Symposium on Toxic Substance Control: Decontamination, April 22 - 24, 1980, Columbus, Ohio.

DTIC Science & Technology

1981-06-01

standard decontaminants is used. TABLE 1. Standard Chemical Decontaminants Decontaminant Agents Used On STB Blister and nerve agents DS-2 All chemical... agents M258 Kit Sodium Hydroxide, Ethanol, G-Series nerve agents Phenol, Water Chloramine B, ZnCI2, Blister ana V-Series Ethanol, Water nerve agents A...is a point source alarm that actively samples ambient air and reacts to low concentrations of nerve agents . The M-8 alarm detector also detects several

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2010 CFR

2010-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2011 CFR

2011-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2012 CFR

2012-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2013 CFR

2013-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

27 CFR 555.220 - Table of separation distances of ammonium nitrate and blasting agents from explosives or blasting...

Code of Federal Regulations, 2014 CFR

2014-04-01

... distances of ammonium nitrate and blasting agents from explosives or blasting agents. 555.220 Section 555... ammonium nitrate and blasting agents from explosives or blasting agents. Table: Department of Defense... Not over Minimum separation distance of acceptor from donor when barricaded (ft.) Ammonium nitrate...

Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika

Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex withmore » the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.« less

GC-MS and LC-MS analysis of nerve agents in body fluids: intra-laboratory verification test using spiked plasma and urine samples.

PubMed

Koller, Marianne; Becker, Christian; Thiermann, Horst; Worek, Franz

2010-05-15

The purpose of this study was to check the applicability of different analytical methods for the identification of unknown nerve agents in human body fluids. Plasma and urine samples were spiked with nerve agents (plasma) or with their metabolites (urine) or were left blank. Seven random samples (35% of all samples) were selected for the verification test. Plasma was worked up for unchanged nerve agents and for regenerated nerve agents after fluoride-induced reactivation of nerve agent-inhibited butyrylcholinesterase. Both extracts were analysed by GC-MS. Metabolites were extracted from plasma and urine, respectively, and were analysed by LC-MS. The urinary metabolites and two blank samples could be identified without further measurements, plasma metabolites and blanks were identified in six of seven samples. The analysis of unchanged nerve agent provided five agents/blanks and the sixth agent after further investigation. The determination of the regenerated agents also provided only five clear findings during the first screening because of a rather noisy baseline. Therefore, the sample preparation was extended by a size exclusion step performed before addition of fluoride which visibly reduced baseline noise and thus improved identification of the two missing agents. The test clearly showed that verification should be performed by analysing more than one biomarker to ensure identification of the agent(s). Copyright (c) 2010 Elsevier B.V. All rights reserved.

27 CFR 555.180 - Prohibitions relating to unmarked plastic explosives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... person shall manufacture any plastic explosive that does not contain a detection agent. (b) No person..., receive, or possess any plastic explosive that does not contain a detection agent. This paragraph does not... Plastic Explosives means the Convention on the Marking of Plastic Explosives for the Purposes of Detection...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2011 CFR

2011-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2012 CFR

2012-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.180 - Prohibitions relating to unmarked plastic explosives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... person shall manufacture any plastic explosive that does not contain a detection agent. (b) No person..., receive, or possess any plastic explosive that does not contain a detection agent. This paragraph does not... Plastic Explosives means the Convention on the Marking of Plastic Explosives for the Purposes of Detection...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2013 CFR

2013-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2014 CFR

2014-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.184 - Statements of process and samples.

Code of Federal Regulations, 2010 CFR

2010-04-01

... regard to any plastic explosive or to any detection agent that is to be introduced into a plastic... importer, upon request, to the Director. (b) Samples of any plastic explosive or detection agent shall be..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic...

27 CFR 555.180 - Prohibitions relating to unmarked plastic explosives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... person shall manufacture any plastic explosive that does not contain a detection agent. (b) No person..., receive, or possess any plastic explosive that does not contain a detection agent. This paragraph does not... Plastic Explosives means the Convention on the Marking of Plastic Explosives for the Purposes of Detection...

Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

NASA Astrophysics Data System (ADS)

Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

2017-09-01

Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

32 CFR 174.16 - Real property containing explosive or chemical agent hazards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... chemical agent hazards from past DoD military munitions-related or chemical warfare-related activities... 32 National Defense 1 2010-07-01 2010-07-01 false Real property containing explosive or chemical... REALIGNMENT Environmental Matters § 174.16 Real property containing explosive or chemical agent hazards. The...

32 CFR 174.16 - Real property containing explosive or chemical agent hazards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chemical agent hazards from past DoD military munitions-related or chemical warfare-related activities... 32 National Defense 1 2014-07-01 2014-07-01 false Real property containing explosive or chemical... REALIGNMENT Environmental Matters § 174.16 Real property containing explosive or chemical agent hazards. The...

32 CFR 174.16 - Real property containing explosive or chemical agent hazards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... chemical agent hazards from past DoD military munitions-related or chemical warfare-related activities... 32 National Defense 1 2012-07-01 2012-07-01 false Real property containing explosive or chemical... REALIGNMENT Environmental Matters § 174.16 Real property containing explosive or chemical agent hazards. The...

32 CFR 174.16 - Real property containing explosive or chemical agent hazards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... chemical agent hazards from past DoD military munitions-related or chemical warfare-related activities... 32 National Defense 1 2013-07-01 2013-07-01 false Real property containing explosive or chemical... REALIGNMENT Environmental Matters § 174.16 Real property containing explosive or chemical agent hazards. The...

32 CFR 174.16 - Real property containing explosive or chemical agent hazards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... chemical agent hazards from past DoD military munitions-related or chemical warfare-related activities... 32 National Defense 1 2011-07-01 2011-07-01 false Real property containing explosive or chemical... REALIGNMENT Environmental Matters § 174.16 Real property containing explosive or chemical agent hazards. The...

A Structural Biology and Protein Engineering Approach to the Development of Antidotes against the Inhibition of Human Acetylcholinesterase by OP-based Nerve Agents

DTIC Science & Technology

2014-03-01

for Biotechnology, Gurgaon, India (Sep, 2013) by Joel L. Sussman, title: “Molecular Basis of How Nerve Agents through anti- Alzheimer Drugs Function...Molecular Basis of How Nerve Agents through anti- Alzheimer Drugs Function: 3D Structure of Acetylcholinesterase • Florida International University...FIU), Miami, FL (Dec 2013) - Invited Lecture by Joel L. Sussman, title: “Molecular Basis of anti- Alzheimer Drugs & Nerve Agents: 3D Structure of

Environmental Training Modules. Module 3 - Shipyard Incident Response Training

DTIC Science & Technology

1999-05-01

112 1.4 Explosives (no significant blast hazard) Orange 114 1.5 Insensitive Explosives; Blasting Agents Orange 112 2.1 Flammable Gas Red 118 2.2 Non...manufacture, distribution, importation, and use of pesticides . Broadly defined, a pesticide is any agent used to kill or control undesired insects...Orange 112 1.4 Explosives (no significant blast hazard) Orange 114 1.5 Very Insensitive Explosives; Blasting Agents Orange 112 2.1 Flammable Gas Red

29 CFR 1926.905 - Loading of explosives or blasting agents.

Code of Federal Regulations, 2012 CFR

2012-07-01

... have contained explosives or blasting agents. (g) No explosives or blasting agents shall be left... no drilling within 50 feet of the hole. (l) When loading a long line of holes with more than one... be left unattended or unprotected. (t) The blaster shall keep an accurate, up-to-date record of...

29 CFR 1926.905 - Loading of explosives or blasting agents.

Code of Federal Regulations, 2013 CFR

2013-07-01

... have contained explosives or blasting agents. (g) No explosives or blasting agents shall be left... no drilling within 50 feet of the hole. (l) When loading a long line of holes with more than one... be left unattended or unprotected. (t) The blaster shall keep an accurate, up-to-date record of...

29 CFR 1926.905 - Loading of explosives or blasting agents.

Code of Federal Regulations, 2014 CFR

2014-07-01

... have contained explosives or blasting agents. (g) No explosives or blasting agents shall be left... no drilling within 50 feet of the hole. (l) When loading a long line of holes with more than one... be left unattended or unprotected. (t) The blaster shall keep an accurate, up-to-date record of...

29 CFR 1926.905 - Loading of explosives or blasting agents.

Code of Federal Regulations, 2011 CFR

2011-07-01

... have contained explosives or blasting agents. (g) No explosives or blasting agents shall be left... no drilling within 50 feet of the hole. (l) When loading a long line of holes with more than one... be left unattended or unprotected. (t) The blaster shall keep an accurate, up-to-date record of...

Cholinesterase Structure: Identification of Mechanisms and Residues Involved in Organophosphate Inhibition and Enzyme Reactivation

DTIC Science & Technology

2005-05-01

nerve agents , soman is the great- terrorist acts. At the same time, OP pesticides , such as est challenge since both the rapid aging of the soman- paraoxon...also from enzyme very slowly (requiring hours, days, or weeks used as nerve warfare agents . Similar to pesticides , nerve for complete dissociation...TERMS acetylcholinesterase, nerve agent antidotes and propylaxis, organophosphate scavenging , oxime reactivation fluorescence spectroscopy, exposure

Evidence of VX nerve agent use from contaminated white mustard plants

PubMed Central

Gravett, Matthew R.; Hopkins, Farrha B.; Self, Adam J.; Webb, Andrew J.; Timperley, Christopher M.; Baker, Matthew J.

2014-01-01

The Chemical Weapons Convention prohibits the development, production, acquisition, stockpiling, retention, transfer or use of chemical weapons by Member States. Verification of compliance and investigations into allegations of use require accurate detection of chemical warfare agents (CWAs) and their degradation products. Detection of CWAs such as organophosphorus nerve agents in the environment relies mainly upon the analysis of soil. We now present a method for the detection of the nerve agent VX and its hydrolysis products by gas chromatography and liquid chromatography mass spectrometry of ethanol extracts of contaminated white mustard plants (Sinapis alba) which retained the compounds of interest for up to 45 days. VX is hydrolysed by the plants to ethyl methylphosphonic acid and then to methylphosphonic acid. The utility of white mustard as a nerve agent detector and remediator of nerve agent-polluted sites is discussed. The work described will help deter the employment of VX in conflict. PMID:25104906

Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication.

PubMed

Dunn, Emily N; Ferrara-Bowens, Teresa M; Chachich, Mark E; Honnold, Cary L; Rothwell, Cristin C; Hoard-Fruchey, Heidi M; Lesyna, Catherine A; Johnson, Erik A; Cerasoli, Douglas M; McDonough, John H; Cadieux, C Linn

2018-06-07

Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34 000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research.

Chemical Warfare Agent Operational Exposure Hazard Assessment Research: FY07 Report and Analysis

DTIC Science & Technology

2010-07-01

of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass...Needham L.L.; Barr, D.B. Quantitation of organophosphorous nerve agent metabolites in human urine using isotope dilution gas chromatography-tandem mass... nerve agents , VX, GB, or GF, and to determine lethal percutaneous (PC) levels of VX. Calibration of Physiologically-based pharmacokinetic biomarkers

[Methods for exposure of recurrent laryngeal nerve in thyroid surgery].

PubMed

Ma, Xiangdong; Han, Xilin; Liu, Tao; Kou, Changhua

2014-10-01

To evaluate different methods to explose recurrent laryngeal nerve (RLN) based on the location of thyroid diseses and anatomic path of the RLN, to avoid the RLN damage in thyroid surgery. A total of 755 cases underwent total lobectomy was studied retrospectively. RLN was explosed in each case. A total of 963 RLN was exposed in 755 cases, among those 658 RLN were exposed by lateral approach, 106 by inferior approach, and 199 by superior approach. It was showed that 694 RLN traveled deep to the inferior throid artery and 119 superficial to the artery, 98 through between two branches of the artery, and 62 with the cross of the nerve branches and the artery branches. Before entering larynx, 578 RLN gave off branches and 385 had no branches. Non-recurrent laryngeal nerves were found in 2 cases. There were 6 cases who presented with hoarseness after thyroidectomy and undergoing reexploration, among them RLN were legated in 4 cases and severed in 2 cases. The anatomic relation of RLN is relatively complicated. Lateral, inferior or superior aproach may be used for exposure of RLN to decrease risks of injury to the nerve.

Emergency management of chemical weapons injuries.

PubMed

Anderson, Peter D

2012-02-01

The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia.

Neuroprotective Effects of Galantamine on Nerve Agent-Induced Neuroglial and Biochemical Changes.

PubMed

Golime, RamaRao; Palit, Meehir; Acharya, J; Dubey, D K

2018-05-01

Neuroprotection from nerve agent such as soman-induced neural damage is a major challenge for existing drugs. Nerve agent exposure can cause many neural effects in survivors arising mainly due to acetylcholinesterase (AChE) inhibition or death within minutes. Unraveling the mechanisms underlying the nerve agent-induced multiple neurological effects is useful to develop better and safe drugs. The present study aimed to understand the molecular response during soman exposure and to evaluate the neuroprotective efficacy of galantamine on nerve agent-induced neurotoxic changes. mRNA expression studies using quantitative real-time PCR revealed significant changes in S-100β, Gfap, c-fos, and Bdnf in the hippocampus and piriform cortex after soman (90 μg/kg, s.c) exposure. Immunoblot analysis showed acute soman exposure significantly increased the protein levels of neuroglial markers (S100-β and GFAP); c-Fos and protein oxidation in discrete rat brain areas indicate their role in nerve agent-induced neurotoxicity. Induction of BDNF levels during soman exposure may indicate the recovery mechanisms activation. AChE was inhibited in the blood and brain up to 82% after soman exposure. Antidotal treatment with galantamine alone (3 mg/kg) and galantamine plus atropine (10 mg/kg) has protected animals from nerve agent-induced intoxication, death, and soman-inhibited AChE up to 45% in the blood and brain. Animal received galantamine displayed increased levels of neuroprotective genes (nAChRα-7, Bcl-2, and Bdnf) in the brain suggest the neuroprotective value of galantamine. Neuroglial changes, c-Fos, and protein oxidation levels significantly reduced after galantamine and galantamine plus atropine treatment indicate their potential antidotal value in nerve agent treatment.

Explosive and chemical threat detection by surface-enhanced Raman scattering: a review.

PubMed

Hakonen, Aron; Andersson, Per Ola; Stenbæk Schmidt, Michael; Rindzevicius, Tomas; Käll, Mikael

2015-09-17

Acts of terror and warfare threats are challenging tasks for defense agencies around the world and of growing importance to security conscious policy makers and the general public. Explosives and chemical warfare agents are two of the major concerns in this context, as illustrated by the recent Boston Marathon bombing and nerve gas attacks on civilians in the Middle East. To prevent such tragic disasters, security personnel must be able to find, identify and deactivate the threats at multiple locations and levels. This involves major technical and practical challenges, such as detection of ultra-low quantities of hazardous compounds at remote locations for anti-terror purposes and monitoring of environmental sanitation of dumped or left behind toxic substances and explosives. Surface-enhanced Raman scattering (SERS) is one of todays most interesting and rapidly developing methods for label-free ultrasensitive vibrational "fingerprinting" of a variety of molecular compounds. Performance highlights include attomolar detection of TNT and DNT explosives, a sensitivity that few, if any, other technique can compete with. Moreover, instrumentation needed for SERS analysis are becoming progressively better, smaller and cheaper, and can today be acquired for a retail price close to 10,000 US$. This contribution aims to give a comprehensive overview of SERS as a technique for detection of explosives and chemical threats. We discuss the prospects of SERS becoming a major tool for convenient in-situ threat identification and we summarize existing SERS detection methods and substrates with particular focus on ultra-sensitive real-time detection. General concepts, detection capabilities and perspectives are discussed in order to guide potential users of the technique for homeland security and anti-warfare purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of pretreatment compounds against nerve-gas agents. Annual report (Final), 16 May 88-30 Sep 90

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carroll, F.I.; Abraham, P.

1990-09-30

The U. S. Army Medical Research and Development Command is interested in research directed toward the development of countermeasures to chemical warfare (CW) agents such as the nerve gas poison soman. Soman and other nerve gas poisons are extremely potent cholinesterase inhibitors. This inhibition leads to a buildup of excess acetylcholine resulting in over-stimulation of both the peripheral and central nervous system and can lead to death. Standard therapy for organophosphate nerve agent poisoning is based on co-administration of an anticholinergic agent such as atropine to antagonize the effects of accumulated acetylcholine and a cholinesterase reactivator such as 2-PAM tomore » dephosphorylate the inhibited enzyme. However, since many problems remain in the treatment of organophosphate nerve agent poisoning, there is considerable interest and need to develop new pretreatment and treatment drugs, particularly for soman poisoning.« less

ARO in Review 2010

DTIC Science & Technology

2010-01-01

develop a fundamental understanding of the key recognition elements in various nerve agents , pesticides , and simulants. Using this knowledge, these groups...SCIENCES DIVISION 29 ARO IN REVIEW 2010 1. Low-power Nerve Agent Detector. Three Phase I CBD-SBIR contracts were awarded to Identizyme Defense...Technologies, Inc., Luna Innovations, Inc., and Lynntech, Inc. to develop a nerve agent detection system that requires little to no operating power

Improved identification of cranial nerves using paired-agent imaging: topical staining protocol optimization through experimentation and simulation

NASA Astrophysics Data System (ADS)

Torres, Veronica C.; Wilson, Todd; Staneviciute, Austeja; Byrne, Richard W.; Tichauer, Kenneth M.

2018-03-01

Skull base tumors are particularly difficult to visualize and access for surgeons because of the crowded environment and close proximity of vital structures, such as cranial nerves. As a result, accidental nerve damage is a significant concern and the likelihood of tumor recurrence is increased because of more conservative resections that attempt to avoid injuring these structures. In this study, a paired-agent imaging method with direct administration of fluorophores is applied to enhance cranial nerve identification. Here, a control imaging agent (ICG) accounts for non-specific uptake of the nerve-targeting agent (Oxazine 4), and ratiometric data analysis is employed to approximate binding potential (BP, a surrogate of targeted biomolecule concentration). For clinical relevance, animal experiments and simulations were conducted to identify parameters for an optimized stain and rinse protocol using the developed paired-agent method. Numerical methods were used to model the diffusive and kinetic behavior of the imaging agents in tissue, and simulation results revealed that there are various combinations of stain time and rinse number that provide improved contrast of cranial nerves, as suggested by optimal measures of BP and contrast-to-noise ratio.

The role of genetic background in susceptibility to chemical warfare nerve agents across rodent and non-human primate models.

PubMed

Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H

2018-01-15

Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.

Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review.

PubMed

Sharma, Rahul; Gupta, Bhanushree; Singh, Namrata; Acharya, J R; Musilek, Kamil; Kuca, Kamil; Ghosh, Kallol Kumar

2015-01-01

Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

Conference on Receptor-Based Biosensors (3rd) Held in Aberdeen Proving Ground, Maryland, September 1987

DTIC Science & Technology

1988-07-01

agents throughout the world had mode the threat to U.S. forces an urgent reality, perhaps more so now than ever. The use of blister and nerve agents ...today we have no capability to detect biological organism, toxins, or anything other then the traditional nerve , blood, and blister type agents . For...anticholinesterase. This kind of result was duplicated by Dr. Valdes at his lab at Edgewood. All the nerve agents that we looked at produced this result

29 CFR 1926.904 - Storage of explosives and blasting agents.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., electric blasting caps, detonating primers, and primed cartridges shall not be stored in the same magazine... feet of explosives and detonator storage magazine. (d) No explosives or blasting agents shall be... least two modes of exit have been provided. (e) Permanent underground storage magazines shall be at...

The effects of hemostatic agents on peripheral nerve function: an experimental study.

PubMed

Alkan, Alper; Inal, Samet; Yildirim, Mehmet; Baş, Burcu; Ağar, Erdal

2007-04-01

In the practice of oral and maxillofacial surgery, hemostatic agents are sometimes placed in close proximity to peripheral nerves. In the present study, we evaluated immediate and delayed effects of 4 hemostatic agents (oxidized regenerated cellulose, 5% colloid silver-added gelatine sponge, bovine collagen, bone wax) on peripheral nerve function. A total of 25 rat sciatic nerves were prepared, and the amplitudes were recorded with a physiological data acquisition system. Animals were randomly assigned to 5 groups: control, oxidized regenerated cellulose, gelatine sponge, bone wax, and bovine collagen. The first hour records are defined as immediate effects of these hemostatic agents on nerve function. The animals were then allowed to recover for 4 weeks. At the end of this period, the same surgical and recording procedures were performed. These final records are defined as delayed effects of hemostatic agents on nerve function. According to nerve conduction velocity (NCV) and compound action potential (CAP) values of the experimental groups, early and delayed effects of each hemostatic agent were statistically compared with Bonferroni corrected test (P < .05). Statistically, NCV was significantly reduced, and the CAP was significantly increased 1 hour after surgery (P < .05) in the group of oxidized regenerated cellulose. However, there were no significant differences after 4 weeks compared with the first records. In the gelatine sponge group, CAP was significantly increased 4 weeks after the application. In the bovine collagen and bone wax groups, NCV and CAP values (1 hour and 4 weeks after the application) were not statistically significant compared with initial control records. The present study shows that bovine collagen is the most suitable hemostatic agent applicable for peripheral nerves.

Minutes of the 23rd Eplosives Safety Seminar, volume 2

NASA Astrophysics Data System (ADS)

1988-08-01

Some areas of discussion at this seminar were: Hazards and risks of the disposal of chemical munitions using a cryogenic process; Special equipment for demilitarization of lethal chemical agent filled munitions; explosive containment room (ECR) repair Johnston Atoll chemical agent disposal system; Sympathetic detonation testing; Blast loads, external and internal; Structural reponse testing of walls, doors, and valves; Underground explosion effects, external airblast; Explosives shipping, transportation safety and port licensing; Explosive safety management; Underground explosion effects, model test and soil rock effects; Chemical risk and protection of workers; and Full scale explosives storage test.

Recent Advances in the Development of Chromophore-Based Chemosensors for Nerve Agents and Phosgene.

PubMed

Chen, Liyan; Wu, Di; Yoon, Juyoung

2018-01-26

The extreme toxicity and ready accessibility of nerve agents and phosgene has caused an increase in the demand to develop effective systems for the detection of these substances. Among the traditional platforms utilized for this purpose, chemosensors including surface acoustic wave (SAW) sensors, enzymes, carbon nanotubes, nanoparticles, and chromophore based sensors have attracted increasing attention. In this review, we describe in a comprehensive manner recent progress that has been made on the development of chromophore-based chemosensors for detecting nerve agents (mimic) and phosgene. This review comprises two sections focusing on studies of the development of chemosensors for nerve agents (mimic) and phosgene. In each of the sections, the discussion follows a format which concentrates on different reaction sites/mechanisms involved in the sensing processes. Finally, chemosensors uncovered in these efforts are compared with those based on other sensing methods and challenges facing the design of more effective chemosensors for the detection of nerve agents (mimic) and phosgene are discussed.

In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of acetylcholine and glutamate.

PubMed

O'Donnell, John C; McDonough, John H; Shih, Tsung-Ming

2011-12-01

Organophosphorus nerve agents such as sarin (GB) and VX irreversibly inhibit acetylcholinesterase, causing a buildup of acetylcholine (ACh) in synapses and neuromuscular junctions, which leads to excess bronchial secretions, convulsions, seizures, coma, and death. Understanding the unique toxic characteristics of different nerve agents is vital in the effort to develop broad spectrum medical countermeasures. To this end, we employed a repeated measure multivariate design with striatal microdialysis collection and high-performance liquid chromatography analysis to measure changes in concentrations of several neurotransmitters (ACh, glutamate, aspartate, GABA) in the same samples during acute exposure to GB or VX in freely moving guinea pigs. Concurrent with microdialysis collection, we used cortical electrodes to monitor brain seizure activity. This robust double multivariate design provides greater fidelity when comparing data while also reducing the required number of subjects. No correlation between nerve agents' propensity for causing seizure and seizure-related lethality was observed. The GB seizure group experienced more rapid and severe cholinergic toxicity and lethality than that of the VX seizure group. Seizures generated from GB and VX exposure resulted in further elevation of ACh level and then a gradual return to baseline. Glutamate levels increased in the GB, but not in the VX, seizure group. There were no consistent changes in either aspartate or GABA as a result of either nerve agent. These observations reinforce findings with other nerve agents that seizure activity per se contributes to the elevated levels of brain ACh observed after nerve agent exposure.

Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.

PubMed

Joosen, Marloes J A; Vester, Stefanie M; Hamelink, Jouk; Klaassen, Steven D; van den Berg, Roland M

2016-11-25

One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

30 CFR 57.6000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... The following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by the Department of Transportation in 49 CFR 173.114a(a). This document is available at any... Metal and Nonmetal Safety and Health district office. Explosive material. Explosives, blasting agents...

30 CFR 57.6000 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... The following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by the Department of Transportation in 49 CFR 173.114a(a). This document is available at any... Metal and Nonmetal Safety and Health district office. Explosive material. Explosives, blasting agents...

30 CFR 57.6000 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... The following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by the Department of Transportation in 49 CFR 173.114a(a). This document is available at any... Metal and Nonmetal Safety and Health district office. Explosive material. Explosives, blasting agents...

30 CFR 57.6000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... The following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by the Department of Transportation in 49 CFR 173.114a(a). This document is available at any... Metal and Nonmetal Safety and Health district office. Explosive material. Explosives, blasting agents...

30 CFR 57.6000 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... The following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by the Department of Transportation in 49 CFR 173.114a(a). This document is available at any... Metal and Nonmetal Safety and Health district office. Explosive material. Explosives, blasting agents...

Biomaterials for mediation of chemical and biological warfare agents.

PubMed

Russell, Alan J; Berberich, Jason A; Drevon, Geraldine F; Koepsel, Richard R

2003-01-01

Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.

A Gas Chromotographic-Mass Spectrometric Approach to Examining Stereoselective Interaction of Human Plasma Proteins with Soman

DTIC Science & Technology

2008-02-01

ABSTRACT See reprint. 15. SUBJECT TERMS Human plasma proteins, soman, nerve agent , bioscavenger, gas chromatography, mass spectrometry 16. SECURITY...usually referred to as nerve agents ) are tabun (ethyl dimethylamidocyanophosphate, or GA ), sarin (iso- propyl methylfluorophosphonate, or GB), soman...Pharmacology and toxicology of chemical warfare agents Ann. Acad. Med. Singapore 2&: 104-107 (1997). 11. C Macilwain. Study proves Iraq used nerve gas . Nature 3

Proceedings of the Annual Chemical Defense Bioscience Review (5th) Held at Columbia, Maryland on 29-31 May 1985. Appendix 2

DTIC Science & Technology

1985-06-01

biocompatible enzyme-like catalyst for the rapid and specific deactivation of sys- temically sorbed nerve agents . We plan to introduce catalytic groups (thiol...mustard, seizures, respiratory failure, atropine, 2-PAM chloride, neurobehavioral effects, nerve agents , soman, cyanide, animal models, chemical casualties...Animal Model ........ .. A-541 Dr. H.L. Williams Effects of Nerve Agents on the Respiratory and e Cardiovascular Systems

Degradation of Toxic Chemicals by Zero-Valent Metal Nanoparticles - A Literature Review

DTIC Science & Technology

2005-11-01

oxidative reactions. Oxidative reactions are of primary interest to us as they have the potential to degrade organophosphorous nerve agents as well...a) mustard and b) nerve agent (general structure). To decontaminate mustard there are two approaches, dechlorination or oxidation of the sulfur, the...later of which is preferable due to the reversibility of the former. To decontaminate the nerve agents oxidation is required to replace X2, X3 and

The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

DTIC Science & Technology

2007-01-01

M., and Mestries, 1. C. 1998. Nerve agent poisoning in primates: antilethal, anti -epileptic and neuroprotective effects of GK-11. Arch. Toxico/. 72...toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent ...rhesus monkey (Macaca mulatta) has traditionally served as the NHP research species of choice to assess nerve agent toxicity and the effectiveness of

Quantification of VX Nerve Agent in Various Food Matrices by Solid-Phase Extraction Ultra-Performance Liquid ChromatographyTime-of-Flight Mass Spectrometry

DTIC Science & Technology

2016-04-01

QUANTIFICATION OF VX NERVE AGENT IN VARIOUS FOOD MATRICES BY SOLID-PHASE EXTRACTION ULTRA-PERFORMANCE...TITLE AND SUBTITLE Quantification of VX Nerve Agent in Various Food Matrices by Solid-Phase Extraction Ultra-Performance Liquid Chromatography... food matrices. The mixed-mode cation exchange (MCX) sorbent and Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) methods were used for

Department of Defense Chemical and Biological Defense Program. Volume I: Annual Report to Congress

DTIC Science & Technology

2002-04-01

The M21 RSCAAL is an automatic scanning, passive infrared sensor that detects nerve ( GA , GB, and GD) and blister (H and L) agent vapor clouds based on...Point Detection GA - tabun, a nerve agent System GAO - General Accounting Office IPE - Individual Protective Equipment GAS - Group A Streptococcus...IPR - In-Process Review GB - sarin , a nerve agent IPT - Integrated Product Team GC - gas chromatography IR&D - Independent Research & Development GD

Comparison of Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to the Nerve Agents Cyclosarin and Tabun in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Comparison of extracellular striatal acetylcholine and brain seizure activity following...lethality; nerve agents; organophosphorus compounds; seizure activity ; tabun 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER...acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs John C

Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

DTIC Science & Technology

2011-09-01

Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a

Nerve Agents: What They Are, How They Work, How to Counter Them.

PubMed

Costanzi, Stefano; Machado, John-Hanson; Mitchell, Moriah

2018-05-16

Nerve agents are organophosphorus chemical warfare agents that exert their action through the irreversible inhibition of acetylcholinesterase, with a consequent overstimulation of cholinergic transmission followed by its shutdown. Beyond warfare, they have notoriously been employed in acts of terrorism as well as high profile assassinations. After a brief historical introduction on the development and deployment of nerve agents, this review provides a survey of their chemistry, the way they affect cholinergic transmission, the available treatment options, and the current directions for their improvement. As the review illustrates, despite their merits, the currently available treatment options present several shortcomings. Current research directions involve the search for improved antidotes, antagonists of the nicotinic receptors, small-molecule pretreatment options, as well as bioscavengers as macromolecular pretreatment options. These efforts are making good progress in many different directions and, hopefully, will lead to a lower target susceptibility, thus reducing the appeal of nerve agents as chemical weapons.

Neurosteroids for the potential protection of humans against organophosphate toxicity.

PubMed

Reddy, Doodipala Samba

2016-08-01

This article describes the therapeutic potential of neurosteroids as anticonvulsant antidotes for chemical intoxication caused by organophosphate pesticides and nerve agents or gases like sarin and soman. Toxic manifestations following nerve agent exposure, as evident in chemical attacks in Japan and Syria, include hypersecretion, respiratory distress, tremors, convulsions leading to status epilepticus (SE), and death. Benzodiazepines, such as diazepam, are the current anticonvulsants of choice for controlling nerve agent-induced life-threatening seizures, SE, and brain injury. Benzodiazepines can control acute seizures when given early, but they are less effective for delayed treatment of SE, which is characterized by rapid desensitization of synaptic GABA A receptors, benzodiazepine resistance, and brain injury. Neurosteroid-sensitive extrasynaptic GABA A receptors, however, remain unaffected by such events. Thus, anticonvulsant neurosteroids may produce more effective protection than benzodiazepines against a broad spectrum of chemical agents, even when given late after nerve agent exposure. © 2016 New York Academy of Sciences.

Quantitation of five organophosphorus nerve agent metabolites in serum using hydrophilic interaction liquid chromatography and tandem mass spectrometry

PubMed Central

Hamelin, Elizabeth I.; Schulze, Nicholas D.; Shaner, Rebecca L.; Coleman, Rebecca M.; Lawrence, Richard J.; Crow, Brian S.; Jakubowski, E. M.; Johnson, Rudolph C.

2015-01-01

Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of the hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman) and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid phase extraction coupled with high performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3–0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101–105%) and high precision (5–8%) for the detection of these five nerve agent hydrolysis products in serum. PMID:24633507

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2013 CFR

2013-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2014 CFR

2014-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2012 CFR

2012-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2011 CFR

2011-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

27 CFR 555.186 - Seizure or forfeiture.

Code of Federal Regulations, 2010 CFR

2010-04-01

... EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.186 Seizure or forfeiture. Any plastic explosive that does not contain a detection agent in violation of 18 U... of this chapter for regulations on summary destruction of plastic explosives that do not contain a...

A short history of fires and explosions caused by anaesthetic agents.

PubMed

MacDonald, A G

1994-06-01

The first recorded fire resulting from the use of an anaesthetic agent occurred in 1850, when ether caught fire during a facial operation. Many subsequent fires and explosions have been reported, caused by ether, acetylene, ethylene and cyclopropane, and there has been one reported explosion involving halothane. Although some of the earlier incidents caused more consternation than injury, many of the later ones caused much death and destruction, particularly after the practice of administering oxygen, instead of air, became established. Many incidents have never been reported and many of those which have reached publication do not record essential details. The use of flammable agents has decreased significantly in recent years and although fires and explosions from nonanaesthetic causes, for example gastrointestinal gases, skin sterilizing agents and laser surgery, may continue to occur, those from gaseous and volatile anaesthetic agents may now be of historical interest only. This article reviews some of the more relevant and enlightening reports of the past 150 yr.

In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

DTIC Science & Technology

2012-01-01

monoisonitrosoacetone (MINA) crossed BBB, provided some degree of CNS AChE reactivation, enhanced survival, and mitigated the seizure activity following nerve agent...tissues (brain regions, diaphragm, heart, skeletal muscle) were collected. AChE activity was measured using the Ellman assay. In GB exposure, pro...therapy. Protecting and/or restoring AChE activity in the brain is a major goal in the treatment of nerve agent intoxication. Our long-term goal is to

The birth of nerve agent warfare: lessons from Syed Abbas Foroutan.

PubMed

Newmark, Jonathan

2004-05-11

The author reviewed Farsi-language articles published recently by Dr. Syed Abbas Foroutan, which constitute the only firsthand clinical descriptions of battlefield nerve agent casualties in the world literature, and the author compares his comments with US and North Atlantic Treaty Organization (NATO) chemical casualty care doctrine. Foroutan's lessons learned reassure us that a robust medical evacuation system, coupled with timely and appropriate medical care of nerve agent poisoning, will save many more lives on future battlefields.

Polymeric Sorbent with Controlled Surface Polarity: An Alternate for Solid-Phase Extraction of Nerve Agents and Their Markers from Organic Matrix.

PubMed

Roy, Kanchan Sinha; Purohit, Ajay Kumar; Chandra, Buddhadeb; Goud, D Raghavender; Pardasani, Deepak; Dubey, Devendra Kumar

2018-06-05

Extraction and identification of lethal nerve agents and their markers in complex organic background have a prime importance from the forensic and verification viewpoint of the Chemical Weapons Convention (CWC). Liquid-liquid extraction with acetonitrile and commercially available solid phase silica cartridges are extensively used for this purpose. Silica cartridges exhibit limited applicability for relatively polar analytes, and acetonitrile extraction shows limited efficacy toward relatively nonpolar analytes. The present study describes the synthesis of polymeric sorbents with tunable surface polarity, their application as a solid-phase extraction (SPE) material against nerve agents and their polar as well as nonpolar markers from nonpolar organic matrices. In comparison with the acetonitrile extraction and commercial silica cartridges, the new sorbent showed better extraction efficiency toward analytes of varying polarity. The extraction parameters were optimized for the proposed method, which included ethyl acetate as an extraction solvent and n-hexane as a washing solvent. Under optimized conditions, method linearity ranged from 0.10 to 10 μg mL -1 ( r 2 = 0.9327-0.9988) for organophosphorus esters and 0.05-20 μg mL -1 ( r 2 = 0.9976-0.9991) for nerve agents. Limits of detection (S:N = 3:1) in the SIM mode were found in the range of 0.03-0.075 μg mL -1 for organophosphorus esters and 0.015-0.025 μg mL -1 for nerve agents. Limits of quantification (S:N = 10:1) were found in the range of 0.100-0.25 μg mL -1 for organophosphorus esters and 0.05-0.100 μg mL -1 for nerve agents in the SIM mode. The recoveries of the nerve agents and their markers ranged from 90.0 to 98.0% and 75.0 to 95.0% respectively. The repeatability and reproducibility (with relative standard deviations (RSDs) %) for organophosphorus esters were found in the range of 1.35-8.61% and 2.30-9.25% respectively. For nerve agents, the repeatability range from 1.00 to 7.75% and reproducibility were found in the range of 2.17-6.90%.

