Novel Treatments of Acrolein-induced Cardiotoxicity
Novel Treatments of Acrolein-induced Cardiotoxicity
批准号:
8610016
负责人:
Daniel Joseph Conklin
金额:
$37.5万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-24 至 2015-08-31
关键词:
1 year old2-butenalAccountingAcroleinAcuteAdultAdverse effectsAgeAnimalsArthritisAsthmaAutonomic nervous systemBiocideBlood PressureBreathingC57BL/6 MouseCalciumCardiacCardiopulmonaryCardiotoxicityCardiovascular systemChemical WarfareChemicalsChronicClinicalDermalDevelopmentDiesel ExhaustDoseDyslipidemiasEchocardiographyEdemaEmergency SituationEvaluationEventExposure toExtravasationEyeFDA approvedFemaleFire - disastersFormaldehydeFoundationsGasesGoalsHeartHerbicidesHumanHydra PolypsIndustryInflammationInjection of therapeutic agentInjuryInterventionIrrigationIrritantsLeadLungMeasuresMediatingMonitorMucinsNatural DisastersNeuronsNoseOilsPainPesticidesPharmaceutical PreparationsPhasePlasmaProductionRelative (related person)RouteSafetyShippingShipsSignal TransductionSkinStructure of parenchyma of lungSystemTRPA1 ChannelTRPV1 geneTestingTherapeuticTherapeutic InterventionToxic effectTranslational ResearchTroponin IWateractivin Aatherogenesiscapsazepinecarbonyl compoundcombateffective interventioneffectiveness measureefficacy testingforesthuman morbidityhuman mortalityimprovedinhibitor/antagonistinsightirritationmalemembernovelolder womenpreclinical studypreconditioningpreventpublic health relevancereceptorrespiratoryresponsesex
中文摘要
丙烯醛心脏毒性的新治疗方法
这个项目的总体目标是开发新的和改进的对策和治疗方法
预防与化学威胁相关的人类死亡和发病率。这种威胁可能是由
恐怖袭击,工业生产中使用的化学品意外泄漏,或在
自然灾害和火灾。与所有这些情况相关的最常见和最丰富的活性化学物质
是活性羰基化合物(RCC)。这一类的典型成员是丙烯醛。丙烯醛及相关物质
RCC是森林和森林中产生的最丰富和最有毒的成分,致死量(600ppm)
结构性火灾。外源性和内源性RCCs对呼吸和心血管的深刻影响
然而,RCCs的毒理作用和它们的毒性机制都没有
都被系统地描绘出来了。同样,年轻人、老年人和妇女对RCC暴露的具体脆弱性
还没有经过评估。最重要的是,没有有效的对策或治疗干预措施
目前可用。可能的治疗干预措施包括使用已知的RCC受体抑制剂进行治疗
作为瞬时受体电位(Trp)通道。这些拮抗剂包括TRPV1和TRPA1抑制剂
承诺减少心血管和肺部系统的疼痛和炎症
高剂量接触肾细胞癌。对高水平RCC暴露后缓解疗法的评估将提供
判断它们在人类受到化学紧急威胁的情况下使用的相对有效性的第一步。
英文摘要
Novel Treatments of Acrolein-induced Cardiotoxicity
The overall goal of this project is to develop new and improved countermeasures and therapeutics for
preventing human mortality and morbidity associated with chemical threats. Such threats might be imposed by
a terrorist attack, accidental leakage of chemicals used in industrial production, or those released during
natural disasters and fires. The most common and abundant reactive chemicals, relevant to all these situations
are reactive carbonyl compounds (RCCs). A prototypical member of this class is acrolein. Acrolein and related
RCCs are the most abundant and toxic constituents generated in lethal amounts (600 ppm) during forest and
structural fires. Profound respiratory and cardiovascular effects of exogenous and endogenous RCCs have
also been described; however, neither the toxicological effects of RCCs nor their mechanisms of toxicity have
been systematically delineated. Similarly, the specific vulnerability of young, old and women to RCC exposure
has not been assessed. Most importantly, no effective countermeasures or therapeutic interventions are
currently available. Possible therapeutic interventions include treatment with inhibitors of RCC receptors known
as transient receptor potential (TRP) channels. These antagonists including TRPV1 and TRPA1 inhibitors hold
promise to diminish the pain and inflammation in the cardiovascular and pulmonary systems associated with
