ISOLATION & CHARACTERIZATION OF CARDIOACTIVE COMPOUNDS IN HI BOX JELLYFISH VENOM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 夏威夷盒子水母属于最臭名昭著的有毒水母类别，立方动物，通常是 产于从夏威夷到澳大利亚的热带和亚热带水域。立方动物的叮咬是极其痛苦的，并可能导致 危及生命的Irukandji综合征，表现为一系列全身体征和症状，包括心肺 苦恼。对急诊室患者的回顾性临床分析表明，约5%的急诊室患者会发生Irukandji综合征 当地的盒子水母叮咬受害者。尽管如此，这种综合征的确切生化基础尚不清楚。在夏威夷、澳大利亚和印度尼西亚， 目前的治疗仅限于对症护理。这项研究建议是由我们最近发现的小分子推动的， 化学上类似于某些昆虫毒素，它在两种情况下都会引起多种生理效应，包括深刻的心脏效应 小龙虾和老鼠。该项目的具体目标是集中努力进行纯化、鉴定和生理特性 这些具有高度心脏活性的化合物。总体目标是对这些措施的作用机制提供亟需的见解 并为更好的临床管理提供依据。 拟议研究的具体目标是： 具体目标1.心脏活性物质的生化分离 具体目标2.心脏活性化合物的生物物理特性 具体目标3.心脏活性化合物的生理特性 心脏毒素的识别和特征及其作用机制的阐明应为开发更具体和有效的临床管理模式提供见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hawaiian box jellyfish (Carybdea alata) belong to the most notoriously toxic class of jellyfish, the cubozoans, which are commonly found in tropical and subtropical waters from Hawaii to Australia. Cubozoan stings are extremely painful and result in potentially life-threatening Irukandji syndrome, which presents as a constellation of systemic signs and symptoms, including cardiopulmonary distress. A retrospective clinical analysis of emergency room patients demonstrates that Irukandji syndrome occurs in about 5% of local box jellyfish sting victims. Still, the precise biochemical basis for this syndrome is unclear. In Hawaii, Australia and Indonesia, current therapy is limited to symptomatic care. This research proposal is prompted by our recent discovery of small molecules, chemically similarly to certain insect toxins, which induce multiple physiological effects including profound cardiac effects in both crayfish and mice. The specific aims of this project are to conduct focused efforts to purify, identify and physiologically characterize these highly cardioactive compounds. The overall goal is to provide much-needed insights into the mechanisms of action of these compounds and provide the basis for better clinical management. The specific aims of the proposed research are: Specific Aim 1. Biochemical separation of cardioactive compounds Specific Aim 2. Biophysical characterization of cardioactive compounds Specific Aim 3. Physiological characterization of cardioactive compounds The identification and characterization of cardiotoxins and the elucidation of their mechanisms of action should provide insights into the development of more specific and effective clinical-management modalities.