Animal Modeling, Photonics, and Antidote Efficacy Core

动物建模、光子学和功效评估核心 (AEC) 摘要 动物建模、光子学和功效评估核心由两个部分组成 基于核心光子学的诊断技术和已建立的 2 种非啮齿动物物种 CN中毒：高度监控中型动物（兔子）（加州大学欧文分校）和大型动物 （猪）模型（科罗拉多大学丹佛分校）。该核心提供的功能 先进的体内动物候选解毒剂诊断、功效测试和功能 用于实时定量测定化学诱导损伤的发展、程度、 以及对治疗的反应。核心支持先进的哺乳动物测试 项目 1、2 和 3 中确定的有希望的候选解毒剂。该集成核心具有 在临床前快速推进此类候选药物测试的能力 评估，以及为早期阶段项目提供反馈迭代 药物科学核心用于增强药物设计，并提供 将样品送至代谢表型和药代动力学核心 (MPPC) 以促进 我们对 CN 中毒后果的机制理解。 基于核心光子学的技术包括漫射光谱和 连续波近红外光谱用于评估代谢的影响 氰化物毒物，以及组织氧合和细胞色素 C 氧化酶氧化还原的监测 兔子和猪模型中的状态以及连续组织的实时微传感器 对代谢性毒物暴露的动物进行乳酸监测。核心还将 提供最先进的兔子测试设施并确定致死和亚致死 支持所有项目的氰化物解毒剂开发模型。先进技术 作为核心交付成果的一部分，功能将扩展到科罗拉多大学，并且 除了持续可用之外，还将在大型动物（猪）模型中发挥作用 在加州大学欧文分校贝克曼激光实验室的兔子测试设施和动物手术室 研究所。正如我们之前的化学防御研究所示，这些核心技术 能够更准确、精确、无创地确定损伤和治疗 有效性，显着加速解毒剂的开发并减少动物 确定结果和成功翻译解毒剂化合物所需的数量 达到治疗用途。

Animal Modeling, Photonics, and Efficacy Evaluation Core (AEC) Abstract The Animal Modeling, Photonics and Efficacy Evaluation Core consists of two core photonics based diagnostic technologies and 2 non-rodent species of established CN poisoning: highly monitored mid-size animal (rabbit) (UC Irvine) and large animal (pig) models (University of Colorado Denver). The core provides the capabilities for advanced in-vivo animal candidate antidote diagnostics, efficacy testing, and capabilities for real time quantitative determination of chemical induced injury development, extent, and response to therapy. The Core supports advanced mammalian testing of the promising antidote candidates identified in projects 1, 2, and 3. This integrated core has the capability to rapidly advance testing of such candidate agents in pre-clinical evaluation, as well as to provide feedback iteration to the earlier phase projects and to the Pharmaceutical Sciences Core for drug design enhancement, and to provide samples to the Metabolic Phenotyping and Pharmacokinetics Core (MPPC) to promote our mechanistic understanding of the consequences of CN poisoning. The Core photonics based technologies include diffuse optical spectroscopy and continuous wave near infrared spectroscopy for assessment of effects of the metabolic poison cyanide, and monitoring of tissue oxygenation and cytochrome C oxidase redox states in the rabbit and swine models, and real-time micro-sensors for continuous tissue lactate monitoring in animals with metabolic poison exposures. The core will also provide a state-of-the-art rabbit testing facility and established lethal and sub-lethal models for cyanide antidote development supporting all projects. Advanced technology capabilities will be extended to the U. of Colorado as part of the Core deliverables, and will function there in the large animal (pig) model in addition to their ongoing availability in the rabbit testing facility and animal operating rooms at UC Irvine Beckman Laser Institute. As shown in our prior chemical defense research, these core technologies enable more accurate, precise, and noninvasive determination of injury and treatment effectiveness, dramatically accelerating antidote development and reducing animal numbers required for definitive results and successful translation of antidote compounds to therapeutic use.