Identification of Structure-Based Antisickling Peptides that Inhibit HBS Polymeri

抑制 HBS 聚合物的基于结构的抗镰化肽的鉴定

• 批准号: 7527400
• 负责人: KAZUHIKO ADACHI
• 金额: $ 20.4万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-22 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7527400
• 关键词: cooperative study; drug design /synthesis /production; hemoglobin Ss; polymerization; protein protein interaction; protein structure; sickle cell anemia; sickling inhibitor

Sickle cell disease (SCD) is the most common serious genetic disease in Africa. In Ghana, 2% of newborns have been found to have homozygous SCD (SCD-SS) or sickle cell disease-SC disease (SCD-SC). In the U.S. and elsewhere outside Africa, bacterial infections, particularly pneumococcal sepsis and meningitis, are the leading cause of death in children with SCD. Childhood mortality from pneumococcal sepsis has been reduced to low levels in the U.S. through early diagnosis in the newborn followed I_ypenicillin prophylaxis, anti-pneumococcal vaccination, and education of parents and health workers about this problem. In Africa, infections are also reported to be the leading cause of death in children with SCD. However, the causes of infection and their relative importance are not precisely determined. Pneumococcal infection is highly prevalent in the general childhood population in Africa, but there are conflicting data on its significance in children with SCD. Penicillin prophylaxis and pneumococcal vaccination are not widely used in young children with SCD in Africa. Host reports list malaria as the leading cause of death in children with SCD in Africa. However, the incidence of acute malaria infection and the risk factors associated with malaria in children with SCD have not been described. Anti-malarial prophylaxis is not practiced uniformly for all children with SCD in Africa. In this study, a cohort of young children with SCD diagnosed from birth will be monitored closely at steady state and during acute illness in order to collect prospective clinical and laboratory data and determine the causes of fever and infection. Parents will be trained to measure temperature and recognize other signs of infection and to bring ill children for evaluation and management. Home visits will be employed to monitor children at home and to reinforce education and preventive care. Blood cultures, malarial smears and hematologic studies will be obtained , during acute illness. Protocols will be implemented to ensure that prompt management is provided all subjects with potential bacterial or acute malarial infection. Incidence and prevalence of bacterial and malarial infections and their associated risk factors will be determined.

镰状细胞病（SCD）是非洲最常见的严重遗传性疾病。在加纳，2% 的新生儿被发现患有纯合子SCD（SCD-SS）或镰状细胞病-SC病 （SCD-SC）。在美国和非洲以外的其他地方，细菌感染，特别是肺炎球菌感染， 败血症和脑膜炎是SCD儿童死亡的主要原因。儿童死亡率 在美国，通过早期诊断， 新生儿接受I_ypenicillin预防，抗肺炎球菌疫苗接种和 家长和卫生工作者对这个问题。在非洲，据报道感染也是 是SCD儿童死亡的主要原因。然而，感染的原因及其相对 重要性并没有被精确地确定。肺炎球菌感染是非常普遍的一般 非洲的儿童人口，但关于其在儿童中的重要性， SCD。青霉素预防和肺炎球菌疫苗接种并未广泛用于幼儿 在非洲的SCD。东道国报告将疟疾列为2004年SCD儿童死亡的主要原因。 非洲然而，急性疟疾感染的发病率和与疟疾有关的危险因素， SCD儿童中的疟疾尚未被描述。没有进行抗疟疾预防 所有非洲的SCD儿童都是如此。 在这项研究中，将监测一组从出生就诊断为SCD的幼儿 在稳态和急性疾病期间密切观察，以收集前瞻性临床和实验室数据。 数据，并确定发烧和感染的原因。父母将接受培训， 温度和识别其他感染迹象，并将患病儿童带到评估， 管理将进行家访，以监测家中的儿童并加强教育 和预防保健。将进行血培养、疟疾涂片和血液学研究， 在急性疾病期间。将执行方案，以确保提供及时管理 所有患有潜在细菌或急性疟疾感染的受试者。发病率和患病率 将确定细菌和疟疾感染及其相关风险因素。