该领域使用的其他药物相比，该药物以一种新颖的方式发挥作用。去纤苷是一种通过可控解聚从哺乳动物肺脱氧核糖核酸中获得的单链多脱氧核糖核苷酸。自1981年以来，我们实验室和临床科室一直在体外实验、动物实验以及其临床药理学和临床应用方面研究新开发的药物去纤苷。我们的一些研究结果已经发表，并与文献进行了比较（参考文献40、43、46）。由于篇幅有限，我们不打算详细回顾文献，而是按以下顺序总结我们对该化合物的观察结果。一、体外实验，二、动物实验，三、人体临床药理学。
