ULTRASONIC METHOD FOR TESTING ANTI SICKLING AGENTS

测试抗镰状剂的超声波方法

基本信息

批准号：
2785832
负责人：
MARTIN Carl BARUCH
金额：
$ 9.94万
依托单位：
EMPIRICAL TECHNOLOGIES CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2000-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2785832
关键词：
biomedical equipment development drug screening /evaluation hemoglobin Ss intracellular transport sickle cell anemia sickling inhibitor technology /technique development ultrasound viscosity

项目摘要

Treatment of sickle cell disease is still largely symptomatic, though there continues to be considerable effort dedicated to the discovery of drugs to prevent or reverse HbS polymerization. Various techniques have been developed to facilitate the in-vitro evaluation of compounds for potential antisick1ing properties. However, none of these methods is easily amenable to large-scale screening of candidate compounds. We propose to develop a simple, robust method that will measure changes in intracellular viscosity caused by polymerization of HbS as well as antisickling agents. The technique is based on directing a beam of ultrasonic energy through a small sample of intact erythrocytes maintained under controlled oxygen tension and temperature. As HbS polymerizes at low pO2 and the intracellular viscosity increases, changes in the phase of ultrasound propagation, the amplitude, and the scattering cross section can be detected. By quantizing the degree to which an antisickling agent can reverse the effect, its effectiveness can be measured and compared. PROPOSED COMMERCIAL APPLICATIONS: Pharmaceutical and research laboratories engaged in the search for antisickling compounds have a strong need for a simple and automated means to screen candidate compounds. Use of the technique could be extended to monitor other structural blood changes, such as platelet function.

尽管人们继续付出相当大的努力致力于发现预防或逆转 HbS 聚合的药物，但镰状细胞病的治疗仍然主要是对症治疗。人们已经开发了各种技术来促进化合物潜在抗病特性的体外评估。然而，这些方法都不容易适合大规模筛选候选化合物。我们建议开发一种简单、可靠的方法来测量 HbS 以及抗镰状剂聚合引起的细胞内粘度变化。该技术的基础是引导超声波能量束穿过保持在受控氧张力和温度下的一小部分完整红细胞样本。由于 HbS 在低 pO2 下聚合且细胞内粘度增加，因此可以检测到超声传播的相位、振幅和散射截面的变化。通过量化抗镰化剂逆转效应的程度，可以测量和比较其有效性。拟议的商业应用：从事抗镰化化合物研究的制药和研究实验室强烈需要一种简单且自动化的方法来筛选候选化合物。该技术的使用可以扩展到监测其他结构性血液变化，例如血小板功能。