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。 夏威夷盒水母属于最臭名昭著的有毒水母类，立方水母，常见于从夏威夷到澳大利亚的热带和亚热带水域。立方动物的叮咬非常痛苦，可能会导致危及生命的Irukandji综合征，表现为一系列全身体征和症状，包括心肺窘迫。一项对急诊室患者的回顾性临床分析表明，Irukandji综合征发生在当地盒子水母叮咬患者中约5%。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，这种小分子在化学上类似于某些昆虫毒素，可以在小龙虾和小鼠身上引起多种生理效应，包括深刻的心脏效应。该项目的具体目标是集中努力提纯、鉴定和生理表征这些具有高度心脏活性的化合物。总体目标是为这些化合物的作用机制提供急需的见解，并为更好的临床管理提供基础。

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.