Gottlieb P, Margolis-Nunno H, Robinson R, Shen L G, Chimezie E, Horowitz B, Ben-Hur E
New York Blood Center, NY 10021, USA.
Photochem Photobiol. 1996 May;63(5):562-5. doi: 10.1111/j.1751-1097.1996.tb05656.x.
Inactivation of the blood-borne parasite Trypanosoma cruzi by UVA and 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) was studied in the blood components fresh frozen plasma (FFP) and platelet concentrate (PC). The AMT was utilized at a concentration of 50 micrograms/mL and the inactivation procedure included the flavonoid rutin (at 0.35 mM), a quencher of type I and type photo-reactants, which we have previously found to maintain platelet integrity during this treatment regimen. Within both FFP and PC, complete inactivation of the infective form of T. cruzi, the trypomastigote, was achieved at a UVA (320-400 nm radiation) fluence of 4.2 J/cm2. We note that while the infectivity of the parasite is eliminated at 4.2 J/cm2 the trypomastigote motility continues for at least 16 h-post-treatment and is inhibited only after much higher light doses. Isolation of total DNA from the parasite cells after treatment in the presence of 3H-AMT indicated that at the lethal UVA influence about 0.5 AMT adducts per kilobase pairs occurred. These results suggest that this psoralen plus UVA methodology which shows promise in enhancing the viral safety of PC, may in addition eliminate bloodborne T. cruzi, the causative agent of Chagas disease.
研究了在新鲜冷冻血浆(FFP)和血小板浓缩液(PC)等血液成分中,UVA和4'-氨甲基-4,5',8-三甲基补骨脂素(AMT)对血源寄生虫克氏锥虫的灭活作用。AMT的使用浓度为50微克/毫升,灭活程序包括黄酮类芦丁(0.35毫摩尔),它是I型和光反应物的猝灭剂,我们之前发现它能在这种治疗方案中维持血小板的完整性。在FFP和PC中,当UVA(320 - 400纳米辐射)通量达到4.2焦/平方厘米时,克氏锥虫的感染性形式即锥鞭毛体完全失活。我们注意到,虽然在4.2焦/平方厘米时寄生虫的感染性被消除,但锥鞭毛体的运动能力在处理后至少持续16小时,并且只有在更高的光照剂量后才会被抑制。在3H-AMT存在下处理后从寄生虫细胞中分离总DNA表明,在致死性UVA作用下,每千碱基对大约出现0.5个AMT加合物。这些结果表明,这种补骨脂素加UVA的方法在提高PC的病毒安全性方面显示出前景,此外还可能消除恰加斯病的病原体血源克氏锥虫。