PATHOBIOLOGY OF INTRAVENOUS LIPID EMULSIONS IN CHILDREN

儿童静脉注射脂质乳剂的病理学

• 批准号: 3317106
• 负责人: JEFFREY A GELFAND
• 金额: $ 10.72万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3317106
• 关键词: adult human (21+); aminoacid analyzer; anaphylatoxins; burn therapy; complement pathway; diet therapy; dosage forms; drug adverse effect; enzyme linked immunosorbent assay; human tissue; liposomes; monocyte; newborn human (0-6 weeks); nutrition related tag; parenteral feedings; physical chemical interaction; protein C; thrombocytopenia; thromboxanes; tissue /cell culture; triglycerides

Intravenous lipid emulsions are an important part of total parenteral nutrition (TPN). Complications of TPN with lipid emulsions are seen, however, and include fever and "pyrogen reactions," abnormal pulmonary function, and thrombocytopenia. It had been our clinical impression that thrombocytopenia is a particular problem of lipid emulsion therapy in some neonates and children with burns. We believe that C-reactive protein (CRP), present in trace amounts in normal plasma but markedly elevated with infection, inflammation, or trauma, combines with the phosphocholine emulsifier of lipid emulsion to create liposomes capable of activating complement, generating anaphylatoxins C3a and C5a, thereby aggregating platelets and causing fever. In clinical studies, we will define the incidence of thrombocytopenia and other adverse reactions in neonates and burned children receiving lipid emulsion therapy, and attempt to correlate these reactions with CRP, anaphylatoxin levels, and a quantitative plasma "creaming" reaction that we have developed. We will also study a small number of adult patients, from whom a larger number of sequential samples can be drawn. We will purify CRP by column chromatography to give us adequate amounts of CRP for in vitro experimentation. In vitro experiments are designed to study the effects of lipid emulsion on two target cells of adverse reactions, the macrophage and the platelets. We will study the elaboraton of IL-1 by monocytes challenged with lipid incubated in different types of plasma. Normal plasma, plasma supplemented with varying concentraions of CRP, various complement deficient plasmas will be used to study the relative contributions of CRP and complement in the elaboration of the endogenous pyrogen, Il-1. We will study platelet activation by lipid-plasma interactions. Complement deficient plasma and F (ab') anti-CRP will be used to determine whether platelet activation involves liposome-CRP binding, C3a generation, or liposome-CRP-Clq binding, or some combination. Finally, we will attempt to further study the pathologic events in rabbits with both normal and elevated CRP levels infused with lipid emulsion, to determine the role of CRP and of complement activation in producing these reactions (fever, neutropenia, thrombocytopenia).

静脉注射脂肪乳剂是全胃肠外给药的重要组成部分， 营养（TPN）。 观察到脂肪乳剂TPN的并发症， 然而，包括发烧和“热原反应”，异常肺 功能和血小板减少症。 我们的临床印象是， 血小板减少症是某些患者脂肪乳剂治疗的特殊问题， 烧伤的新生儿和儿童。 我们认为C反应蛋白 (CRP)，在正常血浆中存在痕量，但在 感染、炎症或创伤，与磷酸胆碱结合， 脂肪乳剂的乳化剂，以产生能够活化的脂质体 补体，产生过敏毒素C3 a和C5 a，从而聚集 血小板减少导致发烧 在临床研究中，我们将定义血小板减少症的发生率， 接受脂质的新生儿和烧伤儿童的其他不良反应 乳剂疗法，并试图将这些反应与CRP相关联， 过敏毒素水平，以及定量血浆“奶油”反应，我们 已经发展。 我们还将研究少数成年患者， 可以抽取大量的连续样本。 我们将通过柱色谱法纯化CRP， 用于体外实验的CRP。 体外实验旨在 研究脂肪乳剂对两种靶细胞的影响， 反应，巨噬细胞和血小板。 我们将研究 IL-1的单核细胞挑战与脂质孵育在不同类型的 等离子体 正常血浆、补充有不同浓度的 CRP，各种补体缺乏血浆将用于研究 CRP和补体在制定 内源性热原，IL-1。 我们将通过脂质-血浆相互作用研究血小板活化。 补充 缺乏血浆和F（ab '）抗CRP将用于确定是否 血小板活化涉及脂质体-CRP结合、C3 a生成或 脂质体-CRP-Clq结合或一些组合。 最后，我们将尝试进一步研究家兔的病理事件 与正常和升高的CRP水平输注脂肪乳剂， 确定CRP和补体激活在产生这些 反应（发热、中性粒细胞减少、血小板减少）。