Analytical Chemistry
分析化学
基本信息
- 批准号:10204120
- 负责人:
- 金额:$ 45.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:ADME StudyAcuteAnalytical ChemistryAnimalsAnti-Inflammatory AgentsAntibodiesAnticonvulsantsBiochemicalBiologicalBiological AssayBiological MarkersBiosensorBrainChemicalsCholinesterase InhibitorsComplexDetectionDoseDrug KineticsEnsureFormulationGoalsImmunoassayIntoxicationIsoflurophateLaboratoriesMass FragmentographyMethodsMusNeuroprotective AgentsOrganophosphatesOryctolagus cuniculusParaoxonPharmaceutical PreparationsPharmacologic SubstancePicrotoxinQuality ControlRattusReagentRecombinantsResourcesSeizuresSignal PathwaySiteSomanSystemTechniquesTimeTrainingTreatment EfficacyWorkadvanced analyticsbasebiomarker identificationchemical threatdesigndetection assaydetection methodimprovedliquid chromatography mass spectrometrymedical countermeasuremetabolomicsnanobodiesneuropathologyneurosteroidsneurotoxicnovelnovel therapeuticspreventreagent standardreceptorsmall moleculetetramethylenedisulfotetraminetherapeutic candidatetherapeutic evaluation
项目摘要
Project Summary – Analytical Chemistry Core – Core A
The overall goal of the UC Davis CounterACT Center of Excellence is to identify and advance improved medical
countermeasures for stopping seizures and preventing long-term consequences resulting from acute intoxication
with chemical threat agents, specifically organophosphate cholinesterase inhibitors like
diisopropylfluorophosphate (DFP), paraoxon and soman, or GABAA receptor blockers like tetramethylene-
disulfotetramine (TETS) or picrotoxin.
The Analytical Chemistry Core (Core A) is a central resource designed to provide state-of-the-art,
comprehensive analytical support to Projects 1, 2, and 3, and the Probe and Pharmaceutical Optimization Core
(Core B). Specifically, Core A will develop methods for the detection of target compounds and their metabolites
by liquid chromatography–mass spectrometry (LC-MS) or gas chromatography–mass spectrometry (GC-MS),
and provide quality control (QC) analysis of standard solutions prior to their use in projects. Core A will use these
methods to perform mouse and rat ADME (absorption, distribution, metabolism, and excretion) studies for
antiseizure drugs, anti-inflammatories and neuroprotectants to assist all Center projects in dose selection and
time of administration post-exposure, and Core B in the optimization of novel therapeutic candidates. Core A will
work with Project 2 and Project 3 to identify biomarkers of seizures and neuropathology to subsequently be used
as a biochemical test of therapeutic efficacy. Metabolomics techniques, both targeted and global, will be
employed. Targeted metabolomics will focus on oxylipins and neurosteroids, since expression of these signaling
pathways are altered after a seizure, while global metabolomics will be employed as needed to identify broader
biomarkers of seizure and therapy. Additionally, Core A will continue improving methods for TETS detection
since the currently existing methods are too insensitive for pharmacokinetics (PK) analysis. During the first
project period, Core A developed a rabbit polyclonal immunoassay for TETS, which will be optimized for high
throughput laboratory use and for field detection. Core A has more recently initiated work to develop a nanobody-
based assay. These small, heat stable reagents are inexpensive to produce and often provide valuable assays
for the detection of small molecules in complex biological matrices. Immunoassays using both the polyclonal and
the nanobody system will be optimized, and packaged in biosensor formats in a field deployable platform for on-
site detection. When there is a clear need from the projects, immunoassays to other biomarkers of exposure and
effect, including other neurotoxic chemicals, and their metabolites, will be created. Having a specialized core
providing analytical support for all projects and cores improves efficiency and ensures consistency across all
components of the CounterACT Center.
项目总结-分析化学核心-核心A
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('BRUCE D HAMMOCK', 18)}}的其他基金
Soluble epoxide hydrolase and epoxide fatty acid involvement in corneal injury after ammonia exposure: Mechanisms of injury and potential therapeutics using sEH inhibitors and biostable EpFA mimics.
可溶性环氧化物水解酶和环氧化物脂肪酸参与氨暴露后角膜损伤:损伤机制和使用 sEH 抑制剂和生物稳定 EpFA 模拟物的潜在治疗方法。
- 批准号:
10708436 - 财政年份:2023
- 资助金额:
$ 45.58万 - 项目类别:
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseases
生物活性脂质作为环境暴露对慢性疾病有害影响的效应物和指标
- 批准号:
10400036 - 财政年份:2019
- 资助金额:
$ 45.58万 - 项目类别:
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseases
生物活性脂质作为环境暴露对慢性疾病有害影响的效应物和指标
- 批准号:
10615675 - 财政年份:2019
- 资助金额:
$ 45.58万 - 项目类别:
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseases
生物活性脂质作为环境暴露对慢性疾病有害影响的效应物和指标
- 批准号:
10153794 - 财政年份:2019
- 资助金额:
$ 45.58万 - 项目类别:
Clinical Paths for Soluble Epoxide Hydrolase Inhibitors at Experimental Biology 2018
2018 年实验生物学中可溶性环氧化物水解酶抑制剂的临床路径
- 批准号:
9544621 - 财政年份:2018
- 资助金额:
$ 45.58万 - 项目类别:
Role of Epoxygenated Fatty Acids in Modulating Pain
环氧化脂肪酸在调节疼痛中的作用
- 批准号:
8446055 - 财政年份:2013
- 资助金额:
$ 45.58万 - 项目类别:
Role of Epoxygenated Fatty Acids in Modulating Pain
环氧化脂肪酸在调节疼痛中的作用
- 批准号:
8619587 - 财政年份:2013
- 资助金额:
$ 45.58万 - 项目类别:
METHODS MONITOR TOXIC SUBSTAN AND/OR INDICATORS OF PRESENCE IN HUMANS&OTHER SPE
监测人类体内有毒物质和/或存在指标的方法
- 批准号:
8362756 - 财政年份:2011
- 资助金额:
$ 45.58万 - 项目类别:
ID AND DEV OF BIOLOGICAL MARKERS OF HUMAN EXPOSURE TO THE INSECTICIDE PERMETHRI
人类接触杀虫剂氯菊酯的生物标志物的识别和开发
- 批准号:
8362754 - 财政年份:2011
- 资助金额:
$ 45.58万 - 项目类别:
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