Recent advances in evaluation of oxime efficacy in nerve agent poisoning by in vitro analysis.

PubMed

Worek, F; Eyer, P; Aurbek, N; Szinicz, L; Thiermann, H

2007-03-01

The availability of highly toxic organophosphorus (OP) warfare agents (nerve agents) underlines the necessity for an effective medical treatment. Acute OP toxicity is primarily caused by inhibition of acetylcholinesterase (AChE). Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents, e.g. soman and cyclosarin. This led to the synthesis and investigation of numerous oximes in the past decades. Reactivation of OP-inhibited AChE is considered to be the most important reaction of oximes. Clinical data from studies with pesticide-poisoned patients support the assumption that the various reactions between AChE, OP and oxime, i.e. inhibition, reactivation and aging, can be investigated in vitro with human AChE. In contrast to animal experiments such in vitro studies with human tissue enable the evaluation of oxime efficacy without being affected by species differences. In the past few years numerous in vitro studies were performed by different groups with a large number of oximes and methods were developed for extrapolating in vitro data to different scenarios of human nerve agent poisoning. The present status in the evaluation of new oximes as antidotes against nerve agent poisoning will be discussed.

Fluorescent discrimination between traces of chemical warfare agents and their mimics.

PubMed

Díaz de Greñu, Borja; Moreno, Daniel; Torroba, Tomás; Berg, Alexander; Gunnars, Johan; Nilsson, Tobias; Nyman, Rasmus; Persson, Milton; Pettersson, Johannes; Eklind, Ida; Wästerby, Pär

2014-03-19

An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.

Investigation of the Persistence of Nerve Agent Degradation ...

EPA Pesticide Factsheets

Journal Article The persistence of chemical warfare nerve agent degradation analytes on surfaces is important for reasons ranging from indicating the presence of nerve agent on that surface to environmental restoration of a site after nerve agent release. This study investigates the persistence of several chemical warfare nerve agent degradation analytes on a number of indoor surfaces and presents an approach for wipe sampling of surfaces, followed by wipe extraction and liquid chromatography-tandem mass spectrometry detection. Multiple commercially available wipe materials were investigated to determine optimal wipe recoveries. Tested surfaces, including several porous/permeable and largely nonporous/impermeable surfaces, were investigated to determine recoveries from these indoor surface materials. Wipe extracts were analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and compared with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) results. UPLC provides a sensitive separation of targeted degradation analytes in addition to being nearly four times faster than HPLC, allowing for greater throughput during a widespread release concerning large-scale contamination and subsequent remediation events. Percent recoveries from nonporous/impermeable surfaces were 60-103% for isopropyl methylphosphonate (IMPA), 61-91 % for ethyl methylphosphonate (EMPA), and 60-98% for pinacolyl methylphosphona

30 CFR 77.1302 - Vehicles used to transport explosives.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicles used to transport explosives. 77.1302... COAL MINES Explosives and Blasting § 77.1302 Vehicles used to transport explosives. (a) Vehicles used to transport explosives, other than blasting agents, shall have substantially constructed bodies, no...

30 CFR 77.1302 - Vehicles used to transport explosives.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Vehicles used to transport explosives. 77.1302... COAL MINES Explosives and Blasting § 77.1302 Vehicles used to transport explosives. (a) Vehicles used to transport explosives, other than blasting agents, shall have substantially constructed bodies, no...

27 CFR 555.180 - Prohibitions relating to unmarked plastic explosives.

Code of Federal Regulations, 2010 CFR

2010-04-01

... unmarked plastic explosives. 555.180 Section 555.180 Alcohol, Tobacco Products, and Firearms BUREAU OF... Marking of Plastic Explosives § 555.180 Prohibitions relating to unmarked plastic explosives. (a) No person shall manufacture any plastic explosive that does not contain a detection agent. (b) No person...

Proceedings of the Army Science Conference (15th) Held at West Point, New York on 17-19 June 1986. Volume 2. Principal Authors H through L.

DTIC Science & Technology

1986-06-20

Page Leonard, Joseph M. See Seiders, Barbara A. B. V 189 Linden, Carol D. See Canonico, Peter G. 1 127 Little, James S. A Potential Nerve Agent II 271...Semi-Automated System for Testing 11 235 Waring, Paul P. the Efficacy of Nerve Agent Hawkins, George S. Protection/Decontamination Powanda, Michael...potential uses. Among them are: 1) detection of organofluoro- phosphate chemicals, 2) non-corrosive decontamination of nerve agent mate- rials

Nerve agent analogues that produce authentic soman, sarin, tabun, and cyclohexyl methylphosphonate-modified human butyrylcholinesterase.

PubMed

Gilley, Cynthia; MacDonald, Mary; Nachon, Florian; Schopfer, Lawrence M; Zhang, Jun; Cashman, John R; Lockridge, Oksana

2009-10-01

The goal was to test 14 nerve agent model compounds of soman, sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) for their suitability as substitutes for true nerve agents. We wanted to know whether the model compounds would form the identical covalent adduct with human butyrylcholinesterase that is produced by reaction with true nerve agents. Nerve agent model compounds containing thiocholine or thiomethyl in place of fluorine or cyanide were synthesized as Sp and Rp stereoisomers. Purified human butyrylcholinesterase was treated with a 45-fold molar excess of nerve agent analogue at pH 7.4 for 17 h at 21 degrees C. The protein was denatured by boiling and was digested with trypsin. Aged and nonaged active site peptide adducts were quantified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of the tryptic digest mixture. The active site peptides were isolated by HPLC and analyzed by MALDI-TOF-TOF mass spectrometry. Serine 198 of butyrylcholinesterase was covalently modified by all 14 compounds. Thiocholine was the leaving group in all compounds that had thiocholine in place of fluorine or cyanide. Thiomethyl was the leaving group in the GF thiomethyl compounds. However, sarin thiomethyl compounds released either thiomethyl or isopropyl, while soman thiomethyl compounds released either thiomethyl or pinacolyl. Thiocholine compounds reacted more rapidly with butyrylcholinesterase than thiomethyl compounds. Labeling with the model compounds resulted in aged adducts that had lost the O-alkyl group (O-ethyl for tabun, O-cyclohexyl for GF, isopropyl for sarin, and pinacolyl for soman) in addition to the thiocholine or thiomethyl group. The nerve agent model compounds containing thiocholine and the GF thiomethyl analogue were found to be suitable substitutes for true soman, sarin, tabun, and GF in terms of the adduct that they produced with human butyrylcholinesterase. However, the soman and sarin thiomethyl compounds yielded two types of adducts, one of which was thiomethyl phosphonate, a modification not found after treatment with authentic soman and sarin.

Disaster preparedness, pediatric considerations in primary blast injury, chemical, and biological terrorism

PubMed Central

Hamele, Mitchell; Poss, William Bradley; Sweney, Jill

2014-01-01

Both domestic and foreign terror incidents are an unfortunate outgrowth of our modern times from the Oklahoma City bombings, Sarin gas attacks in Japan, the Madrid train bombing, anthrax spores in the mail, to the World Trade Center on September 11th, 2001. The modalities used to perpetrate these terrorist acts range from conventional weapons to high explosives, chemical weapons, and biological weapons all of which have been used in the recent past. While these weapons platforms can cause significant injury requiring critical care the mechanism of injury, pathophysiology and treatment of these injuries are unfamiliar to many critical care providers. Additionally the pediatric population is particularly vulnerable to these types of attacks. In the event of a mass casualty incident both adult and pediatric critical care practitioners will likely be called upon to care for children and adults alike. We will review the presentation, pathophysiology, and treatment of victims of blast injury, chemical weapons, and biological weapons. The focus will be on those injuries not commonly encountered in critical care practice, primary blast injuries, category A pathogens likely to be used in terrorist incidents, and chemical weapons including nerve agents, vesicants, pulmonary agents, cyanide, and riot control agents with special attention paid to pediatric specific considerations. PMID:24834398

Changes in Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to Nerve Against in Freely Moving Guinea Pigs

DTIC Science & Technology

2010-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Changes in extracellular striatal acetylcholine and brain seizure activity following...Acetylcholine, acetylcholinesterase, choline, guinea pig, in vivo microdialysis, nerve agents, organophosphorus compounds, sarin, seizure activity ...RESEARCH ARTICLE Changes in extracellular striatal acetylcholine and brain seizure activity following acute exposure to nerve agents in freely

Ultrasensitive detection of explosives and chemical warfare agents by low-pressure photoionization mass spectrometry.

PubMed

Sun, Wanqi; Liang, Miao; Li, Zhen; Shu, Jinian; Yang, Bo; Xu, Ce; Zou, Yao

2016-08-15

On-spot monitoring of threat agents needs high sensitive instrument. In this study, a low-pressure photoionization mass spectrometer (LPPI-MS) was employed to detect trace amounts of vapor-phase explosives and chemical warfare agent mimetics under ambient conditions. Under 10-s detection time, the limits of detection of 2,4-dinitrotoluene, nitrotoluene, nitrobenzene, and dimethyl methyl phosphonate were 30, 0.5, 4, and 1 parts per trillion by volume, respectively. As compared to those obtained previously with PI mass spectrometric techniques, an improvement of 3-4 orders of magnitude was achieved. This study indicates that LPPI-MS will open new opportunities for the sensitive detection of explosives and chemical warfare agents. Copyright © 2016 Elsevier B.V. All rights reserved.

Nerve agent intoxication: Recent neuropathophysiological findings and subsequent impact on medical management prospects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collombet, Jean-Marc, E-mail: jmcollombet@imassa.fr

This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3 months after soman poisoning. Indeed, an increasedmore » proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents. - Highlights: > This review focuses on neuropathophysiology following nerve agent poisoning in mice. > Extensive data on long-term neuropathology and related inflammation are provided here. > Delayed self-repair attempts encountered in lesioned rodent brains are also described. > Cell therapy is considered as a valuable treatment against nerve agent intoxication.« less

Neurosciences and research on chemical weapons of mass destruction in Nazi Germany.

PubMed

Schmaltz, Florian

2006-09-01

As a side-product of industrial research, new chemical nerve agents (Tabun, Sarin, Soman) superior to those available to the Allied Forces were discovered in Nazi Germany. These agents were never used by Germany, even though they were produced at a large scale. This article explores the toxicological and physiological research into the mechanisms of action of these novel nerve agents, and the emergence of military research objectives in neurophysiological and neurotoxicological research. Recently declassified Allied military intelligence files document secret nerve agent research, leading to intensified research on anticholinesterase agents in the peripheral and the central nervous system. The article discusses the involvement of IG Farben scientists, educational, medical and military institutions, and of Nobel Prize laureate Richard Kuhn, director of the Kaiser Wilhelm Institute for Medical Research.

MICROCHIP ENZYMATIC ASSAY OF ORGANOPHOSPHATE NERVE AGENTS. (R830900)

EPA Science Inventory

An on-chip enzymatic assay for screening organophosphate (OP) nerve agents, based on a pre-column reaction of organophosphorus hydrolase (OPH), electrophoretic separation of the phosphonic acid products, and their contactless-conductivity detection, is described. Factors affec...

Post-exposure therapy with recombinant human BuChE following percutaneous VX challenge in guinea-pigs

PubMed Central

Mumford, Helen; Troyer, John K.

2011-01-01

Poisoning by nerve agents via the percutaneous (p.c.) route is an issue because the slow absorption of agent could result in poisoning which outlasts the protection provided by conventional pharmacological therapy. The bioscavenger approach is based on the concept of binding nerve agent in the bloodstream, thus preventing nerve agent from reaching the target tissues and inhibiting acetylcholinesterase activity. One bioscavenger that has been extensively studied is human butyrylcholinesterase (huBuChE). Protexia® is a pegylated form of recombinant huBuChE. We used a guinea-pig model of p.c. nerve agent poisoning, using an implanted telemetry system to collect physiological data. Guinea-pigs were poisoned with the nerve agent VX (0.74 mg/kg) (~2.5×LD50). Two hours following VX exposure, Protexia (72 mg/kg) or saline control was administered intramuscularly. All guinea-pigs treated with Protexia (n=8) survived, compared to no survivors in a saline-treated control group (n=8). Survival following VX and Protexia treatment was associated with minimal incapacitation and observable signs of poisoning, and the mitigation or prevention of the detrimental physiological changes (e.g. seizure, bradycardia and hypothermia) observed in control animals. The opportunity for post-exposure treatment may have utility in both civilian and military scenarios, and this is a promising indication for the use of a bioscavenger. PMID:21620937

Fingerprinting malathion vapor: a simulant for VX nerve agent

NASA Astrophysics Data System (ADS)

Song, Renbo; Ding, Yujie J.; Zotova, Ioulia B.

2008-04-01

Being motivated by the possibility of fingerprinting and detecting VX nerve agent, we have investigated its stimulant, i.e. malathion vapor, which is less toxic and commercially available, in the far-infrared/THz transition region and THz frequency range. Such a spectroscopic study was carried out by using Fourier transform infrared spectroscopy (FTIR). Our intention is to obtain a specific spectroscopic signature of VX nerve agent as a chemical warfare agent. Following our experimental result, we have successfully observed eleven new absorption peaks from malathion vapor in the spectral ranges from 15 cm -1 to 68 cm -1 and from 75 cm -1 to 640 cm -1. Specifically, in the far-infrared/THz transition region, we have observed eight peaks and whereas in the THz region we have identified three relatively weak transition peaks. In addition, we have investigated the dependence of the absorption spectra on temperature in the range from room temperature to 60°C. In both of the frequency ranges, we have found that absorption coefficients significantly increase with increasing temperature. By comparing the transition peaks in the two frequency ranges, we have concluded that the frequency range of 400-640cm -1 is an optimal range for fingerprinting this chemical specie. We have designated two peaks for effectively and accurately identifying the VX nerve agents and one peak for differentiating between malathion and VX nerve agent.

Crystal Structures of Human Carboxylesterase 1 in Covalent Complexes with the Chemical Warfare Agents Soman and Tabun†,‡

PubMed Central

Fleming, Christopher D.; Edwards, Carol C.; Kirby, Stephen D.; Maxwell, Donald M.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

2008-01-01

The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 Å resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 104-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure. PMID:17407327

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

PubMed

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Stabilizing Acetylcholinesterase on Carbon Electrodes Using Peptide Nanotubes to Produce Effective Biosensors

DTIC Science & Technology

2012-03-22

of pesticide . Plans for the cleanup of nerve gas attacks involve hosing affected areas down with bleach and water, which may also lead to water...They have been widely used in agriculture as pesticides and are also used as deadly nerve agents in chemical weapons. Chromatography and...Amperometric Detection of Organophosphorus Pesticides and Nerve Agents ,” Electroanalysis 16, Nos. 1-2: 145-149 (2004). Norouzi, Parviz, Farnoush

30 CFR 77.1301 - Explosives; magazines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... than 6 feet high. (h) Ammonium nitrate-fuel oil blasting agents shall be physically separated from... explosion hazard. (d) Box-type magazines used to store explosives or detonators in work areas shall be...

Reactivation of Brain Acetylcholinesterase by Monoisonitrosoacetone Increases the Therapeutic Efficacy Against Nerve Agents in Guinea Pigs

DTIC Science & Technology

2010-01-01

hese findings support previous reports that protection of ChE nzyme activity in the brain as well as in peripheral tissues with entrally acting... activity . Animals were injected s.c. with either saline (0.5ml/kg) or a 1.0× LD50 dose of GB (42.0g/kg), GF (57.0g/kg), or VX (8.0g/kg). The severity...of toxic signs of each animal was scored at 13min after nerve agent. Fifteen minutes after nerve agent injection, when the inhibition of ChE activity

The impact of warfare on the soil environment

NASA Astrophysics Data System (ADS)

Certini, Giacomo; Scalenghe, Riccardo; Woods, William I.

2013-12-01

One of the most dramatic ways humans can affect soil properties is through the performance of military activities. Warfare-induced disturbances to soil are basically of three types - physical, chemical, and biological - and are aimed at causing direct problems to enemies or, more often, are indirect, undesired ramifications. Physical disturbances to soil include sealing due to building of defensive infrastructures, excavation of trenches or tunnels, compaction by traffic of machinery and troops, or cratering by bombs. Chemical disturbances consist of the input of pollutants such as oil, heavy metals, nitroaromatic explosives, organophosphorus nerve agents, dioxins from herbicides, or radioactive elements. Biological disturbances occur as unintentional consequences of the impact on the physical and chemical properties of soil or the deliberate introduction of microorganisms lethal to higher animals and humans such as botulin or anthrax. Soil represents a secure niche where such pathogens can perpetuate their virulence for decades.

Environmental Protection for Hazardous Materials Incidents. Volume 1. Hazardous Materials Incident Management System

DTIC Science & Technology

1990-11-01

radioactive) - Determine class of HAZMAT (Class A Explosive, Class B Explosive, Class C Explosive, Blasting Agent , Flammable Gas , Non- flammable Gas ... agent . Specific health and safety plans related to IRP actions amy be obtained from the same source. 2. Interaction of Fire Departments with the...such as digging near a gas line, a fuel tank, or buried explo- sives, the fire department would be briefed before beginning the work, and, under

Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

PubMed Central

Munro, N

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review.

PubMed

Lenz, David E; Yeung, David; Smith, J Richard; Sweeney, Richard E; Lumley, Lucille A; Cerasoli, Douglas M

2007-04-20

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and soman were administered in a series of three injections of 1.5xLD(50), 2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. Efforts have now been expanded to identify a catalytic protein capable of not only binding, but also rapidly hydrolyzing the standard threat nerve agents. Recent work has focused on paraoxonase-1 (PON1), a naturally occurring human serum enzyme with the capacity to catalyze the hydrolysis of nerve agents, albeit too slowly to afford dramatic protection. Using rational design, several amino acids involved in substrate binding have been identified and site-directed mutations have revealed that residue H115 plays an important role in binding. In addition, the stereospecificity of PON1 for the catalytic hydrolysis of soman has been examined. The enzyme exhibits a slight stereospecificity for the C+P+ isomer of soman, which is due more to preferential binding than to selective hydrolysis of this isomer. The results suggest that it may be possible to engineer a mutant form of PON1 with enhanced activity and stereospecificity for the most toxic nerve agent isoforms.

REMOTE BIOSENSOR FOR IN SITU MONITORING OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

EPA Science Inventory

A remote electrochemical biosensor for field monitoring of organophosphate nerve agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a submersible amperometric probe design. This combination resu...

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

PubMed

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Soman increases neuronal COX-2 levels: possible link between seizures and protracted neuronal damage.

PubMed

Angoa-Pérez, Mariana; Kreipke, Christian W; Thomas, David M; Van Shura, Kerry E; Lyman, Megan; McDonough, John H; Kuhn, Donald M

2010-12-01

Nerve agent-induced seizures cause neuronal damage in brain limbic and cortical circuits leading to persistent behavioral and cognitive deficits. Without aggressive anticholinergic and benzodiazepine therapy, seizures can be prolonged and neuronal damage progresses for extended periods of time. The objective of this study was to determine the effects of the nerve agent soman on expression of cyclooxygenase-2 (COX-2), the initial enzyme in the biosynthetic pathway of the proinflammatory prostaglandins and a factor that has been implicated in seizure initiation and propagation. Rats were exposed to a toxic dose of soman and scored behaviorally for seizure intensity. Expression of COX-2 was determined throughout brain from 4h to 7 days after exposure by immunohistochemistry and immunoblotting. Microglial activation and astrogliosis were assessed microscopically over the same time-course. Soman increased COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was induced in neurons, and not in microglia or astrocytes, and remained elevated through 7 days. The magnitude of COX-2 induction was correlated with seizure intensity. COX-1 expression was not changed by soman. Increased expression of neuronal COX-2 by soman is a late-developing response relative to other signs of acute physiological distress caused by nerve agents. COX-2-mediated production of prostaglandins is a consequence of the seizure-induced neuronal damage, even after survival of the initial cholinergic crisis is assured. COX-2 inhibitors should be considered as adjunct therapy in nerve agent poisoning to minimize nerve agent-induced seizure activity. Published by Elsevier B.V.

Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.

PubMed

Fawcett, William P; Aracava, Yasco; Adler, Michael; Pereira, Edna F R; Albuquerque, Edson X

2009-02-01

This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.

30 CFR 57.6100 - Separation of stored explosive material.

Code of Federal Regulations, 2010 CFR

2010-07-01

... shall not be stored in the same magazine with other explosive material. (b) When stored in the same magazine, blasting agents shall be separated from explosives, safety fuse, and detonating cord to prevent...

Zirconium Hydroxide-coated Nanofiber Mats for Nerve Agent Decontamination.

PubMed

Kim, Sohee; Ying, Wu Bin; Jung, Hyunsook; Ryu, Sam Gon; Lee, Bumjae; Lee, Kyung Jin

2017-03-16

Diverse innovative fabrics with specific functionalities have been developed for requirements such as self-decontamination of chemical/biological pollutants and toxic nerve agents. In this work, Zr(OH) 4 -coated nylon-6,6 nanofiber mats were fabricated for the decontamination of nerve agents. Nylon-6,6 fabric was prepared via the electrospinning process, followed by coating with Zr(OH) 4 , which was obtained by the hydrolysis of Zr(OBu) 4 by a sol-gel reaction on nanofiber surfaces. The reaction conditions were optimized by varying the amounts of Zr(OBu) 4 ,the reaction time, and the temperature of the sol-gel reaction. The composite nanofibers show high decontamination efficiency against diisopropylfluorophosphate, which is a nerve agent analogue, due to its high nucleophilicity that aids in the catalysis of the hydrolysis of the phosphonate ester bonds. Composite nanofiber mats have a large potential and can be applied in specific fields such as military and medical markets. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

High pressure-resistant nonincendive emulsion explosive

DOEpatents

Ruhe, Thomas C.; Rao, Pilaka P.

1994-01-01

An improved emulsion explosive composition including hollow microspheres/bulking agents having high density and high strength. The hollow microspheres/bulking agents have true particle densities of about 0.2 grams per cubic centimeter or greater and include glass, siliceous, ceramic and synthetic resin microspheres, expanded minerals, and mixtures thereof. The preferred weight percentage of hollow microspheres/bulking agents in the composition ranges from 3.0 to 10.0 A chlorinated paraffin oil, also present in the improved emulsion explosive composition, imparts a higher film strength to the oil phase in the emulsion. The emulsion is rendered nonincendive by the production of sodium chloride in situ via the decomposition of sodium nitrate, a chlorinated paraffin oil, and sodium perchlorate. The air-gap sensitivity is improved by the in situ formation of monomethylamine perchlorate from dissolved monomethylamine nitrate and sodium perchlorate. The emulsion explosive composition can withstand static pressures to 139 bars and dynamic pressure loads on the order of 567 bars.

Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world.

PubMed

Devereaux, Asha; Amundson, Dennis E; Parrish, J S; Lazarus, Angeline A

2002-10-01

Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.

Midazolam: An Improved Anticonvulsant Treatment for Nerve Agent-Induced Seizures

DTIC Science & Technology

2002-01-01

variety of compounds that different authors had championed as being capable of stopping or moderating nerve agent seizures (e.g., memantine , clonidine...e.g., memantine , neuroactive steroids; EEG seizures were still evident) or required such a narrow dose range or specific treatment conditions that

Options for the destruction of chemical weapons and management of the associated risks.

PubMed

Manley, Ron G

2006-09-01

The destruction of chemical weapons is a hazardous operation. The degree of hazard posed, however, is not uniform and is dependent on the specific chemical agent and the configuration of the weapon or bulk storage vessel in which it is contained. For example, a highly volatile nerve agent in an explosively configured munition, such as a rocket, poses a very different hazard from that of a bulk storage container of viscous mustard gas. Equally the handling of recovered, often highly corroded, World War (WW)I or WWII chemical munitions will pose a very different hazard from that associated with dealing with modern chemical weapons stored under the appropriate conditions. Over the years, a number of technologies have been developed for the destruction of chemical weapons. Each has its advantages and disadvantages. None of them provide a universal solution to the problem. When assessing options for the destruction of these weapons and the management of the associated risks, therefore, it is important to give due consideration and weight to these differences. To ensure that the destruction technology selected takes due account of them and that the resulting overall risk assessment accurately reflects the actual risks involved.

Army Science Conference Proceedings, 12-15 June 1990, Volume 2: Principal Authors G-M

DTIC Science & Technology

1990-07-30

The Excitatory Amino Acid Antagonist MK-801 Prevents Nerve Agent -induced Neuropathology Even When Given After the Onset of Convulsions See Johnson...Smejkal, Ruthann M. See Sharp, Edward J. See O’Neill, Timothy R. See Coffee, Terence P. Oxidative Decontamination of the Chemical Nerve Agent See...190, 1955. 5 Hoskin, F. C. G.,and Roush, A. H. "Hydrolysis of Nerve Gas by Squid Type Diisopropylphosphorofluoridate Hydrolyzing Enzyme on Agarose

[Perspectives in the treatments of poisonings by organophosphorus insecticides and warfare nerve agents].

PubMed

Sogorb-Sánchez, M A; Vilanova-Gisbert, E; Carrera-González, V

Organophosphorus compounds are worldwide employed as insecticides and are yearly responsible of several millions of poisonings. The chemical structure of most of the warfare nerve agents also corresponds with an organophosphorus compound. Organophosphorus insecticides and warfare nerve agents exert their main toxicological effects through inhibition of acetylcholinesterase. Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The administration of phosphotriesterases (enzymes involved in the detoxication of organophosphorus compounds through hydrolysis) is a very effective treatment against poisonings by organophosphorus insecticides and warfare nerve agents. There are experimental preventive treatments based on the simultaneous administration of carbamates and certain antimuscarinic drugs, different from atropine, which notably improve the efficacy of the classical treatments applied after poisonings by warfare nerve agents. The treatments based in the administration of phosphotriesterases might be the response to the call of the World Health Organization for searching new treatments with capability to reduce the high mortality recorded in the cases of poisonings by organophosphorus compounds. These treatments can be applied in a preventive way without the intrinsic neurotoxicity associated to the preventive treatments based on carbamates and antimuscarinic drugs. Therefore, these treatments are specially interesting for people susceptible to suffer severe exposures, i.e. sprayers in the farms.

29 CFR 1910.109 - Explosives and blasting agents.

Code of Federal Regulations, 2012 CFR

2012-07-01

... devices. Examples of explosive-actuated power devices are jet tappers and jet perforators. (3) Explosive... more magazines, as a group, must be considered as one magazine, and the total quantity of explosives... located in the same building when one is used only for blasting caps in quantities not in excess of 5,000...

29 CFR 1910.109 - Explosives and blasting agents.

Code of Federal Regulations, 2014 CFR

2014-07-01

... devices. Examples of explosive-actuated power devices are jet tappers and jet perforators. (3) Explosive... more magazines, as a group, must be considered as one magazine, and the total quantity of explosives... located in the same building when one is used only for blasting caps in quantities not in excess of 5,000...

29 CFR 1910.109 - Explosives and blasting agents.

Code of Federal Regulations, 2013 CFR

2013-07-01

... devices. Examples of explosive-actuated power devices are jet tappers and jet perforators. (3) Explosive... more magazines, as a group, must be considered as one magazine, and the total quantity of explosives... located in the same building when one is used only for blasting caps in quantities not in excess of 5,000...

Department of Defense Chemical, Biological, Radiological, and Nuclear Defense Program, Annual Report to Congress, 2004

DTIC Science & Technology

2004-05-01

foldable/ portable emergency smoke hoods with extended gas sorption capabilities and regenerable, biological pathogen-destroying and gas-sorbing...traditional agents. • Cyanide Countermeasures – Potential pretreatment compounds (e.g., methemoglobin formers and sulfide donors) and regimen are being...evaluated for safety and efficacy as pretreatments. • Nerve agent antidotes – New nerve agent antidote compounds that are water soluble, have a broader

Identification and Characterization of Novel Catalytic Bioscavengers of Organophosphorus Nerve Agents

DTIC Science & Technology

2013-01-01

hydrolase activity . These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca. Lysates from A. oxalaticus had...warfare agents [1–3]. OP nerve agents readily bind covalently to the active site serine in acetylcho- linesterase (AChE), thereby inhibiting the ability...muscarinic receptors, whereas 2-pralidoxime chloride, an oxime nucleophile, reactivates AChE by displacing the phospho- nyl group left on the active site

Comparison of extracellular striatal acetylcholine and brain seizure activity following acute exposure to the nerve agents cyclosarin and tabun in freely moving guinea pigs.

PubMed

O'Donnell, John C; Acon-Chen, Cindy; McDonough, John H; Shih, Tsung-Ming

2010-11-01

Organophosphorus nerve agents like cyclosarin and tabun are potent cholinesterase inhibitors. The inhibition of acetylcholinesterase, which is responsible for breaking down acetylcholine (ACh) at the synapse and neuromuscular junction, leads to a build-up of extracellular ACh and a series of toxic consequences including hypersecretion, tremor, convulsion/seizure, respiratory distress, coma, and death. This study employed simultaneous and continuous electroencephalographic recording and striatal microdialysis collection for quantification of ACh changes (via subsequent HPLC analysis) during acute exposure to a 1.0 × LD(50) subcutaneous dose of either cyclosarin or tabun to investigate differences in cholinergic and behavioral effects. Information about the unique mechanisms and consequences of different nerve agents is intended to aid in the development of broad-spectrum medical countermeasures for nerve agents. At the dose administered, non-seizure and sustained seizure responses were observed in both agent groups and in the tabun-exposed group some subjects experienced an unsustained seizure response. Significant extracellular ACh increases were only observed in seizure groups. Cyclosarin and tabun were found to exhibit some unique cholinergic and ictogenic characteristics. Lethality only occurred in subjects experiencing sustained seizure, and there was no difference in lethality between agent groups that progressed to sustained seizure.

Toxicology of organophosphorus compounds in view of an increasing terrorist threat.

PubMed

Worek, Franz; Wille, Timo; Koller, Marianne; Thiermann, Horst

2016-09-01

The implementation of the Chemical Weapon Convention (CWC), prohibiting the development, production, storage and use of chemical weapons by 192 nations and the ban of highly toxic OP pesticides, especially class I pesticides according to the WHO classification, by many countries constitutes a great success of the international community. However, the increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents new challenges to our societies. Almost seven decades of research on organophosphorus compound (OP) toxicology was mainly focused on a small number of OP nerve agents despite the fact that a huge number of OP analogues, many of these agents having comparable toxicity to classical nerve agents, were synthesized and published. Only limited physicochemical, toxicological and medical information on nerve agent analogues is available in the open literature. This implies potential gaps of our capabilities to detect, to decontaminate and to treat patients if nerve agent analogues are disseminated and may result in inadequate effectiveness of newly developed countermeasures. In summary, our societies may face new, up to now disregarded, threats by toxic OP which calls for increased awareness and appropriate preparedness of military and civilian CBRN defense, a broader approach for new physical and medical countermeasures and an integrated system of effective detection, decontamination, physical protection and treatment.

BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. 1. POTENTIOMETRIC ENZYME ELECTRODE. (R823663)

EPA Science Inventory

A potentiometric enzyme electrode for the direct measurement of organophosphate (OP)
nerve agents was developed. The basic element of this enzyme electrode was a pH electrode
modified with an immobilized organophosphorus hydrolase (OPH) layer formed by cross-linking
OPH ...

AMPEROMETRIC THICK-FILM STRIP ELECTRODES FOR MONITORING ORGANOPHOSPHATE NERVE AGENTS BASED ON IMMOBILIZED ORGANOPHOSPHORUS HYDROLASE. (R823663)

EPA Science Inventory

An amperometric biosensor based on the immobilization of organophosphorus hydrolase
(OPH) onto screen-printed carbon electrodes is shown useful for the rapid, sensitive, and low-cost
detection of organophosphate (OP) nerve agents. The sensor relies upon the sensitive and ra...

Metal organic frameworks (MOFs) for degradation of nerve agent simulant parathion

USDA-ARS?s Scientific Manuscript database

Parathion, a simulant of nerve agent VX, has been studied for degradation on Fe3+, Fe2+ and zerovalent iron supported on chitosan. Chitosan, a naturally occurring biopolymer derivative of chitin, is a very good adsorbent for many chemicals including metals. Chitosan is used as supporting biopolymer ...

Metal organic frameworks (MOFs) for degrdation of nerve agent simulant parathion

USDA-ARS?s Scientific Manuscript database

Parathion, a simulant of nerve agent VX, has been studied for degradation on Fe3+, Fe2+ and zerovalent iron supported on chitosan. Chitosan, a naturally occurring biopolymer derivative of chitin, is a very good adsorbent for many chemicals including metals. Chitosan is used as supporting biopolymer ...

FIBER-OPTIC BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS. (R823663)

EPA Science Inventory

A fiber-optic enzyme biosensor for the direct measurement of organophosphate nerve
agents was developed. The basic element of this biosensor is organophosphorus hydrolase
immobilized on a nylon membrane and attached to the common end of a bifurcated optical fiber
bundle....

Using Nanotechnology to Detect Nerve Agents

DTIC Science & Technology

2011-01-01

56 | Air & Space Power Journal Air Force Institute of Technology Using Nanotechnology to Detect Nerve Agents Lt Col Mark N. Goltz , PhD, USAF...Retired Dr. Dong Shik Kim Maj LeeAnn Racz, PhD, USAF* *Lieutenant Colonel Goltz and Major Racz are faculty members in the Department of Systems and

Proceedings of the U.S. Army Chemical Research, Development and Engineering Center Scientific Conference on Chemical Defense Research Held in Aberdeen Proving Ground, Maryland on 14-17 November 1989

DTIC Science & Technology

1990-08-01

to react in a similar electrochemical manner to the agent 2,21- dichlorodiethylsulfide (Mustard gas or HD). As a simulant for the nerve agents ...attack which may permit effective discrimination of pesticides from nerve agents in a chemical agent detector. Table 1 shows the results of film badge...amount of CASARM agent ( GA , GB, HD or VX) was placed into a 5 mm O.D. Pyrex NMR tube and 1.0 ml of the decontaminating solution was added. The tube was

Polarimetry and infrared spectroscopy in the detection of low-volatility chemical threats

NASA Astrophysics Data System (ADS)

Petryk, Michael W. P.; Marenco, Armando J.

2011-05-01

The polarization modulation infrared reflection absorption spectroscopy (PMIRRAS) spectra of the nerve agents GB (O-isopropyl methylphosphonofluoridate) and GF (cyclohexyl methylphoshonofluoridate) were recorded for the first time. A comparison of these spectra with the nerve agent VX (ethyl S-2-diisopropylaminoethyl methylphosphonothiolate) and the spectra of some trialkyl phosphates indicates that it is easy to distinguish between chemical warfare agents and simulants on militarily-relevant surfaces using PMIRRAS.

Engineering of Paraoxonases for Pre- and Post-treatment of Intoxication by a Broad Spectrum of Nerve Agents and Pesticides

DTIC Science & Technology

2014-08-01

chemical warfare nerve agents (CWNA). Enzymes identified in these screens should be capable of catalytically neutralizing the target agent under...soluble form. 4. Large-scale production of selected enzyme candidates, and their kinetic, structural and pharmacological evaluation 6...employed, with an enzyme protein concentration of 0.5-2 mM in the assay cuvette, the activity measured was indistinguishable from the rate of

Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samanta, Uttamkumar; Kirby, Stephen D.; Srinivasan, Prabhavathi

The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P{submore » R} and P{sub S} stereoisomers at the P-chiral center. The tabun complex displayed only the P{sub R} stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.« less

Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes.

PubMed

Samanta, Uttamkumar; Kirby, Stephen D; Srinivasan, Prabhavathi; Cerasoli, Douglas M; Bahnson, Brian J

2009-08-15

The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P(R) and P(S) stereoisomers at the P-chiral center. The tabun complex displayed only the P(R) stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.

Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design.

PubMed

Melzer, Marco; Chen, Julian C-H; Heidenreich, Anne; Gäb, Jürgen; Koller, Marianne; Kehe, Kai; Blum, Marc-Michael

2009-12-02

Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall enhanced activity against tested nerve agents. The reversed stereochemical preference is explained through modeling studies and the crystal structures of the two mutants. Using the engineered mutants in combination with wild-type DFPase leads to significantly enhanced activity and detoxification, which is especially important for personal decontamination. Our findings may also be of relevance for the structurally related enzyme human paraoxonase (PON), which is of considerable interest as a potential catalytic in vivo scavenger in case of organophosphorus poisoning.

Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

PubMed

Masson, Patrick

2011-09-25

After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

History and perspectives of bioanalytical methods for chemical warfare agent detection.

PubMed

Black, Robin M

2010-05-15

This paper provides a short historical overview of the development of bioanalytical methods for chemical warfare (CW) agents and their biological markers of exposure, with a more detailed overview of methods for organophosphorus nerve agents. Bioanalytical methods for unchanged CW agents are used primarily for toxicokinetic/toxicodynamic studies. An important aspect of nerve agent toxicokinetics is the different biological activity and detoxification pathways for enantiomers. CW agents have a relatively short lifetime in the human body, and are hydrolysed, metabolised, or adducted to nucleophilic sites on macromolecules such as proteins and DNA. These provide biological markers of exposure. In the past two decades, metabolites, protein adducts of nerve agents, vesicants and phosgene, and DNA adducts of sulfur and nitrogen mustards, have been identified and characterized. Sensitive analytical methods have been developed for their detection, based mainly on mass spectrometry combined with gas or liquid chromatography. Biological markers for sarin, VX and sulfur mustard have been validated in cases of accidental and deliberate human exposures. The concern for terrorist use of CW agents has stimulated the development of higher throughput analytical methods in support of homeland security. Copyright (c) 2010. Published by Elsevier B.V.

29 CFR 1926.903 - Underground transportation of explosives.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Trucks used for the transportation of explosives underground shall have the electrical system checked weekly to detect any failures which may constitute an electrical hazard. A certification record which... powered by the truck's electrical system, shall be prohibited. (g) Explosives and blasting agents shall be...

29 CFR 1926.903 - Underground transportation of explosives.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Trucks used for the transportation of explosives underground shall have the electrical system checked weekly to detect any failures which may constitute an electrical hazard. A certification record which... powered by the truck's electrical system, shall be prohibited. (g) Explosives and blasting agents shall be...

29 CFR 1926.903 - Underground transportation of explosives.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Trucks used for the transportation of explosives underground shall have the electrical system checked weekly to detect any failures which may constitute an electrical hazard. A certification record which... powered by the truck's electrical system, shall be prohibited. (g) Explosives and blasting agents shall be...

29 CFR 1926.903 - Underground transportation of explosives.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Trucks used for the transportation of explosives underground shall have the electrical system checked weekly to detect any failures which may constitute an electrical hazard. A certification record which... powered by the truck's electrical system, shall be prohibited. (g) Explosives and blasting agents shall be...

29 CFR 1926.903 - Underground transportation of explosives.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Trucks used for the transportation of explosives underground shall have the electrical system checked weekly to detect any failures which may constitute an electrical hazard. A certification record which... powered by the truck's electrical system, shall be prohibited. (g) Explosives and blasting agents shall be...

Disability following combat-sustained nerve injury of the upper limb.

PubMed

Rivera, J C; Glebus, G P; Cho, M S

2014-02-01

Injuries to the limb are the most frequent cause of permanent disability following combat wounds. We reviewed the medical records of 450 soldiers to determine the type of upper limb nerve injuries sustained, the rate of remaining motor and sensory deficits at final follow-up, and the type of Army disability ratings granted. Of 189 soldiers with an injury of the upper limb, 70 had nerve-related trauma. There were 62 men and eight women with a mean age of 25 years (18 to 49). Disabilities due to nerve injuries were associated with loss of function, neuropathic pain or both. The mean nerve-related disability was 26% (0% to 70%), accounting for over one-half of this cohort's cumulative disability. Patients injured in an explosion had higher disability ratings than those injured by gunshot. The ulnar nerve was most commonly injured, but most disability was associated with radial nerve trauma. In terms of the final outcome, at military discharge 59 subjects (84%) experienced persistent weakness, 48 (69%) had a persistent sensory deficit and 17 (24%) experienced chronic pain from scar-related or neuropathic pain. Nerve injury was the cause of frequent and substantial disability in our cohort of wounded soldiers.

Detection of nerve gases using surface-enhanced Raman scattering substrates with high droplet adhesion

NASA Astrophysics Data System (ADS)

Hakonen, Aron; Rindzevicius, Tomas; Schmidt, Michael Stenbæk; Andersson, Per Ola; Juhlin, Lars; Svedendahl, Mikael; Boisen, Anja; Käll, Mikael

2016-01-01

Threats from chemical warfare agents, commonly known as nerve gases, constitute a serious security issue of increasing global concern because of surging terrorist activity worldwide. However, nerve gases are difficult to detect using current analytical tools and outside dedicated laboratories. Here we demonstrate that surface-enhanced Raman scattering (SERS) can be used for sensitive detection of femtomol quantities of two nerve gases, VX and Tabun, using a handheld Raman device and SERS substrates consisting of flexible gold-covered Si nanopillars. The substrate surface exhibits high droplet adhesion and nanopillar clustering due to elasto-capillary forces, resulting in enrichment of target molecules in plasmonic hot-spots with high Raman enhancement. The results may pave the way for strategic life-saving SERS detection of chemical warfare agents in the field.Threats from chemical warfare agents, commonly known as nerve gases, constitute a serious security issue of increasing global concern because of surging terrorist activity worldwide. However, nerve gases are difficult to detect using current analytical tools and outside dedicated laboratories. Here we demonstrate that surface-enhanced Raman scattering (SERS) can be used for sensitive detection of femtomol quantities of two nerve gases, VX and Tabun, using a handheld Raman device and SERS substrates consisting of flexible gold-covered Si nanopillars. The substrate surface exhibits high droplet adhesion and nanopillar clustering due to elasto-capillary forces, resulting in enrichment of target molecules in plasmonic hot-spots with high Raman enhancement. The results may pave the way for strategic life-saving SERS detection of chemical warfare agents in the field. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06524k

Solid-phase microextraction coupled to gas chromatography for the determination of 2,3-dimethyl-2,3-dinitrobutane as a marking agent for explosives.

PubMed

Li, Xiujuan; Zeng, Zhaorui; Zeng, Yi

2007-06-15

This paper investigates the detection of 2,3-dimethyl-2,3-dinitrobutane (DMNB), a marking agent in explosives, by gas chromatography (GC) with electron capture detection using solid-phase microextraction (SPME) as a sample preparation technique. The 25,27-dihydroxy-26,28-oxy (2',7'-dioxo-3',6'-diazaoctyl) oxy-p-tert-butylcalix[4]arene/hydroxy-terminated silicone oil coated fiber was highly sensitive to trap DMNB from ammonium nitrate matrix. The analysis was performed by extracting 2g of explosives for 30s at room temperature and then immediately introducing into the heated GC injector for 1min of thermal desorption. The method showed good linearity in the range from 0.01 to 1.0mug/g. The relative standard deviations for these extractions were <8%. The calculated limit of detection for DMNB (S/N=3) was 4.43x10(-4)mug/g, which illustrates that the proposed systems are suitable for explosive detection at trace level. This is the first report of an SPME-GC system shown to extract marking agent in explosives for subsequent detection in a simple, rapid, sensitive, and inexpensive manner.

An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents.

PubMed

Rezk, Peter E; Zdenka, Pierre; Sabnekar, Praveena; Kajih, Takwen; Mata, David G; Wrobel, Chester; Cerasoli, Douglas M; Chilukuri, Nageswararao

2015-01-01

In this study, we determined the ability of recombinant human liver prolidase to hydrolyze nerve agents in vitro and its ability to afford protection in vivo in mice. Using adenovirus containing the human liver prolidase gene, the enzyme was over expressed by 200- to 300-fold in mouse liver and purified to homogeneity by affinity and gel filtration chromatography. The purified enzyme hydrolyzed sarin, cyclosarin and soman with varying rates of hydrolysis. The most efficient hydrolysis was with sarin, followed by soman and by cyclosarin {apparent kcat/Km [(1.9 ± 0.3), (1.7 ± 0.2), and (0.45 ± 0.04)] × 10(5 )M(-1 )min(-1), respectively}; VX and tabun were not hydrolyzed by the recombinant enzyme. The enzyme hydrolyzed P (+) isomers faster than the P (-) isomers. The ability of recombinant human liver prolidase to afford 24 hour survival against a cumulative dose of 2 × LD50 of each nerve agent was investigated in mice. Compared to mice injected with a control virus, mice injected with the prolidase expressing virus contained (29 ± 7)-fold higher levels of the enzyme in their blood on day 5. Challenging these mice with two consecutive 1 × LD50 doses of sarin, cyclosarin, and soman resulted in the death of all animals within 5 to 8 min from nerve agent toxicity. In contrast, mice injected with the adenovirus expressing mouse butyrylcholinesterase, an enzyme which is known to afford protection in vivo, survived multiple 1 × LD50 challenges of these nerve agents and displayed no signs of toxicity. These results suggest that, while prolidase can hydrolyze certain G-type nerve agents in vitro, the enzyme does not offer 24 hour protection against a cumulative dose of 2 × LD50 of G-agents in mice in vivo.

Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats: Effects on Brain and Behavior

DTIC Science & Technology

2015-03-01

Analysis of seizure activity and dendritic spine density following exposure to sarin during puberty Methods Female rats were surgically implanted...effects were observed in rats exposed to GB on PND 7 or 21. This study shows that nerve agent exposure during puberty results in severe and life

Using NMR Spectroscopy to Investigate the Solution Behavior of Nerve Agents and Their Binding to Acetylcholinesterase

DTIC Science & Technology

2016-01-01

USING NMR SPECTROSCOPY TO INVESTIGATE THE SOLUTION BEHAVIOR OF NERVE AGENTS AND THEIR BINDING TO...XX-01-2016 2. REPORT TYPE Final 3. DATES COVERED (From - To) Jan – Jun 2015 4. TITLE AND SUBTITLE Using NMR Spectroscopy to Investigate the...MOLECULAR MOTIONS AND NMR SPECTROSCOPY ...................................................................................................3 4. THE

Chemical warfare and the Gulf War: a review of the impact on Gulf veterans' health.

PubMed

Riddle, James R; Brown, Mark; Smith, Tyler; Ritchie, Elspeth Cameron; Brix, Kelley Ann; Romano, James

2003-08-01

It is unlikely that Gulf War veterans are suffering chronic effects from illnesses caused by chemical warfare nerve agent exposure. Extensive investigation and review by several expert panels have determined that no evidence exists that chemical warfare nerve agents were used during the Gulf War. At no time before, during, or after the war was there confirmation of symptoms among anyone, military or civilian, caused by chemical warfare nerve agent exposure. However, studies of Gulf War veterans have found belief that chemical weapons were used, significantly associated with both severe and mild-moderate illnesses. The psychological impact of a chemical warfare attack, either actual or perceived, can result in immediate and long-term health consequences. The deployment or war-related health impact from life-threatening experiences of the Gulf War, including the perceived exposure to chemical warfare agents, should be considered as an important cause of morbidity among Gulf War veterans.

29 CFR 1926.900 - General provisions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... explosives. (b) Smoking, firearms, matches, open flame lamps, and other fires, flame or heat producing... magazine. (e) No explosives or blasting agents shall be abandoned. (f) No fire shall be fought where the fire is in imminent danger of contact with explosives. All employees shall be removed to a safe area...

29 CFR 1926.900 - General provisions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... explosives. (b) Smoking, firearms, matches, open flame lamps, and other fires, flame or heat producing... magazine. (e) No explosives or blasting agents shall be abandoned. (f) No fire shall be fought where the fire is in imminent danger of contact with explosives. All employees shall be removed to a safe area...

29 CFR 1926.900 - General provisions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... explosives. (b) Smoking, firearms, matches, open flame lamps, and other fires, flame or heat producing... magazine. (e) No explosives or blasting agents shall be abandoned. (f) No fire shall be fought where the fire is in imminent danger of contact with explosives. All employees shall be removed to a safe area...

Numerical Modeling of Mixing and Venting from Explosions in Bunkers

NASA Astrophysics Data System (ADS)

Liu, Benjamin

2005-07-01

2D and 3D numerical simulations were performed to study the dynamic interaction of explosion products in a concrete bunker with ambient air, stored chemical or biological warfare (CBW) agent simulant, and the surrounding walls and structure. The simulations were carried out with GEODYN, a multi-material, Godunov-based Eulerian code, that employs adaptive mesh refinement and runs efficiently on massively parallel computer platforms. Tabular equations of state were used for all materials with the exception of any high explosives employed, which were characterized with conventional JWL models. An appropriate constitutive model was used to describe the concrete. Interfaces between materials were either tracked with a volume-of-fluid method that used high-order reconstruction to specify the interface location and orientation, or a capturing approach was employed with the assumption of local thermal and mechanical equilibrium. A major focus of the study was to estimate the extent of agent heating that could be obtained prior to venting of the bunker and resultant agent dispersal. Parameters investigated included the bunker construction, agent layout, energy density in the bunker and the yield-to-agent mass ratio. Turbulent mixing was found to be the dominant heat transfer mechanism for heating the agent.

Modification of human serum albumin by the nerve agent VX: microbore liquid chromatography/electrospray ionization high-resolution time-of-flight tandem mass spectrometry method for detection of phosphonylated tyrosine and novel cysteine containing disulfide adducts.

PubMed

Kranawetvogl, Andreas; Worek, Franz; Thiermann, Horst; John, Harald

2016-10-15

Organophosphorus nerve agents still constitute a considerable threat to the health of military personnel and the civilian population. Long-term biomarkers are crucial for reliable verification of exposure to banned substances. Therefore, current research focuses on identification of endogenous protein targets showing covalent modifications by organophosphorus nerve agents (adducts). Purified human serum albumin and human plasma were incubated with the nerve agent VX followed by enzymatic proteolysis with pronase. Resulting peptide cleavage products were separated by microbore liquid chromatography (μLC) online coupled to positive electrospray ionization (ESI) with subsequent high-resolution time-of-flight tandem mass spectrometry (HR MS/MS) allowing identification of known and novel adducts. In addition to known phosphonylation of various tyrosine residues, albumin was found to be modified at diverse cysteine residues by covalent attachment of the leaving group of VX. These novel disulfide adducts were cleaved from at least two regions of the intact protein as dipeptides containing cysteine and proline either as CP or PC. A rapid and sensitive method was developed for simultaneous detection of the diverse covalent modifications of human albumin by VX. Identification of the novel leaving group adducts with human albumin expands the basic knowledge on molecular toxicology of the nerve agent VX. Furthermore, the presented μLC/ESI HR MS/MS method might be of relevance for verification of VX poisoning. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Supralethal poisoning by any of the classical nerve agents is effectively counteracted by procyclidine regimens in rats.

PubMed

Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

2015-09-01

A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of oxime reactivation and aging of nerve agent-inhibited monkey and human acetylcholinesterases.

PubMed

Luo, Chunyuan; Tong, Min; Maxwell, Donald M; Saxena, Ashima

2008-09-25

Non-human primates are valuable animal models that are used for the evaluation of nerve agent toxicity as well as antidotes and results from animal experiments are extrapolated to humans. It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the aging and reactivation of human and different monkey (Rhesus, Cynomolgus, and African Green) AChEs inhibited by GF, GD, and VR. The oximes examined include the traditional oxime 2-PAM, two H-oximes HI-6 and HLo-7, and the new candidate oxime MMB4. Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. The maximum difference in the second-order reactivation rate constant between human and three monkey AChEs or between AChEs from different monkey species was 5-fold. Aging rate constants of GF-, GD-, and VR-inhibited monkey AChEs were very similar to human AChE except for GF-inhibited monkey AChEs, which aged 2-3 times faster than the human enzyme. The results of this study suggest that all three monkey species are suitable animal models for nerve agent antidote evaluation since monkey AChEs possess similar biochemical/pharmacological properties to human AChE.

The efficacy of HI-6 DMS in a sustained infusion against percutaneous VX poisoning in the guinea-pig.

PubMed

Whitmore, C; Cook, A R; Mann, T; Price, M E; Emery, E; Roughley, N; Flint, D; Stubbs, S; Armstrong, S J; Rice, H; Tattersall, J E H

2018-09-01

Post-exposure nerve agent treatment usually includes administration of an oxime, which acts to restore function of the enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the oxime such as pralidoxime, atropine and diazepam. In addition to the autoinjector, it is likely that personnel exposed to nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities. As such, there is a need to understand the relationship between dose rate, plasma concentration, reactivation of AChE activity and efficacy, to provide supporting evidence for oxime infusions in nerve agent poisoning. Here, it has been demonstrated that intravenous infusion of HI-6, in combination with atropine, is efficacious against a percutaneous VX challenge in the conscious male Dunkin-Hartley guinea-pig. Inclusion of HI-6, in addition to atropine in the treatment, improved survival when compared to atropine alone. Additionally, erythrocyte AChE activity following poisoning was found to be dose dependent, with an increased dose rate of HI-6 (0.48mg/kg/min) resulting in increased AChE activity. As far as we are aware, this is the first study to correlate the pharmacokinetic profile of HI-6 with both its pharmacodynamic action of reactivating nerve agent inhibited AChE and with its efficacy against a persistent nerve agent exposure challenge in the same conscious animal. Copyright © 2017 Crown Copyright. Published by Elsevier B.V. All rights reserved.

Human Metabolism and Interactions of Deployment-Related Chemicals

DTIC Science & Technology

2003-08-01

with individual test compounds (final concentration, 100 PM), agent pyridostigmine bromide to protect against possible nerve gas NADPH-generating system...an insect repellent (N,N-diethyl-m- toluamide) a nerve gas prophyllactic (pyridostigmine bromide) did not cause the inhibition of trans-permethrin...mechanism of organophosphorus anticholinesterase agents , namely; covalent modification of the active site of the esterases in question. Carbaryl, another

Nerve Agent Sensing Biopolymer Wipe

DTIC Science & Technology

2003-04-01

3. Urease and BChE (at two concentrations) activity as function of pH. ..... 10 Figure 4. Reaction scheme Agentase nerve agent sensor...11 Figure 5. Signal development in Agentase’s Traffic Light Sensor Construct.......... 11 Figure 6. Effect of BChE/ urease ...between two competing enzyme reactions. BChE catalyzed butyrylcholine hydrolysis results in the production of acid (decreasing pH) while urease - catalyzed

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

New Non-Intrusive Inspection Technologies for Nuclear Security and Nonproliferation

NASA Astrophysics Data System (ADS)

Ledoux, Robert J.

2015-10-01

Comprehensive monitoring of the supply chain for nuclear materials has historically been hampered by non-intrusive inspection systems that have such large false alarm rates that they are impractical in the flow of commerce. Passport Systems, Inc. (Passport) has developed an active interrogation system which detects fissionable material, high Z material, and other contraband in land, sea and air cargo. Passport's design utilizes several detection modalities including high resolution imaging, passive radiation detection, effective-Z (EZ-3D™) anomaly detection, Prompt Neutrons from Photofission (PNPF), and Nuclear Resonance Fluorescence (NRF) isotopic identification. These technologies combine to: detect fissionable, high-Z, radioactive and contraband materials, differentiate fissionable materials from high-Z shielding materials, and isotopically identify actinides, Special Nuclear Materials (SNM), and other contraband (e.g. explosives, drugs, nerve agents). Passport's system generates a 3-D image of the scanned object which contains information such as effective-Z and density, as well as a 2-D image and isotopic and fissionable information for regions of interest.

LOW OZONE-DEPLETING HALOCARBONS AS TOTAL-FLOOD AGENTS: VOLUME 2. LABORATORY-SCALE FIRE SUPPRESSION AND EXPLOSION PREVENTION TESTING

EPA Science Inventory

The report gives results from (1) flame suppression testing of potential Halon-1301 (CF3Br) replacement chemicals in a laboratory cup burner using n-heptane fuel and (2) explosion prevention (inertion) testing in a small-scale explosion sphere using propane and methane as fuels. ...

78 FR 26655 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Statement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-07

...-Marking of Plastic Explosives for the Purpose of Detection ACTION: 30-Day notice. The Department of...) Title of the Form/Collection: Statement of Process-Marking of Plastic Explosives for the Purpose of... used to ensure that plastic explosives contain a detection agent as required by law. (5) An estimate of...

Vibrational spectroscopy standoff detection of threat chemicals

NASA Astrophysics Data System (ADS)

Ortiz-Rivera, William; Pacheco-Londoño, Leonardo C.; Castro-Suarez, John R.; Felix-Rivera, Hilsamar; Hernandez-Rivera, Samuel P.

2011-06-01

Spectroscopy based standoff detection systems: Raman and FTIR have been tested for detection of threat chemicals, including highly energetic materials, homemade explosives, explosives formulations and high explosives mixtures. Other threat chemicals studied included toxic industrial compounds (TIC) and chemical agent simulants. Microorganisms and biological threat agent simulants have also been detected at standoff distances. Open Path FTIR has been used to detect vapors and chemicals deposited on metal surfaces at μg/cm2 levels at distances as far as 30 m in active mode and 60 m in passive mode. In the case of Raman telescope, standoff distances for acetonitrile and ammonium nitrate were 140 m.

Standoff detection of explosives and chemical agents using broadly tuned external-cavity quantum cascade lasers (EC-QCLs)

NASA Astrophysics Data System (ADS)

Takeuchi, Eric B.; Rayner, Timothy; Weida, Miles; Crivello, Salvatore; Day, Timothy

2007-10-01

Civilian soft targets such as transportation systems are being targeted by terrorists using IEDs and suicide bombers. Having the capability to remotely detect explosives, precursors and other chemicals would enable these assets to be protected with minimal interruption of the flow of commerce. Mid-IR laser technology offers the potential to detect explosives and other chemicals in real-time and from a safe standoff distance. While many of these agents possess "fingerprint" signatures in the mid-IR (i.e. in the 3-20 micron regime), their effective interrogation by a practical, field-deployable system has been limited by size, complexity, reliability and cost constraints of the base laser technology. Daylight Solutions has addressed these shortcomings by developing compact, portable, broadly tunable mid-IR laser sources based upon external-cavity quantum cascade technology. This technology is now being applied by Daylight in system level architectures for standoff and remote detection of explosives, precursors and chemical agents. Several of these architectures and predicted levels of performance will be presented.

Microfluidic chip with optical sensor for rapid detection of nerve agent Sarin in water samples

NASA Astrophysics Data System (ADS)

Tan, Hsih Yin; Nguyen, Nam-Trung; Loke, Weng Keong; Tan, Yong Teng

2007-12-01

The chemical warfare agent Sarin is an organophosphate that is highly toxic to humans as they can act as cholinesterase inhibitors, that disrupts neuromuscular transmission. As these nerve agents are colorless, odorless and highly toxic, they can be introduced into drinking water as a means of terrorist sabotage. Hence, numerous innovative devices and methods have been developed for rapid detection of these organophosphates. Microfluidic technology allows the implementation of fast and sensitive detection of Sarin. In this paper, a micro-total analysis systems (TAS), also known as Lab-on-a-chip, fitted with an optical detection system has been developed to analyze the presence of the nerve agent sarin in water samples. In the present set-up, inhibition of co-introduced cholinesterase and water samples containing trace amounts of nerve agent sarin into the microfluidic device was used as the basis for selective detection of sarin. The device was fabricated using polymeric micromachining with PMMA (poly (methymethacrylate)) as the substrate material. A chromophore was utilized to measure the activity of remnant cholinesterase activity, which is inversely related to the amount of sarin present in the water samples. Comparisons were made between two different optical detection techniques and the findings will be presented in this paper. The presented measurement method is simple, fast and as sensitive as Gas Chromatography.

Standoff detection of chemical and biological threats using laser-induced breakdown spectroscopy.

PubMed

Gottfried, Jennifer L; De Lucia, Frank C; Munson, Chase A; Miziolek, Andrzej W

2008-04-01

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for real-time chemical and biological warfare agent detection in the field. We have demonstrated the detection and discrimination of the biological warfare agent surrogates Bacillus subtilis (BG) (2% false negatives, 0% false positives) and ovalbumin (0% false negatives, 1% false positives) at 20 meters using standoff laser-induced breakdown spectroscopy (ST-LIBS) and linear correlation. Unknown interferent samples (not included in the model), samples on different substrates, and mixtures of BG and Arizona road dust have been classified with reasonable success using partial least squares discriminant analysis (PLS-DA). A few of the samples tested such as the soot (not included in the model) and the 25% BG:75% dust mixture resulted in a significant number of false positives or false negatives, respectively. Our preliminary results indicate that while LIBS is able to discriminate biomaterials with similar elemental compositions at standoff distances based on differences in key intensity ratios, further work is needed to reduce the number of false positives/negatives by refining the PLS-DA model to include a sufficient range of material classes and carefully selecting a detection threshold. In addition, we have demonstrated that LIBS can distinguish five different organophosphate nerve agent simulants at 20 meters, despite their similar stoichiometric formulas. Finally, a combined PLS-DA model for chemical, biological, and explosives detection using a single ST-LIBS sensor has been developed in order to demonstrate the potential of standoff LIBS for universal hazardous materials detection.

Toxicity studies on agent GA (Phase 2): 90 day subchronic study of GA (Tabun) in cd rats. Appendices. Final report, July 1985-August 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-03-01

The purpose of the report is to provide essential toxicologic information on Tabun administration over a 90 day period. This toxicologic information may be used to adjust the maximum-tolerated dose for subsequent dominant-lethal and two-generation reproduction studies. The objectives were to determine the toxic effects of nerve agent exposure (e.g., target organs); and to determine the effects of nerve agent GA on sperm morphology and motility and vaginal cytology.

Processing of Lewisite munitions in the explosive destruction system.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shepodd, Timothy J.; Didlake, John E., Jr.; Bradshaw, Robert W., PhD

2005-03-01

The Explosive Destruction System (EDS) is a transportable system designed to treat chemical munitions. The EDS is transported on an open trailer that provides a mounting surface for major system components and an operator's work platform. The trailer is towed by a prime mover. An explosive containment vessel contains the shock, munition fragments, and the chemical agent during the munition opening process, and then provides a vessel for the subsequent chemical treatment of the agent. A fragmentation suppression system houses the chemical munition and protects the containment vessel from high velocity fragments. An explosive accessing system uses shaped charges tomore » cut the munition open and attack the burster. A firing system detonates the shaped charges. A chemical feed system supplies neutralizing reagents and water to the containment vessel. A waste handling system drains the treated effluent.« less

Investigation of the persistence of nerve agent degradation analytes on surfaces through wipe sampling and detection with ultrahigh performance liquid chromatography-tandem mass spectrometry.

PubMed

Willison, Stuart A

2015-01-20

The persistence of chemical warfare nerve agent degradation analytes on surfaces is important, from indicating the presence of nerve agent on a surface to guiding environmental restoration of a site after a release. Persistence was investigated for several chemical warfare nerve agent degradation analytes on indoor surfaces and presents an approach for wipe sampling of surfaces, followed by wipe extraction and liquid chromatography-tandem mass spectrometry detection. Commercially available wipe materials were investigated to determine optimal wipe recoveries. Tested surfaces included porous/permeable (vinyl tile, painted drywall, and wood) and largely nonporous/impermeable (laminate, galvanized steel, and glass) surfaces. Wipe extracts were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). UPLC provides a separation of targeted degradation analytes in addition to being nearly four times faster than high-performance liquid chromatography, allowing for greater throughput after a large-scale contamination incident and subsequent remediation events. Percent recoveries from nonporous/impermeable surfaces were 60-103% for isopropyl methylphosphonate (IMPA), GB degradate; 61-91% for ethyl methylphosphonate (EMPA), VX degradate; and 60-98% for pinacolyl methylphosphonate (PMPA), GD degradate. Recovery efficiencies for methyl phosphonate (MPA), nerve agent degradate, and ethylhydrogen dimethylphosphonate (EHDMAP), GA degradate, were lower, perhaps due to matrix effects. Diisopropyl methylphosphonate, GB impurity, was not recovered from surfaces. The resulting detection limits for wipe extracts were 0.065 ng/cm(2) for IMPA, 0.079 ng/cm(2) for MPA, 0.040 ng/cm(2) for EMPA, 0.078 ng/cm(2) for EHDMAP, and 0.013 ng/cm(2) for PMPA. The data indicate that laboratories may hold wipe samples for up to 30 days prior to analysis. Target analytes were observed to persist on surfaces for at least 6 weeks.

Hazards of chemical weapons release during war: new perspectives.

PubMed Central

Reutter, S

1999-01-01

The two major threat classes of chemical weapons are mustard gas and the nerve agents, and this has not changed in over 50 years. Both types are commonly called gases, but they are actually liquids that are not remarkably volatile. These agents were designed specifically to harm people by any route of exposure and to be effective at low doses. Mustard gas was used in World War I, and the nerve agents were developed shortly before, during, and after World War II. Our perception of the potency of chemical weapons has changed, as well as our concern over potential effects of prolonged exposures to low doses and potential target populations that include women and children. Many of the toxicologic studies and human toxicity estimates for both mustard and nerve agents were designed for the purpose of quickly developing maximal casualties in the least sensitive male soldier. The "toxicity" of the chemical weapons has not changed, but our perception of "toxicity" has. PMID:10585902

Mobile Robot Enabled Detection of Explosives and Biological Agents

DTIC Science & Technology

2006-11-01

Detection of Explosives and Biological Agents 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e...TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Wayne State University, SSIM Program, Detroit, Michigan 48202 8...PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM( S ) 11. SPONSOR

Symposium on Explosives and Pyrotechnics, 13th, Hilton Head Island, SC, Dec. 2-4, 1986, Proceedings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-01-01

The present conference on explosive and pyrotechnic technologies discusses the shock-sensitivity of RDX, the thermodynamic properties of RDX, TNT, nitroglycerine, and HMX energetic molecules, the dynamic resistivity of exploding conductors, the decomposition of azides, the critical shock-initiation energy of emulsion explosives, actuator valve optimization, pyrotechnic aerosolization from novel imbibed liquid matrices, tetrazole initiators, and polymeric binders for red phosphorus pellets. Also discussed are channel-effect studies, the dynamic desensitization of coal mine explosives, the electromagnetic and electrostatic protection of explosives, the reliability of fuze explosive trains, the hazardous properties of explosive chemicals, the emulsification of an explosive with a chemical foamingmore » agent, and low energy ignition of HMX using a foil bridge.« less

Letterman Army Institute of Research Annual Research Progress Report, FY 1981.

DTIC Science & Technology

1981-10-01

with physiology and mech- anisms of skin damage and repair. The mechanisms by which nerve agents and vesicants produce physiologic aberration and...enzyme vital for nerve function. Organophos- phates react rapidly and covalently with the enzyme to produce an in- active enzyme. Reactivation of the...warfare agents . These organic molecules may also alter the natural defense mechanism by activating or deactivating enzymes in the skin that destroy

Characterisation of a Cell Culture System for Investigating Nerve Agent Neurotoxicology. Part 1

DTIC Science & Technology

2012-03-01

eds. CRC Press), pp. 1-24. Sawyer,T.W., Weiss,M.T., and Unger,R.J. (1992). Anticholinesterase activity of organophosphate nerve agents in neuronal...were confirmed. The presence of muscarinic receptors and acetylcholinesterase activity was determined. Importantly, differential acetylcholinesterase... activity assays that will provide the basis for an ongoing research programme. The neuroblastoma cell lines chosen can potentially be used as a

Using an object-based grid system to evaluate a newly developed EP approach to formulate SVMs as applied to the classification of organophosphate nerve agents

NASA Astrophysics Data System (ADS)

Land, Walker H., Jr.; Lewis, Michael; Sadik, Omowunmi; Wong, Lut; Wanekaya, Adam; Gonzalez, Richard J.; Balan, Arun

2004-04-01

This paper extends the classification approaches described in reference [1] in the following way: (1.) developing and evaluating a new method for evolving organophosphate nerve agent Support Vector Machine (SVM) classifiers using Evolutionary Programming, (2.) conducting research experiments using a larger database of organophosphate nerve agents, and (3.) upgrading the architecture to an object-based grid system for evaluating the classification of EP derived SVMs. Due to the increased threats of chemical and biological weapons of mass destruction (WMD) by international terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat biochemical warfare. This paper reports the integration of multi-array sensors with Support Vector Machines (SVMs) for the detection of organophosphates nerve agents using a grid computing system called Legion. Grid computing is the use of large collections of heterogeneous, distributed resources (including machines, databases, devices, and users) to support large-scale computations and wide-area data access. Finally, preliminary results using EP derived support vector machines designed to operate on distributed systems have provided accurate classification results. In addition, distributed training time architectures are 50 times faster when compared to standard iterative training time methods.

Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munro, N.B.; Ambrose, K.R.; Watson, A.P.

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is not evidence that itmore » causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. 187 refs., 3 figs., 7 tabs.« less

X-Ray Crystallographic Studies on Acetylcholinesterase and Related Enzymes.

DTIC Science & Technology

1999-10-01

nerve gas intoxication, as well as of insecticide poisoning. Such structures can yield direct information concerning the functional groups and steric...Glyll7His mutant (48). Recent solution of the 3D structures of conjugates of the nerve agents , sarin, soman, DFP and VX with 7cAChE (49, 50) has revealed... pesticides and chemical warfare agents is a topic of considerable environmental and toxicological importance. Hence, a substantial research effort is being

Acute Toxicity Estimation and Operational Risk Management of Chemical Warfare Agent Exposures

DTIC Science & Technology

2004-05-01

Following absorption into the body, nerve agents bind with and inhibit the activity of cholinesterases (ChE) that are present in the blood and...other tissues. Blood ChE activity depression by itself is not considered an adverse effect but (particularly red blood cell cholinesterase (RBC-ChE...chemical, such as an organophosphate , that blocks nerve impulses by inhibiting the activity of the enzyme cholinesterase (adapted from University of

Fluoride Ion Regeneration of Cyclosarin (Gf) from Minipig Tissue and Fluids Following Whole Body GF Vapor Exposure

DTIC Science & Technology

2006-11-01

Quantitation of organophosphorus nerve agent metabolites in human urine using isotope dilution gas chromatography- tandem mass spectrometry. J. Anal...Recent developments to improve nerve agent biomarker techniques include methods for measuring fluoride regenerated Sarin (GB) in blood and tissue...Our efforts extend the fluoride ion regeneration method to be able to determine cyclosarin (GF) in red blood cells, plasma, and tissue of minipig

The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302

DTIC Science & Technology

2014-11-01

to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the cur- rent US Food and Drug... status epilepticus (SE), which are initiated by the excessive stimulation of cholinergic receptors. If immediate death is prevented by adequate...5-yl)ethyl] decahydroisoquinoline-3-carboxylic acid; PBS, phosphate-buffered saline; SE, status epilepticus ; UBP302, (S)-3-(2-carboxybenzyl

Effects of subacute pretreatment with carbamate together with acute adjunct pretreatment against nerve agent exposure. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, D.R.; Harris, L.W.; Lennox, W.J.

1991-12-31

Acute carbamate pretreatment, in conjunction with atropine pretreatment or followed by atropine and oxime therapy has been shown to protect rabbits, rats, guinea pigs and monkeys against multiple lethal doses of soman. In those experiments, pretreated animals were usually challenged with soman at the time of peak whole blood acetylcholinesterase (AChE) inhibition by the carbamate or when the concentration of carbamate in the blood was expected to be rapidly diminishing. However, soldiers in a chemical environment, having taken carbamate orally might well be exposed to nerve agent shortly thereafter. Thus, both active carbamate and nerve agent would be entering themore » blood simultaneously. In a recent study it was reported that subacute administration of physostigmine (Phy), via subcutaneously implanted 28 day osmotic minipump, afforded protection against an iv challenge of soman on the 27th day.« less

Hydrolysis of Nerve Agents by Model Nucleophiles: A Computational Study

PubMed Central

Beck, Jeremy M.

