Diversity Supplement - Belinda Mahama

 描述(申请人提供)：硫化氢(H_2S)是一种无色、具有高度神经毒性的气体，带有“臭鸡蛋”的气味。它是一种环境污染物，在石油和天然气行业、集约化养殖业、下水道和废水处理厂、纸浆和造纸以及天然气储存设施等多个行业中都是一种职业危害。人们还对使用硫化氢作为大规模杀伤性武器，特别是在地下交通设施等受限空间使用硫化氢表示严重关切。灾难性的工业事故也是一个令人担忧的问题。在这种情况下，硫化氢有可能造成大量平民伤亡。急性接触者的症状包括癫痫发作、呼吸窘迫和死亡。挥之不去的神经后遗症包括神经行为和认知障碍、听力障碍和永久植物人状态等。目前，推荐的硫化氢中毒治疗方法包括静脉注射亚硝酸盐和高压氧。然而，这些救治方式都不适合大规模伤亡的野战救治。此外，亚硝酸盐的疗效既有争议，也与低血压等主要副作用有关。在野外治疗大量硫化氢中毒受害者需要肌肉注射(IM)的药物，类似于EpiPen(注册商标)或ComboPen(注册商标)。考宾胺是一种新药，我们的初步研究表明，它对C57黑鼠模型中H_2S所致的神经毒性有有效的治疗作用。与目前的治疗方法相比，考宾胺有一个显著的优势，因为它是稳定的，可以进行IM。这项拟议的研究的目的是调查可比胺作为硫化氢中毒解毒剂的疗效。这项拟议的研究有两个具体目标。在特定的目标#1中，我们将充分描述我们的硫化氢诱导的神经毒性的小鼠模型。在具体目标#2中，我们将进行一系列实验，以评估可比酰胺预防和治疗硫化氢引起的神经毒性的效果。这项研究的结果将用于开发竞争性赠款申请，以便在NIH中和其他相关资金计划下提供未来的支持。

 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.