ULTRASONIC METHOD FOR TESTING ANTI SICKLING AGENTS

测试抗镰状剂的超声波方法

• 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
• 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

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.

镰状细胞病的治疗在很大程度上仍然是对症治疗，尽管仍有相当大的努力致力于发现预防或逆转HbS聚合的药物。已经开发了各种技术来促进化合物的潜在抗疾病特性的体外评估。然而，这些方法都不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，可靠的方法来测量由HbS和抗镰状细胞剂聚合引起的细胞内粘度的变化。这项技术的基础是引导一束超声波能量穿过一小块保持在可控氧张力和温度下的完整红细胞样本。当HbS在低pO2下聚合时，细胞内粘度增加，可以检测到超声传播相位、振幅和散射截面的变化。通过量化一种抗镰状结剂能逆转这种效应的程度，就可以测量和比较它的有效性。建议的商业应用：从事抗镰状细胞病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。