2008-01-01

Density functional theory calculations were employed to study the reaction of five nerve agents with model nucleophiles, including EtX− and EtXH (X = O, S, Se) for serine, cysteine and selenocysteine, respectively. Calculations at the B3LYP/6-311++G(2d,p) level of theory predict an exothermic reaction between ethoxide and all of the nerve agents studied. As compared to EtO− as a nucleophile, these reactions become ~30 kcal/mol more endothermic for EtS−, and by ~40 kcal/mol for EtSe−. The equivalent reactions with the neutral nucleophiles (EtXH) were more endothermic. The effect of solvation on the reaction thermochemistry was determined using a polarizable continuum model simulating the dielectric constant of chloroform. While there was a large exothermic shift for reactions involving charged nucleophiles with solvation modeling, the corresponding shift was minimal for the reaction with neutral nucleophiles. PMID:18538754

A common-path optical coherence tomography based electrode for structural imaging of nerves and recording of action potentials

NASA Astrophysics Data System (ADS)

Islam, M. Shahidul; Haque, Md. Rezuanul; Oh, Christian M.; Wang, Yan; Park, B. Hyle

2013-03-01

Current technologies for monitoring neural activity either use different variety of electrodes (electrical recording) or require contrast agents introduced exogenously or through genetic modification (optical imaging). Here we demonstrate an optical method for non-contact and contrast agent free detection of nerve activity using phase-resolved optical coherence tomography (pr-OCT). A common-path variation of the pr-OCT is recently implemented and the developed system demonstrated the capability to detect rapid transient structural changes that accompany neural spike propagation. No averaging over multiple trials was required, indicating its capability of single-shot detection of individual impulses from functionally stimulated Limulus optic nerve. The strength of this OCT-based optical electrode is that it is a contactless method and does not require any exogenous contrast agent. With further improvements in accuracy and sensitivity, this optical electrode will play a complementary role to the existing recording technologies in future.

The role of the oximes HI-6 and HS-6 inside human acetylcholinesterase inhibited with nerve agents: a computational study.

PubMed

Cuya, Teobaldo; Gonçalves, Arlan da Silva; da Silva, Jorge Alberto Valle; Ramalho, Teodorico C; Kuca, Kamil; C C França, Tanos

2017-10-27

The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS-6) are isomers differing from each other only by the position of the carbamoyl group on the pyridine ring. However, this slight difference was verified to be responsible for big differences in the percentual of reactivation of acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin, cyclosarin, and VX. In order to try to find out the reason for this, a computational study involving molecular docking, molecular dynamics, and binding energies calculations, was performed on the binding modes of HI-6 and HS-6 on human AChE (HssAChE) inhibited by those nerve agents.

Screening of nerve agent degradation products by MALDI-TOFMS.

PubMed

Shu, You-Ren; Su, An-Kai; Liu, Ju-Tsung; Lin, Cheng-Huang

2006-07-01

A novel method for the rapid screening of degradation products derived from nerve agents by matrix-assisted laser desorption ionization time-of-flight mass spectrometry is described. Five standard products were selected as model compounds, including isopropyl methylphosphonic acid (IMPA), pinacolyl methylphosphonic acid (PMPA), ethyl methylphosphonic acid (EMPA), isobutyl methylphosphonic acid (i-BuMPA), and cyclohexyl methylphosphonic acid (CHMPA), which are degradation products of Sarin (GB), Soman (GD), VX, Russian VX (RVX), and GF, respectively. For comparison, CHCA (alpha-cyano-4-hydroxycinnamic acid) and DCCA (7-(diethylamino)coumarin-3-carboxylic acid) were used as the MALDI-matrix when the third harmonic generation (355 nm) of a Nd:YAG laser and a hydrogen Raman laser (multifrequency laser) were used, respectively. The method permitted the five nerve agent degradation products to be screened rapidly and successfully, suggesting that it has the potential for use as a routine monitoring tool.

Molecular and dissociative adsorption of DMMP, Sarin and Soman on dry and wet TiO2(110) using density functional theory

NASA Astrophysics Data System (ADS)

Quintero, Yenny Cardona; Nagarajan, Ramanathan

2018-09-01

Titania, among the metal oxides, has shown promising characteristics for the adsorption and decontamination of chemical warfare nerve agents, due to its high stability and rapid decomposition rates. In this study, the adsorption energy and geometry of the nerve agents Sarin and Soman, and their simulant dimethyl methyl phosphonate (DMMP) on TiO2 rutile (110) surface were calculated using density functional theory. The molecular and dissociative adsorption of the agents and simulant on dry as well as wet metal oxide surfaces were considered. For the wet system, computations were done for the cases of both molecularly adsorbed water (hydrated conformation) and dissociatively adsorbed water (hydroxylated conformation). DFT calculations show that dissociative adsorption of the agents and simulant is preferred over molecular adsorption for both dry and wet TiO2. The dissociative adsorption on hydrated TiO2 shows higher stability among the different configurations considered. The dissociative structure of DMMP on hydrated TiO2 (the most stable one) was identified as the dissociation of a methyl group and its adsorption on the TiO2 surface. For the nerve agents Sarin and Soman on hydrated TiO2 the dissociative structure was by the dissociation of the F atom from the molecule and its interaction with a Ti atom from the surface, which could indicate a reduction in the toxicity of the products. This study shows the relevance of water adsorption on the metal oxide surface for the stability and dissociation of the simulant DMMP and the nerve agents Sarin and Soman on TiO2.

Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987.

PubMed

Keegan, Thomas J; Carpenter, Lucy M; Brooks, Claire; Langdon, Toby; Venables, Katherine M

2017-12-15

The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK's centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28-51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

A structure-activity analysis of the variation in oxime efficacy against nerve agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

2008-09-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

Fluorescent sensors for the detection of chemical warfare agents.

PubMed

Burnworth, Mark; Rowan, Stuart J; Weder, Christoph

2007-01-01

Along with biological and nuclear threats, chemical warfare agents are some of the most feared weapons of mass destruction. Compared to nuclear weapons they are relatively easy to access and deploy, which makes them in some aspects a greater threat to national and global security. A particularly hazardous class of chemical warfare agents are the nerve agents. Their rapid and severe effects on human health originate in their ability to block the function of acetylcholinesterase, an enzyme that is vital to the central nervous system. This article outlines recent activities regarding the development of molecular sensors that can visualize the presence of nerve agents (and related pesticides) through changes of their fluorescence properties. Three different sensing principles are discussed: enzyme-based sensors, chemically reactive sensors, and supramolecular sensors. Typical examples are presented for each class and different fluorescent sensors for the detection of chemical warfare agents are summarized and compared.

Nerve Agent Induced Status Epilepticus: From Seizure Onset to Long Lasting Pathology

DTIC Science & Technology

2014-01-31

of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev 25:297-323 168. Martin LF, Kem WR, Freedman R. 2004. Alpha-7...Pharmacol 82:931-42 220. Paxinos G, Watson C. 2005. The Rat Brain in Stereotaxic Coordinates. New York NY: Elsevier 221. Petras JM. 1981. Soman...neurotoxicity. Fundam Appl Toxicol 1 :242 222. Petras JM. 1994. Neurology and neuropathology of Soman-induced brain injury: an overview. J Exp Anal

Tertiary Oximes on Brain Acetylcholinesterase and Central Excitatory Effects of Nerve Agents

DTIC Science & Technology

2012-01-01

5 test doses of the oxime. Animals were euthanized 45 min after oxime treatment when blood and target tissues were collected. AChE activity was...the ability of MINA and DHAP to block or terminate nerve agent-induced electroencephalographic (EEG) seizure activity was evaluated. Animals...instrumented to record brain EEG activity were challenged with a seizure-inducing dose (2.0 x LD50) of GB, GF, or VX, and oxime was administered one min

In Vivo Microdialysis and Electroencephalographic Activity in Freely Moving Guinea Pigs Exposed to Organophosphorus Nerve Agents Sarin and VX: Analysis of Acetylcholine and Glutamate

DTIC Science & Technology

2011-01-01

3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs 5a...microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of...brain seizure activity . This robust double multi- variate design provides greater fidelity when comparing data while also reducing the required number

Examination of plasma PON1 paraoxonase activity and genotype in Gulf War veterans

DTIC Science & Technology

2017-10-01

cholinergic” effects (e.g., personal pesticide use, exposure to OP nerve agents) in subgroups of veterans with different PON1192 genotype. (2...associations between GWI and GW-related exposures with the potential for “cholinergic” effects (e.g., personal pesticide use, exposure to OP nerve agents) in...learning and careers in science, technology, and the humanities . What do you plan to do during the next reporting period to accomplish the goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Worek, Franz, E-mail: franzworek@bundeswehr.org; Wille, Timo; Aurbek, Nadine

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary highmore » MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning.« less

The postwar hospitalization experience of Gulf War Veterans possibly exposed to chemical munitions destruction at Khamisiyah, Iraq.

PubMed

Gray, G C; Smith, T C; Knoke, J D; Heller, J M

1999-09-01

Using Department of Defense hospital data, the authors examined the postwar hospitalization experience from March 1991 through September 1995 of US Gulf War veterans who were near Khamisiyah, Iraq, during nerve agent munition destruction in March 1991. Multiple sources of meteorologic, munition, and toxicology data were used to circumscribe geographic areas of low level, vaporized nerve agent for 4 days after the destruction. Plume estimates were overlaid on military unit positions, and exposure was estimated for the 349,291 US Army Gulf War veterans. Exposure was classified as not exposed (n = 224,804), uncertain low dose exposure (n = 75,717), and specific estimated subclinical exposure (n = 48,770) categorized into three groups for dose-response evaluation. Using Cox proportional hazard modeling, the authors compared the postwar experiences of these exposure groups for hospitalization due to any cause, for diagnoses in 15 unique categories, and for specific diagnoses an expert panel proposed as most likely to reflect latent disease from such subclinical exposure. There was little evidence that veterans possibly exposed to the nerve agent plumes experienced unusual postwar morbidity. While there were several differences in hospitalization risk, none of the models suggested a dose-response relation or neurologic sequelae. These data, having a number of limitations, do not support the hypothesis that Gulf War veterans are suffering postwar morbidity from subclinical nerve agent exposure.

Green primary explosives: 5-Nitrotetrazolato-N2-ferrate hierarchies

PubMed Central

Huynh, My Hang V.; Coburn, Michael D.; Meyer, Thomas J.; Wetzler, Modi

2006-01-01

The sensitive explosives used in initiating devices like primers and detonators are called primary explosives. Successful detonations of secondary explosives are accomplished by suitable sources of initiation energy that is transmitted directly from the primaries or through secondary explosive boosters. Reliable initiating mechanisms are available in numerous forms of primers and detonators depending upon the nature of the secondary explosives. The technology of initiation devices used for military and civilian purposes continues to expand owing to variations in initiating method, chemical composition, quantity, sensitivity, explosive performance, and other necessary built-in mechanisms. Although the most widely used primaries contain toxic lead azide and lead styphnate, mixtures of thermally unstable primaries, like diazodinitrophenol and tetracene, or poisonous agents, like antimony sulfide and barium nitrate, are also used. Novel environmentally friendly primary explosives are expanded here to include cat[FeII(NT)3(H2O)3], cat2[FeII(NT)4(H2O)2], cat3[FeII(NT)5(H2O)], and cat4[FeII(NT)6] with cat = cation and NT− = 5-nitrotetrazolato-N2. With available alkaline, alkaline earth, and organic cations as partners, four series of 5-nitrotetrazolato-N2-ferrate hierarchies have been prepared that provide a plethora of green primaries with diverse initiating sensitivity and explosive performance. They hold great promise for replacing not only toxic lead primaries but also thermally unstable primaries and poisonous agents. Strategies are also described for the systematic preparation of coordination complex green primaries based on appropriate selection of ligands, metals, and synthetic procedures. These strategies allow for maximum versatility in initiating sensitivity and explosive performance while retaining properties required for green primaries. PMID:16803957

Green primary explosives: 5-nitrotetrazolato-N2-ferrate hierarchies.

PubMed

Huynh, My Hang V; Coburn, Michael D; Meyer, Thomas J; Wetzler, Modi

2006-07-05

The sensitive explosives used in initiating devices like primers and detonators are called primary explosives. Successful detonations of secondary explosives are accomplished by suitable sources of initiation energy that is transmitted directly from the primaries or through secondary explosive boosters. Reliable initiating mechanisms are available in numerous forms of primers and detonators depending upon the nature of the secondary explosives. The technology of initiation devices used for military and civilian purposes continues to expand owing to variations in initiating method, chemical composition, quantity, sensitivity, explosive performance, and other necessary built-in mechanisms. Although the most widely used primaries contain toxic lead azide and lead styphnate, mixtures of thermally unstable primaries, like diazodinitrophenol and tetracene, or poisonous agents, like antimony sulfide and barium nitrate, are also used. Novel environmentally friendly primary explosives are expanded here to include cat[Fe(II)(NT)(3)(H(2)O)(3)], cat(2)[Fe(II)(NT)(4)(H(2)O)(2)], cat(3)[Fe(II)(NT)(5)(H(2)O)], and cat(4)[Fe(II)(NT)(6)] with cat = cation and NT(-) = 5-nitrotetrazolato-N(2). With available alkaline, alkaline earth, and organic cations as partners, four series of 5-nitrotetrazolato-N(2)-ferrate hierarchies have been prepared that provide a plethora of green primaries with diverse initiating sensitivity and explosive performance. They hold great promise for replacing not only toxic lead primaries but also thermally unstable primaries and poisonous agents. Strategies are also described for the systematic preparation of coordination complex green primaries based on appropriate selection of ligands, metals, and synthetic procedures. These strategies allow for maximum versatility in initiating sensitivity and explosive performance while retaining properties required for green primaries.

EPA Science Matters Newsletter: Chemical Warfare Agent Analytical Standards Facilitate Lab Testing (Published November 2013)

EPA Pesticide Factsheets

Learn about the EPA chemists' efforts to develop methods for detecting extremely low concentrations of nerve agents, such as sarin, VX, soman and cyclohexyl sarin, and the blister agent sulfur mustard.

Catalytic degradation of the nerve agent VX by water-swelled polystyrene-supported ammonium fluorides.

PubMed

Marciano, Daniele; Goldvaser, Michael; Columbus, Ishay; Zafrani, Yossi

2011-10-21

The catalytic degradation of the nerve agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) by water-swelled polymer-supported ammonium fluorides is described. VX (0.06-0.53 mol/mol F(-)) is rapidly degraded (t(1/2) ∼ 10-30 min) to form the "G-analogue" (O-ethyl methylphosphonofluoridate), which hydrolyzes (t(1/2) ∼ 1-1.5 h) to the nontoxic EMPA (ethyl methylphosphonic acid). The toxic desethyl-VX is not formed. The catalytic effect of fluoride is maintained even when 6 equiv of VX are loaded. GB (O-isopropyl methylphosphonofluoridate) and desethyl-VX agents are also degraded under these conditions.

High-sensitivity, high-selectivity detection of chemical warfare agents

NASA Astrophysics Data System (ADS)

Pushkarsky, Michael B.; Webber, Michael E.; Macdonald, Tyson; Patel, C. Kumar N.

2006-01-01

We report high-sensitivity detection of chemical warfare agents (nerve gases) with very low probability of false positives (PFP). We demonstrate a detection threshold of 1.2ppb (7.7μg/m3 equivalent of Sarin) with a PFP of <1:106 in the presence of many interfering gases present in an urban environment through the detection of diisopropyl methylphosphonate, an accepted relatively harmless surrogate for the nerve agents. For the current measurement time of ˜60s, a PFP of 1:106 corresponds to one false alarm approximately every 23months. The demonstrated performance satisfies most current homeland and military security requirements.

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes.

PubMed

RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

2014-04-04

Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2×LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and subsequent long term neurological effects induced by nerve agents.

Managing traumatic brain injury secondary to explosions.

PubMed

Burgess, Paula; E Sullivent, Ernest; M Sasser, Scott; M Wald, Marlena; Ossmann, Eric; Kapil, Vikas

2010-04-01

Explosions and bombings are the most common deliberate cause of disasters with large numbers of casualties. Despite this fact, disaster medical response training has traditionally focused on the management of injuries following natural disasters and terrorist attacks with biological, chemical, and nuclear agents. The following article is a clinical primer for physicians regarding traumatic brain injury (TBI) caused by explosions and bombings. The history, physics, and treatment of TBI are outlined.

Method and apparatus for selective capture of gas phase analytes using metal .beta.-diketonate polymers

DOEpatents

Harvey, Scott D [Kennewick, WA

2011-06-21

A process and sensor device are disclosed that employ metal .beta.-diketonate polymers to selectively capture gas-phase explosives and weaponized chemical agents in a sampling area or volume. The metal .beta.-diketonate polymers can be applied to surfaces in various analytical formats for detection of: improvised explosive devices, unexploded ordinance, munitions hidden in cargo holds, explosives, and chemical weapons in public areas.

Portable Sensor for Chemical Nerve Agents and Organophosphorus Compounds

DTIC Science & Technology

2015-08-18

as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of the high toxicity and the...agents have been exploited for use as pesticides in crop, livestock, and poultry products and as chemical and biological warfare agents. As a result of

[The error analysis and experimental verification of laser radar spectrum detection and terahertz time domain spectroscopy].

PubMed

Liu, Wen-Tao; Li, Jing-Wen; Sun, Zhi-Hui

2010-03-01

Terahertz waves (THz, T-ray) lie between far-infrared and microwave in electromagnetic spectrum with frequency from 0.1 to 10 THz. Many chemical agent explosives show characteristic spectral features in the terahertz. Compared with conventional methods of detecting a variety of threats, such as weapons and chemical agent, THz radiation is low frequency and non-ionizing, and does not give rise to safety concerns. The present paper summarizes the latest progress in the application of terahertz time domain spectroscopy (THz-TDS) to chemical agent explosives. A kind of device on laser radar detecting and real time spectrum measuring was designed which measures the laser spectrum on the bases of Fourier optics and optical signal processing. Wedge interferometer was used as the beam splitter to wipe off the background light and detect the laser and measure the spectrum. The result indicates that 10 ns laser radar pulse can be detected and many factors affecting experiments are also introduced. The combination of laser radar spectrum detecting, THz-TDS, modern pattern recognition and signal processing technology is the developing trend of remote detection for chemical agent explosives.

Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors

PubMed Central

2016-01-01

Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides. PMID:27551784

Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors.

PubMed

Lockridge, Oksana; Norgren, Robert B; Johnson, Rudolph C; Blake, Thomas A

2016-09-19

Acetylcholinesterase (AChE) is the physiologically important target for organophosphorus toxicants (OP) including nerve agents and pesticides. Butyrylcholinesterase (BChE) in blood serves as a bioscavenger that protects AChE in nerve synapses from inhibition by OP. Mass spectrometry methods can detect exposure to OP by measuring adducts on the active site serine of plasma BChE. Genetic variants of human AChE and BChE do exist, but loss of function mutations have been identified only in the BCHE gene. The most common AChE variant, His353Asn (H322N), also known as the Yt blood group antigen, has normal AChE activity. The most common BChE variant, Ala567Thr (A539T) or the K-variant in honor of Werner Kalow, has 33% reduced plasma BChE activity. The genetic variant most frequently associated with prolonged response to muscle relaxants, Asp98Gly (D70G) or atypical BChE, has reduced activity and reduced enzyme concentration. Early studies in young, healthy males, performed at a time when it was legal to test nerve agents in humans, showed that individuals responded differently to the same low dose of sarin with toxic symptoms ranging in severity from minimal to moderate. Additionally, animal studies indicated that BChE protects from toxicants that have a higher reactivity with AChE than with BChE (e.g., nerve agents) but not from toxicants that have a higher reactivity with BChE than with AChE (e.g., OP pesticides). As a corollary, we hypothesize that individuals with genetic variants of BChE may be at increased risk of toxicity from nerve agents but not from OP pesticides.

Activity Based Protein Profiling Leads to Identification of Novel Protein Targets for Nerve Agent VX.

PubMed

Carmany, Dan; Walz, Andrew J; Hsu, Fu-Lian; Benton, Bernard; Burnett, David; Gibbons, Jennifer; Noort, Daan; Glaros, Trevor; Sekowski, Jennifer W

2017-04-17

Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt symptoms is the disruption of cholinergic pathways. While much is known about the primary toxicity mechanisms of nerve agents, there remains a paucity of information regarding impacts on other pathways and systemic effects. These are important for establishing a comprehensive understanding of the toxic mechanisms of OP nerve agents. To identify novel proteins that interact with VX, and that may give insight into these other mechanisms, we used activity-based protein profiling (ABPP) employing a novel VX-probe on lysates from rat heart, liver, kidney, diaphragm, and brain tissue. By making use of a biotin linked VX-probe, proteins covalently bound by the probe were isolated and enriched using streptavidin beads. The proteins were then digested, labeled with isobarically distinct tandem mass tag (TMT) labels, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Quantitative analysis identified 132 bound proteins, with many proteins found in multiple tissues. As with previously published ABPP OP work, monoacylglycerol lipase associated proteins and fatty acid amide hydrolase (FAAH) were shown to be targets of VX. In addition to these two and other predicted neurotransmitter-related proteins, a number of proteins involved with energy metabolism were identified. Four of these enzymes, mitochondrial isocitrate dehydrogenase 2 (IDH2), isocitrate dehydrogenase 3 (IDH3), malate dehydrogenase (MDH), and succinyl CoA (SCS) ligase, were assayed for VX inhibition. Only IDH2 NADP+ activity was shown to be inhibited directly. This result is consistent with other work reporting animals exposed to OP compounds exhibit reduced IDH activity. Though clearly a secondary mechanism for toxicity, this is the first time VX has been shown to directly interfere with energy metabolism. Taken together, the ABPP work described here suggests the discovery of novel protein-agent interactions, which could be useful for the development of novel diagnostics or potential adjuvant therapeutics.

Limitations and challenges in treatment of acute chemical warfare agent poisoning.

PubMed

Thiermann, Horst; Worek, Franz; Kehe, Kai

2013-12-05

Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new and promising option. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical warfare nerve agents. A review of cardiopulmonary pathophysiology and resuscitation. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franz, D.R.

1986-12-01

The purpose of this document is to provide the medical research community with a digest of the open and internal literature related to cardiopulmonary pathophysiology, resuscitation, and animal modeling of chemical warfare nerve agent intoxication. Though not comprehensive, this review makes available to the reader a cross section of what research was done in this small but important part of the medical chemical defense research program between World War II and the early 1980's.

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2013-08-01

GFAP,IL6,CCL2, TNF, L118, Lif, IL10 Hip, Ctx Ctx Ctx CORT=corticosterone;(200mg/L) for days 7-14 P8= pyridostigmine bromide ;P8(2.5 mg/kg/day, s.c...reversible acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These...acetylcholinesterase (AChE) inhibitor, pyridostigmine bromide (PB), the insect repellent, DEET, and, potentially, acutely to the nerve agent sarin. Previously, we

Stoichiometric and Catalytic Scavengers as Protection Against Nerve Agent Toxicity: A Mini Review

DTIC Science & Technology

2007-01-01

signs of nerve agent toxicity following exposure . Assessments of motor activity , coordination, and acquisition of spatial memory were performed for 2...serious side occur before endogenous AChE is affected (approxi- effects if administered in the absence of cholinesterase mately 2 min after exposure to an...after guinea pigs of cholinesterase in the blood and the level of protec- were administered 60mg/kg of HuBuChE (-󈧎-fold tion against OP poisoning

Enhanced catalytic activity through the tuning of micropore environment and supercritical CO2 processing: Al(porphyrin)-based porous organic polymers for the degradation of a nerve agent simulant.

PubMed

Totten, Ryan K; Kim, Ye-Seong; Weston, Mitchell H; Farha, Omar K; Hupp, Joseph T; Nguyen, SonBinh T

2013-08-14

An Al(porphyrin) functionalized with a large axial ligand was incorporated into a porous organic polymer (POP) using a cobalt-catalyzed acetylene trimerization strategy. Removal of the axial ligand afforded a microporous POP that is catalytically active in the methanolysis of a nerve agent simulant. Supercritical CO2 processing of the POP dramatically increased the pore size and volume, allowing for significantly higher catalytic activities.

Perspectives on the Use of Scopolamine as an Adjunct Treatment to Enhance Survival Following Organophosphorus Nerve Agent Poisoning

DTIC Science & Technology

2010-11-01

particular nerve agent and oxime uti- lized in the treatment regimen. Atropine is the universal treatment for organophospho- rus anticholinesterase poisoning...general, to the recovery of AChE activity either through decarbamylation of PB protected enzyme or by use of an effective oxime. The results against...this protected enzyme in the first few minutes after intoxication and treat- ment provides sufficient enzyme activity to sustain survival.̂ ’"* A

Improving the Catalytic Activity of Hyperthermophilic Pyrococcus horikoshii Prolidase for Detoxification of Organophosphorus Nerve Agents over a Broad Range of Temperatures

DTIC Science & Technology

2011-01-01

affinity for metal, and increased thermostability compared to P. furiosus prolidase, Pf prol (PF1343). To obtain a better enzyme for OP nerve agent...decontamination and to investigate the structural factors that may influence protein thermostability and thermoactivity, randomly mutated Ph1prol enzymes ...Introduction Pyrococcus horikoshii and Pyrococcus furiosus are both hyper- thermophilic archaea, growing optimally at 98 –100◦C that were isolated from a

Subacute Low Dose Nerve Agent Exposure Causes DNA Fragmentation in Guinea Pig Leukocytes

DTIC Science & Technology

2005-10-01

1 SUBACUTE LOW DOSE NERVE AGENT EXPOSURE CAUSES DNA FRAGMENTATION IN GUINEA PIG LEUKOCYTES. Jitendra R. Dave1, John R. Moffett1, Sally M...DNA fragmentation in blood leukocytes from guinea pigs by ‘Comet’ assay after exposure to soman at doses ranging from 0.1LD50 to 0.4 LD50, once per...computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA treated guinea pigs as

High power, electrically tunable quantum cascade lasers

NASA Astrophysics Data System (ADS)

Slivken, Steven; Razeghi, Manijeh

2016-02-01

Mid-infrared laser sources (3-14 μm wavelengths) which have wide spectral coverage and high output power are attractive for many applications. This spectral range contains unique absorption fingerprints of most molecules, including toxins, explosives, and nerve agents. Infrared spectroscopy can also be used to detect important biomarkers, which can be used for medical diagnostics by means of breath analysis. The challenge is to produce a broadband midinfrared source which is small, lightweight, robust, and inexpensive. We are currently investigating monolithic solutions using quantum cascade lasers. A wide gain bandwidth is not sufficient to make an ideal spectroscopy source. Single mode output with rapid tuning is desirable. For dynamic wavelength selection, our group is developing multi-section laser geometries with wide electrical tuning (hundreds of cm-1). These devices are roughly the same size as a traditional quantum cascade lasers, but tuning is accomplished without any external optical components. When combined with suitable amplifiers, these lasers are capable of multi-Watt single mode output powers. This manuscript will describe our current research efforts and the potential for high performance, broadband electrical tuning with the quantum cascade laser.

27 CFR 555.124 - Records maintained by licensed dealers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... following the date of purchase or other acquisition of explosive materials (except as provided in paragraph... identification. (4) Quantity (applicable quantity units, such as pounds of explosives, number of detonators, number of display fireworks, etc.). (5) Description (dynamite (dyn), blasting agents (ba), detonators...

27 CFR 555.122 - Records maintained by licensed importers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... quantity units, such as pounds of explosives, number of detonators, number of display fireworks, etc.). (5) Description (dynamite (dyn), blasting agents (ba), detonators (det), display fireworks (df), etc.) and size... identification. (4) Quantity (applicable quantity units, such as pounds of explosives, number of detonators...

27 CFR 555.124 - Records maintained by licensed dealers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... following the date of purchase or other acquisition of explosive materials (except as provided in paragraph... identification. (4) Quantity (applicable quantity units, such as pounds of explosives, number of detonators, number of display fireworks, etc.). (5) Description (dynamite (dyn), blasting agents (ba), detonators...

27 CFR 555.122 - Records maintained by licensed importers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... quantity units, such as pounds of explosives, number of detonators, number of display fireworks, etc.). (5) Description (dynamite (dyn), blasting agents (ba), detonators (det), display fireworks (df), etc.) and size... identification. (4) Quantity (applicable quantity units, such as pounds of explosives, number of detonators...

A Nerve Clamp Electrode Design for Indirect Stimulation of Skeletal Muscle

DTIC Science & Technology

2010-10-01

neurons. This device enables stimulation of muscle contraction indirectly as opposed to contraction from direct muscle stimulation. The electrode is able...to stimulate indirect muscle contraction when tested on ex vivo preparations from rodent phrenic nerve-hemidiaphragm muscle in similar fashion to...unsuccessful in stimulating indirect muscle contraction . Therefore, this novel electrode is useful for physiological assessment of nerve agents and

[Danger from exploding fireworks and blank firearms].

PubMed

Just, T; Pau, H W; Kaduk, W; Hingst, V

2000-12-01

Explosive amusement and deterrent articles such as New Year's Eve cannons and rockets, toy pistols, and blank guns are not at all harmless items. Their potential dangerousness is often extremely underestimated. Two damaging mechanisms are important: during explosions, high pressures and temperatures develop and a considerable sound pressure level can be measured. If the explosion happens near the human body (intentionally or inadvertently), not only superficial lesions can occur, but also (mainly due to contact shots) serious, deep-seated tissue damage, especially in the head and neck region with its endangered sense organs such as eye and ear, the vessels and nerves supplying the brain, the speech- and voice-forming apparatus, and in particular the face, can be the consequence. Their mutilation can lead to serious and extensive interpersonalchanges. Accidents are published in the relevant otological and forensic medical papers, but nevertheless it seems important to us to point out the dangerousness of these readily available items.

Multiple-Purpose Project, Little Blue River Basin, Little Blue River, Missouri: Longview Lake Operation and Maintenance Manual. Appendix 5. Embankment Criteria and Performance Report

DTIC Science & Technology

1990-11-01

cutoff trench be fractured and removed using a non-explosive demolition agent on a IV on 1H slope. No. 40 Required the additional rock excavation of the...Sniabar limestone in Modification 33 be extended downstream through the cutoff trench using the same non-explosive demolition agent . No. 41 Changed the...O45,913 i!~~C ~ &E~J----------- - -- - r - - - - --- USARMY ENGINEER DISTRICT COPPS OF ENGINEERS KIANSAS CITfY MISSOURI 1 LITTLE BLOE RIVERMISSOJRI R G~ 0

Detoxification of Chemical Warfare Agents Using a Zr6 -Based Metal-Organic Framework/Polymer Mixture.

PubMed

Moon, Su-Young; Proussaloglou, Emmanuel; Peterson, Gregory W; DeCoste, Jared B; Hall, Morgan G; Howarth, Ashlee J; Hupp, Joseph T; Farha, Omar K

2016-10-10

Owing to their high surface area, periodic distribution of metal sites, and water stability, zirconium-based metal-organic frameworks (Zr 6 -MOFs) have shown promising activity for the hydrolysis of nerve agents GD and VX, as well as the simulant, dimethyl 4-nitrophenylphosphate (DMNP), in buffered solutions. A hurdle to using MOFs for this application is the current need for a buffer solution. Here the destruction of the simulant DMNP, as well as the chemical warfare agents (GD and VX) through hydrolysis using a MOF catalyst mixed with a non-volatile, water-insoluble, heterogeneous buffer is reported. The hydrolysis of the simulant and nerve agents in the presence of the heterogeneous buffer was fast and effective. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of anticholinesterase agents on airway epithelial function. Annual report, 15 July 1888-14 August 1989

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marin, M.G.

1989-09-15

Irreversible anticholinesterase compounds have potential serious health effects when employed as chemical warfare agents. Intoxication with these agents will cause an accumulation of acetylcholine at nerve muscle and nerve-gland junctions. Because tracheal glands have rich cholinergic innervation, we hypothesized that exposure to anticholinesterase agents, such as soman, would stimulate glandular secretion. This would cause pathological changes in the important lung defense mechanism of mucociliary clearance. Initial work on this contract revealed a dose-related increase in mucociliary transport in the ferret in response to soman. This effect could be inhibited by atropine but not by pralidoxime. The investigation described in thismore » report relates to the effects of soman and its antidotes on glycoconjugate secretion of ferret trachea in vitro.« less

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghanem, Eman; Raushel, Frank M.

2005-09-01

Organophosphates have been widely used as insecticides and chemical warfare agents. The health risks associated with these agents have necessitated the need for better detoxification and bioremediation tools. Bacterial enzymes capable of hydrolyzing the lethal organophosphate nerve agents are of special interest. Phosphotriesterase (PTE) isolated from the soil bacteria Pseudomonas diminuta displays a significant rate enhancement and substrate promiscuity for the hydrolysis of organophosphate triesters. Directed evolution and rational redesign of the active site of PTE have led to the identification of new variants with enhanced catalytic efficiency and stereoselectivity toward the hydrolysis of organophosphate neurotoxins. PTE has been utilizedmore » to protect against organophosphate poisoning in vivo. Biotechnological applications of PTE for detection and decontamination of insecticides and chemical warfare agents are developing into useful tools. In this review, the catalytic properties and potential applications of this remarkable enzyme are discussed.« less

Effects of anesthetic agents on in vivo axonal HCN current in normal mice.

PubMed

Osaki, Yusuke; Nodera, Hiroyuki; Banzrai, Chimeglkham; Endo, Sachiko; Takayasu, Hirokazu; Mori, Atsuko; Shimatani, Yoshimitsu; Kaji, Ryuji

2015-10-01

The objective was to study the in vivo effects of anesthetic agents on peripheral nerve excitability. Normal male mice were anesthetized by either isoflurane inhalation or a combination of medetomidine, midazolam, and butorphanol intraperitoneal injection ("triple agents"). Immediately after induction, the tail sensory nerve action potential was recorded and its excitability was monitored. Under both anesthetic protocols, there was an interval excitability change by long hyperpolarizing currents. There was greater threshold reduction approximately 30min post induction, in comparison to immediately post induction. Other excitability parameters were stable over time. Modeling suggested interval suppression of internodal H conductance or leak current. Anesthetic agents affected responses to long hyperpolarizing currents. Axonal excitability during intraoperative monitoring may be affected by anesthetic agents. Interpretation of interval excitability changes under anesthesia requires caution, especially with long hyperpolarizing currents. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Managing traumatic brain injury secondary to explosions

PubMed Central

Burgess, Paula; E Sullivent, Ernest; M Sasser, Scott; M Wald, Marlena; Ossmann, Eric; Kapil, Vikas

2010-01-01

Explosions and bombings are the most common deliberate cause of disasters with large numbers of casualties. Despite this fact, disaster medical response training has traditionally focused on the management of injuries following natural disasters and terrorist attacks with biological, chemical, and nuclear agents. The following article is a clinical primer for physicians regarding traumatic brain injury (TBI) caused by explosions and bombings. The history, physics, and treatment of TBI are outlined. PMID:20606794

Chemically-functionalized microcantilevers for detection of chemical, biological and explosive material

DOEpatents

Pinnaduwage, Lal A [Knoxville, TN; Thundat, Thomas G [Knoxville, TN; Brown, Gilbert M [Knoxville, TN; Hawk, John Eric [Olive Branch, MS; Boiadjiev, Vassil I [Knoxville, TN

2007-04-24

A chemically functionalized cantilever system has a cantilever coated on one side thereof with a reagent or biological species which binds to an analyte. The system is of particular value when the analyte is a toxic chemical biological warfare agent or an explosive.

Epidemiologic evidence of health effects from long-distance transit of chemical weapons fallout from bombing early in the 1991 Persian Gulf War.

PubMed

Haley, Robert W; Tuite, James J

2013-01-01

Military intelligence data published in a companion paper explain how chemical fallout from US and Coalition bombing of Iraqi chemical weapons facilities early in the air campaign transited long distance, triggering nerve agent alarms and exposing US troops. We report the findings of a population-based survey designed to test competing hypotheses on the impact on chronic Gulf War illness of nerve agent from early-war bombing versus post-war demolition. The US Military Health Survey performed computer-assisted telephone interviews of a stratified random sample of Gulf War-era veterans (n = 8,020). Early-war exposure was measured by having heard nerve agent alarms and post-war exposure, by the computer-generated plume from the Khamisiyah demolition. Gulf War illness was measured by two widely published case definitions. The OR (95% CI) for the association of alarms with the Factor case definition was 4.13 (95% CI 2.51-6.80) compared with 1.21 (95% CI 0.86-1.69) for the Khamisiyah plume. There was a dose-related trend for the number of alarms (p(trend) < 0.001) but not for the number of days in the Khamisiyah plume (p(trend) = 0.17). Exposure to low-level sarin nerve agent in fallout from bombing early in the air campaign contributed more to chronic illness than post-war demolition. Copyright © 2012 S. Karger AG, Basel.

Reactivation of organophosphate-inhibited human, Cynomolgus monkey, swine and guinea pig acetylcholinesterase by MMB-4: a modified kinetic approach.

PubMed

Worek, Franz; Wille, Timo; Aurbek, Nadine; Eyer, Peter; Thiermann, Horst

2010-12-15

Treatment of poisoning by highly toxic organophosphorus compounds (OP, nerve agents) is a continuous challenge. Standard treatment with atropine and a clinically used oxime, obidoxime or pralidoxime is inadequate against various nerve agents. For ethical reasons testing of oxime efficacy has to be performed in animals. Now, it was tempting to investigate the reactivation kinetics of MMB-4, a candidate oxime to replace pralidoxime, with nerve agent-inhibited acetylcholinesterase (AChE) from human and animal origin in order to provide a kinetic basis for the proper assessment of in vivo data. By applying a modified kinetic approach, allowing the use of necessary high MMB-4 concentrations, it was possible to determine the reactivation constants with sarin-, cyclosarin-, VX-, VR- and tabun-inhibited AChE. MMB-4 exhibited a high reactivity and low affinity towards OP-inhibited AChE, except of tabun-inhibited enzyme where MMB-4 had an extremely low reactivity. Species differences between human and animal AChE were low (Cynomolgus) to moderate (swine, guinea pig). Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Additional studies are necessary to determine the in vivo toxicity, tolerability and pharmacokinetics of MMB-4 in humans in order to enable a proper assessment of the value of this oxime as an antidote against nerve agent poisoning. Copyright © 2010 Elsevier Inc. All rights reserved.

The application of single particle aerosol mass spectrometry for the detection and identification of high explosives and chemical warfare agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Audrey Noreen

2006-01-01

Single Particle Aerosol Mass Spectrometry (SPAMS) was evaluated as a real-time detection technique for single particles of high explosives. Dual-polarity time-of-flight mass spectra were obtained for samples of 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX), and pentaerythritol tetranitrate (PETN); peaks indicative of each compound were identified. Composite explosives, Comp B, Semtex 1A, and Semtex 1H were also analyzed, and peaks due to the explosive components of each sample were present in each spectrum. Mass spectral variability with laser fluence is discussed. The ability of the SPAMS system to identify explosive components in a single complex explosive particle (~1 pg) without the need formore » consumables is demonstrated. SPAMS was also applied to the detection of Chemical Warfare Agent (CWA) simulants in the liquid and vapor phases. Liquid simulants for sarin, cyclosarin, tabun, and VX were analyzed; peaks indicative of each simulant were identified. Vapor phase CWA simulants were adsorbed onto alumina, silica, Zeolite, activated carbon, and metal powders which were directly analyzed using SPAMS. The use of metal powders as adsorbent materials was especially useful in the analysis of triethyl phosphate (TEP), a VX stimulant, which was undetectable using SPAMS in the liquid phase. The capability of SPAMS to detect high explosives and CWA simulants using one set of operational conditions is established.« less

Effect of O-methyl-β-cyclodextrin-modified magnetic nanoparticles on the uptake and extracellular level of l-glutamate in brain nerve terminals.

PubMed

Horák, Daniel; Beneš, Milan; Procházková, Zuzana; Trchová, Miroslava; Borysov, Arsenii; Pastukhov, Artem; Paliienko, Konstantin; Borisova, Tatiana

2017-01-01

Changes in cholesterol concentration in the plasma membrane of presynaptic nerve terminals nonspecifically modulate glutamate transport and homeostasis in the central nervous system. Reduction of the cholesterol content in isolated rat brain nerve terminals (synaptosomes) using cholesterol-depleting agents decreases the glutamate uptake and increases the extracellular level of glutamate in nerve terminals. Extraction of cholesterol from the plasma membrane and its further removal from the synaptosomes by external magnetic field can be achieved by means of magnetic nanoparticles with immobilized cholesterol-depleting agent such as O-methyl-β-cyclodextrin (MCD). A simple approach is developed for preparation of maghemite (γ-Fe 2 O 3 ) nanoparticles containing chemically bonded MCD. The method is based on preparation of a silanization agent containing MCD. It is synthesized by the reaction of triethoxy(3-isocyanatopropyl)silane with MCD. Base-catalyzed silanization of superparamagnetic γ-Fe 2 O 3 provides a relatively stable colloid product containing 48μmol of MCDg -1 . MCD-modified γ-Fe 2 O 3 nanoparticles decrease the initial rate of the uptake and accumulation of l-[ 14 C]glutamate and increase the extracellular l-[ 14 C]glutamate level in the preparation of nerve terminals. The effect of MCD-immobilized nanoparticles is the same as that of MCD solution; moreover, magnetic manipulation of the nanoparticles enables removal of bonded cholesterol. Copyright © 2016 Elsevier B.V. All rights reserved.

Primary screen for potential sheep scab control agents.

PubMed

Dunn, J A; Prickett, J C; Collins, D A; Weaver, R J

2016-07-15

The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole). Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Catalytic degradation of organophosphorous nerve agent simulants by polymer beads@graphene oxide with organophosphorus hydrolase-like activity based on rational design of functional bimetallic nuclear ligand.

PubMed

Ma, Xuejuan; Zhang, Lin; Xia, Mengfan; Zhang, Xiaohong; Zhang, Yaodong

2018-05-15

The degradation of organophosphorous nerve agents is of primary concern due to the severe toxicity of these agents. Based on the active center of organophosphorus hydrolase (OPH), a bimetallic nuclear ligand, (5-vinyl-1,3-phenylene)bis(di(1H-imidazol-2-yl) methanol) (VPIM), was designed and synthesized, which contains four imidazole groups to mimic the four histidines at OPH active center. By grafting VPIM on graphene oxide (GO) surface via polymerization, the VPIM-polymer beads@GO was produced. The obtained OPH mimics has an impressive activity in dephosphorylation reactions (turnover frequency (TOF) towards paraoxon: 2.3 s -1 ). The synergistic catalytic effect of the bimetallic Zn 2+ nuclear center and carboxyl groups on surface of GO possibly contributes to the high hydrolysis on organophosphate substrate. Thus, a biomimetic catalyst for efficient degradation of some organophosphorous nerve agent simulants, such as paraoxon and chlorpyrifos, was prepared by constructing catalytic active sites. The proposed mechanism and general synthetic strategy open new avenues for the engineering of functional GOs for biomimetic catalysts. Copyright © 2018 Elsevier B.V. All rights reserved.

Stable adducts of nerve agents sarin, soman and cyclosarin with TRIS, TES and related buffer compounds--characterization by LC-ESI-MS/MS and NMR and implications for analytical chemistry.

PubMed

Gäb, Jürgen; John, Harald; Melzer, Marco; Blum, Marc-Michael

2010-05-15

Buffering compounds like TRIS are frequently used in chemical, biochemical and biomedical applications to control pH in solution. One of the prerequisites of a buffer compound, in addition to sufficient buffering capacity and pH stability over time, is its non-reactivity with other constituents of the solution. This is especially important in the field of analytical chemistry where analytes are to be determined quantitatively. Investigating the enzymatic hydrolysis of G-type nerve agents sarin, soman and cyclosarin in buffered solution we have identified stable buffer adducts of TRIS, TES and other buffer compounds with the nerve agents. We identified the molecular structure of these adducts as phosphonic diesters using 1D (1)H-(31)P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates with TRIS and TES are fast enough to compete with spontaneous hydrolysis in aqueous solution and to yield substantial amounts (up to 20-40%) of buffer adduct over the course of several hours. A reaction mechanism is proposed in which the amino function of the buffer serves as an intramolecular proton acceptor rendering the buffer hydroxyl groups nucleophilic enough for attack on the phosphorus atom of the agents. Results show that similar buffer adducts are formed with a range of hydroxyl and amino function containing buffers including TES, BES, TRIS, BIS-TRIS, BIS-TRIS propane, Tricine, Bicine, HEPES and triethanol amine. It is recommended to use alternative buffers like MOPS, MES and CHES when working with G-type nerve agents especially at higher concentrations and over prolonged times. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Human Metabolism and Interactions of Deployment-Related Chemicals

DTIC Science & Technology

2008-08-01

metabolic detoxification pathway for permethrin. Other deployment related compounds, an insect repellent (N,N-diethyl-m- toluamide) a nerve gas ...Leo, K. U. 1997. Metabolism of proposed nerve agent pretreatment, pyridostigmine bromine. Walter Reed Army Institute of Research Report No. NTIS/AD...against possible nerve gas attack. It has been reported that chlorpyrifos and DEET are metabo- lized by human P450s (Tang et al., 2001; Usmani et al., 2002

Neural control of renal tubular sodium reabsorption of the dog.

PubMed

DiBona, G F

1978-04-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies demonstrate adrenergic nerve terminals in direct contact with basement membranes of mammalian renal tubular epithelial cells. Low level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. The antinatriuresis is prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney upon renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. Reflex diminutions in renal nerve activity (left atrial distention, stellate ganglion stimulation) produce a decrease in renal tubular sodium reabsorption independent of glomerular filtration rate or renal blood flow. The anatomically described adrenergic innervation of the renal tubules participates in the direct regulation of renal tubular sodium reabsorption.

2010 Department of Defense (DoD) Chemical and Biological Defense Program (CBDP) Portfolio

DTIC Science & Technology

2010-03-01

a new oxime and (2) obtaining approval for use of pyridostigmine bromide , the component of Soman Nerve Agent Pretreatment Pyridostigmine (SNAPP) for...Pralidoxime Chloride Autoinjector N/A 6505-01-125-3248 11704-620-01 N/A DLA 8 Pyridostigmine Bromide Tabs USP 30 mg I.S. (SNAPP) N/A 6505-01-178-7903 N...Soman Nerve Agent Pretreatment Pyridostigmine (SNAPP) N/A 6505-01-483-7162 N/A N/A N/A N/A Vaccines Anthrax Vaccine Adsorbed (AVA) N/A 6505-01-399

Soman Induces Ictogenesis in the Amygdala and Interictal Activity in the Hippocampus That Are Blocked by a GluR5 Kainate Receptor Antagonist In Vitro

DTIC Science & Technology

2009-01-01

to organophosphorus nerve agents in- uces brain seizures, which can cause profound brain dam- ge resulting in death or long-term cognitive deficits...The mygdala and the hippocampus are two of the most seizure- rone brain structures, but their relative contribution to the eneration of seizures after...nerve agent exposure is unclear. ere, we report that application of 1 M soman for 30 min, in at coronal brain slices containing both the hippocampus

Assessing Protection Against OP Pesticides and Nerve Agents Provided by Wild-Type HuPON1 Purified from Trichoplusia ni Larvae or Induced via Adenoviral Infection

DTIC Science & Technology

2013-01-01

times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic...metabolite of the OP pesticide chlorpyrifos . In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then...mice are dramati- cally more susceptible to the toxic metabolites of the OP pesticides diazinon and chlorpyrifos (diazoxon and chlorpyrifos oxon

Presynaptic facilitatory adenosine A2A receptors mediate fade induced by neuromuscular relaxants that exhibit anticholinesterase activity.

PubMed

Bornia, Elaine Cs; Correia-de-Sá, Paulo; Alves-Do-Prado, Wilson

2011-03-01

1. Pancuronium, cisatracurium and vecuronium are antinicotinic agents that, in contrast with d-tubocurarine and hexamethonium, exhibit anticholinesterase activity. Pancuronium-, cisatracurium- and vecuronium-induced fade results from blockade of facilitatory nicotinic receptors on motor nerves, but fade produced by such agents also depends on the presynaptic activation of inhibitory muscarinic M2 receptors by acetylcholine released from motor nerve terminals and activation of inhibitory adenosine A1 receptors by adenosine released from motor nerves and muscles. The participation of presynaptic facilitatory A2A receptors in fade caused by pancuronium, cisatracurium and vecuronium has not yet been investigated. In the present study, we determined the effects of ZM241385, an antagonist of presynaptic facilitatory A2A receptors, on fade produced by these neuromuscular relaxants in the rat phrenic nerve-diaphragm (PND) preparation. 2. The muscles were stimulated indirectly at 75±3Hz to induce a sustained tetanizing muscular contraction. The lowest concentration at which each antinicotinic agent produced fade without modifying initial tetanic tension (presynaptic action) was determined. 3. d-Tubocurarine-induced fade occurred only at 55 nmol/L, a concentration that also reduced maximal tetanic tension (post-synaptic action). At 10 nmol/L, ZM 241385 alone did not produce fade, but it did attenuate pancuronium (0.32 μmol/L)-, cisatracurium (0.32 μmol/L)- and vecuronium (0.36 μmol/L)-induced fade. 4. The fade induced by the 'pure' antinicotinic agents d-tubocurarine (55 nmol/L) and hexamethonium (413 μmol/L) was not altered by 10 nmol/L ZM 241385, indicating that presynaptic adenosine A2A receptors play a significant role in the fade produced by antinicotinic agents when such agents have anticholinesterase activity. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Microcantilever technology for law enforcement and anti-terrorism applications: chemical, biological, and explosive material detection

NASA Astrophysics Data System (ADS)

Adams, J. D.; Rogers, B.; Whitten, R.

2005-05-01

The remarkable sensitivity, compactness, low cost, low power-consumption, scalability, and versatility of microcantilever sensors make this technology among the most promising solutions for detection of chemical and biological agents, as well as explosives. The University of Nevada, Reno, and Nevada Nanotech Systems, Inc (NNTS) are currently developing a microcantilever-based detection system that will measure trace concentrations of explosives, toxic chemicals, and biological agents in air. A baseline sensor unit design that includes the sensor array, electronics, power supply and air handling has been created and preliminary demonstrations of the microcantilever platform have been conducted. The envisioned device would measure about two cubic inches, run on a small watch battery and cost a few hundred dollars. The device could be operated by untrained law enforcement personnel. Microcantilever-based devices could be used to "sniff out" illegal and/or hazardous chemical and biological agents in high traffic public areas, or be packaged as a compact, low-power system used to monitor cargo in shipping containers. Among the best detectors for such applications at present is the dog, an animal which is expensive, requires significant training and can only be made to work for limited time periods. The public is already accustomed to explosives and metal detection systems in airports and other public venues, making the integration of the proposed device into such security protocols straightforward.

Temporary Blindness after Inferior Alveolar Nerve Block.

PubMed

Barodiya, Animesh; Thukral, Rishi; Agrawal, Shaila Mahendra; Rai, Anshul; Singh, Siddharth

2017-03-01

Inferior Alveolar Nerve Block (IANB) anaesthesia is one of the common procedures in dental clinic. This procedure is safe, but complications may still occur. Ocular complications such as diplopia, loss of vision, or ophthalmoplegia are extremely rare. This case report explains an event where due to individual anatomic variation of the sympathetic vasoconstrictor nerve and maxillary and middle meningeal arteries, intravascular administration of anaesthetic agent caused unusual ocular signs and symptoms such as temporary blindness.

78 FR 14120 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Statement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

...--Marking of Plastic Explosives for the Purpose of Detection ACTION: 60-Day notice. The Department of... currently approved collection. (2) Title of the Form/Collection: Statement of Process--Marking of Plastic... information will be used to ensure that plastic explosives contain a detection agent as required by law. (5...

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

PubMed Central

2014-01-01

Background Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Results Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2 × LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Conclusion Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and subsequent long term neurological effects induced by nerve agents. PMID:24708580

[The role of the biological damaging factor in the explosive injury].

PubMed

Popov, V L; Kadochnikov, D S; Minaeva, P V

2015-01-01

This article describes the specific features of the action of the biological damaging factors on the human organism associated with the explosive injury. Both the direct action of the damaging agents contained in the biological weapons and their secondary effects in the form of systemic and local infectious complications of the inflicted wounds are considered. The criteria for the evaluation of the degree of harm to the health of the victims of explosion attributable to the action of the biological damaging factor are proposed.

Functionalized polymer nanofibre membranes for protection from chemical warfare stimulants

NASA Astrophysics Data System (ADS)

Ramaseshan, Ramakrishnan; Sundarrajan, Subramanian; Liu, Yingjun; Barhate, R. S.; Lala, Neeta L.; Ramakrishna, S.

2006-06-01

A catalyst for the detoxification of nerve agents is synthesized from β-cyclodextrin (β-CD) and o-iodosobenzoic acid (IBA). Functionalized polymer nanofibre membranes from PVC polymer are fabricated with β-CD, IBA, a blend of β-CD+IBA, and the synthesized catalyst. These functionalized nanofibres are then tested for the decontamination of paraoxon, a nerve agent stimulant, and it is observed that the stimulant gets hydrolysed. The kinetics of hydrolysis is investigated using UV spectroscopy. The rates of hydrolysis for different organophosphate hydrolyzing agents are compared. The reactivity and amount of adsorption of these catalysts are of higher capacity than the conventionally used activated charcoal. A new design for protective wear is proposed based on the functionalized nanofibre membrane.

Biosensor Based on Self-Assembling Acetylcholinesterase on Carbon Nanotubes for Flow injection/Amperometric Detection of Organophosphate Pesticides and Nerve Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guodong; Lin, Yuehe

A highly sensitive flow-injection amperometric biosensor for organophosphate pesticides and nerve agents based on self-assembly of acetylcholinesterase (AChE) on carbon nanotube (CNT)-modified glassy carbon (GC) electrode is described. AChE is immobilized on the negatively-charged CNT surface by alternatively assembling a cationic polydiallyldimethylammonium chloride (PDDA) layer and an AChE layer. Transmission electron microscopy images confirm the formation of layer-by-layer nanostructures on carboxyl functionalized CNTs. The unique sandwich-like structure (PDDA/AChE/PDDA) on the CNT surface formed by self-assembly provides a favorable microenvironment to keep the bioactivity of AChE and to prevent enzyme molecule leakage. The electrocatalytic activity of CNT leads to a greatlymore » improved electrochemical detection of the enzymatically generated thiocholine product, including a low oxidation overvoltage (+150 mV), higher sensitivity, and stability. The developed PDDA/AChE/PDDA/CNT/GC biosensor integrated into a flow injection system was used to monitor organophosphate pesticides and nerve agents, such as paraoxon. The sensor performance, including inhibition time and regeneration conditions, was optimized with respect to operating conditions. Under the optimal conditions, the biosensor was used to measure as low as 0.4 pM paraoxon with a 6-min inhibition time. The biosensor had excellent operational lifetime stability with no decrease in the activity of enzymes for more than 20 repeated measurements over a 1-week period. The developed biosensor system is an ideal tool for online monitoring of organophosphate pesticides and nerve agents.« less

Pseudocatalytic scavenging of the nerve agent VX with human blood components and the oximes obidoxime and HI-6.

PubMed

Wille, Timo; von der Wellen, Jens; Thiermann, Horst; Worek, Franz

2017-03-01

Despite six decades of extensive research in medical countermeasures against nerve agent poisoning, a broad spectrum acetylcholinesterase (AChE) reactivator is not yet available. One current approach is directed toward synthesizing oximes with high affinity and reactivatability toward butyrylcholinesterase (BChE) in plasma to generate an effective pseudocatalytic scavenger. An interim solution could be the administration of external AChE or BChE from blood products to augment pseudocatalytic scavenging with slower but clinically approved oximes to decrease nerve agent concentrations in the body. We here semiquantitatively investigate the ability of obidoxime and HI-6 to decrease the inhibitory activity of VX with human AChE and BChE from whole blood, erythrocyte membranes, erythrocytes, plasma, clinically available fresh frozen plasma and packed red blood cells. The main findings are that whole blood showed a VX concentration-dependent decrease in inhibitory activity with HI-6 being more potent than obidoxime. Using erythrocytes and erythrocyte membranes again, HI-6 was more potent compared to obidoxime. With freshly prepared plasma, obidoxime and HI-6 showed comparable results for the decrease in VX. The use of the clinically available blood products revealed that packed red blood cells showed similar kinetics as fresh erythrocytes. Fresh frozen plasma resulted in a slower and incomplete decrease in inhibitory plasma compared to freshly prepared plasma. In conclusion, the administration of blood products in combination with available oximes augments pseudocatalytic scavenging and might be useful to decrease the body load of persistent, highly toxic nerve agents.

Antidotes and treatments for chemical warfare/terrorism agents: an evidence-based review.

PubMed

Rodgers, G C; Condurache, C T

2010-09-01

This article reviews the evidence supporting the efficacy of antidotes used or recommended for the potential chemical warfare agents of most concern. Chemical warfare agents considered include cyanide, vesicants, pulmonary irritants such as chlorine and phosgene, and nerve agents. The strength of evidence for most antidotes is weak, highlighting the need for additional research in this area.

VX toxicity in the Göttingen minipig.

PubMed

Langston, Jeffrey L; Myers, Todd M

2016-12-15

The present experiments determined the intramuscular LD 50 of VX in male Göttingen minipigs at two stages of development. In pubertal animals (115 days old), the LD 50 of VX was indeterminate, but approximated 33.3μg/kg. However, in sexually mature animals (152 days old), the LD 50 was estimated to be only 17.4μg/kg. Signs of nerve agent toxicity in the Göttingen minipig were similar to those described for other species, with some notable exceptions (such as urticaria and ejaculation). Latencies to the onset of sustained convulsions were inversely related to the administered dose of VX in both ages of minipigs. Additionally, actigraphy was used to quantify the presence of tremor and convulsions and, in some cases, was useful for precisely estimating time of death. The main finding indicates that in minipigs, as in other species, even relatively small differences in age can substantially alter the toxicity of nerve agents. Additionally, actigraphy can serve as a non-invasive method of characterizing the tremors and convulsions that often accompany nerve agent intoxication. Published by Elsevier Ireland Ltd.

A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions

PubMed Central

Rosenberg, Yvonne J.; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

2015-01-01

Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1–2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product. PMID:26268538

A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions.

PubMed

Rosenberg, Yvonne J; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

2015-08-13

Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product.

An Acetylcholinesterase-Based Chronoamperometric Biosensor for Fast and Reliable Assay of Nerve Agents

PubMed Central

Pohanka, Miroslav; Adam, Vojtech; Kizek, Rene

2013-01-01

The enzyme acetylcholinesterase (AChE) is an important part of cholinergic nervous system, where it stops neurotransmission by hydrolysis of the neurotransmitter acetylcholine. It is sensitive to inhibition by organophosphate and carbamate insecticides, some Alzheimer disease drugs, secondary metabolites such as aflatoxins and nerve agents used in chemical warfare. When immobilized on a sensor (physico-chemical transducer), it can be used for assay of these inhibitors. In the experiments described herein, an AChE- based electrochemical biosensor using screen printed electrode systems was prepared. The biosensor was used for assay of nerve agents such as sarin, soman, tabun and VX. The limits of detection achieved in a measuring protocol lasting ten minutes were 7.41 × 10−12 mol/L for sarin, 6.31 × 10−12 mol/L for soman, 6.17 × 10−11 mol/L for tabun, and 2.19 × 10−11 mol/L for VX, respectively. The assay was reliable, with minor interferences caused by the organic solvents ethanol, methanol, isopropanol and acetonitrile. Isopropanol was chosen as suitable medium for processing lipophilic samples. PMID:23999806

Graphene oxide/MnO2 nanocomposite as destructive adsorbent of nerve-agent simulants in aqueous media

NASA Astrophysics Data System (ADS)

Šťastný, Martin; Tolasz, Jakub; Štengl, Václav; Henych, Jiří; Žižka, David

2017-08-01

Graphene oxide/MnO2 nanocomposite was prepared by thermal hydrolysis of potassium permanganate (KMnO4) and 2-chloroacetamide aqueous solutions with graphene oxide (GO) suspension. The synthesized samples were characterized by specific surface area (BET) and porosity determination (BJH), X-ray Diffraction (XRD) and high-resolution electron microscopes (HRSEM, HRTEM). These nanocomposites were used in an experimental evaluation of their adsorption activity with nerve agent simulants dimethyl methyl phosphonate (DMMP) and triethyl phosphate (TEP) in aqueous media. The nanocomposites exhibited enhanced adsorptive degradation ability compared to pure manganese oxide (MnO2) and GO. The GO amount in the nanocomposites affected their degradation activity substantially. The best adsorption efficiency was observed for samples with moderate GO amount. Three methods were used to observe the mechanism of the nerve-agent simulants deactivation: Gas chromatography with mass spectrometry (GC-MS), High-Performance Liquid Chromatography (HPLC) and in situ Infrared spectroscopy (FTIR). It was shown that the hydrolysis on the surface of prepared nanocomposites yields volatile primary alcohols (methanol and ethanol) as the main hydrolysis products.

Numerical Simulation of Shock-Dispersed Fuel Charges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bell, John B.; Day, Marcus; Beckner, Vincent

Successfully attacking underground storage facilities for chemical and biological (C/B) weapons is an important mission area for the Department of Defense. The fate of a C/B agent during an attack depends critically on the pressure and thermal environment that the agent experiences. The initial environment is determined by the blast wave from an explosive device. The byproducts of the detonation provide a fuel source that burn when mixed with oxidizer (after burning). Additional energy can be released by the ignition of the C/B agent as it mixes with the explosion products and the air in the chamber. Hot plumes ventingmore » material from any openings in the chamber can provide fuel for additional energy release when mixed with additional oxidizer. Assessment of the effectiveness of current explosives as well as the development of new explosive systems requires a detailed understanding of all of these modes of energy release. Using methodologies based on the use of higher-order Godunov schemes combined with Adaptive Mesh Refinement (AMR), implemented in a parallel adaptive framework suited to the massively parallel computer systems provided by the DOD High-Performance Computing Modernization program, we use a suite of programs to develop predictive models for the simulation of the energetics of blast waves, deflagration waves and ejecta plumes. The programs use realistic reaction kinetic and thermodynamic models provided by standard components (such as CHEMKIN) as well as other novel methods to model enhanced explosive devices. The work described here focuses on the validation of these models against a series of bomb calorimetry experiments performed at the Ernst-Mach Institute. In this paper, we present three-dimensional simulations of the experiments, examining the explosion dynamics and the role of subsequent burning on the explosion products on the thermal and pressure environment within the calorimeter. The effects of burning are quantified by comparing two sets of computations, one in which the calorimeter is filled with nitrogen so there is no after burning and a second in which the calorimeter contains air.« less

Smart phones: platform enabling modular, chemical, biological, and explosives sensing

NASA Astrophysics Data System (ADS)

Finch, Amethist S.; Coppock, Matthew; Bickford, Justin R.; Conn, Marvin A.; Proctor, Thomas J.; Stratis-Cullum, Dimitra N.

2013-05-01

Reliable, robust, and portable technologies are needed for the rapid identification and detection of chemical, biological, and explosive (CBE) materials. A key to addressing the persistent threat to U.S. troops in the current war on terror is the rapid detection and identification of the precursor materials used in development of improvised explosive devices, homemade explosives, and bio-warfare agents. However, a universal methodology for detection and prevention of CBE materials in the use of these devices has proven difficult. Herein, we discuss our efforts towards the development of a modular, robust, inexpensive, pervasive, archival, and compact platform (android based smart phone) enabling the rapid detection of these materials.

Bioengineered nerve regeneration and muscle reinnervation

PubMed Central

Kingham, Paul J; Terenghi, Giorgio

2006-01-01

The peripheral nervous system has the intrinsic capacity to regenerate but the reinnervation of muscles is often suboptimal and results in limited recovery of function. Injuries to nerves that innervate complex organs such as the larynx are particularly difficult to treat. The many functions of the larynx have evolved through the intricate neural regulation of highly specialized laryngeal muscles. In this review, we examine the responses of nerves and muscles to injury, focusing on changes in the expression of neurotrophic factors, and highlight differences between the skeletal limb and laryngeal muscle systems. We also describe how artificial nerve conduits have become a useful tool for delivery of neurotrophic factors as therapeutic agents to promote peripheral nerve repair and might eventually be useful in the treatment of laryngeal nerve injury. PMID:17005023

The role of oxidative stress in organophosphate and nerve agent toxicity

PubMed Central

Pearson, Jennifer N.; Patel, Manisha

2016-01-01

Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures. PMID:27371936

A comparison of organophosphate degradation genes and bioremediation applications.

PubMed

Iyer, Rupa; Iken, Brian; Damania, Ashish

2013-12-01

Organophosphates (OPs) form the bulk of pesticides that are currently in use around the world accounting for more than 30% of the world market. They also form the core for many nerve-based warfare agents including sarin and soman. The widespread use and the resultant build-up of OP pesticides and chemical nerve agents has led to the development of major health problems due to their extremely toxic interaction with any biological system that encounters them. Growing concern over the accumulation of OP compounds in our food products, in the soils from which they are harvested and in wastewater run-off has fuelled a growing interest in microbial biotechnology that provides cheap, efficient OP detoxification to supplement expensive chemical methods. In this article, we review the current state of knowledge of OP pesticide and chemical agent degradation and attempt to clarify confusion over identification and nomenclature of two major families of OP-degrading enzymes through a comparison of their structure and function. The isolation, characterization, utilization and manipulation of the major detoxifying enzymes and the molecular basis of degradation of OP pesticides and chemical nerve agents are discussed as well as the achievements and technological advancements made towards the bioremediation of such compounds. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Derivatization of organophosphorus nerve agent degradation products for gas chromatography with ICPMS and TOF-MS detection.

PubMed

Richardson, Douglas D; Caruso, Joseph A

2007-06-01

Separation and detection of seven V-type (venomous) and G-type (German) organophosphorus nerve agent degradation products by gas chromatography with inductively coupled plasma mass spectrometry (GC-ICPMS) is described. The nonvolatile alkyl phosphonic acid degradation products of interest included ethyl methylphosphonic acid (EMPA, VX acid), isopropyl methylphosphonic acid (IMPA, GB acid), ethyl hydrogen dimethylamidophosphate sodium salt (EDPA, GA acid), isobutyl hydrogen methylphosphonate (IBMPA, RVX acid), as well as pinacolyl methylphosphonic acid (PMPA), methylphosphonic acid (MPA), and cyclohexyl methylphosphonic acid (CMPA, GF acid). N-(tert-Butyldimethylsilyl)-N-methyltrifluroacetamide with 1% TBDMSCl was utilized to form the volatile TBDMS derivatives of the nerve agent degradation products for separation by GC. Exact mass confirmation of the formation of six of the TBDMS derivatives was obtained by GC-time of flight mass spectrometry (TOF-MS). The method developed here allowed for the separation and detection of all seven TBDMS derivatives as well as phosphate in less than ten minutes. Detection limits for the developed method were less than 5 pg with retention times and peak area precisions of less than 0.01 and 6%, respectively. This method was successfully applied to river water and soil matrices. To date this is the first work describing the analysis of chemical warfare agent (CWA) degradation products by GC-ICPMS.

Immobilization of Enzymes in Nanoporous Host Materials: A Nanobiotechnological Approach to Decontamination and Demilitarization of Chemical and Biological Warfare Agents

DTIC Science & Technology

2002-05-06

Organophosphorus compounds (OPs) are highly toxic and found extensive use as pesticides , insecticides and potential chemical warfare (CW) agents . Recently...commonly used substrate, the serine protease inhibitor diisopropyl fluorophosphates (DFP), and different fluoride-containing G-type nerve agents such as...

Combining SBR systems for chemical and biological treatment: the destruction of the nerve agent VX.

PubMed

Irvine, R L; Haraburda, S S; Galbis-Reig, C

2004-01-01

The US Army is pilot testing the neutralization of VX nerve agent stockpiled at Newport, Indiana using caustic hydrolysis in a Sequencing Batch Reactor (SBR). The resulting hydrolysate was tested at the bench-scale for treatment with activated sludge biodegradation in two distinct studies, one in the SBR and another, in the PACT process. The feed to both biological systems was pretreated to enhance the biodegradability of the hydrolysis products. Both biodegradation studies demonstrated that the hydrolysate could easily meet the Chemical Weapons Convention treaty and US environmental regulations following pretreatment.

Treatment of great auricular neuralgia with real-time ultrasound-guided great auricular nerve block

PubMed Central

Jeon, Younghoon; Kim, Saeyoung

2017-01-01

Abstract Rationale: The great auricular nerve can be damaged by the neck surgery, tumor, and long-time pressure on the neck. But, great auricular neuralgia is very rare condition. It was managed by several medication and landmark-based great auricular nerve block with poor prognosis. Patient concerns: A 25-year-old man presented with a pain in the left lateral neck and auricle. Diagnosis: He was diagnosed with great auricular neuralgia. Interventions: His pain was not reduced by medication. Therefore, the great auricular nerve block with local anesthetics and steroid was performed under ultrasound guidance. Outcomes: Ultrasound guided great auricular nerve block alleviated great auricular neuralgia. Lessons: This medication-resistant great auricular neuralgia was treated by the ultrasound guided great auricular nerve block with local anesthetic agent and steroid. Therefore, great auricular nerve block can be a good treatment option of medication resistant great auricular neuralgia. PMID:28328811

29 CFR 1910.109 - Explosives and blasting agents.

Code of Federal Regulations, 2011 CFR

2011-07-01

... more magazines, as a group, must be considered as one magazine, and the total quantity of explosives... located in the same building when one is used only for blasting caps in quantities not in excess of 5,000... distance of at least one hundred and fifty (150) feet shall be maintained between class II magazines and...

May the Inferior Petrosal Sinus Recanalization During Endovascular Treatment for Carotid-Cavernous Fistulas Increase the Risk of Sixth Nerve Palsy?

PubMed

Robert, Thomas; Valsecchi, Daniele; Sylvestre, Philippe; Blanc, Raphaël; Ciccio, Gabriele; Smajda, Stanislas; Redjem, Hocine; Piotin, Michel

2018-05-03

Sixth nerve palsy is a common complication of endovascular treatment for carotid-cavernous fistulas (CCF). Two hypotheses are evoked: the spontaneous venous congestion into the cavernous sinus and the direct compression of the nerve by the embolic agent into the cavernous sinus. Nevertheless, the evidence is still uncertain. Knowing the vicinity of the sixth nerve with the inferior petrosal sinus (IPS) in the Dorello canal, we hypothesized that the recanalization of the IPS increased the risk of nerve damage. We analyzed a prospective database of patients treated for CCFs from March 2009 to April 2016. We excluded patients who did not need treatment, cases of high-flow CCF, and patients lost to follow-up, obtaining a homogeneous population of 82 patients with indirect CCFs. This population was divided in 2 groups: patients without new-onset/worsening of sixth nerve palsy and patients with this postprocedural complication. Our main endpoints were the potential differences between patients with or without recanalization of IPS and between those who underwent or not an embolization with Onyx-18. We did not find any statistically meaningful difference between the 2 groups concerning the necessity of IPS recanalization (P > 0.999, odds ratio 0.97, 95% confidence interval 0.32-2.96) or with the use of Onyx-18 as an embolic agent (P = 0.56; odds ratio 1.41, 95% confidence interval 0.41-2.45). The recanalization of a thrombosed IPS does not increase the risk of procedural sixth nerve damage. The initial injury seems to relate with development/worsening of a sixth nerve palsy. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of a microinstillation model of inhalation exposure to assess lung injury following exposure to toxic chemicals and nerve agents in Guinea pigs.

PubMed

Nambiar, Madhusoodana P; Wright, Benjamin S; Rezk, Peter E; Smith, Kelvin B; Gordon, Richard K; Moran, Theodore S; Richards, Shannon M; Sciuto, Alfred M

2006-01-01

Respiratory disturbances due to chemical warfare nerve agents (CWNAs) are the starting point of mass casualty and the primary cause of death by these weapons of terror and mass destruction. However, very few studies have been implemented to assess respiratory toxicity and exacerbation induced by CWNAs, especially methylphosphonothioic acid S-(2-(bis(1-methylethyl)amino)ethyl)O-ethyl ester (VX). In this study, we developed a microinstillation technique of inhalation exposure to assess lung injury following exposure to CWNAs and toxic chemicals. Guinea pigs were gently intubated by placing a microcatheter into the trachea 1.5 to 2.0 cm centrally above the bifurcation. This location is crucial to deliver aerosolized agents uniformly to the lung's lobes. The placement of the tube is calculated by measuring the distance from the upper front teeth to the tracheal bifurcation, which is typically 8.5 cm for guinea pigs of equivalent size and a weight range of 250 g to 300 g. The catheter is capable of withstanding 100 psi pressure; the terminus has five peripheral holes to pump air that aerosolizes the nerve agent that is delivered in the central hole. The microcatheter is regulated by a central control system to deliver the aerosolized agent in a volume lower than the tidal volume of the guinea pigs. The average particle size of the nerve agent delivered was 1.48 +/- 0.07 micrometer. The microinstillation technology has been validated by exposing the animals to Coomassie brilliant blue, which showed a uniform distribution of the dye in different lung lobes. In addition, the concentration of the dye in the lungs correlated with the dose/time of exposure. Furthermore, histopathological analysis confirmed the absence of barotraumas following micoinstillation. This novel technique delivers the agent safely, requires less amount of agent, avoids exposure to skin, pelt, and eye, and circumvents the concern of deposition of the particles in the nasal and palette due to the switching of breathing from nasal to oronasal in whole-body dynamic chamber or nose only exposure. Currently, we are using this inhalation exposure technique to investigate lung injuries and respiratory disturbances following direct exposure to VX.

Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

PubMed

Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

2018-01-01

A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

Detonation Velocity-Diameter Relation in Gelled Explosive with Inert Inclusions

NASA Astrophysics Data System (ADS)

Higgins, Andrew; Loiseau, Jason; Mi, Xiaocheng

2017-06-01

The detonation velocity is measured in a gelled explosive that has been sensitized via the addition of glass microballoons (GMBs) and additionally diluted via the inclusion of large scale (300-700 micron) inert inclusions. The base explosive is nitromethane that has been gelled via the addition of poly(methyl methacrylate) and then sensitized via hot-spot inducing glass microballoons. Inert inclusions (e.g., glass, steel beads) are then added to the explosive to make a heterogeneous explosive with heterogeneities that are at a scale disparate from those of the microballoons. This system has the potential to be a synthetic explosive that can be tuned to have the properties of more complex commercial blasting agents. The velocity-diameter relation is studied using weak confinement (polyvinyl chloride) and time-of-arrival gages. The results are also used to further explore the phenomenon of anomalous scaling between axisymmetric charges (cylinders) and two-dimensional (slab) charges.

Multiphoton Microscopy of Prostate and Periprostatic Neural Tissue: A Promising Imaging Technique for Improving Nerve-Sparing Prostatectomy

PubMed Central

Yadav, Rajiv; Mukherjee, Sushmita; Hermen, Michael; Tan, Gerald; Maxfield, Frederick R.; Webb, Watt W.

2009-01-01

Abstract Background and Purpose Various imaging modalities are under investigation for real-time tissue imaging of periprostatic nerves with the idea of improving the results of nerve-sparing radical prostatectomy. We explored multiphoton microscopy (MPM) for real-time tissue imaging of the prostate and periprostatic neural tissue in a male Sprague-Dawley rat model. The unique advantage of this technique is the acquisition of high-resolution images without necessitating any extrinsic labeling agent and with minimal phototoxic effect on tissue. Materials and Methods The prostate and cavernous nerves were surgically excised from male Sprague-Dawley rats. The imaging was carried out using intrinsic fluorescence and scattering properties of the tissues without any exogenous dye or contrast agent. A custom-built MPM, consisting of an Olympus BX61WI upright frame and a modified MRC 1024 scanhead, was used. A femtosecond pulsed titanium/sapphire laser at 780-nm wavelength was used to excite the tissue; laser power under the objective was modulated via a Pockels cell. Second harmonic generation (SHG) signals were collected at 390 (±35 nm), and broadband autofluorescence was collected at 380 to 530 nm. The images obtained from SHG and from tissue fluorescence were then merged and color coded during postprocessing for better appreciation of details. The corresponding tissues were subjected to hematoxylin and eosin staining for histologic confirmation of the structures. Results High-resolution images of the prostate capsule, underlying acini, and individual cells outlining the glands were obtained at varying magnifications. MPM images of adipose tissue and the neural tissues were also obtained. Histologic confirmation and correlation of the prostate gland, fat, cavernous nerve, and major pelvic ganglion validated the findings of MPM. Conclusion Real-time imaging and microscopic resolution of prostate and periprostatic neural tissue using MPM is feasible without the need for any extrinsic labeling agents. Integration of this imaging modality with operative technique has the potential to improve the precision of nerve-sparing prostatectomy. PMID:19425823

International Symposium on Special Topics in Chemical Propulsion (8th): Advancements in Energetic Materials and Chemical Propulsion Held in Cape Town, South Africa on 2-6 November 2009

DTIC Science & Technology

2009-11-06

Hydrogen azide is well-known as an endothermic explosion gas for a long time, but there is a lack of understanding about the detailed kinetics of its...Martin, K.K. Kuo, R. Houim, and M. Degges Lidar Detection of Explosives Vapors Using Excimer Laser (Log #127) S. Bobrovnikov, E. Gorlov, G...Agents for High Energy Propellants (Log #190) B.M. Kosowski, J. Consaga, and A. Condo Formulation & Development of an Explosive that Allows

Nanoparticle-Based Electrochemical Immunosensor for the Detection of Phosphorylated Acetylcholinesterase: An Exposure Biomarker of Organophosphate Pesticides and Nerve AgentsOrganophosphate Pesticides and Nerve Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guodong; Wang, Jun; Barry, Richard C.

A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE) adducts, which is a potential exposure biomarker for organophosphate pesticides (OP) and chemical warfare nerve agent exposures. Zirconia nanoparticles (ZrO2 NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to track the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO2 NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemicalmore » stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as a model OP insecticide to prepare the phosphorylated AChE adduct to demonstrate the proof of principle for this sensor technology. The paraoxon-AChE adduct was characterized by Fourier Transform Infrared Spectrum, and the binding affinity of anti-AChE to the paraoxon-AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO2 NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM paraoxon-AChE, and the limit of detection is estimated to be 8 pM. This new nanoparticle-based electrochemical immunosensor thus provides a sensitive and quantitative tool for biomonitoring exposure to OP pesticides and nerve agents.« less

A High-Throughput UHPLC-MS/MS Method for the Quantification of Five Aged Butyrylcholinesterase Biomarkers from Human Exposure to Organophosphorus Nerve Agents

PubMed Central

Graham, Leigh Ann; Johnson, Darryl; Carter, Melissa D.; Stout, Emily G.; Erol, Huseyin A.; Isenberg, Samantha L.; Mathews, Thomas P.; Thomas, Jerry D.; Johnson, Rudolph C.

2017-01-01

Organophosphorus nerve agents (OPNAs) are toxic compounds that are classified as prohibited Schedule 1 chemical weapons. In the body, OPNAs bind to butyrylcholinesterase (BChE) to form nerve agent adducts (OPNA-BChE). OPNA-BChE adducts can provide a reliable, long-term protein biomarker for assessing human exposure. A major challenge facing OPNA-BChE detection is hydrolysis (aging), which can continue to occur after a clinical specimen has been collected. During aging, the o-alkyl phosphoester bond hydrolyzes, and the specific identity of the nerve agent is lost. To better identify OPNA exposure events, a high throughput method for the detection of five aged OPNA-BChE adducts was developed. This is the first diagnostic panel to allow for the simultaneous quantification of any Chemical Weapons Convention Schedule 1 OPNA by measuring the aged adducts methyl phosphonate (MeP-BChE), ethyl phosphonate (EtP-BChE), propyl phosphonate (PrP-BChE), ethyl phosphoryl (ExP-BChE), phosphoryl (P-BChE), and unadducted BChE. The calibration range for all analytes is 2.00 – 250. ng/mL, which is consistent with similar methodologies used to detect unaged OPNA-BChE adducts. Each analytical run is three minutes making the time to first unknown results, including calibration curve and quality controls, less than one hour. Analysis of commercially purchased individual serum samples demonstrated no potential interferences with detection of aged OPNA-BChE adducts, and quantitative measurements of endogenous levels of BChE were similar to those previously reported in other OPNA-BChE adduct assays. PMID:27572107

Ion spectrometric detection technologies for ultra-traces of explosives: a review.

PubMed

Mäkinen, Marko; Nousiainen, Marjaana; Sillanpää, Mika

2011-01-01

In recent years, explosive materials have been widely employed for various military applications and civilian conflicts; their use for hostile purposes has increased considerably. The detection of different kind of explosive agents has become crucially important for protection of human lives, infrastructures, and properties. Moreover, both the environmental aspects such as the risk of soil and water contamination and health risks related to the release of explosive particles need to be taken into account. For these reasons, there is a growing need to develop analyzing methods which are faster and more sensitive for detecting explosives. The detection techniques of the explosive materials should ideally serve fast real-time analysis in high accuracy and resolution from a minimal quantity of explosive without involving complicated sample preparation. The performance of the in-field analysis of extremely hazardous material has to be user-friendly and safe for operators. The two closely related ion spectrometric methods used in explosive analyses include mass spectrometry (MS) and ion mobility spectrometry (IMS). The four requirements-speed, selectivity, sensitivity, and sampling-are fulfilled with both of these methods. Copyright © 2011 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burrows, T.A.; Thoma, P.J.

Two types of ion-mobility detectors were evaluated in both laboratory and field tests. Laboratory test results show that these detectors are highly sensitive to dynamite and pistol powder and have good false-alarm agent rejection. Field tests of these two detectors revealed that they would detect dynamite and Ball-C-Propellent in free air. However, neither of the ion-mobility detectors would detect these explosives if the explosives were concealed.

Comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koplovitz, I.; Stewart, J.R.

1994-12-31

This study compared the efficacy of H16 and 2-PAM against nerve agent (soman tabun sarin and VX) -induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted ofoxime (l00umol/lkg) + atropine 13 mg(kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 35 timesmore » more effective than 2-PAM. In contrast 1116 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + H16 alone. Both oximes were highly effective against satin and VX. These findings suggest that Hifi could replace 2-PAM as therapy for nerve agent poisoning because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.« less

Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

PubMed Central

Munro, N B; Watson, A P; Ambrose, K R; Griffin, G D

1990-01-01

Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers. PMID:2088748

Preliminary assessment of the health and environmental impacts of transporting M55 rockets from Lexington-Blue Grass Depot activity, Anniston Army depot, and Umatilla depot activity to alternative disposal facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnes, S.A.; Breck, J.E.; Copenhaver, E.D.

1986-03-01

This assessment discusses the potential health and environmental impacts of transporting M55 rockets filled with nerve agent GB or VX from various existing Army storage depots to alternative Army depots for disposal. The origin depots include Anniston Army Depot in Alabama, Lexington-Blue Grass Depot Activity in Kentucky, and Umatilla Depot Activity in Oregon. The destination depots include Pine Bluff Arsenal in Arkansas, Tooele Army Depot in Utah, and the facility on Johnston Island in the central Pacific Ocean. This assessment considers the possible impacts of normal transport operations and of two postulated accident scenarios on the air quality, ground andmore » surface water, aquatic ecology, terrestrial ecology, human health, and cultural and socioeconomic resources of the various transport corridors involved. The impacts of these scenarios are assessed for truck, train, and air transport for each orgin-destination pair. The analysis considers three basic scenario during transport: (1) normal operations with no atmospheric release of nerve agent; (2) a minor agent spill (the contents of one rocket being released to the biosphere); and (3) a worst-case accident involving the release of a large, specified quantity of nerve agent to the biosphere. The extremely low probabilities of such accidents, which are reported elsewhere, are noted.« less

Absorption of the nerve agent VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methyl phosphonothioate) through pig, human and guinea pig skin in vitro.

PubMed

Dalton, Christopher H; Hattersley, Ian J; Rutter, Stephen J; Chilcott, Robert P

2006-12-01

The physico-chemical properties of VX make the skin the most likely route of absorption into the human body. The development of effective medical countermeasures against such percutaneous threat agents relies on the use of appropriate animal models, as the inherent toxicity of nerve agents precludes the use of human volunteers. Previous studies have characterised the mechanism of nerve agent toxicity in rodent models, however, it is generally accepted that one of the most appropriate animal models for human skin absorption is the domestic pig. The purpose of the present study was to measure and compare the skin absorption kinetics of VX in vitro using pig, human and guinea pig skin to highlight any potential species differences in skin permeability. When undiluted VX was applied directly to the skin, the permeability of guinea pig skin was approximately 7-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. When VX diluted with isopropyl alcohol was applied to the skin, the permeability of guinea pig skin was approximately 4-fold greater than human skin. There was no significant difference in the permeability of pig and human skin. From this data it may be inferred that dermatomed, abdominal pig skin is an appropriate model for the human skin absorption of VX.

Explosion suppression system

DOEpatents

Sapko, Michael J.; Cortese, Robert A.

1992-01-01

An explosion suppression system and triggering apparatus therefor are provided for quenching gas and dust explosions. An electrically actuated suppression mechanism which dispenses an extinguishing agent into the path ahead of the propagating flame is actuated by a triggering device which is light powered. This triggering device is located upstream of the propagating flame and converts light from the flame to an electrical actuation signal. A pressure arming device electrically connects the triggering device to the suppression device only when the explosion is sensed by a further characteristic thereof beside the flame such as the pioneer pressure wave. The light powered triggering device includes a solar panel which is disposed in the path of the explosion and oriented between horizontally downward and vertical. Testing mechanisms are also preferably provided to test the operation of the solar panel and detonator as well as the pressure arming mechanism.

Nitrotyrosine localization to dermal nerves in borderline leprosy.

PubMed

Schön, T; Hernández-Pando, R; Baquera-Heredia, J; Negesse, Y; Becerril-Villanueva, L E; Eon-Contreras, J C L; Sundqvist, T; Britton, S

2004-03-01

Nerve damage is a common and disabling feature of leprosy, with unclear aetiology. It has been reported that the peroxidizing agents of myelin lipids-nitric oxide (NO) and peroxynitrite-are produced in leprosy skin lesions. To investigate the localization of nitrotyrosine (NT)-a local end-product of peroxynitrite-in leprosy lesions where dermal nerves are affected by a granulomatous reaction. We investigated by immunohistochemistry and immunoelectron microscopy the localization of the inducible NO synthase (iNOS) and NT in biopsies exhibiting dermal nerves from patients with untreated leprosy. There were abundant NT-positive and iNOS-positive macrophages in the borderline leprosy granulomas infiltrating peripheral nerves identified by light microscopy, S-100 and neurofilament immunostaining. Immunoelectron microscopy showed NT reactivity in neurofilament aggregates and in the cell wall of Mycobacterium leprae. Our results suggest that NO and peroxynitrite could be involved in the nerve damage following borderline leprosy.

Synthesis, Characterization, and Multimillion-Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat

DTIC Science & Technology

2013-04-01

DTRA-TR-13-23 Synthesis, Characterization, and Multimillion -Atom Simulation of Halogen-Based Energetic Materials for Agent Defeat Approved for...reagents for the destruction of biologically active materials and a simulation of their reactions on a multimillion atom scale with quantum...explosives for destruction of chemical & biological agents. Multimillion -atom molecular dynamics simulations with quantum mechanical accuracy were

Ion mobility spectrometric analysis of vaporous chemical warfare agents by the instrument with corona discharge ionization ammonia dopant ambient temperature operation.

PubMed

Satoh, Takafumi; Kishi, Shintaro; Nagashima, Hisayuki; Tachikawa, Masumi; Kanamori-Kataoka, Mieko; Nakagawa, Takao; Kitagawa, Nobuyoshi; Tokita, Kenichi; Yamamoto, Soichiro; Seto, Yasuo

2015-03-20

The ion mobility behavior of nineteen chemical warfare agents (7 nerve gases, 5 blister agents, 2 lachrymators, 2 blood agents, 3 choking agents) and related compounds including simulants (8 agents) and organic solvents (39) was comparably investigated by the ion mobility spectrometry instrument utilizing weak electric field linear drift tube with corona discharge ionization, ammonia doping, purified inner air drift flow circulation operated at ambient temperature and pressure. Three alkyl methylphosphonofluoridates, tabun, and four organophosphorus simulants gave the intense characteristic positive monomer-derived ion peaks and small dimer-derived ion peaks, and the later ion peaks were increased with the vapor concentrations. VX, RVX and tabun gave both characteristic positive monomer-derived ions and degradation product ions. Nitrogen mustards gave the intense characteristic positive ion peaks, and in addition distinctive negative ion peak appeared from HN3. Mustard gas, lewisite 1, o-chlorobenzylidenemalononitrile and 2-mercaptoethanol gave the characteristic negative ion peaks. Methylphosphonyl difluoride, 2-chloroacetophenone and 1,4-thioxane gave the characteristic ion peaks both in the positive and negative ion mode. 2-Chloroethylethylsulfide and allylisothiocyanate gave weak ion peaks. The marker ion peaks derived from two blood agents and three choking agents were very close to the reactant ion peak in negative ion mode and the respective reduced ion mobility was fluctuated. The reduced ion mobility of the CWA monomer-derived peaks were positively correlated with molecular masses among structurally similar agents such as G-type nerve gases and organophosphorus simulants; V-type nerve gases and nitrogen mustards. The slope values of the calibration plots of the peak heights of the characteristic marker ions versus the vapor concentrations are related to the detection sensitivity, and within chemical warfare agents examined the slope values for sarin, soman, tabun and nitrogen mustards were higher. Some CWA simulants and organic solvents gave the ion peaks eluting at the similar positions of the CWAs, resulting in false positive alarms. Copyright © 2015 Elsevier B.V. All rights reserved.

Hand-Held Devices Detect Explosives and Chemical Agents

NASA Technical Reports Server (NTRS)

2010-01-01

Ion Applications Inc., of West Palm Beach, Florida, partnered with Ames Research Center through Small Business Innovation Research (SBIR) agreements to develop a miniature version ion mobility spectrometer (IMS). While NASA was interested in the instrument for detecting chemicals during exploration of distant planets, moons, and comets, the company has incorporated the technology into a commercial hand-held IMS device for use by the military and other public safety organizations. Capable of detecting and identifying molecules with part-per-billion sensitivity, the technology now provides soldiers with portable explosives and chemical warfare agent detection. The device is also being adapted for detecting drugs and is employed in industrial processes such as semiconductor manufacturing.

High energy chemical laser system

DOEpatents

Gregg, D.W.; Pearson, R.K.

1975-12-23

A high energy chemical laser system is described wherein explosive gaseous mixtures of a reducing agent providing hydrogen isotopes and interhalogen compounds are uniformly ignited by means of an electrical discharge, flash- photolysis or an electron beam. The resulting chemical explosion pumps a lasing chemical species, hydrogen fluoride or deuterium fluoride which is formed in the chemical reaction. The generated lasing pulse has light frequencies in the 3- micron range. Suitable interhalogen compounds include bromine trifluoride (BrF$sub 3$), bromine pentafluoride (BrF$sub 5$), chlorine monofluoride (ClF), chlorine trifluoride (ClF$sub 3$), chlorine pentafluoride (ClF$sub 5$), iodine pentafluoride (IF$sub 5$), and iodine heptafluoride (IF$sub 7$); and suitable reducing agents include hydrogen (H$sub 2$), hydrocarbons such as methane (CH$sub 4$), deuterium (D$sub 2$), and diborane (B$sub 2$H$sub 6$), as well as combinations of the gaseous compound and/or molecular mixtures of the reducing agent.

[Pay attention to the secondary optic neuropathy and the safe appropriate applications of optic neuroprotection].

PubMed

Zhong, Y

2016-12-11

Secondary optic neuropathy of optic nerve abnormalities is the leading cause of persistent visual impairment. Previous ocular neuroprotection studies have proved that the nerve growth factor and other agents are of significant in the preservation of optic nerve axon and retinal ganglion cells. However, finding novel safe and effective approach as well as the appropriate applications of optic neuroprotection should be highly emphasized and would be very helpful in the treatment of optic neuropathy. (Chin J Ophthalmol, 2016, 52: 881 - 884) .

Efficacy of ketamine hydrochloride administered as a basilar sesamoid nerve block in alleviating foot pain in horses caused by natural disease.

PubMed

Schumacher, J; DeGraves, F; Cesar, F; Duran, S

2014-09-01

A local anaesthetic agent capable of temporarily resolving lameness after being administered perineurally would be helpful because rapid return of lameness would allow for other analgesic techniques to be performed within a short period of time. To determine if a 3% solution of ketamine hydrochloride (HCl), administered around the palmar nerves at the level of the base of the proximal sesamoid bones, can improve naturally occurring lameness that can be improved or abolished with a basilar sesamoid nerve block performed using lidocaine HCl and to compare the change in gait produced using lidocaine to the change in gait produced using ketamine by using objective lameness assessment. Experimental trial using research horses with naturally occurring lameness. Seven horses, chronically lame on a thoracic limb, were chosen for the study. A wireless, inertial, sensor-based, motion analysis system was used to evaluate lameness before and after administration of 2% lidocaine and later, before and after administration of 3% ketamine over the palmar digital nerves at the base of the proximal sesamoid bones (a basilar sesamoid nerve block) at 5 min intervals for 30 min. Lameness scores obtained before and after administration of lidocaine and ketamine HCl were compared using repeated measures analysis. Gait significantly improved after basilar sesamoid nerve blocks using 2% lidocaine, but gait did not significantly improve after performing the same nerve block using 3% ketamine HCl. Ketamine (3%) administered perineurally for regional anaesthesia of the digit does not desensitise the digit to the same extent as does lidocaine and thus 3% ketamine appears to have no value as a local anaesthetic agent for diagnostic regional anaesthesia. © 2013 EVJ Ltd.

75 FR 56489 - Separation Distances of Ammonium Nitrate and Blasting Agents From Explosives or Blasting Agents...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... combustible, organic material calculated as carbon, or (3) ammonium nitrate-based fertilizers containing... that passes the insensitivity test prescribed in the definition of ammonium nitrate fertilizer issued by the Fertilizer Institute'' in its ``Definition and Test Procedures for Ammonium Nitrate Fertilizer...

49 CFR 173.2 - Hazardous materials classes and index to hazard class definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Explosives (with no significant blast hazard) 173.50 1 1.5 Very insensitive explosives; blasting agents 173.50 1 1.6 Extremely insensitive detonating substances 173.50 2 2.1 Flammable gas 173.115 2 2.2 Non-flammable compressed gas 173.115 2 2.3 Poisonous gas 173.115 3 Flammable and combustible liquid 173.120 4 4...

Estimated Chemical Warfare Agent Surface Clearance Goals for Remediation Pre-Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dolislager, Frederick; Bansleben, Dr. Donald; Watson, Annetta Paule

2010-01-01

Health-based surface clearance goals, in units of mg/cm2, have been developed for the persistent chemical warfare agents sulfur mustard (HD) and nerve agent VX as well as their principal degradation products. Selection of model parameters and critical receptor (toddler child) allow calculation of surface residue estimates protective for the toddler child, the general population and adult employees of a facilty that has undergone chemical warfare agent attack.

Chemical warfare agents.

PubMed

Kuca, Kamil; Pohanka, Miroslav

2010-01-01

Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

Free-surface microfluidics for detection of airborne explosives

NASA Astrophysics Data System (ADS)

Meinhart, Carl; Piorek, Brian; Banerjee, Sanjoy; Lee, Seung Joon; Moskovits, Martin

2008-11-01

A novel microfluidic, remote-sensing, chemical detection platform has been developed for real-time sensing of airborne agents. The key enabling technology is a newly developed concept termed Free-Surface Fluidics (FSF), where one or more fluidic surfaces of a microchannel flow are confined by surface tension and exposed to the surrounding atmosphere. The result is a unique open channel flow environment that is driven by pressure through surface tension, and not subject to body forces, such as gravity. Evaporation and flow rates are controlled by microchannel geometry, surface chemistry and precisely-controlled temperature profiles. The free-surface fluidic architecture is combined with Surface-Enhanced Raman Spectroscopy (SERS) to allow for real-time profiling of atmospheric species and detection of airborne agents. The aggregation of SERS nanoparticles is controlled using microfluidics, to obtain dimer nanoparticle clusters at known streamwise positions in the microchannel. These dimers form SERS hot-spots, which amplify the Raman signal by 8 -- 10 orders of magnitude. Results indicate that explosive agents such as DNT, TNT, RDX, TATP and picric acid in the surrounding atmosphere can be readily detected by the SERS system. Due to the amplification of the SERS system, explosive molecules with concentrations of parts per trillion can be detected, even in the presence of interferent molecules having six orders of magnitude higher concentration.

Computing the stresses and deformations of the human eye components due to a high explosive detonation using fluid-structure interaction model.

PubMed

Karimi, Alireza; Razaghi, Reza; Navidbakhsh, Mahdi; Sera, Toshihiro; Kudo, Susumu

2016-05-01

In spite the fact that a very small human body surface area is comprised by the eye, its wounds due to detonation have recently been dramatically amplified. Although many efforts have been devoted to measure injury of the globe, there is still a lack of knowledge on the injury mechanism due to Primary Blast Wave (PBW). The goal of this study was to determine the stresses and deformations of the human eye components, including the cornea, aqueous, iris, ciliary body, lens, vitreous, retina, sclera, optic nerve, and muscles, attributed to PBW induced by trinitrotoluene (TNT) explosion via a Lagrangian-Eulerian computational coupling model. Magnetic Resonance Imaging (MRI) was employed to establish a Finite Element (FE) model of the human eye according to a normal human eye. The solid components of the eye were modelled as Lagrangian mesh, while an explosive TNT, air domain, and aqueous were modelled using Arbitrary Lagrangian-Eulerian (ALE) mesh. Nonlinear dynamic FE simulations were accomplished using the explicit FE code, namely LS-DYNA. In order to simulate the blast wave generation, propagation, and interaction with the eye, the ALE formulation with Jones-Wilkins-Lee (JWL) equation defining the explosive material were employed. The results revealed a peak stress of 135.70kPa brought about by detonation upsurge on the cornea at the distance of 25cm. The highest von Mises stresses were observed on the sclera (267.3kPa), whereas the lowest one was seen on the vitreous body (0.002kPa). The results also showed a relatively high resultant displacement for the macula as well as a high variation for the radius of curvature for the cornea and lens, which can result in both macular holes, optic nerve damage and, consequently, vision loss. These results may have implications not only for understanding the value of stresses and strains in the human eye components but also giving an outlook about the process of PBW triggers damage to the eye. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distributed optimization system and method

DOEpatents

Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

2003-06-10

A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

Distributed Optimization System

DOEpatents

Hurtado, John E.; Dohrmann, Clark R.; Robinett, III, Rush D.

2004-11-30

A search system and method for controlling multiple agents to optimize an objective using distributed sensing and cooperative control. The search agent can be one or more physical agents, such as a robot, and can be software agents for searching cyberspace. The objective can be: chemical sources, temperature sources, radiation sources, light sources, evaders, trespassers, explosive sources, time dependent sources, time independent sources, function surfaces, maximization points, minimization points, and optimal control of a system such as a communication system, an economy, a crane, and a multi-processor computer.

[Effects of nootropic agents on visual functions and lacrimal antioxidative activity in patients with primary open-angle glaucoma].

PubMed

Davydova, N G; Kuznetsova, T P; Borisova, S A; Abdulkadyrova, M Zh

2006-01-01

The paper presents the results of an investigation of the effect of the nootropic agents pantogam and nooclerine on visual functions in patients with primary open-angle glaucoma. These agents have been found to have a beneficial effect on the functional activity of the retina and optic nerve, light sensitivity, hemo- and hydrodynamics of the eye.

Portable Analytical Systems for On-Site Diagnosis of Exposure to Pesticides and Nerve Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yuehe; Wang, Jun; Liu, Guodong

In this chapter, we summarize recent work in our laboratory on the development of sensitive portable analytical systems for use in on-site detection of exposure to organophosphate (OP) pesticides and chemical nerve agents. These systems are based on various nanomaterials functioning as transducers; recognition agents or labels and various elelectrochemical/immunoassay techniques. The studied nanomaterials included functionalized carbon nanotubes (CNT), zirconia nanoparticles (NPs) and quantum dots (QDs). Three biomarkers e.g. the free OPs, metabolites of OPs and protein-OP adducts in biological matrices have been employed for biomonitoring of OP exposure with our developed system. It has been found that the nanomaterial-basedmore » portable analytical systems have high sensitivity for the detection of the biomarkers, which suggest that these technologies offer great promise for the rapid and on-site detection and evaluation of OP exposure.« less

A review of Explosives Used in Explosive Excavation Research Laboratory Projects Since 1969

DTIC Science & Technology

1974-12-01

Boron compounds Potassium dichramat« Antimony compounds Bismuth compounds P«riodat«s Litharge Guar gum (polysaccSarid«) Storch Acrylomid... gum , and gelled with a cross- linking agent. The i-arliest slurries used Government surplus TNT as a fuel-sensitizer, but the majority o...Nonexplosive TNT PETN RDX Rentalite Composition B Guanidine nitrate Smokeless powder Nitres*: ch Alky’amine nitrates Nit.omannite Aluminum Sugar

DOD Ammunition and Explosives Safety Standards

DTIC Science & Technology

2008-02-29

8. The equivalent explosive weight of the hybrid rocket system N2O4 liquid oxidizer combined with PBAN solid fuel was evaluated as 15 percent for an...separate isolated system and fitting types to preclude intermixing, and the energetic liquids are of required purity. Otherwise, equivalent...Water outlets in a toxic chemical agent operational facility shall be fitted with backflow devices. C11.8.2.7. Dedicated liquid waste systems

Heme-Containing Metal-Organic Frameworks for the Oxidative Degradation of Chemical Warfare Agents

DTIC Science & Technology

2016-04-14

stability of the oxo without sacrificing its inherent reactivity, we have synthesized a new framework featuring fluorinated groups in the ortho...especially suitable for the degradation of electrophilic phosphorous center, leading to the cleavage of P-S or P-O bond present in VX nerve agents

Detection of vapor-phase organophosphate threats using wearable conformable integrated epidermal and textile wireless biosensor systems.

PubMed

Mishra, Rupesh K; Martín, Aida; Nakagawa, Tatsuo; Barfidokht, Abbas; Lu, Xialong; Sempionatto, Juliane R; Lyu, Kay Mengjia; Karajic, Aleksandar; Musameh, Mustafa M; Kyratzis, Ilias L; Wang, Joseph

2018-03-15

Flexible epidermal tattoo and textile-based electrochemical biosensors have been developed for vapor-phase detection of organophosphorus (OP) nerve agents. These new wearable sensors, based on stretchable organophosphorus hydrolase (OPH) enzyme electrodes, are coupled with a fully integrated conformal flexible electronic interface that offers rapid and selective square-wave voltammetric detection of OP vapor threats and wireless data transmission to a mobile device. The epidermal tattoo and textile sensors display a good reproducibility (with RSD of 2.5% and 4.2%, respectively), along with good discrimination against potential interferences and linearity over the 90-300mg/L range, with a sensitivity of 10.7µA∙cm 3 ∙mg -1 (R 2 = 0.983) and detection limit of 12mg/L in terms of OP air density. Stress-enduring inks, used for printing the electrode transducers, ensure resilience against mechanical deformations associated with textile and skin-based on-body sensing operations. Theoretical simulations are used to estimate the OP air density over the sensor surface. These fully integrated wearable wireless tattoo and textile-based nerve-agent vapor biosensor systems offer considerable promise for rapid warning regarding personal exposure to OP nerve-agent vapors in variety of decentralized security applications. Copyright © 2017 Elsevier B.V. All rights reserved.

(-)-Phenserine Attenuates Soman-Induced Neuropathology

PubMed Central

Chen, Jun; Pan, Hongna; Chen, Cynthia; Wu, Wei; Iskandar, Kevin; He, Jeffrey; Piermartiri, Tetsade; Jacobowitz, David M.; Yu, Qian-Sheng; McDonough, John H.; Greig, Nigel H.; Marini, Ann M.

2014-01-01

Organophosphorus (OP) nerve agents are deadly chemical weapons that pose an alarming threat to military and civilian populations. The irreversible inhibition of the critical cholinergic degradative enzyme acetylcholinesterase (AChE) by OP nerve agents leads to cholinergic crisis. Resulting excessive synaptic acetylcholine levels leads to status epilepticus that, in turn, results in brain damage. Current countermeasures are only modestly effective in protecting against OP-induced brain damage, supporting interest for evaluation of new ones. (-)-Phenserine is a reversible AChE inhibitor possessing neuroprotective and amyloid precursor protein lowering actions that reached Phase III clinical trials for Alzheimer's Disease where it exhibited a wide safety margin. This compound preferentially enters the CNS and has potential to impede soman binding to the active site of AChE to, thereby, serve in a protective capacity. Herein, we demonstrate that (-)-phenserine protects neurons against soman-induced neuronal cell death in rats when administered either as a pretreatment or post-treatment paradigm, improves motoric movement in soman-exposed animals and reduces mortality when given as a pretreatment. Gene expression analysis, undertaken to elucidate mechanism, showed that (-)-phenserine pretreatment increased select neuroprotective genes and reversed a Homer1expression elevation induced by soman exposure. These studies suggest that (-)-phenserine warrants further evaluation as an OP nerve agent protective strategy. PMID:24955574

Chiral separation of G-type chemical warfare nerve agents via analytical supercritical fluid chromatography.

PubMed

Kasten, Shane A; Zulli, Steven; Jones, Jonathan L; Dephillipo, Thomas; Cerasoli, Douglas M

2014-12-01

Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G-type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical-scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(-) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(-) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc.

Quantification of nerve agent VX-butyrylcholinesterase adduct biomarker from an accidental exposure.

PubMed

Solano, Maria I; Thomas, Jerry D; Taylor, James T; McGuire, Jeffrey M; Jakubowski, Edward M; Thomson, Sandra A; Maggio, Vincent L; Holland, Kerry E; Smith, J Richard; Capacio, Benedict; Woolfitt, Adrian R; Ashley, David L; Barr, John R

2008-01-01

The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80 nM, it can be calculated that inhibition levels of >or= 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.

An explosion in the mouth caused by a firework.

PubMed

Di Benedetto, Giovanni; Grassetti, Luca; Forlini, William; Bertani, Aldo

2009-06-01

Explosion and gunshot mouth injuries represent a challenging problem with regard to restoring optimal oral function. These wounds exhibit a spectrum of complexity and mostly include extensive soft tissue trauma complicated by burns, foreign bodies, fractures and concomitant traumas. To gain maximal restoration of oral function, the use of reconstructive techniques, together with microsurgical techniques, such as grafting of nerves, vessels and soft tissue, as an acute free flap to cover a large defect, are immediately necessary. We report the case of a young Caucasian patient who destroyed the middle and lower thirds of the face when a firecracker blasted in his mouth. His clinical history is unusual in terms of the modality of injury, i.e. a Russian roulette game, and the lesions suffered, in the reconstruction of which we used both surgical and microsurgical techniques.

31 CFR 549.313 - Financial, material, or technological support.

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2012-07-01

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31 CFR 548.313 - Financial, material, or technological support.

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2012-07-01

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31 CFR 549.313 - Financial, material, or technological support.

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2014-07-01

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2011-07-01

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2014-07-01

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2013-07-01

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2013-07-01

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Characterization of chemical warfare G-agent hydrolysis products by surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Inscore, Frank E.; Gift, Alan D.; Maksymiuk, Paul; Farquharson, Stuart

2004-12-01

The United States and its allies have been increasingly challenged by terrorism, and since the September 11, 2001 attacks and the war in Afghanistan and Iraq, homeland security has become a national priority. The simplicity in manufacturing chemical warfare agents, the relatively low cost, and previous deployment raises public concern that they may also be used by terrorists or rogue nations. We have been investigating the ability of surface-enhanced Raman spectroscopy (SERS) to detect extremely low concentrations (e.g. part-per-billion) of chemical agents, as might be found in poisoned water. Since trace quantities of nerve agents can be hydrolyzed in the presence of water, we have expanded our studies to include such degradation products. Our SERS-active medium consists of silver or gold nanoparticles incorporated into a sol-gel matrix, which is immobilized in a glass capillary. The choice of sol-gel precursor allows controlling hydrophobicity, while the porous silica network offers a unique environment for stabilizing the SERS-active metals. Here we present the use of these metal-doped sol-gels to selectively enhance the Raman signal of the hydrolyzed products of the G-series nerve agents.

A T-cell-dependent humoral immune response is preserved during the administration of the nerve agent pre-treatment pyridostigmine bromide in a murine model.

PubMed

Griffiths, Gareth D; Telford, Gary; Hooi, Doreen S W; Cook, David L; Wilkinson, Lucy J; Green, Christopher A; Pritchard, David I

2005-03-01

Immune regulation, either via the autonomic nervous system or by a proposed "non-neuronal" cholinergic system, suggests that the immune system may be susceptible to perturbation by compounds affecting cholinergic function. Here, the current UK and US nerve agent pre-treatment, pyridostigmine bromide (PB) and the related anti-acetylcholinesterase (AChE) compounds physostigmine (PHY) and BW284c51 were tested for their ability to affect mouse splenocyte function in vitro. In addition, PB, at a dose equivalent to that received during pre-treatment for nerve agent poisoning, was tested for its effect on a T-cell-dependent humoral response to antigen in vivo in the mouse. None of the anti-AChEs tested affected concanavalin A (Con A)-, anti-CD3- or lipopolysaccharide LPS-driven splenocyte proliferation, in vitro, at concentrations expected to give effective nerve agent pre-treatment. However, higher concentrations (>100 microM) particularly of PHY caused some inhibition of the proliferative responses. In vivo, PB or saline was administered via 28-day mini-osmotic pumps to give a 25-40% inhibition of whole blood AChE in the PB-treated animals. During PB or saline administration, primary and secondary doses (i.p.) of sheep red blood cells (SRBC) were given and the humoral response determined by monitoring anti-SRBC IgM and IgG levels. Splenocytes isolated from the experimental animals were also examined for their proliferative and cytokine responses to stimulation. No remarkable effects of PB were seen during the period of AChE inhibition on the humoral immune response. However, a modest elevation in IL-2 and IFN(gamma) in Con A-stimulated lymphocytes was seen in PB-treated animals following pump removal. Overall these data suggest that, in vivo, the SRBC stimulated T-cell-dependent immune response is unaffected by the administration of PB at pre-treatment doses.

Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung injury following inhalation exposure to nerve agent VX.

PubMed

Graham, Jacob R; Wright, Benjamin S; Rezk, Peter E; Gordon, Richard K; Sciuto, Alfred M; Nambiar, Madhusoodana P

2006-06-01

Respiratory disturbances play a central role in chemical warfare nerve agent (CWNA) induced toxicity; they are the starting point of mass casualty and the major cause of death. We developed a microinstillation technique of inhalation exposure to nerve agent VX and assessed lung injury by biochemical analysis of the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea pig BALF has a significant amount of cholinesterase activity. Treatment with Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity, indicating the predominance of BChE in BALF. A predominance of BChE expression in the lung lavage was seen in both genders. Substrate specific inhibition indicated that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and lung tissue AChE and BChE activities were strongly inhibited in guinea pigs exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15 min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity was increased 77% and 88% after 24 h of recovery following 5 min inhalation exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver and present in the plasma, an increase in BALF indicates endothelial barrier injury and leakage of plasma into lung interstitium. Therefore, a measure of increased levels of AChE and BChE in the lung lavage can be used to determine the chronology of barrier damage as well as the extent of lung injury following exposure to chemical warfare nerve agents.

Stereo-specific Synthesis of Analogs of Nerve Agents And Their Utilization For Selection And Characterization of Paraoxonase (PON1) Catalytic Scavengers

PubMed Central

Ashani, Y.; Gupta, R.D.; Goldsmith, M.; Silman, I.; Sussman, J.L.; Tawfik, D. S.; Leader, H.

2010-01-01

Fluorogenic organophosphate inhibitors of acetylcholinesterase (AChE) homologous in structure to nerve agents provide useful probes for high throughput screening of mammalian paraoxonase (PON1) libraries generated by directed evolution of an engineered PON1 variant with wild-type like specificity (rePON1). Wt PON1 and rePON1 hydrolyze preferentially the less-toxic RP enantiomers of nerve agents and of their fluorogenic surrogates containing the fluorescent leaving group, 3-cyano-7-hydroxy-4-methylcoumarin (CHMC). To increase the sensitivity and reliability of the screening protocol so as to directly select rePON1 clones displaying stereo-preference towards the toxic SP enantiomer, and to determine accurately Km and kcat values for the individual isomers, two approaches were used to obtain the corresponding SP and RP isomers: (a) stereo-specific synthesis of the O-ethyl, O-n-propyl, and O-i-propyl analogs; (b) enzymic resolution of a racemic mixture of O-cyclohexyl methylphosphonylated CHMC. The configurational assignments of the SP and RP isomers, as well as their optical purity, were established by X-ray diffraction, reaction with sodium fluoride, hydrolysis by selected rePON1 variants, and inhibition of AChE. The SP configuration of the tested surrogates was established for the enantiomer with the more potent anti-AChE activity, with SP/RP inhibition ratios of 10–100, whereas the RP isomers of the O-ethyl and O-n-propyl were hydrolyzed by wt rePON1 about 600- and 70-fold faster, respectively, than the SP counterpart. Wt rePON1-induced RP/SP hydrolysis ratios for the O-cyclohexyl and O-i-propyl analogs are estimated to be ≫1000. The various SP enantiomers of O-alkyl-methylphosphonyl esters of CHMC provide suitable ligands for screening rePON1 libraries, and can expedite identification of variants with enhanced catalytic proficiency towards the toxic nerve agents. PMID:20303930

Pharmacokinetic profile and quantitation of protection against soman poisoning by the antinicotinic compound MB327 in the guinea-pig.

PubMed

Price, Matthew E; Docx, Cerys J; Rice, Helen; Fairhall, Sarah J; Poole, Sarah J C; Bird, Michael; Whiley, Luke; Flint, Daniel P; Green, A Christopher; Timperley, Christopher M; Tattersall, John E H

2016-02-26

Current organophosphorus nerve agent medical countermeasures do not directly address the nicotinic effects of poisoning. A series of antinicotinic bispyridinium compounds has been synthesized in our laboratory and screened in vitro. Their actions can include open-channel block at the nicotinic receptor which may contribute to their efficacy. The current lead compound from these studies, MB327 1,1'-(propane-1,3-diyl)bis(4-tert-butylpyridinium) as either the diiodide (I2) or dimethanesulfonate (DMS) has been examined in vivo for efficacy against nerve agent poisoning. MB327 I2 (0-113mgkg(-1)) or the oxime HI-6 DMS (0-100mgkg(- 1)), in combination with atropine and avizafone (each at 3mgkg(-1)) was administered to guinea-pigs 1min following soman poisoning. Treatment increased the LD50 of soman in a dose-dependent manner. The increase was statistically significant (p<0.01) at the 33.9mgkg(-1) (MB327) or 30mgkg(-1) (HI-6) dose with a comparable degree of protection obtained for both compounds. Following administration of 10mgkg(-1) (i.m.), MB327 DMS reached plasma Cmax of 22μM at 12min with an elimination t1/2 of 22min. In an adverse effect study, in the absence of nerve agent poisoning, a dose of 100mgkg(-1) or higher of MB327 DMS was lethal to the guinea-pigs. A lower dose of MB327 DMS (30mgkg(-1)) caused flaccid paralysis accompanied by respiratory impairment. Respiration normalised by 30min, although the animals remained incapacitated to 4h. MB327 or related compounds may be of utility in treatment of nerve agent poisoning as a component of therapy with atropine, anticonvulsant and oxime, or alternatively as an infusion under medical supervision. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

An Advanced ESTCP PELAN System for Surface and Near-surface UXO Discrimination

DTIC Science & Technology

2009-03-01

system was designed and assembled at SAIC. Test slugs representing 30mm to 105mm shells were constructed and filled with inert materials and explosives...results and system design, ESTCP decided to discontinue the effort before the prototype was constructed and demonstrated. iii TABLE OF CONTENTS...RDX and non-explosive plasticizers ) cps counts per second CW Chemical Warfare agent d-T deuterium-tritium DoD Department of Defense DOE

31 CFR 594.317 - Financial, material, or technological support.

Code of Federal Regulations, 2013 CFR

2013-07-01

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31 CFR 542.304 - Financial, material, or technological support.

Code of Federal Regulations, 2014 CFR

2014-07-01

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31 CFR 588.312 - Financial, material, or technological support.

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2012-07-01

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31 CFR 594.317 - Financial, material, or technological support.

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2014-07-01

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31 CFR 594.317 - Financial, material, or technological support.

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2011-07-01

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2013-07-01

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31 CFR 594.317 - Financial, material, or technological support.

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2010-07-01

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2012-07-01

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2014-07-01

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2011-07-01

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Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

PubMed

Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

2016-01-01

Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Structural characterization of chemical warfare agent degradation products in decontamination solutions with proton band-selective (1)H-(31)P NMR spectroscopy.

PubMed

Koskela, Harri; Hakala, Ullastiina; Vanninen, Paula

2010-06-15

Decontamination solutions, which are usually composed of strong alkaline chemicals, are used for efficient detoxification of chemical warfare agents (CWAs). The analysis of CWA degradation products directly in decontamination solutions is challenging due to the nature of the matrix. Furthermore, occasionally an unforeseen degradation pathway can result in degradation products which could be eluded to in standard analyses. Here, we present the results of the application of proton band-selective (1)H-(31)P NMR spectroscopy, i.e., band-selective 1D (1)H-(31)P heteronuclear single quantum coherence (HSQC) and band-selective 2D (1)H-(31)P HSQC-total correlation spectroscopy (TOCSY), for ester side chain characterization of organophosphorus nerve agent degradation products in decontamination solutions. The viability of the approach is demonstrated with a test mixture of typical degradation products of nerve agents sarin, soman, and VX. The proton band-selective (1)H-(31)P NMR spectroscopy is also applied in characterization of unusual degradation products of VX in GDS 2000 solution.

In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.

Recently, Zr-based metal organic frameworks (MOFs) were shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. Here, we report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination ofmore » DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. Our experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.« less

In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.

Zr-based metal organic frameworks (MOFs) have been recently shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. We report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination ofmore » DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. These experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.« less

In Situ Probes of Capture and Decomposition of Chemical Warfare Agent Simulants by Zr-Based Metal Organic Frameworks

DOE PAGES

Plonka, Anna M.; Wang, Qi; Gordon, Wesley O.; ...

2016-12-30

Recently, Zr-based metal organic frameworks (MOFs) were shown to be among the fastest catalysts of nerve-agent hydrolysis in solution. Here, we report a detailed study of the adsorption and decomposition of a nerve-agent simulant, dimethyl methylphosphonate (DMMP), on UiO-66, UiO-67, MOF-808, and NU-1000 using synchrotron-based X-ray powder diffraction, X-ray absorption, and infrared spectroscopy, which reveals key aspects of the reaction mechanism. The diffraction measurements indicate that all four MOFs adsorb DMMP (introduced at atmospheric pressures through a flow of helium or air) within the pore space. In addition, the combination of X-ray absorption and infrared spectra suggests direct coordination ofmore » DMMP to the Zr6 cores of all MOFs, which ultimately leads to decomposition to phosphonate products. Our experimental probes into the mechanism of adsorption and decomposition of chemical warfare agent simulants on Zr-based MOFs open new opportunities in rational design of new and superior decontamination materials.« less

Global Explosive Ordnance Disposal Conference and Exhibition Held in Fort Walton Beach, Florida on 4-5 May 2011

DTIC Science & Technology

2011-05-05

technology that may be used by rogue states or terrorists to make chemical, biological or nuclear weapons OEE Priorities • WMD Proliferation • Terrorism...to locate and return shipments to OEE Agents • Export Enforcement Agents can detain any outgoing shipment suspected of being illegal Disrupt…using

Designing a Successful Acupuncture Treatment Program for Gulf War Illness

DTIC Science & Technology

2017-10-01

altered white matter microstructural integrity in organophosphate (OP) pesticide, sarin nerve agent and pyridogstigmine bromide (PB) anti-nerve gas... Integration for chronic low back pain" PI: Jacobson (3/4/ 2011-6/21/2013) N = 46. Study Site: Spaulding Rehabilitation Hospital (SRH). In this cohort... integration (SI) plus outpatient rehabili- tation (OR) versus OR alone. The details of the study are described in a recent publication (Jacobson et al

Effects of nicergoline on the cardiovascular system of dogs and rats.

PubMed

Huchet, A M; Mouillé, P; Chelly, J; Lucet, B; Doursout, M F; Lechat, P; Schmitt, H

1981-01-01

In pentobarbitalized closed-chest dogs, nicergoline (10--100 microgram/kg, i.v.) reduced blood pressure, heart rate, and splanchnic nerve activity. Intracisternal administration of nicergoline (3 microgram/kg) only reduced splanchnic nerve activity. In open-chest dogs, nicergoline reduced blood pressure, cardiac output, and total peripheral resistance but did not change heart rate. In pithed rats treated with a beta-adrenoceptor-blocking agent, nicergoline reduced the pressor responses to noradrenaline and adrenaline. Nicergoline slightly attenuated the pressor responses of dogs to noradrenaline and tyramine and, in addition, reversed the hypertension induced by adrenaline and dimethylphenylpiperazinium. Nicergoline (100 microgram/kg) increased the tachycardia induced in dogs by stimulation of the right cardiovascular nerve and prevented the inhibitory effect of clonidine on this response. However, nicergoline only partially antagonized the effect of clonidine once it was fully established. Nicergoline did not antagonize the hypotensive and bradycardic effects of clonidine when they were established. Nicergoline did not affect the vagally mediated bradycardia evoked by carotid nerve stimulation in beta-adrenoceptor-blocked dogs. The compound did not change blood pressure in Cl spinal cord transected dogs. In conclusion, nicergoline appears to decrease blood pressure by blocking alpha-adrenoceptors and, at least at some doses, by a central inhibition of the sympathetic tone. Nicergoline appears to be a preferential alpha 1-adrenoceptor-blocking agent.

31 CFR 546.313 - Financial, material, or technological support.

Code of Federal Regulations, 2013 CFR

2013-07-01

...; weapons or related materiel; chemical or biological agents; explosives; false documentation or..., tables, engineering designs and specifications, manuals, or other recorded instructions. [77 FR 6465, Feb...

31 CFR 543.313 - Financial, material, or technological support.

Code of Federal Regulations, 2012 CFR

2012-07-01

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2014-07-01

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2012-07-01

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2014-07-01

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31 CFR 543.313 - Financial, material, or technological support.

Code of Federal Regulations, 2013 CFR

2013-07-01

... transmission of value; weapons or related materiel; chemical or biological agents; explosives; false..., formulae, tables, engineering designs and specifications, manuals, or other recorded instructions. [77 FR...

Encyclopedia of Explosives and Related Items. Volume 9

DTIC Science & Technology

1980-01-01

the target. The chemical agent may about 20000g for a high-velocity tank gun, be a gas for producing a toxic or harassing with 30000 to 40000g in...prepd by redn of primarily for use in vertical holes in open-cut H2 SeO 3 with SO 2 gas . Thus, S02 is passed at work where the expl or blasting agent is...mixts contain thickening agents as well as commercial use of SE and SBA has experienced ingredients that act as aerating agents or gas a continuous and

Surface Analysis of Nerve Agent Degradation Products by ...

EPA Pesticide Factsheets

Report This sampling and analytical procedure was developed and applied by a single laboratory to investigate nerve agent degradation products, which may persist at a contaminated site, via surface wiping followed by analytical characterization. The performance data presented demonstrate the fitness-for-purpose regarding surface analysis in that single laboratory. Surfaces (laminate, glass, galvanized steel, vinyl tile, painted drywall and treated wood) were wiped with cotton gauze wipes, sonicated, extracted with distilled water, and filtered. Samples were analyzed with direct injection electrospray ionization liquid chromatography tandem mass spectrometry (ESI-LC/MS/MS) without derivatization. Detection limit data were generated for all analytes of interest on a laminate surface. Accuracy and precision data were generated from each surface fortified with these analytes.

Acute and Long-Term Impact of Chemical Weapons: Lessons from the Iran-Iraq War.

PubMed

Haines, D D; Fox, S C

2014-07-01

Chemical weapons have given the human experience of warfare a uniquely terrifying quality that has inspired a general repugnance and led to periodic attempts to ban their use. Nevertheless, since ancient times, toxic agents have been consistently employed to kill and terrorize target populations. The evolution of these weapons is examined here in ways that may allow military, law enforcement, and scientific professionals to gain a perspective on conditions that, in the past, have motivated their use - both criminally and as a matter of national policy during military campaigns. Special emphasis is placed on the genocidal use of chemical weapons by the regime of Saddam Hussein, both against Iranians and on Kurdish citizens of his own country, during the Iran-Iraq War of 1980-88. The historical development of chemical weapons use is summarized to show how progressively better insight into biochemistry and physiology was adapted to this form of warfare. Major attributes of the most frequently used chemical agents and a description of how they affected military campaigns are explained. Portions of this review describing chemical-casualty care devote particular focus to Iranian management of neurotoxic (nerve) agent casualties due to the unique nature of this experience. Both nerve and blistering "mustard" agents were used extensively against Iranian forces. However, Iran is the only nation in history to have sustained large-scale attacks with neurotoxic weapons. For this reason, an understanding of the successes and failures of countermeasures to nerve-agent use developed by the Iranian military are particularly valuable for future civil defense and military planning. A detailed consideration of these strategies is therefore considered. Finally, the outcomes of clinical research into severe chronic disease triggered by mustard-agent exposure are examined in the context of the potential of these outcomes to determine the etiology of illness among US and Allied veterans of the 1991 Persian Gulf War. Copyright © 2014 Central Police University.

Acute toxicity of some nerve agents and pesticides in rats.

PubMed

Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

2015-01-01

Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

Air Remedial Investigation. Version 3.1. Volume 1

DTIC Science & Technology

1988-08-01

1987. Construction of facilities for the production of Sarin (CB) nerve agent began in 1950 and was completed in 1953. Manufacture of CB was continued...and chemical warfare agents . Although production has ceased at the South Plants’ facilities, contaminants have been observed in ground water near the... agents , were introduced to Basin A since 1943. Inorganic metals as well as inorganic non-metals are also present. The near-surface soil contamination is

Cardiovascular Regulation in Obstructive Sleep Apnea

PubMed Central

Ziegler, Michael G.; Milic, Milos; Elayan, Hamzeh

2011-01-01

The majority of patients with obstructive sleep apnea (OSA) suffer from hypertension as a complication of both the metabolic syndrome and OSA. In animal studies, intermittent hypoxia that simulates changes seen in OSA leads to chemoreceptor and chromaffin cell stimulation of sympathetic nerve activity, endothelial damage and impaired blood pressure modulation. Human studies reveal activation of sympathetic nerves, endothelial damage and exaggerated pressor responses to sympathetic neurotransmitters and endothelin. Although treatment of the OSA normalizes sympathetic nerve responses, it only lowers blood pressure modestly. Agents that block the consequences of sympathetic over activity, such as β1 blockers and angiotensin antagonists have effectively lowered blood pressure. Diuretics have been less successful. Treatment of hypertensive patients with OSA usually requires consideration of both increased sympathetic nerve activity and the metabolic syndrome. PMID:22125570

29 CFR 1910.109 - Explosives and blasting agents.

Code of Federal Regulations, 2010 CFR

2010-07-01

... prescribed in the definition of ammonium nitrate fertilizer promulgated by the National Plant Food Institute... competent persons. (*Definition and Test Procedures for Ammonium Nitrate Fertilizer, National Plant Food...

Chemical Stockpile Disposal Program Final Programmatic Environmental Impact Statement Volume 3: Appendices A-S

DTIC Science & Technology

1988-01-01

nerve and blister agents evaluated in this appendix have been especially formulated to cause -major injuries or death to enemy forces in wartime...days. Hallucinations, particularly of visual type. Patients may exhibit selfdestructive acts l Seizures may occur, but true convulsions arc rare l Rare...lesions produced in experimental animals by GB and interprets the damage as caused by convulsions or seizure activity that kill neurons (nerve cells

A Structure-Activity Analysis of the Variation in Oxime Efficacy Against Nerve Agents

DTIC Science & Technology

2008-01-01

Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A structure- activity analysis of the variation in oxime...structure– activity analysis of the variation in oxime efficacy against nerve agents☆ Donald M. Maxwell a,⁎, Irwin Koplovitz a, Franz Worek b, Richard E...structure– activity analysi Received 22 February 2008 Revised 8 April 2008 Accepted 13 April 2008 Available online 22 April 2008 Keywords: Organophosphorus

Neurogenic regulation of renal tubular sodium reabsorption.

PubMed

DiBona, G F

1977-08-01

The evidence supporting a role for direct neurogenic control of renal tubular sodium reabsorption is reviewed. Electron microscopic and fluorescence histochemical studies have demonstrated adrenergic nerve terminals in direct contact with basement membranes of mammalian (rat, dog, and monkey) renal tubular epithelial cells. Low-level direct or baroreceptor reflex stimulation of renal sympathetic nerves produces an increase in renal tubular sodium reabsorption without alterations in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Antinatriuresis was prevented by prior treatment of the kidney with guanethidine or phenoxybenzamine. Rat kidney micropuncture studies have localized a site of enhanced tubular sodium reabsorption to the proximal tubule. Possible indirect mediation of the antinatriuresis by other humoral agents known to be released from the kidney on renal nerve stimulation (angiotensin II, prostaglandin) was excluded by experiments with appropriate blocking agents. The possible effects of anesthesia and uncertainties about the completeness of surgical renal denervation and other tubular segmental sites of action are critically analyzed. The clinical implications of this mechanism in pathologic conditions of sodium and water retention are discussed and and a prospectus for future work is presented.

Technological advancements for the detection of and protection against biological and chemical warfare agents.

PubMed

Eubanks, Lisa M; Dickerson, Tobin J; Janda, Kim D

2007-03-01

There is a growing need for technological advancements to combat agents of chemical and biological warfare, particularly in the context of the deliberate use of a chemical and/or biological warfare agent by a terrorist organization. In this tutorial review, we describe methods that have been developed both for the specific detection of biological and chemical warfare agents in a field setting, as well as potential therapeutic approaches for treating exposure to these toxic species. In particular, nerve agents are described as a typical chemical warfare agent, and the two potent biothreat agents, anthrax and botulinum neurotoxin, are used as illustrative examples of potent weapons for which countermeasures are urgently needed.

Chiral Separation of G-type Chemical Warfare Nerve Agents via Analytical Supercritical Fluid Chromatography

PubMed Central

Kasten, Shane A; Zulli, Steven; Jones, Jonathan L; Dephillipo, Thomas; Cerasoli, Douglas M

2014-01-01

Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G-type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical-scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(–) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(–) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents. Chirality 26:817–824, 2014. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc. PMID:25298066

Midazolam as an anticonvulsant antidote for organophosphate intoxication− A pharmacotherapeutic appraisal

PubMed Central

Reddy, Sandesh D.; Reddy, Doodipala Samba

2015-01-01

SUMMARY Objective This review summarizes the therapeutic potential of midazolam as an anticonvulsant antidote for organophosphate (OP) intoxication. Methods Benzodiazepines are widely used for acute seizures and status epilepticus (SE), a neurological emergency of persistent seizures that can lead to severe neuronal damage or death. Midazolam is a benzodiazepine hypnotic with a rapid onset and short duration of action. Results Midazolam is considered the new drug of choice for persistent acute seizures and SE, including those caused by neurotoxic OPs and nerve agents. Midazolam is a positive allosteric modulator of synaptic GABA-A receptors in the brain. It potentiates GABAergic inhibition and thereby controls hyperexcitability and seizures. Midazolam is administered intravenously or intramuscularly to control acute seizures and SE. Due to its favorable pharmacokinetic features, midazolam is being considered as a replacement anticonvulsant for diazepam in the antidote kit for nerve agents. Clinical studies such as the recent RAMPART trial have confirmed the anticonvulsant efficacy of midazolam in SE in prehospital settings. Significance In experimental models, midazolam is effective when given at the onset of seizures caused by nerve agents. However, benzodiazepines are less effective at terminating seizures when given 30 min or later after OP exposure or seizure onset likely because of internalization or down-regulation of synaptic, but not extrasynaptic, GABA-A receptors, which can lead to diminished potency and seizure recurrence. PMID:26032507

30 CFR 56.6130 - Explosive material storage facilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... authorities for over-the-road use. Facilities other than magazines used to store blasting agents shall contain... appropriate warning signs that indicate the contents and are visible from each approach. ...

30 CFR 56.6130 - Explosive material storage facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... authorities for over-the-road use. Facilities other than magazines used to store blasting agents shall contain... appropriate warning signs that indicate the contents and are visible from each approach. ...

30 CFR 56.6130 - Explosive material storage facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... authorities for over-the-road use. Facilities other than magazines used to store blasting agents shall contain... appropriate warning signs that indicate the contents and are visible from each approach. ...

[Even more critical medicine: a retrospective analysis of casualties admitted to the intensive care unit in the Spanish Military Hospital in Herat (Afghanistan)].

PubMed

Navarro Suay, R; Bartolomé Cela, E; Jara Zozaya, I; Hernández Abadía de Barbará, A; Gutiérrez Ortega, C; García Labajo, J D; Planas Roca, A; Gilsanz Rodríguez, F

2011-04-01

To analyze casualties from firearm and explosives injuries who were admitted to the Intensive Care Unit in the Spanish ROLE-2E from December 2005 to December 2008 and to evaluate which damaging agent had produced the highest morbidity-mortality in our series using score indices with anatomical base (ISS and NISS). Observational and retrospective study performed between 2005 and 2008. Polyvalent Intensive Care Unit in the Spanish Military Hospital of those deployed in Afghanistan. The inclusion criteria were all patients who had been wounded by firearm or by explosive devices and who had been admitted in ICU in Spanish Military Hospital in Herat (Afghanistan). The anatomic scores Injury Severity Score and the New Injury Severity Score (NISS) were applied to all the selected patients to estimate the grade of severity of their injuries. Independent: damaging agent, injured anatomical area, protection measures and dependent: mortality, surgical procedure applied, score severity and socio-demographics and control variables. Eighty-six casualties, 30 by firearm and 56 by explosive devices. Applying the NISS, 38% of the casualties had suffered severe injuries. Mean stay in the ICU was 2.8 days and mortality was 10%. Significant differences in admission to the ICU for the damaging agent were not observed (P=.142). No significant differences were observed in the need for admission and stay in the ICU according to the damaging agent. The importance of the strategy, care and logistics of the intensive care military physician in Intensive Medicine in the Operating Room in Afghanistan is stressed. © 2010 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Military Role in Countering Terrorist Use of Weapons of Mass Destruction

DTIC Science & Technology

1999-04-01

chemical and biological mobile point detection. “The M21 Remote Sensing Chemical Agent Alarm (RSCAAL) is an automatic scanning, passive infrared sensor...The M21 detects nerve and blister agent clouds based on changes in the background infrared spectra caused by the presence of the agent vapor.”15...required if greater than 3 years since last vaccine. VEE Yes Multiple vaccines required. VHF No Botulism Yes SEB No Ricin No Mycotoxin s No Source

Relative potency estimates of acceptable residues and reentry intervals after nerve agent release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watson, A.P.; Jones, T.D.; Adams, J.D.

1992-06-01

In the event of an unplanned release of a chemical warfare agent during any stage of the Chemical Stockpile Disposal Program, the potential exists for off-post contamination of drinking water, forage crops, grains, garden produce, and livestock. The more persistent agents, such as the organophosphate nerve agent VX, pose the greatest human health concern for reentry. A relative potency approach comparing the toxicity of VX to organophosphate insecticide analogues is developed and used to estimate allowable residues for VX in agricultural products and reentry intervals for public access to contaminated areas. Analysis of mammalian LD50 data by all exposure routesmore » indicates that VX is 10(3) to 10(4) times more toxic than most commercially available organophosphate insecticides. Thus, allowable residues of VX could be considered at concentration levels 10(3) to 10(4) lower than those established for certain insecticides by the U.S. EPA. Evaluation of reentry intervals developed for these organophosphate analogues indicate that, if environmental monitoring cannot reliably demonstrate acceptable levels of VX, restricted access to suspect or contaminated areas may be on the order of weeks to months following agent release. Planning for relocation, mass care centers, and quarantine should take this time period into account.« less

Clinical aspects of percutaneous poisoning by the chemical warfare agent VX: effects of application site and decontamination.

PubMed

Hamilton, Murray G; Hill, Ira; Conley, John; Sawyer, Thomas W; Caneva, Duane C; Lundy, Paul M

2004-11-01

O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) is an extremely toxic organophosphate nerve agent that has been weaponized and stockpiled in a number of different countries, and it has been used in recent terrorist events. It differs from other well-known organophosphate nerve agents in that its primary use is as a contact poison rather than as an inhalation hazard. For this reason, we examined the effects of application site and skin decontamination on VX toxicity in anesthetized domestic swine after topical application. VX applied to the surface of the ear rapidly resulted in signs of toxicity consistent with the development of cholinergic crisis, including apnea and death. VX on the epigastrium resulted in a marked delayed development of toxic signs, reduced toxicity, and reduction in the rate of cholinesterase depression compared with animals exposed on the ear. Skin decontamination (15 minutes post-VX on the ear) arrested the development of clinical signs and prevented further cholinesterase inhibition and death. These results confirm earlier work that demonstrates the importance of exposure site on the resultant toxicity of this agent and they also show that decontamination postexposure has the potential to be an integral and extremely important component of medical countermeasures against this agent.

The sympathetic hazards of airborne ultrasound on ultrasound sensitive mice.

PubMed

Ohmori, M; Ogawa, K

1982-01-01

A commercially available ultrasonic equipment (55-50 kHz/sec, 425 W) operated at a distance of 4 m air space caused death in some mice. The physical energy propagated was quite small, being calculated at less than 0.21 W/cm2. Among many strains of mice, the RIII strain was especially sensitive to ultrasound, and the peak of sensitivity was at 3 to 4 weeks of age at which the mortality rate was 95/149 (64%). No death occurred when mice were pretreated by (a) removing all body hair, (b) by administration of morphine hydrochloridum with a tail reaction, and (c) administration of a sympathetic blocking agent. From these results it is assumed that the ultrasound energy absorbed by the body fur reaches the hypothalamus through the sensory nerves of the hair roots. After the hypothalamus where central sympathetic nerve functions are localized, the stimulus passes down the descending tract of the sympathetic nerve, reaching the cardiac nerves via the autonomic nerve ganglion. Thus, death could occur by shock of the sympathetic nerve reflex.

30 CFR 57.6130 - Explosive material storage facilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... local authorities for over-the-road use. Facilities other than magazines used to store blasting agents... or other appropriate warning signs that indicate the contents and are visible from each approach. ...

30 CFR 57.6130 - Explosive material storage facilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... local authorities for over-the-road use. Facilities other than magazines used to store blasting agents... or other appropriate warning signs that indicate the contents and are visible from each approach. ...

30 CFR 57.6130 - Explosive material storage facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... local authorities for over-the-road use. Facilities other than magazines used to store blasting agents... or other appropriate warning signs that indicate the contents and are visible from each approach. ...

Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

von Bredow, J.; Corcoran, K.; Maitland, G.

1991-12-31

Pretreatment of nonhuman primates with physostigmine (Phy) and scopolamine or physostigmine and trihexyphenidyl 25 min before exposure to 2 LD50 soman im resulted in complete survival without convulsions or loss of consciousness. When identically pretreated animals were challenged with 5 LD50s of soman followed by atropine and 2-PAM therapy 1 min later, all animals experienced a loss of consciousness for approximately 10 min followed by functional recovery within an additional 20 min. These findings indicated that a pretreatment regimen composed of Phy and cholinolytic is capable of protecting primates from an absolute lethal dose of soman with rapid recovery frommore » incapacitation. Physostigmine, nerve agent pretreatment, cynomolgus monkeys soman (GD).« less

[Chronic Inflammatory Demyelinating Polyneuropathy].

PubMed

Balke, M; Wunderlich, G; Brunn, A; Fink, G R; Lehmann, H C

2016-12-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic progressive or relapsing autoimmune neuropathy with heterogeneous clinical presentation. Symptoms typically include symmetrical, proximal and/or distal paresis and sensory loss. Atypical CIDP variants are increasingly recognized, including subtypes with rapid onset as well as variants with pure sensory, focal or marked asymmetrical deficits. Diagnosis is established by compatible symptoms, characteristic electrophysiological features and cerebrospinal fluid analysis. In unequivocal cases, inflammatory infiltrates in sural nerve biopsy support the diagnosis. Recent studies suggest that diagnostic imaging techniques such as MRI and nerve ultrasound may become useful tools for establishing the diagnosis. First-line therapies include immunoglobulines, steroids, and plasmapheresis. Immunosuppressant agents and monoclonal antibodies are used in therapy-refractory cases or as cortison-saving agents. © Georg Thieme Verlag KG Stuttgart · New York.

Synthesis and characterization of hydrogen-bond acidic functionalized graphene

NASA Astrophysics Data System (ADS)

Yang, Liu; Han, Qiang; Pan, Yong; Cao, Shuya; Ding, Mingyu

2014-05-01

Hexafluoroisopropanol phenyl group functionalized materials have great potential in the application of gas-sensitive materials for nerve agent detection, due to the formation of strong hydrogen-bonding interactions between the group and the analytes. In this paper, take full advantage of ultra-large specific surface area and plenty of carbon-carbon double bonds and hexafluoroisopropanol phenyl functionalized graphene was synthesized through in situ diazonium reaction between -C=C- and p-hexafluoroisopropanol aniline. The identity of the as-synthesis material was confirmed by transmission electron microscopy, Raman spectroscopy, ultraviolet visible spectroscopy, X-ray photoelectron spectroscopy and thermo gravimetric analysis. The synthesis method is simply which retained the excellent physical properties of original graphene. In addition, the novel material can be assigned as an potential candidate for gas sensitive materials towards organophosphorus nerve agent detection.

Compact fluorescence and white-light imaging system for intraoperative visualization of nerves

NASA Astrophysics Data System (ADS)

Gray, Dan; Kim, Evgenia; Cotero, Victoria; Staudinger, Paul; Yazdanfar, Siavash; tan Hehir, Cristina

2012-02-01

Fluorescence image guided surgery (FIGS) allows intraoperative visualization of critical structures, with applications spanning neurology, cardiology and oncology. An unmet clinical need is prevention of iatrogenic nerve damage, a major cause of post-surgical morbidity. Here we describe the advancement of FIGS imaging hardware, coupled with a custom nerve-labeling fluorophore (GE3082), to bring FIGS nerve imaging closer to clinical translation. The instrument is comprised of a 405nm laser and a white light LED source for excitation and illumination. A single 90 gram color CCD camera is coupled to a 10mm surgical laparoscope for image acquisition. Synchronization of the light source and camera allows for simultaneous visualization of reflected white light and fluorescence using only a single camera. The imaging hardware and contrast agent were evaluated in rats during in situ surgical procedures.

A compact fluorescence and white light imaging system for intraoperative visualization of nerves

NASA Astrophysics Data System (ADS)

Gray, Dan; Kim, Evgenia; Cotero, Victoria; Staudinger, Paul; Yazdanfar, Siavash; Tan Hehir, Cristina

2012-03-01

Fluorescence image guided surgery (FIGS) allows intraoperative visualization of critical structures, with applications spanning neurology, cardiology and oncology. An unmet clinical need is prevention of iatrogenic nerve damage, a major cause of post-surgical morbidity. Here we describe the advancement of FIGS imaging hardware, coupled with a custom nerve-labeling fluorophore (GE3082), to bring FIGS nerve imaging closer to clinical translation. The instrument is comprised of a 405nm laser and a white light LED source for excitation and illumination. A single 90 gram color CCD camera is coupled to a 10mm surgical laparoscope for image acquisition. Synchronization of the light source and camera allows for simultaneous visualization of reflected white light and fluorescence using only a single camera. The imaging hardware and contrast agent were evaluated in rats during in situ surgical procedures.

Prophylaxis against Organophosphorous Nerve Agents - State of the Art (profylaxe tegen organofosfaat zenuwgassen - stand van zaken)

DTIC Science & Technology

2005-12-01

consists of those that catalytically hydrolyze (in some cases stereoselectively) OP’s into non-toxic alkyl methyl phosphonic acids. These enzymes are so...8217fluorosphatase’, nowadays known as OPH, capable of hydrolyzing organophosphates. For therapy and/or profylaxis, a hydrolytic enzyme could be...HuPON hydrolyzes OP insecticides and nerve gases and a relationship was found between the amount of enzyme in different species and the toxic response

27 CFR 555.206 - Location of magazines.

Code of Federal Regulations, 2013 CFR

2013-04-01

... in the table of distances for storage of explosive materials in § 555.218. (2) Ammonium nitrate and... for the separation of ammonium nitrate and blasting agents in § 555.220. However, the minimum...

27 CFR 555.206 - Location of magazines.

Code of Federal Regulations, 2014 CFR

2014-04-01

... in the table of distances for storage of explosive materials in § 555.218. (2) Ammonium nitrate and... for the separation of ammonium nitrate and blasting agents in § 555.220. However, the minimum...

27 CFR 555.206 - Location of magazines.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in the table of distances for storage of explosive materials in § 555.218. (2) Ammonium nitrate and... for the separation of ammonium nitrate and blasting agents in § 555.220. However, the minimum...

27 CFR 555.206 - Location of magazines.

Code of Federal Regulations, 2012 CFR

2012-04-01

... in the table of distances for storage of explosive materials in § 555.218. (2) Ammonium nitrate and... for the separation of ammonium nitrate and blasting agents in § 555.220. However, the minimum...

