Efficacy of Cobinamide for Treatment of Hydrogen Sulfide-induced Neurotoxicity
钴酰胺治疗硫化氢引起的神经毒性的功效
基本信息
- 批准号:8796347
- 负责人:
- 金额:$ 37.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-30 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdverse effectsAgricultureAnimal ModelAntidotesApplications GrantsBehaviorBehavioralBiochemicalBiological MarkersBody Weight decreasedBrainCellsCessation of lifeChemical WeaponsClinicalCognitive deficitsConfined SpacesCyanidesCytochromesDataDental PulpDevelopmentDopamineDoseEnvironmental PollutantsExposure toFundingFutureGasesGlutamatesHumanHydrogen SulfideHyperbaric OxygenHypotensionIndividualIndustrial AccidentsIndustryIntoxicationIntramuscularIntramuscular InjectionsInvestigationLivestockMapsMediatingModalityModelingMovement DisordersMusNeurologicNeurotransmittersNitritesOccupationalOilsOrganOxidasesOxygenPaperPathologyPermanent Vegetative StatesPersistent Vegetative StatePharmaceutical PreparationsPlantsPoisoningPreventionResearchRespiratory distressSeizuresSeriesSerotoninSmell PerceptionSulfitesSulfurSurvivorsSymptomsTestingTimeTreatment EfficacyUnited States National Institutes of HealthValidationcobinamideegggamma-Aminobutyric Acidhearing impairmentinsightinterestintravenous injectionmass casualtymortalitymouse modelneurobehavioralneurochemistryneuropathologyneurotoxicneurotoxicitynoveloccupational hazardoperationpreventprogramspublic health relevanceresearch studyresponseweapons of mass destruction
项目摘要
DESCRIPTION (provided by applicant): Hydrogen sulfide (H2S), the gas with a "rotten egg" smell, is a colorless highly neurotoxic gas. It is an environmental pollutant and an occupational hazard in several industries including the oil and gas industry, intensive animal farming operations, sewer and wastewater treatment plants, pulp and paper, and gas storage facilities, among others. There is also a significant concern about the use H2S as a weapon of mass destruction, particularly in confined spaces such as underground transit facilities. Catastrophic industrial accidents are also a concern. Hydrogen sulfide has the potential to cause mass civilian casualties under these circumstances. Symptoms in acutely exposed individuals include seizures, respiratory distress, and death. Lingering neurological sequelae include neurobehavioral and cognitive deficits, hearing impairment, and permanent vegetative states, among others. Currently, recommended treatment for H2S poisoning includes intravenous injections of nitrites, and the administration of hyperbaric oxygen. However, none of these treatment modalities is suitable for field treatment of mass casualties. Besides, the efficacy of nitrites is both debatable and associated with major side effects such as hypotension. Treatment of mass victims of H2S poisoning in the field requires medications that can be given by intramuscular (IM) injections, similar to the EpiPen(R) or ComboPen(R). Cobinamide is a novel drug and our preliminary investigations have shown that it is efficacious for treatment of H2S-induced neurotoxicity in the C57 Black mouse animal model. Cobinamide has a significant advantage over current therapies in that it is stable and can be given IM. The objective of the proposed study is to investigate the efficacy of cobinamide as an antidote to H2S poisoning. The proposed study has two Specific Aims. In Specific Aim #1 we will fully characterize our mouse model of H2S-induced neurotoxicity. In Specific Aim #2 we will conduct a series of experiments to evaluate the efficacy of cobinamide to prevent and treat H2S-induced neurotoxicity. Results of this study will be used for development of competitive grant applications for future support under the NIH CounterAct and other relevant funding programs.
描述(由申请人提供):硫化氢(H2S)是一种无色的高神经毒性气体,具有“臭鸡蛋”气味。它是一种环境污染物,也是几个行业的职业危害,包括石油和天然气行业、集约化畜牧业、下水道和废水处理厂、纸浆和造纸以及天然气储存设施等。人们还对使用H2S作为大规模毁灭性武器表示严重关切,特别是在地下运输设施等密闭空间中。灾难性的工业事故也是一个令人关切的问题。在这种情况下,硫化氢有可能造成大规模平民伤亡。急性接触者的症状包括癫痫发作、呼吸窘迫和死亡。神经系统后遗症包括神经行为和认知缺陷、听力障碍和永久性植物人状态等。目前,H2S中毒的推荐治疗包括静脉注射亚硝酸盐和高压氧。然而,这些治疗方式都不适合大规模伤亡的现场治疗。此外,亚硝酸盐的疗效是有争议的,并与主要的副作用,如低血压。在现场治疗H2S中毒的大规模受害者需要通过肌肉注射(IM)给予药物,类似于EpiPen(R)或ComboPen(R)。Cobinamide是一种新型药物,我们的初步研究表明,它可有效治疗C57黑小鼠动物模型中H2S诱导的神经毒性。Cobinamide相对于目前的治疗具有显著的优势,因为它是稳定的,可以IM给药。拟议研究的目的是调查可宾胺作为H2S中毒解毒剂的有效性。这项研究有两个具体目标。在具体目标#1中,我们将充分表征H2S诱导的神经毒性小鼠模型。在具体目标#2中,我们将进行一系列实验,以评估可宾酰胺预防和治疗H2S诱导的神经毒性的功效。本研究的结果将用于开发竞争性赠款申请,以供NIH反法案和其他相关资助计划的未来支持。
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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WILSON Kiiza RUMBEIHA其他文献
WILSON Kiiza RUMBEIHA的其他文献
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{{ truncateString('WILSON Kiiza RUMBEIHA', 18)}}的其他基金
ISU VDL Capacity Building and Methods Development Grant
ISU VDL 能力建设和方法开发补助金
- 批准号:
10190334 - 财政年份:2020
- 资助金额:
$ 37.24万 - 项目类别:
ISU VDL Capacity Building and Methods Development Grant
ISU VDL 能力建设和方法开发补助金
- 批准号:
10189623 - 财政年份:2020
- 资助金额:
$ 37.24万 - 项目类别:
ISU VDL Capacity Building and Methods Development Grant
ISU VDL 能力建设和方法开发补助金
- 批准号:
10424404 - 财政年份:2020
- 资助金额:
$ 37.24万 - 项目类别:
ISU VDL Capacity Building and Methods Development Grant
ISU VDL 能力建设和方法开发补助金
- 批准号:
9677436 - 财政年份:2018
- 资助金额:
$ 37.24万 - 项目类别:
ISU Vet-LIRN Infrastructure Grant Proposal
ISU Vet-LIRN 基础设施拨款提案
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9535744 - 财政年份:2017
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$ 37.24万 - 项目类别:
ISU Vet-LIRN Infrastructure Grant Proposal
ISU Vet-LIRN 基础设施拨款提案
- 批准号:
9475009 - 财政年份:2017
- 资助金额:
$ 37.24万 - 项目类别:
Toxicology Mentoring and Skills Development Training Program
毒理学指导和技能发展培训计划
- 批准号:
9310432 - 财政年份:2016
- 资助金额:
$ 37.24万 - 项目类别:
Toxicology Mentoring and Skills Development Training Program
毒理学指导和技能发展培训计划
- 批准号:
9001085 - 财政年份:2016
- 资助金额:
$ 37.24万 - 项目类别:
Efficacy of Cobinamide for Treatment of Hydrogen Sulfide-induced Neurotoxicity
钴酰胺治疗硫化氢引起的神经毒性的功效
- 批准号:
8932845 - 财政年份:2014
- 资助金额:
$ 37.24万 - 项目类别:
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