PREVENTING TRANSMISSION OF DISEASES--AIDS VIA BLOOD

预防疾病传播——艾滋病通过血液传播

• 批准号: 3362110
• 负责人: JAMES L MATTHEWS
• 金额: $ 23.97万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-15 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3362110
• 关键词: Macaca mulatta; Trypanosoma cruzi; animal tissue; antiviral agents; baboons; blood banks; blood preservation; blood transfusion; chemical synthesis; communicable disease control; communicable disease transmission; cytomegalovirus; dyes; human immunodeficiency virus; human tissue; lasers; natural gene amplification; nonvisual photosensitivity; photochemistry; provirus; radiosensitizer; simian AIDSs

The project objectives are to develop a photodynamic treatment to render blood bank products free from envelope viruses including cytomegalovirus (CMV) and human immunodeficiency virus (HIV) and to kill malarial organisms and trypanosomes known to be transmitted via transfusion. A means to treat blood is essential because semlogic tests cannot identify all infected blood. Preliminary research in our laboratory has shown photodynamic killing of enveloped viruses (CMV, ERV, and others), malaria, and T. cruzi in free suspension as well as in whole blood and HIV within infected H9 cells. Tbe photoactive compound dihematoporphyrin ether (DHE) was activated in a flowing system using 630 mn light at 5 J/cm2. Initial tests for effects of the system on blood quality were also done as the proposed system must kill infectious agents without modification of essential blood elements. To further develop this photoactive system with DHE, a simian immunodeficiency virus andffl model will be used for infectivity testing including detection of provirus in cells by the polymemse chain reaction. Human and baboon blood will be used for other tests including RBC life span, platelet function, and pmtein integrity. A scaled up prototype system allows blood to be processed in 500 ml units. Additional toxicity and mutagenicity studies of DHE will be done. Although the DHE system will be fully developed, other photoactive dyes will be investigated in an effort to increase the efficiency of the photokilling system. The present system limits the light power that can be delivered because hemoglobin also absorbs at 630 nin. Preliminary tests here on other dyes that absorb at 700 nm (minimal hemoglobin absorption) and are more efficient at low light levels indicate that othcr dyes are worthy of intensive investigation. Collaborative arrangements have been established between our organic synthesis laboratory and three other university laboratories to develop new candidate dyes for antiviral screening and development. If these dyes prove advantageous over the existing system, they will be fully tested in the aninial model. The most efficient new dyes will follow the DHE test protocol. Our goal is the development of an efficient system for the inactivation of viral pathogens in free suspension and within ceus that also kills malaria and T. cruzi . The system should retain the integrity of all blood components, process a unit of blood in less than 10 minutes, and be adaptable for blood banks.

项目目标是开发光动力处理以渲染 血库产品免受信封病毒的免费 （CMV）和人类免疫缺陷病毒（HIV）并杀死疟疾 已知通过输血传播的生物体和锥虫。一个 手段治疗血液是必不可少的，因为塞术测试无法识别 所有感染的血液。我们实验室的初步研究表明 光动力杀死包裹病毒（CMV，ERV等）， 疟疾和T. cruzi在自由悬浮以及全血和 感染H9细胞内的HIV。 TBE光活性复合二甲肾上腺素 Ether（DHE）在流动系统中使用630 MN的光线在5处激活 J/CM2。该系统对血质质量影响的初步测试也是 作为拟议系统必须杀死传染剂，而无需 修改基本血液元素。进一步发展 带有DHE的光活性系统，猿类免疫缺陷病毒和FFFL模型 将用于感染测试，包括检测病毒 细胞通过聚合链反应。人类和狒狒的血将 用于其他测试，包括RBC寿命，血小板功能和 PMTEIN完整性。扩展的原型系统可以使血液为 以500毫升单位进行处理。其他毒性和诱变性研究 DHE将完成。尽管DHE系统将得到充分开发，但是 将研究其他光活性染料，以增加 光功能系统的效率。当前系统限制了 可以传递的轻功率，因为​​血红蛋白也在630处吸收 宁。这里对700 nm吸收的其他染料进行初步测试（最小 血红蛋白吸收），在低光水平上更有效 表明OTHCR染料值得进行深入研究。 我们有机之间已经建立了协作安排 合成实验室和其他三个发展的实验室 用于抗病毒筛查和发育的新候选染料。 如果这些 染料证明在现有系统上是有利的，它们将完全 在动态模型中进行了测试。最有效的新染料将遵循 DHE测试协议。我们的目标是开发有效的系统 自由悬浮液中病毒病原体的失活 这也杀死了疟疾和克鲁兹。系统应保留 所有血液成分的完整性，处理一个小于小于的血液单位 10分钟，适合血库。