high dose exposure to RCC. Evaluation of mitigation therapies following high level RCC exposure will provide
the first step in judging their relative efficacy for use in the case of a chemical emergency threat in humans.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Cardiovascular Benefits of Inhaled Biogenic Volatile Organic Compounds
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批准号:10459548
-
项目类别:
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资助金额:$19.56万
-
财政年份:2021
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardiovascular Benefits of Inhaled Biogenic Volatile Organic Compounds
-
批准号:10288039
-
项目类别:
-
资助金额:$23.41万
-
财政年份:2021
-
负责人:Daniel Joseph Conklin
-
依托单位:
Animal Models and Phenotyping Core
-
批准号:10208902
-
项目类别:
-
资助金额:$19.76万
-
财政年份:2018
-
负责人:Daniel Joseph Conklin
-
依托单位:
Animal Models and Phenotyping Core
-
批准号:10452736
-
项目类别:
-
资助金额:$19.76万
-
财政年份:2018
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core B: Tobacco Product Evaluation and Exposure Core
-
批准号:8595396
-
项目类别:
-
资助金额:$74.85万
-
财政年份:2013
-
负责人:Daniel Joseph Conklin
-
依托单位:
Novel Treatments of Acrolein-induced Cardiotoxicity
-
批准号:8740481
-
项目类别:
-
资助金额:$37.5万
-
财政年份:2013
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardioprotective Mechanisms of Glutathione S-transferase P
-
批准号:7838943
-
项目类别:
-
资助金额:$23.55万
-
财政年份:2009
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardioprotective Mechanisms of Glutathione S-transferase P
-
批准号:8212058
-
项目类别:
-
资助金额:$36.63万
-
财政年份:2008
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardioprotective Mechanisms of Glutathione S-transferase P
-
批准号:7466262
-
项目类别:
-
资助金额:$37.0万
-
财政年份:2008
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardioprotective Mechanisms of Glutathione S-transferase P
-
批准号:7788879
-
项目类别:
-
资助金额:$37.0万
-
财政年份:2008
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardioprotective Mechanisms of Glutathione S-transferase P
-
批准号:8053818
-
项目类别:
-
资助金额:$37.0万
-
财政年份:2008
-
负责人:Daniel Joseph Conklin
-
依托单位:
Cardioprotective Mechanisms of Glutathione S-transferase P
-
批准号:7612771
-
项目类别:
-
资助金额:$37.0万
-
财政年份:2008
-
负责人:Daniel Joseph Conklin
-
依托单位:
Aldehydes and Coronary Artery Vasospasm
-
批准号:6357612
-
项目类别:
-
资助金额:$14.2万
-
财政年份:2002
-
负责人:Daniel Joseph Conklin
-
依托单位:
CALCIUM OVERLOAD AND APOPTOSIS IN VASCULAR TOXICITY
-
批准号:2520437
-
项目类别:
-
资助金额:$1.17万
-
财政年份:1998
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core D - Animal Models and Phenotyping Core
-
批准号:8711508
-
项目类别:
-
资助金额:$14.82万
-
财政年份:--
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core B: Tobacco Product Evaluation and Exposure Core
-
批准号:8906925
-
项目类别:
-
资助金额:$56.95万
-
财政年份:--
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core D - Animal Models and Phenotyping Core
-
批准号:9130199
-
项目类别:
-
资助金额:$14.82万
-
财政年份:--
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core B: Tobacco Product Evaluation and Exposure Core
-
批准号:8737961
-
项目类别:
-
资助金额:$56.89万
-
财政年份:--
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core D - Animal Models and Phenotyping Core
-
批准号:9300981
-
项目类别:
-
资助金额:$14.82万
-
财政年份:--
-
负责人:Daniel Joseph Conklin
-
依托单位:
Core D - Animal Models and Phenotyping Core
-
批准号:8601970
-
项目类别:
-
资助金额:$14.82万
-
财政年份:--
-
负责人:Daniel Joseph Conklin
-
依托单位: