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在存在猝灭剂的情况下,使用补骨脂素和紫外线A光对血小板浓缩物进行病毒灭活

Virus sterilization in platelet concentrates with psoralen and ultraviolet A light in the presence of quenchers.

作者信息

Margolis-Nunno H, Williams B, Rywkin S, Geacintov N, Horowitz B

机构信息

New York Blood Center, New York.

出版信息

Transfusion. 1992 Jul-Aug;32(6):541-7. doi: 10.1046/j.1537-2995.1992.32692367198.x.

Abstract

The virucidal and functional effect of the treatment of platelet concentrates (PCs) with long-wave ultraviolet light (UVA) and the psoralen derivative 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) was studied. Cell-free vesicular stomatitis virus (VSV) was completely inactivated (greater than or equal to 6.5 log10) on treatment of PCs with 25 micrograms per mL (85 microM) of AMT and with 20.7 J per cm2 (30 min) of UVA in the presence of air, or with 82.8 J per cm2 (2 hours) of UVA under conditions of reduced oxygen tension. When treatment was in air, the extent and rate of platelet aggregation in response to collagen measured after overnight storage were reduced to about 70 and 50 percent of control values, respectively; however, aggregation responses were similar to those of controls when PCs were treated under reduced oxygen tension. As a means of eliminating the necessity of oxygen depletion during AMT and UVA treatment, we examined the effects of the addition of quenchers of reactive oxygen species. The presence of 2 mM (2 mmol/L) mannitol during treatment of PCs with 25 micrograms per mL of AMT and 20.7 J per cm2 of UVA in air significantly improved the aggregation response and other in vitro indicators of platelet function and had little or no effect on VSV inactivation. Less benefit was observed with the other quenchers examined. Thus, the nucleic acid specificity of psoralen photoinactivation under reduced oxygen conditions may also be attainable when selected free radical scavengers such as mannitol are present during treatment in air.

摘要

研究了用长波紫外线(UVA)和补骨脂素衍生物4'-氨甲基-4,5',8-三甲基补骨脂素(AMT)处理血小板浓缩物(PCs)的杀病毒和功能效果。在空气中,用每毫升25微克(85微摩尔)的AMT和每平方厘米20.7焦耳(30分钟)的UVA处理PCs时,无细胞水泡性口炎病毒(VSV)被完全灭活(大于或等于6.5个对数10);或者在低氧张力条件下,用每平方厘米82.8焦耳(2小时)的UVA处理时,VSV也被完全灭活。当在空气中处理时,过夜储存后测量的对胶原蛋白的血小板聚集程度和速率分别降至对照值的约70%和50%;然而,当在低氧张力下处理PCs时,聚集反应与对照相似。作为消除AMT和UVA处理过程中耗氧必要性的一种方法,我们研究了添加活性氧淬灭剂的效果。在空气中用每毫升25微克的AMT和每平方厘米20.7焦耳的UVA处理PCs时,加入2毫摩尔(2毫摩尔/升)甘露醇可显著改善聚集反应和血小板功能的其他体外指标,并且对VSV灭活几乎没有影响。在所研究的其他淬灭剂中观察到的益处较少。因此,当在空气中处理时存在诸如甘露醇等选定的自由基清除剂时,在低氧条件下补骨脂素光灭活的核酸特异性也可能实现。

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