ULTRASONIC METHOD FOR TESTING ANTI SICKLING AGENTS

镰状细胞病的治疗在很大程度上仍然是症状性的，尽管继续有相当大的努力致力于发现药物来预防或逆转HbS聚合。已经开发了各种技术来促进化合物的潜在抗粘性能的体外评价。然而，这些方法中没有一种容易适用于候选化合物的大规模筛选。我们建议开发一种简单，稳健的方法，将测量由HbS聚合以及抗凝血剂引起的细胞内粘度的变化。该技术是基于引导一束超声能量通过保持在受控氧张力和温度下的完整红细胞的小样本。当HbS在低pO2下聚合并且细胞内粘度增加时，可以检测到超声传播的相位、振幅和散射截面的变化。通过量化一种防粘剂可以逆转这种效果的程度，可以测量和比较它的有效性。拟议的商业应用：从事抗剪切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，如血小板功能。

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.