PROTAMINE HYPERSENSITIVITY AND HEPARIN FRAGMENT BIOLOGY

鱼精蛋白过敏和肝素片段生物学

• 批准号: 3133319
• 负责人: John M Weiler
• 金额: $ 11.68万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3133319
• 关键词: antidotes; chemical structure function; complement inhibitors; complement pathway; delayed hypersensitivity; diabetes mellitus; drug hypersensitivity; eosinophil; heart surgery; heparin; human subject; immediate hypersensitivity; immunoglobulin E; immunoglobulin G; polysaccharides; protamines; proteins; sulfates; vas deferens surgery

Heparin and Protamine Sulfate are charged substances which are widely used clinically. Recently it has been appreciated that protamine may cause serious adverse reactions when it is given to reserve the anticoagulant effects of heparin. In the first part of this project, we will examine the mechanism by which protamene may exert these reactions. We will study whether they are due to Type I hypersensitivity and/or whether the effect may be mediated through complement. We will examine the prevalence of positive immediate or delayed skin tests and IgG and IgE anti-protamine in patients who have received protamine containing insulin; in diabetics who have not received protamine containing insulin; in men who have had vasectomy; in other patients who have received protamine; in patients with Type I hypersensitivity to fish; and in a normal population. We will determine the true incidence and the mechanism(s) of hypersensitivity to protamine when the drug is given, to reverse the anticoagulant effect of heparin, to patients who will undergo cardiac catheterization and to patients who will undergo open heart surgery. In the second part of the project, we will examine heparin more fully to determine the Structure Activity Relationship between its fragments and complements. We will study the following polysaccharide mixtures to see which fragments are active in regulating complement: tetrasaccharides, hexasaccharide, octasaccharide, decasaccharide and larger polysaccharides. We will search for heparin fragments of very low MW which have the minimum structure necessary to regulate complement as actively as does commercial heparin. We will examine other heparin-like molecules to determine if they are able to exert the same effects on complement. We will examine other polycations to determine whether they have the same effect. Finally, we will determine if Major Basic Protein, an important constitutent of the eosinophil, may similarly modulate the complement system.

肝素和硫酸鱼精蛋白是广泛使用的带电物质 临床上。 最近人们认识到鱼精蛋白可能会导致 预留抗凝剂时出现严重不良反应 肝素的作用。 在该项目的第一部分中，我们将研究 鱼精蛋白可能发挥这些反应的机制。 我们将学习 是否是由于 I 型超敏反应和/或效果是否 可能通过补体介导。 我们将检查以下情况的流行程度： 立即或延迟皮试以及抗鱼精蛋白 IgG 和 IgE 呈阳性 接受过含有鱼精蛋白的胰岛素的患者；在糖尿病患者中 未接受过含有鱼精蛋白的胰岛素；在曾经有过 输精管结扎术；其他接受鱼精蛋白治疗的患者；在患者中 对鱼I型过敏；以及在正常人群中。 我们将 确定过敏的真实发生率和机制 给药时加入鱼精蛋白，以逆转药物的抗凝作用 肝素，对于将接受心导管插入术的患者以及 将接受心脏直视手术的患者。 在第二部分中 项目中，我们将更全面地检查肝素以确定其结构 活动 其片段和补体之间的关系。 我们将学习 以下多糖混合物，看看哪些片段具有活性 调节补体：四糖、六糖、八糖、 十糖和较大的多糖。 我们将寻找肝素 分子量非常低的碎片，具有必要的最小结构 与商业肝素一样积极调节补体。 我们将 检查其他肝素样分子以确定它们是否能够发挥作用 对补体有同样的作用。 我们将检查其他聚阳离子 判断它们是否具有相同的效果。 最后，我们将确定是否 主要碱性蛋白是嗜酸性粒细胞的重要组成部分， 类似地调节补体系统。