ULTRASONIC METHOD FOR TESTING ANTI SICKLING AGENTS

镰状细胞病的治疗在很大程度上仍然是有症状的，尽管仍有相当多的努力致力于发现防止或逆转HBS聚合的药物。已经开发了各种技术来促进化合物潜在的抗病性能的体外评估。然而，这些方法都不容易适应大规模筛选候选化合物。我们建议开发一种简单、可靠的方法来测量由HBS聚合以及抗病毒剂引起的细胞内粘度的变化。这项技术的基础是将超声波能量束引导到一小部分完整的红细胞中，这些红细胞保持在受控的氧分压和温度下。随着HBS在低pO2下聚合和细胞内粘度的增加，可以检测到超声传播的相位、幅度和散射截面的变化。通过量化抗呕吐剂逆转效果的程度，可以测量和比较其有效性。拟议的商业应用：从事抗呕吐化合物研究的制药和研究实验室强烈需要一种简单和自动化的手段来筛选候选化合物。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.