Neonatal and Pediatric Platelet Function and Pharmacology

新生儿和儿童血小板功能和药理学

• 批准号: 9292339
• 负责人: SCOTT L DIAMOND
• 金额: $ 24.89万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9292339
• 关键词: Address; Adhesions; Adult; Age; Agonist; Animal Model; Antiplatelet Drugs; Arterial Injury; Aspirin; Biochemical; Biological; Biological Assay; Blood; Blood Platelets; Blood Vessels; Cardiac; Caring; Child; Childhood; Clinical Trials; Complex; Congenital Heart Defects; Critical Illness; Deposition; Development; Diagnostic tests; Diamond; Disease; Dose; Drug Monitoring; Drug effect disorder; Enrollment; Epidemic; Event; FDA approved; Fibrinolytic Agents; Future; Heart; Human; In Vitro; Infant; Intravenous; Knowledge; Lesion; Life; Light; Limb structure; Measures; Mediating; Microfluidic Microchips; Microfluidics; Mission; Monitor; Neonatal; Operative Surgical Procedures; Oral; Pain; Pathway interactions; Patient risk; Patients; Pharmaceutical Preparations; Pharmacology; Physiological; Population; Prevention; Production; Public Health; Pulmonary artery structure; Repair Complex; Research; Risk; Savings; Scanning; Second Messenger Systems; Shunt Device; Signal Pathway; Signal Transduction; Site; Stimulus; Surface; System; Techniques; Technology; Therapeutic; Thrombosis; Thrombus; Translations; Transplanted tissue; Work; age group; age related; base; clinically relevant; clopidogrel; cohort; congenital heart disorder; design; drug development; drug efficacy; falls; high throughput screening; in vitro Assay; in vivo; inhibitor/antagonist; injured; neonate; novel; palliative; patient population; pediatric patients; prevent; public health relevance; release of sequestered calcium ion into cytoplasm; response; tertiary care

 DESCRIPTION (provided by applicant): Arterial thromboembolic disease is rapidly becoming the new epidemic of pediatric tertiary care centers due to an increase in invasive monitoring, life saving technologies such as ECMO, and new surgical techniques and graft materials used to repair complex congenital heart lesions. Yet, therapeutic options for preventing or treating this life and limb threatening disorder are limited. Major obstacles to drug development include: (i) A deficiency in knowledge of the extent to which platelets from neonates, infants, and children can form thrombi in injured blood vessels, (ii) limited information on the ability of various agents to curtail pediatric platelet- mediated adhesion and activation under physiologically relevant conditions, and (iii) a lack of sophisticated technologies that permit rapid assessment of pediatric platelet responses to agonists and antagonists in a high-throughput manner using a minimum quantity of blood. To address these clinically relevant issues, low volume microfluidic devices and high throughput screens (HTS) will be used to predict platelet responses to multiple combinations of agonists as well as antagonists, while a novel biological platform will be used for the in vivo assessment of drug efficacy in the prevention of pediatric platelet-mediated thrombosis. Critical questions to be addressed include: Can sophisticated technologies be developed that permit rapid assessment of pediatric platelet responses to agonists and antagonists in a high- throughput manner using a minimum quantity of blood? Can novel agents be identified for future development or use? Are there age related differences in function that would preclude the use of specific anti-platelet agents in certain subsets of pediatric patients? Can a small animal model be developed to better assess pediatric platelet responses to anti-thrombotic agents? Can in vitro assays be predictive of drug efficacy in vivo? Ultimately, we believe the work outlined in this proposal will lead to a better understanding of the appropriate class of anti-platelet agent to use for at risk pediatric patients. Moreover, it may be possible to define the feasibility and enrollment criteria for future clinical trials to test the diagnostic utlity of our in vitro approaches. The proposed work is also relevant to the mission of the agency, which is to encourage translational and collaborative research to advance our knowledge of underlying mechanisms of drug action and response in children at various developmental stages.

 描述（由申请人提供）：动脉血栓栓塞疾病正在迅速促进培养基中心的新流行病，在侵入性监测，生命中增加 保存ECMO等技术，用于修复有竞争力的心脏病变的新型手术和移植材料。受伤的血管离子在各种药物的能力上 减少儿科血小板中科学的良好条件，以及（iii）允许以高通量方式对激动剂和拮抗剂快速评估的小儿血小板来解决这些临床相关的ISS。 ）将血小板对激动剂作为-ASNTAGONIST的多个PLE组合，而Anolel生物平台将Beuill Beuill Beuill Beuill Beuill Beuill beuill beuill beuill somesh somesh一些预防小儿血小板介导的临界问题。用高通量数量以高通量的方式向激动剂和拮抗剂的小儿血小板可以确定新的药物，或者是否可以在小儿患者的某些子集中进行特定的差异？小儿血小板对抗栓性药物的反应吗？可能 定义未来的feasteria，以确定我们在我们的诊断中的诊断性。RK也与该机构的使命相关，这是针对我们对UF潜在的药物行动和反应的知识来促进我们对毒品行动和反应的了解各个发育阶段的孩子。