INACTIVATION OF VIRUSES IN BLOOD

接受输血的人面临病毒传播的风险， 肝炎病毒仍然是最频繁的；然而，艾滋病的传播 进入普通捐赠者群体引发了对未来艾滋病毒风险的担忧 并面临不明病毒的风险。我们的目标是开发出 病毒灭菌，适用于红细胞(RBCC)和血小板 浓缩物(PC)，这将消除这种风险。研究将强调 光敏剂，特别是铝酞菁(AIPC)衍生物 用于治疗RBCC和PC，补骨脂素治疗PC。 目前磺化AIPC的有利结果将与 带正电的和两性的酞菁。每个人都表现出了优越的一面 在其他生物系统中的反应性。AMT的当前结果(a 带正电的补骨脂素)将被延长。人们的注意力将集中在 ···使用···使用羟基自由基猝灭剂和其他L型反应物，其 最近被证明在消除不受欢迎的方面是有利的 用光动力染料和补骨脂素观察的反应-没有 降低病毒杀灭的速度或程度。同时清除这两种物质的灭绝者 L型自由基和单线态氧也将进行测试。病毒杀伤力 用水疱性口炎病毒(和其他标志性病毒)进行检测， 艾滋病毒和丙型肝炎病毒。核酸修饰的测量将 也会被制造出来。将监测红细胞和血小板的完整性 治疗后立即接受治疗并在标准血库下储存 条件。测量将包括血红蛋白释放、K+渗漏、免疫球蛋白 结合代谢指标，如葡萄糖利用、细胞内 红细胞的ATP和2，3-DPG，以及血小板数量、形态、pH、 聚集反应和选定膜的出现/消失 抗原，以及纠正阿司匹林诱导的血小板减少症的能力 在狒狒身上。对于RBCC和PC，循环恢复和半衰期都将 在兔和狒狒身上进行自体输血后进行评估。 新免疫原性将在这些狒狒研究中进行评估，也将在一个 用人RBCC和PC制作兔模型。可获得的有关 提供有利结果的化合物的毒理学将被审查，并 进行了Ames测试。

Blood transfusion recipients are at risk of virus transmission, with hepatitis virus remaining the most frequent; however, the spread of AIDS into the general donor population raises fears concerning future HIV risk and risk from unidentified viruses. Our objective is to develop methods of virus sterilization, applicable to red cell (RBCC) and platelet concentrates (PC), which will eliminate this risk. Research will emphasize photosensitizers, especially aluminum phthalocyanine (AIPc) derivatives for the treatment of RBCC and PC, and psoralens for the treatment of PC. Current favorable results with sulfonated AIPc will be compared with positively charged and amphoteric phthalocyanines. Each has shown superior reactivity in other biological systems. Current results with AMT (a positively charged psoralen) will be extended. Attention will focus on the use of quenchers of hydroxyl radicals and other "type l" reactants, which were recently shown to be advantageous in eliminating undesired side reactions observed with both photodynamic dyes and psoralens - without reducing the rate or extent of virus kill. Quenchers which scavenge both type l radicals and singlet oxygen will also be tested. Virus killing will be measured with vesicular stomatitis virus (and other marker viruses), HIV, and hepatitis C virus. Measurements of nucleic acid modification will also be made. Red cell and platelet integrity will be monitored immediately following treatment and on storage under standard blood bank conditions. Measurements will include hemoglobin release, K+ leakage, IgG binding, metabolic indicators such as glucose utilization, intracellular ATP and 2,3-DPG for RBC, and changes in platelet number, morphology, pH, aggregation response, and appearance/disappearance of selected membrane antigens, and the ability to correct an aspirin-induced thrombocytopathy in baboons. For both RBCC and PC, circulatory recovery and half-life, will be evaluated following autologous transfusion in rabbits and baboons. Neoimmunogenicity will be assessed in these baboon studies and also in a rabbit model using human RBCC and PC. Available information regarding the toxicology of compounds giving favorable results will be reviewed, and Ames testing performed.