[Show abstract][Hide abstract] ABSTRACT: First comprehensive evaluation of leading AChE oxime reactivators•All oximes are compared against current U.S. therapy 2-PAM Cl•Relative therapeutic oxime efficacies against OP CWNA and pesticides•Contribution to more effective antidotes for civilian and military populations
Toxicology and Applied Pharmacology 10/2014; 281(3):254-65. · 3.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Seizurogenic chemicals include a variety of toxic agents, including chemical warfare agents, toxic industrial chemicals, and natural toxins. Chemical weapons such as sarin and VX, and pesticides such as parathion and carbaryl cause hyperstimulation of cholinergic receptors and an increase in excitatory neurotransmission. Glutamatergic hyperstimulation can occur after exposure to excitatory amino acid toxins such as the marine toxin domoic acid. Other pesticides such as lindane and strychnine do not affect excitatory neurotransmission directly, but rather, they block the inhibitory regulation of neurotransmission by antagonism of inhibitory GABA and glycine synapses. In this article is a discussion of chemicals that cause seizures by a variety of molecular mechanisms and pathways.
[Show abstract][Hide abstract] ABSTRACT: Pesticides represent one of the largest classes of toxic chemicals produced, stored, and used in the United States and abroad. These chemicals are designed to be toxic and many, besides being toxic to the pests they are intended to control, are also toxic to nontarget species including humans. The article gives a brief review of their toxicity to humans with emphasis on their effects on the nervous system. Examples of case studies are included to illustrate their toxicity. A discussion of the possible contribution of occupational and other pesticide exposures to neurologic diseases and disorders is also included.
[Show abstract][Hide abstract] ABSTRACT: The National Institutes of Health has developed a comprehensive research program that includes research centers of excellence, individual research projects, small business projects, contracts, and interagency agreements to conduct basic, translational, and clinical research aimed at the discovery and/or identification of better medical countermeasures against chemical threat agents. Chemical threats include chemical warfare agents, toxic industrial and agricultural chemicals, and toxins and other chemicals that could be used intentionally as an act of terror or by large-scale accidents or natural disasters. The overarching goal of this research program is to enhance our medical response capabilities during an emergency. The program is named Countermeasures Against Chemical Threats (CounterACT). It supports translational research, applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of mortality and morbidity caused by chemical threat agents. The categories of research supported under this program include creation and development of screening assays and animal models for therapy development, identification of candidate therapeutics, obtaining preliminary proof-of-principle data on the efficacy of candidate therapeutics, advanced efficacy and preclinical safety studies with appropriate animal models using Good Laboratory Practices (GLP), and clinical studies, including clinical trials with new drugs. Special consideration is given to research relevant to people who are particularly vulnerable, including the young, the elderly, and individuals with pre-existing medical conditions.
Proceedings of the American Thoracic Society 07/2010; 7(4):254-6.
[Show abstract][Hide abstract] ABSTRACT: The National Institutes of Health (NIH) supports research about and the development of better therapies for treating exposure to toxic chemicals that could be used in a terrorist attack or released during an industrial accident. A review of recent research published by NIH investigators working in this field indicates that scientific advances in this area also have implications for reducing the burden of other neurological diseases and disorders. Some key examples discussed include studies on the development of therapeutic drugs to treat seizures and the neuropathology caused by chemical nerve agents, which may help find better cures for epilepsy, stroke, and neurodegenerative diseases.
Science translational medicine 03/2010; 2(23):23ps12. · 14.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of chemical warfare agents (CWAs) has historically been a primary concern of military personnel due to their devastating physical and psychological effects when employed on the battlefield. As a result of these new threats, agencies within the Department of Health and Human Services (DHHS) and other federal agencies have sustained a highly focused effort to assess and, if necessary, improve upon current emergency response capabilities in the event of an actual terrorist event. These efforts include both nonmedical countermeasures such as personal protective equipment for first responders who must enter a contaminated site, and medical capabilities such as safe and effective antidotes and diagnostic tools to reduce mortality and morbidity after a chemical attack or accident. In 2006, the US Congress appropriated funds to the National Institutes of Health (NIH) to implement the National Strategic Plan and Research Agenda for Medical Chemical Countermeasures. The goal of the CounterACT program is to develop safer and more effective therapeutics to treat victims exposed during a chemical incident. Complementing this goal, the CounterACT program also supports the research and development of novel diagnostic technologies, which could be utilized after a chemical incident to determine the proper course of medical intervention.
Handbook of Toxicology of Chemical Warfare Agents, 1st edited by Ramesh C. Gupta, 03/2009: chapter 59: pages 889-895; Academic Press., ISBN: 978-0-12-374484-5
[Show abstract][Hide abstract] ABSTRACT: Presented below is a brief description of research supported by the National Institutes of Health (NIH) on cholinesterases that was discussed at the IXth International Meeting on Cholinesterases in Suzhou, China. It is a partial description of the research conducted by researchers at academic and other institutions supported by the NIH, and by some of the researchers in NIH intramural laboratories. It does not represent a comprehensive survey of all research supported by the NIH related to cholinesterases, but rather a brief discussion of some of the studies discussed at the IXth International Meeting on Cholinesterases. The article describes exciting basic, translational and clinical research on therapies for neurological and other diseases. In addition, cholinesterases that may treat substance abuse are discussed, and pesticide and chemical warfare agents that inhibit cholinesterases are highlighted as part of the NIH portfolio. It is the intent of this article to share with the international community some of the research being supported by the NIH on cholinesterases that complements many of the studies being conducted elsewhere. The information was obtained only from published articles or from abstracts available to the public within the NIH CRISP database (http://crisp.cit.nih.gov/).
[Show abstract][Hide abstract] ABSTRACT: he Centers for Disease Control and Prevention urge physicians to become familiar with chemical and biological weapons. Preparedness among neurologists is especially im- portant because several of these agents affect the nervous system. This article reviews 4 agents that have a history of military or terrorist use: cyanide poisons, organophos- phate poisons, botulinum toxin, and anthrax. Cyanide and organophosphate poisons are charac- terized by dose-dependent impairment of neurological function with nonspecific symptoms such as headache or dizziness at one end of the spectrum and convulsions and coma at the other. Neu- rological examinations help clinicians to differentiate these agents from other intoxications. Botu- linum toxin has a delayed onset of action and results in descending paralysis and prominent cra- nialnervepalsies.Anthraxfrequentlycausesfulminatinghemorrhagicmeningitis.Earlyrecognition of these chemical and biological weapons is key to instituting specific therapy and preventing ca- sualties within the health care team and the community at large. Arch Neurol. 2003;60:21-25 Several chemical and biological weapons affect the nervous system, increasing the likelihood of a neurological consulta- tion.Ofthemanyagentsthatmightbeem- ployed,thisarticlefocusesoncyanide,cho- linesteraseinhibitors,botulinumtoxin,and anthraxbecausetheyhaveprominentneu- rological manifestations. This article re- views the weapon applications, clinical manifestations, and treatments of these agents.
Annals of Neurology 02/2007; 61(1):9-13. · 11.91 Impact Factor