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.

镰状细胞疾病的治疗仍然很大程度上是有症状的，尽管仍然有巨大的努力致力于发现药物以预防或逆转HBS聚合。已经开发了各种技术来促进对潜在抗抗菌特性的化合物的体外评估。但是，这些方法都不容易受到候选化合物的大规模筛选。我们建议开发一种简单，健壮的方法，该方法将测量由HBS的聚合以及抗质剂引起的细胞内粘度的变化。该技术基于通过在受控的氧张力和温度下维持的一小部分完整的红细胞样品引导一束超声波能量。随着HBS在低PO2处的聚合和细胞内粘度的增加，可以检测到超声传播相的变化，幅度和散射横截面可以检测到。通过量化抗激剂可以扭转效果的程度，可以测量和比较其有效性。拟议的商业应用：从事抗抗药化合物的药物和研究实验室非常需要一种简单而自动化的方法来筛选候选化合物。该技术的使用可以扩展以监测其他结构性血液变化，例如血小板功能。