Molecular Design of Sulfonated Triblock Copolymer Permselective Membranes

DTIC Science & Technology

2008-07-03

factors governing sorption and permeability ofphosphoorganic agents in PEM made of sulfonated triblock copolymers of styrene and lower olefins by means...membrane morphology at environmental conditions, and the membrane sorption and transport properties with respect to water and nerve gas simulant...and chemical factors governing sorption and permeability of phosphoorganic agents in PEM made of sulfonated triblock copolymers of styrene and lower

Spectroscopic investigation of the noncovalent association of the nerve agent simulant diisopropyl methylphosphonate (DIMP) with zinc(II) porphyrins.

PubMed

Maza, William A; Vetromile, Carissa M; Kim, Chungsik; Xu, Xue; Zhang, X Peter; Larsen, Randy W

2013-11-07

Organophosphonates pose a significant threat as chemical warfare agents, as well as environmental toxins in the form of pesticides. Thus, methodologies to sense and decontaminate these agents are of significant interest. Porphyrins and metalloporphyrins offer an excellent platform to develop chemical threat sensors and photochemical degradation systems. These highly conjugated planar molecules exhibit relatively long-lived singlet and triplet states with high quantum yields and also form self-associated complexes with a wide variety of molecules. A significant aspect of porphyrins is the ability to functionalize the peripheral ring system either directly to the pyrrole rings or to the bridging methine carbons. In this report, steady-state absorption and fluorescence are utilized to probe binding affinities of a series of symmetric and asymmetric zinc(II) metalloporphyrins for the nerve agent simulant diisopropyl methylphosphonate (DIMP) in hexane. The red shifts in the absorption and emission spectra observed for all of the metalloporphyrins probed are discussed in the frame of Gouterman's four orbital model and a common binding motif involving coordination between the metalloporphyrin and DIMP via interaction between the zinc metal center of the porphyrin and phosphoryl oxygen of DIMP (Zn-O═P) is proposed.

Deceptive Tactics for Protecting Cities Against Vehicle Borne Improvised Explosive Devices

DTIC Science & Technology

2008-03-01

burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching...INTENTIONALLY LEFT BLANK xiii LIST OF ABBREVIATIONS ABS Agent Based Simulation ANA Agent Network Attack DVF Detection Value Function GIS Geographic...any other behavior (than perceptive) may be advantageous to the attacker. - A communicative behavior proves particularly effective over time for the

RSDL decontamination of human skin contaminated with the nerve agent VX.

PubMed

Thors, L; Lindberg, S; Johansson, S; Koch, B; Koch, M; Hägglund, L; Bucht, A

2017-03-05

Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31 P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

[Burns in adolescents].

PubMed

Ortiz Rodríguez, R; Domínguez Amillo, E; Soto Beauregard, C; Díaz González, M; López Gutiérrez, J C; Ros Mar, Z; Tovar Larrucea, J A

2012-04-01

The aim of this study was to know the epidemiology of burns in teenagers. Burn patients over 11 years old admitted in our Institution in the last 10 years were included. Etiology, burn size, hospital stay, quirurgical interventions and long term sequelae were registered. One thousand and eight patients were admitted, 89 were over 11 years (8.8%), 70.7% were boys and 29.3% girls. Fire was the principal agent in 58 cases (65.1%), due to fireworks in 13 (22.4%), alcohol in 7 (12%), explosion of flammable containers (spray) in 4 (6.8%) and gasoline in 3 (5.2%). Fireworks injuries and spray explosions affected face and hand in 88% cases. The median hospital stay was 8 days after admission (1 to 90). 83.1% required surgical treatment with mean of 1.8 +/- 1.4 interventions and 21.3% had long-term sequelaes that required at least one surgical intervention. Fire is the main cause of burns in adolescents. Fireworks injuries represented a quarter of that lesions, and highlights paint spray explosions as new causative agents. Considering the high morbidity in this age group, with permanent functional and aesthetic sequelae, prevention campaigns are needed to reduce such accidents.

A brief historical review of non-anaesthetic causes of fires and explosions in the operating room.

PubMed

Macdonald, A G

1994-12-01

Fires and explosions have occurred in the operating theatre for many years. Flammable inhalation anaesthetic agents were responsible for many incidents in the past, but these are no longer available in many countries. Other causes of fires and explosions still exist in the operating theatre and, from time to time, result in serious and occasionally fatal injury. Flammable gastrointestinal gases have been the cause of injury to patients during gastric surgery, laparoscopy and during examination of the large bowel with electrical instrumentation. Gases formed in the bladder during urological procedures have ignited, causing rupture. Alcohol-based skin cleaning agents have resulted in severe burns to the skin. Equipment used for storage and delivery of oxygen to patients has caused fires in a variety of ways. Adhesive skin drapes have resulted recently in two tragic deaths. The increasing use of laser therapy, particularly in ear, nose and throat surgery, and in oral surgery, has brought about a renewed awareness of the risk of fire. The relevant factors which should be borne in mind and the precautions which should be adopted when laser therapy is to be used in the airway are discussed.

Workshop on Problems in Chemical Toxicology

DTIC Science & Technology

1980-06-20

that is mustard gas , however, there is no proof of that. In Laos and Cambodia there seems to be three agents that they are using, tear- gas or CS...which Is non-lethal for most normal and healthy individuals. Then they are using a nerve agent of unknown origin probably an. organphosphate, but that...use some persistent agent such as "thickened" Soman or you could use mustard gas just as well. Tou would probably figure that they would move about

Multiscale modeling of nerve agent hydrolysis mechanisms: a tale of two Nobel Prizes

NASA Astrophysics Data System (ADS)

Field, Martin J.; Wymore, Troy W.

2014-10-01

The 2013 Nobel Prize in Chemistry was awarded for the development of multiscale models for complex chemical systems, whereas the 2013 Peace Prize was given to the Organisation for the Prohibition of Chemical Weapons for their efforts to eliminate chemical warfare agents. This review relates the two by introducing the field of multiscale modeling and highlighting its application to the study of the biological mechanisms by which selected chemical weapon agents exert their effects at an atomic level.

Enzymatic Neutralization of the Chemical Warfare Agent VX: Evolution of Phosphotriesterase for Phosphorothiolate Hydrolysis

PubMed Central

Bigley, Andrew N.; Xu, Chengfu; Henderson, Terry J.; Harvey, Steven P.; Raushel, Frank M.

2013-01-01

The V-type nerve agents (VX and VR) are among the most toxic substances known. The high toxicity and environmental persistence of VX makes the development of novel decontamination methods particularly important. The enzyme phosphotriesterase (PTE) is capable of hydrolyzing VX but with an enzymatic efficiency more than 5-orders of magnitude lower than with its best substrate, paraoxon. PTE has previously proven amenable to directed evolution for the improvement of catalytic activity against selected compounds through the manipulation of active site residues. Here, a series of sequential two-site mutational libraries encompassing twelve active site residues of PTE was created. The libraries were screened for catalytic activity against a new VX analogue (DEVX), which contains the same thiolate leaving group of VX coupled to a di-ethoxy phosphate core rather than the ethoxy, methylphosphonate core of VX. The evolved catalytic activity with DEVX was enhanced 26-fold relative to wildtype PTE. Further improvements were facilitated by targeted error-prone PCR mutagenesis of Loop-7 and additional PTE variants were identified with up to a 78-fold increase in the rate of DEVX hydrolysis. The best mutant hydrolyzed the racemic nerve agent VX with a value of kcat/Km of 7×104 M−1 s−1; a 230-fold improvement relative to the wild-type PTE. The highest turnover number achieved by the mutants created for this investigation was 137 s−1; an enhancement of 152-fold relative to wild-type PTE. The stereoselectivity for the hydrolysis of the two enantiomers of VX was relatively low. These engineered mutants of PTE are the best catalysts ever reported for the hydrolysis of nerve agent VX. PMID:23789980

Enzymatic neutralization of the chemical warfare agent VX: evolution of phosphotriesterase for phosphorothiolate hydrolysis.

PubMed

Bigley, Andrew N; Xu, Chengfu; Henderson, Terry J; Harvey, Steven P; Raushel, Frank M

2013-07-17

The V-type nerve agents (VX and VR) are among the most toxic substances known. The high toxicity and environmental persistence of VX make the development of novel decontamination methods particularly important. The enzyme phosphotriesterase (PTE) is capable of hydrolyzing VX but with an enzymatic efficiency more than 5 orders of magnitude lower than with its best substrate, paraoxon. PTE has previously proven amenable to directed evolution for the improvement of catalytic activity against selected compounds through the manipulation of active-site residues. Here, a series of sequential two-site mutational libraries encompassing 12 active-site residues of PTE was created. The libraries were screened for catalytic activity against a new VX analogue, DEVX, which contains the same thiolate leaving group of VX coupled to a diethoxyphosphate core rather than the ethoxymethylphosphonate core of VX. The evolved catalytic activity with DEVX was enhanced 26-fold relative to wild-type PTE. Further improvements were facilitated by targeted error-prone PCR mutagenesis of loop-7, and additional PTE variants were identified with up to a 78-fold increase in the rate of DEVX hydrolysis. The best mutant hydrolyzed the racemic nerve agent VX with a value of kcat/Km = 7 × 10(4) M(-1) s(-1), a 230-fold improvement relative to wild-type PTE. The highest turnover number achieved by the mutants created for this investigation was 137 s(-1), an enhancement of 152-fold relative to wild-type PTE. The stereoselectivity for the hydrolysis of the two enantiomers of VX was relatively low. These engineered mutants of PTE are the best catalysts ever reported for the hydrolysis of nerve agent VX.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halbrook, R.S.; Shugart, L.R.; Watson, A.P.

1992-09-01

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. Amore » framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.« less

Development of a novel drug release system, time-controlled explosion system (TES). I. Concept and design.

PubMed

Ueda, S; Hata, T; Asakura, S; Yamaguchi, H; Kotani, M; Ueda, Y

1994-01-01

A novel controlled drug release system. Time-Controlled Explosion System (TES) has been developed. TES has a four-layered spherical structure, which consists of core, drug, swelling agent and water insoluble polymer membrane. TES is characterized by a rapid drug release with a precisely programmed lag time; i.e. expansion of the swelling agent by water penetrating through the outer membrane, destruction of the membrane by stress due to swelling force and subsequent rapid drug release. For establishing the concept and development strategy, TES was designed using metoprolol and polystyrene balls (size: 3.2 mm in diameter) as a model drug and core particles. Among the polymers screened, low-substituted hydroxypropylcellulose (L-HPC) and ethylcellulose (EC) were selected for a swelling agent and an outer water insoluble membrane, respectively. The release profiles of metoprolol from the system were not affected by the pH of the dissolution media. Lag time was controlled by the thickness of the outer EC membrane; thus, a combination of TES particles possessing different lag times could offer any desired release profile of the model compound, metoprolol.

Advances in Raman spectroscopy for explosive identification in aviation security

NASA Astrophysics Data System (ADS)

Santillán, Javier D.; Brown, Christopher D.; Jalenak, Wayne

2007-04-01

In the operational airport environment, the rapid identification of potentially hazardous materials such as improvised explosive devices, chemical warfare agents and flammable and explosive liquids is increasingly critical. Peroxide-based explosives pose a particularly insidious threat because they can be made from commonly available and relatively innocuous household chemicals, such as bleach and hydrogen peroxide. Raman spectroscopy has been validated as a valuable tool for rapid identification of chemicals, explosives, and narcotics and their precursors while allowing "line-of-sight" interrogation through bottles or other translucent containers. This enables safe identification of both precursor substances, such as acetone, and end-products, such as TATP, without direct sampling, contamination and exposure by security personnel. To date, Raman systems have been laboratory-based, requiring careful operation and maintenance by technology experts. The capital and ongoing expenses of these systems is also significant. Recent advances in Raman component technologies have dramatically reduced the footprint and cost, while improving the reliability and ease of use of Raman spectroscopy systems. Such technologies are not only bringing the lab to the field, but are also protecting civilians and security personnel in the process.

Ultraviolet Raman scattering from persistent chemical warfare agents

NASA Astrophysics Data System (ADS)

Kullander, Fredrik; Wästerby, Pär.; Landström, Lars

2016-05-01

Laser induced Raman scattering at excitation wavelengths in the middle ultraviolet was examined using a pulsed tunable laser based spectrometer system. Droplets of chemical warfare agents, with a volume of 2 μl, were placed on a silicon surface and irradiated with sequences of laser pulses. The Raman scattering from V-series nerve agents, Tabun (GA) and Mustard gas (HD) was studied with the aim of finding the optimum parameters and the requirements for a detection system. A particular emphasis was put on V-agents that have been previously shown to yield relatively weak Raman scattering in this excitation band.

The Blood Volume of the Guinea Pig: Effects of Epinephrine and Isoproterenol upon the Red Cell and Plasma Volumes, Heart Rate, and Mean Arterial Pressure,

DTIC Science & Technology

1987-09-01

capillaries (4), blood volumes calculated from plasma volume measures must correct for label that has left the system between the time of the injected dose...Splenic sequestration and contraction are mediated by the autonomic nervous system and blood-borne agents (10). Sympathetic nerve fibers from the truncus...sympathlcus and parasympathetic neurons of the nervus vagus (cranial nerve X) innervate the celiac plexus (8, 11). A subdivision of the celiac plexus

High-speed imaging and small-scale explosive characterization techniques to understand effects of primary blast-induced injury on nerve cell structure and function

NASA Astrophysics Data System (ADS)

Piehler, T.; Banton, R.; Zander, N.; Duckworth, J.; Benjamin, R.; Sparks, R.

2018-01-01

Traumatic brain injury (TBI) is often associated with blast exposure. Even in the absence of penetrating injury or evidence of tissue injury on imaging, blast TBI may trigger a series of neural/glial cellular and functional changes. Unfortunately, the diagnosis and proper treatment of mild traumatic brain injury (mTBI) caused by explosive blast is challenging, as it is not easy to clinically distinguish blast from non-blast TBI on the basis of patient symptoms. Damage to brain tissue, cell, and subcellular structures continues to occur slowly and in a manner undetectable by conventional imaging techniques. The threshold shock impulse levels required to induce damage and the cumulative effects upon multiple exposures are not well characterized. Understanding how functional and structural damage from realistic blast impact at cellular and tissue levels at variable timescales after mTBI events may be vital for understanding this injury phenomenon and for linking mechanically induced structural changes with measurable effects on the nervous system. Our working hypothesis is that there is some transient physiological dysfunction occurring at cellular and subcellular levels within the central nervous system due to primary blast exposure. We have developed a novel in vitro indoor experimental system that uses real military explosive charges to more accurately represent military blast exposure and to probe the effects of primary explosive blast on dissociated neurons. We believe this system offers a controlled experimental method to analyze and characterize primary explosive blast-induced cellular injury and to understand threshold injury phenomenon. This paper will also focus on the modeling aspect of our work and how it relates to the experimental work.

Development of a rat model for studying blast-induced traumatic brain injury.

PubMed

Cheng, Jingmin; Gu, Jianwen; Ma, Yuan; Yang, Tao; Kuang, Yongqin; Li, Bingcang; Kang, Jianyi

2010-07-15

Blast-induced traumatic brain injury (TBI) has been the predominant cause of neurotrauma in current military conflicts, and it is also emerging as a potential threat in civilian terrorism. The etiology of TBI, however, is poorly understood. Further study on the mechanisms and treatment of blast injury is urgently needed. We developed a unique rat model to simulate blast effects that commonly occur on the battlefield. An electric detonator with the equivalent of 400 mg TNT was developed as the explosive source. The detonator's peak overpressure and impulse of explosion shock determined the explosion intensity in a distance-dependent manner. Ninety-six male adult Sprague-Dawley rats were randomly divided into four groups: 5-cm, 7.5-cm, 10-cm, and control groups. The rat was fixed in a specially designed cabin with an adjustable aperture showing the frontal, parietal, and occipital parts of the head exposed to explosion; the eyes, ears, mouth, and nose were protected by the cabin. After each explosion, we assessed the physiologic, neuropathologic, and neurobehavioral consequences of blast injury. Changes of brain tissue water content and neuron-specific enolase (NSE) expression were detected. The results in the 7.5-cm group show that 87% rats developed apnea, limb seizure, poor appetite, and limpness. Diffuse subarachnoid hemorrhage and edema could be seen within the brain parenchyma, which showed a loss of integrity. Capillary damage and enlarged intercellular and vascular space in the cortex, along with a tattered nerve fiber were observed. These findings demonstrate that we have provided a reliable and reproducible blast-induced TBI model in rats. Copyright 2010 Elsevier B.V. All rights reserved.

Synthesis and biodegradation of the VX nerve agent derivative 2-DIISO-propylaminoethylsulfonic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warner, C.H.; Labare, M.P.; Wessel, T.E.

1996-10-01

The United States is currently examining biodegradation methods to demilitarize chemical weapons. The nerve agent, O-ethyl-S-(2-diisopropylamino-ethyl)methylphosphonothiolate (VX) is first chemically inactivated with water at 90% yielding two fragments. One fragment is 2-diisopropylaminoethanethiol which quickly reacts with another thiol fragment forming the disulfide, bis(2-diisopropylaminoethyl)disulfide. The presence of the disulfide bond in this compound renders it resistant to biodegradation. Methods for converting the disulfide to the sulfonic acid are currently being pursued by treatment with performic acid. However, the sulfonic: acid has been synthesized by an independent method. Preliminary experiments indicate that the sulfonic acid at 1.0 and 0.5 mM is degradedmore » by Rhodococcus dp. strain IGTS8 as evidenced by an increase in the optical density at 600 nm.« less

Cluster headache: present and future therapy.

PubMed

Leone, Massimo; Giustiniani, Alessandro; Cecchini, Alberto Proietti

2017-05-01

Cluster headache is characterized by severe, unilateral headache attacks of orbital, supraorbital or temporal pain lasting 15-180 min accompanied by ipsilateral lacrimation, rhinorrhea and other cranial autonomic manifestations. Cluster headache attacks need fast-acting abortive agents because the pain peaks very quickly; sumatriptan injection is the gold standard acute treatment. First-line preventative drugs include verapamil and carbolithium. Other drugs demonstrated effective in open trials include topiramate, valproic acid, gabapentin and others. Steroids are very effective; local injection in the occipital area is also effective but its prolonged use needs caution. Monoclonal antibodies against calcitonin gene-related peptide are under investigation as prophylactic agents in both episodic and chronic cluster headache. A number of neurostimulation procedures including occipital nerve stimulation, vagus nerve stimulation, sphenopalatine ganglion stimulation and the more invasive hypothalamic stimulation are employed in chronic intractable cluster headache.

Hydrolysis of DFP and the Nerve Agent (S)-Sarin by DFPase Proceeds Along Two Different Reaction Pathways: Implica-tions for Engineering Bioscavengers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wymore, Troy W; Langan, Paul; Smith, Jeremy C

Organophosphorus (OP) nerve agents such as (S)-sarin are among the most highly toxic compounds that have been synthesized. Engineering enzymes that catalyze the hydrolysis of nerve agents ( bioscavengers ) is an emerging prophylactic approach to diminishing their toxic effects. Although its native function is not known, diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris catalyzes the hydrolysis of OP compounds. Here, we investigate the mechanisms of diisopropylfluorophosphate (DFP) and (S)-sarin hydrolysis by DFPase with quantum mechanical/molecular mechanical (QM/MM) umbrella sampling simulations. We find that the mechanism for hydrolysis of DFP involves nucleophilic attack by Asp229 on phosphorus to form a pentavalentmore » intermediate. P F bond dissociation then yields a phosphoacyl enzyme intermediate in the rate-limiting step. The simulations suggest that a water molecule, coordinated to the catalytic Ca2+, donates a proton to Asp121 and then attacks the tetrahedral phosphoacyl intermediate to liberate the diisopropylphosphate product. In contrast, the calculated free energy barrier for hydrolysis of (S)-sarin by the same mechanism is highly unfavorable, primarily due to the instability of the pentavalent phosphoenzyme species. Instead, simulations suggest that hydrolysis of (S)-sarin proceeds by a mechanism in which Asp229 could activate an intervening water molecule for nucleophilic attack on the substrate. These findings may lead to improved strategies for engineering DFPase and related six-bladed -propeller folds for more efficient degradation of OP compounds.« less

Hydrolysis of DFP and the Nerve Agent (S)-Sarin by DFPase Proceeds along Two Different Reaction Pathways: Implications for Engineering Bioscavengers

PubMed Central

2015-01-01

Organophosphorus (OP) nerve agents such as (S)-sarin are among the most highly toxic compounds that have been synthesized. Engineering enzymes that catalyze the hydrolysis of nerve agents (“bioscavengers”) is an emerging prophylactic approach to diminish their toxic effects. Although its native function is not known, diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris catalyzes the hydrolysis of OP compounds. Here, we investigate the mechanisms of diisopropylfluorophosphate (DFP) and (S)-sarin hydrolysis by DFPase with quantum mechanical/molecular mechanical umbrella sampling simulations. We find that the mechanism for hydrolysis of DFP involves nucleophilic attack by Asp229 on phosphorus to form a pentavalent intermediate. P–F bond dissociation then yields a phosphoacyl enzyme intermediate in the rate-limiting step. The simulations suggest that a water molecule, coordinated to the catalytic Ca2+, donates a proton to Asp121 and then attacks the tetrahedral phosphoacyl intermediate to liberate the diisopropylphosphate product. In contrast, the calculated free energy barrier for hydrolysis of (S)-sarin by the same mechanism is highly unfavorable, primarily because of the instability of the pentavalent phosphoenzyme species. Instead, simulations suggest that hydrolysis of (S)-sarin proceeds by a mechanism in which Asp229 could activate an intervening water molecule for nucleophilic attack on the substrate. These findings may lead to improved strategies for engineering DFPase and related six-bladed β-propeller folds for more efficient degradation of OP compounds. PMID:24720808

Encyclopedia of Explosives and Related Items. Volume 10

DTIC Science & Technology

1983-01-01

trinitroethyl stearate 6 E330 Ethyiphosphorodimethylamidycyanadate se Ethyl-substituted acid amides, N-trinitro derivs GA chemical warfare agent 2.C 167; 6...6 GI Galex 6 G8-G9 GA (chemical warfare agent ) 6 G 1 Galil rifle 6 G9 GA see Dimethylaminocyanophosphoric acid Galil rifle 6 G9 5 D1308-D1309 Gabeaud...G45 Gas volumes produced on expln or detonation Gelatina explosiva de guerra 6 G45 of expls 6 G36-G41 Gelatina gomma 6 G45 Gas warfare agents 2 C165

Facilitatory effects of piracetam on excitability of motor nerve terminals and neuromuscular transmission.

PubMed

Hall, E D; Von Voigtlander, P F

1987-11-01

The possible in vivo facilitatory effects of the pyrrolidine acetamide no-otropic agent piracetam on neuromuscular transmission, were studied based upon reports of enhancement of central cholinergic function. Piracetam was shown to antagonize the lethal effects of the neuromuscular blocking agent hemicholinium-3 (HC-3), in female CF-1 mice when administered in a dose of 100 mg/kg (i.p.) simultaneously with HC-3. A 30 mg/kg (i.p.) dose of piracetam was ineffective by itself, although it potentiated the protective effects of choline (25 mg/kg i.p.). The analogs of piracetam, aniracetam, oxiracetam, pramiracetam and dupracetam also significantly antagonized the lethality of HC-3 at doses over a 30-300 mg/kg range. The acute facilitatory properties of piracetam on neuromuscular transmission were examined in more detail in vivo in the soleus nerve muscle preparation of the cat. A 100 mg/kg (i.v.) dose of piracetam, while having no effect on its own, significantly enhanced the ability of a 200 micrograms/kg (i.v.) dose of edrophonium to produce a potentiation of muscle contraction dependent on repetitive discharges in the soleus motor nerve terminals. In preparations in which the motor nerve terminals of the soleus were in a partially degenerated state as a result of section of the motor axons 48 hr earlier, piracetam acted to restore their sensitivity to edrophonium. Furthermore, in both normal and partially degenerated preparations, piracetam significantly decreased the neuromuscular blocking effects of a 150 micrograms/kg (i.v.) dose of d-tubocurarine. The mechanism of the neuromuscular facilitatory effects of piracetam on neuromuscular transmission is discussed in terms of an enhanced excitability of motor nerve terminals together with an action to increase the synthesis and/or release of acetylcholine.

Facial nerve conduction after sclerotherapy in children with facial lymphatic malformations: report of two cases.

PubMed

Lin, Pei-Jung; Guo, Yuh-Cherng; Lin, Jan-You; Chang, Yu-Tang

2007-04-01

Surgical excision is thought to be the standard treatment of choice for lymphatic malformations. However, when the lesions are limited to the face only, surgical scar and facial nerve injury may impair cosmetics and facial expression. Sclerotherapy, an injection of a sclerosing agent directly through the skin into a lesion, is an alternative method. By evaluating facial nerve conduction, we observed the long-term effect of facial lymphatic malformations after intralesional injection of OK-432 and correlated the findings with anatomic outcomes. One 12-year-old boy with a lesion over the right-side preauricular area adjacent to the main trunk of facial nerve and the other 5-year-old boy with a lesion in the left-sided cheek involving the buccinator muscle were enrolled. The follow-up data of more than one year, including clinical appearance, computed tomography (CT) scan and facial nerve evaluation were collected. The facial nerve conduction study was normal in both cases. Blink reflex in both children revealed normal results as well. Complete resolution was noted on outward appearance and CT scan. The neurophysiologic data were compatible with good anatomic and functional outcomes. Our report suggests that the inflammatory reaction of OK-432 did not interfere with adjacent facial nerve conduction.

Discrimination of non-explosive and explosive samples through nitrocellulose fingerprints obtained by capillary electrophoresis.

PubMed

Fernández de la Ossa, Ma Ángeles; Ortega-Ojeda, Fernando; García-Ruiz, Carmen

2013-08-09

This work is focused on a novel procedure to discriminate nitrocellulose-based samples with non-explosive and explosive properties. The nitrocellulose study has been scarcely approached in the literature due to its special polymeric properties such as its high molar mass and complex chemical and structural characteristics. These properties require the nitrocellulose analysis to be performed by using a few organic solvents and in consequence, they limit the number of adequate analytical techniques for its study. In terms of identification of pre-blast explosives, mass spectrometry is one of the most preferred technique because it allows to obtain structural information. However, it has never been used to analyze polymeric nitrocellulose. In this study, the differentiation of non-explosive and explosive samples through nitrocellulose fingerprints obtained by capillary electrophoresis was investigated. A batch of 30 different smokeless gunpowders and 23 different everyday products were pulverized, derivatized with a fluorescent agent and analyzed by capillary electrophoresis with laser-induced fluorescence detection. Since this methodology is specific to d-glucopyranose derivatives (cellulosic and related compounds), and paper samples could be easily found in explosion scenes, 11 different paper samples were also included in the study as potential interference samples. In order to discriminate among samples, multivariate analysis (principal component analysis and soft independent modeling of class analogy) was applied to the obtained electrophoretic profiles. To the best of our knowledge, this represents the first study that achieve a successful discrimination between non-explosive and explosive nitrocellulose-based samples, as well as potential cellulose interference samples, and posterior classification of unknown samples into their corresponding groups using CE-LIF and chemometric tools. Copyright © 2013 Elsevier B.V. All rights reserved.

Subscale testing of prompt agent defeat formulations

NASA Astrophysics Data System (ADS)

Knott, A.; Stamatis, D.; Svingala, F.; Lightstone, J.; Miller, K.; Bensman, M.; Bohmke, M.

2017-01-01

There is a need to improve the current bioagent defeat systems with formulations that produce lower peak pressure and impulse, sustained high temperatures, and release of biocidal species for prompt defeat applications. In this work, explosive charge configurations similar to fuel-air explosives were detonated in a semi-enclosed chamber configuration. Binder type and fuel-to-oxidizer ratios were varied to observe the effects on combustion performance. Thermocouple measurements and high-speed video were used to monitor the combustion of the dispersed formulation. The down-selected formulations were then tested in a sub-scale vented agent defeat system developed to evaluate performance of formulations against aerosolized Bacillus thuringiensis (Bt) spores. Diagnostics including thermocouples and piezoelectric pressure gauges were utilized to characterize the detonation event. Biological sampling with surface coupons, liquid impingement, and filters of the post detonation environment were utilized to determine spore survivability and to rank the relative effectiveness of each formulation.

Infrared point sensors for homeland defense applications

NASA Astrophysics Data System (ADS)

Thomas, Ross C.; Carter, Michael T.; Homrighausen, Craig L.

2004-03-01

We report recent progress toward the development of infrared point sensors for the detection of chemical warfare agents and explosive related chemicals, which pose a significant threat to both health and environment. Technical objectives have focused on the development of polymer sorbents to enhance the infrared response of these hazardous organic compounds. For example, infrared point sensors which part-per-billion detection limits have been developed that rapidlypartition chemical warfare agents and explosive related chemicals into polymer thin films with desirable chemical and physical properties. These chemical sensors demonstrate novel routes to reversible sensing of hazardous organic compounds. The development of small, low-power, sensitive, and selective instruments employing these chemical sensors would enhance the capabilities of federal, state, and local emergency response to incidents involving chemical terrorism. Specific applications include chemical defense systems for military personnel and homeland defense, environmental monitors for remediation and demilitarization, and point source detectors for emergency and maintenance response teams.

Quadriplegic areflexic ICU illness: selective thick filament loss and normal nerve histology.

PubMed

Sander, Howard W; Golden, Marianna; Danon, Moris J

2002-10-01

Areflexic quadriplegia that occurs in the intensive care unit (ICU) is commonly ascribed to critical illness polyneuropathy based upon electrophysiology or muscle light microscopy. However, electron microscopy often documents a selective thick filament loss myopathy. Eight ICU patients who developed areflexic quadriplegia underwent biopsy. Seven patients had received steroids, and 2 had also received paralytic agents. Electrodiagnostic studies revealed absent or low-amplitude motor responses in 7. Sensory responses were normal in 5 of 6 and absent in 1. Initial electromyography revealed absent (n = 3), small (n = 3), or polyphasic (n = 1) motor unit potentials, and diffuse fibrillation potentials (n = 5). In all 8, light microscopy of muscle revealed numerous atrophic-angulated fibers and corelike lesions, and electron microscopy revealed extensive thick filament loss. Morphology of sural and intramuscular nerves, and, in one autopsied case, of the obturator nerve and multiple nerve roots, was normal. Although clinical, electrodiagnostic, and light microscopic features mimicked denervating disease, muscle electron microscopy revealed thick filament loss, and nerve histology was normal. This suggests that areflexic ICU quadriplegia is a primary myopathy and not an axonal polyneuropathy. Copyright 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 499-505, 2002

Fast neutron sensor for detection of explosives and chemical warfare agents.

PubMed

Valkovic, Vladivoj; Sudac, Davorin; Matika, Dario

2010-01-01

Once the presence of the anomaly on the bottom of the shallow coastal sea water has been confirmed it is necessary to establish if it contains explosive or chemical warfare charge. We propose that this be performed by using neutron sensor installed within an underwater vessel. When positioned above the object, or to its side, the system can inspect the object for the presence of the threat materials by using alpha particle tagged neutrons from the sealed tube d+t neutron generator. Copyright 2009 Elsevier Ltd. All rights reserved.

Noninvasive Study of Explosive Materials by Time Domain Spectroscopy and FTIR

NASA Astrophysics Data System (ADS)

Huang, Feng; Federici, John; Gary, Dale; Barat, Robert; Zimdars, David

2005-04-01

Transmission and reflection spectroscopy in the Terahertz (THz) range (˜ 3 to 0.1 mm) is potentially useful for the detection of explosives and biological agents. This paper describes the use of THz time domain spectroscopy (TDS) applied in transmission to the 1,3,5 trinitro-s-triazine (RDX), C4, Amonium Nitrate, etc. Samples were also subjected to Fourier Transform Infrared (FTIR) spectroscopy over the same range for comparison. General agreement confirms the absorption features found. The nature of THz technology applied in the noninvasive detection of such material is discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capacio, B.R.; Harris, L.W.; Anderson, D.R.

The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepan, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. AH compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (micrometer ol/kg) values and peak effect tunes were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepwn,more » 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock MES and subcutaneous pentylenetetrazol (scMET)). I serve agents, anticonvulsants, diazepam, accelerating rotarod, motor performance.« less

Description of a new approach for great auricular and auriculotemporal nerve blocks: A cadaveric study in foxes and dogs.

PubMed

Stathopoulou, Thaleia-Rengina; Pinelas, Rui; Haar, Gert Ter; Cornelis, Ine; Viscasillas, Jaime

2018-05-01

Otitis externa is a painful condition that may require surgical intervention in dogs. A balanced analgesia protocol should combine systemic analgesic agents and local anaesthesia techniques. The aim of the study was to find anatomical landmarks for the great auricular and the auriculotemporal nerves that transmit nociceptive information from the ear pinna and to develop the optimal technique for a nerve block. The study consisted of two phases. In phase I, one fox cadaver was used for dissection and anatomical localization of the auricular nerves to derive landmarks for needle insertion. Eight fox cadavers were subsequently used to evaluate the accuracy of the technique by injecting methylene blue bilaterally. In phase II findings from phase I were applied in four Beagle canine cadavers. A block was deemed successful if more than 0.6 cm of the nerve's length was stained. Successful great auricular nerve block was achieved by inserting the needle superficially along the wing of the atlas with the needle pointing towards the jugular groove. For the auriculotemporal nerve block the needle was inserted perpendicular to the skin at the caudal lateral border of the zygomatic arch, close to the temporal process. The overall success rate was 24 out of 24 (100%) and 22 out of 24 (91%) for the great auricular and the auriculotemporal nerves, respectively, while the facial nerve was stained on three occasions. Our results suggest that it is feasible to achieve a block of the auricular nerves, based on anatomical landmarks, without concurrently affecting the facial nerve. © 2018 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.

Real-time, label-free, intraoperative visualization of peripheral nerves and micro-vasculatures using multimodal optical imaging techniques

PubMed Central

Cha, Jaepyeong; Broch, Aline; Mudge, Scott; Kim, Kihoon; Namgoong, Jung-Man; Oh, Eugene; Kim, Peter

2018-01-01

Accurate, real-time identification and display of critical anatomic structures, such as the nerve and vasculature structures, are critical for reducing complications and improving surgical outcomes. Human vision is frequently limited in clearly distinguishing and contrasting these structures. We present a novel imaging system, which enables noninvasive visualization of critical anatomic structures during surgical dissection. Peripheral nerves are visualized by a snapshot polarimetry that calculates the anisotropic optical properties. Vascular structures, both venous and arterial, are identified and monitored in real-time using a near-infrared laser-speckle-contrast imaging. We evaluate the system by performing in vivo animal studies with qualitative comparison by contrast-agent-aided fluorescence imaging. PMID:29541506

Proceedings of the Army Numerical Analysis Conference (11th) Held at Frankford Arsenal, Philadelphia, Pa., on 13-14 February 1974

DTIC Science & Technology

1974-12-01

incineration of chemical agent mustard and pesticides are presented. 1. EDGEWOOD ARSENAL INCINERATION PROGRAM The name of the program which we...only 5 elements to a compound read. -This was fine for mustard, but had to be altered when we wished to simulate the incineration of a nerve agent VX...input data to this program. A process flow sheet of the scrubber system is shown in Figure 1. The incinerator burns Mustard Agent . The off gas from

Times and locations of explosions; U.S. Geological Survey 1962 field season

USGS Publications Warehouse

Roller, John C.

1962-01-01

The U.S. Geological Survey detonated 86 large charges of chemical explosives in the western United States from 6 June to 9 August 1962, in a study of crustal structure in the western United States. This Technical Letter consists of two tables containing information about these explosions. Table I gives a brief geographical description of the shotpoints, and Table II gives the date, time, location, charge size, surface elevation, and some general information about the shots. In the Remarks column (Table II), the configuration and depth of most of the charges are given. This part of the table is not complete, as some of this information has not yet been compiled. Three types of explosives were used in the program. These were: Nitramon WW, a carbo-nitrate blasting agent; Composition B, a mixture of RDX and TNT; and Tovex-Gel, a non-nitroglycerin blasting slurry. The loading, firing, and surveying was done by United ElectroDynamics, Inc., of Pasadena, California. The timing was done by the U.S. Geological Survey.

Remote detection of explosives using field asymmetric ion mobility spectrometer installed on multicopter.

PubMed

Kostyukevich, Yury; Efremov, Denis; Ionov, Vladimir; Kukaev, Eugene; Nikolaev, Eugene

2017-11-01

The detection of explosives and drugs in hard-to-reach places is a considerable challenge. We report the development and initial experimental characterization of the air analysis system that includes Field Asymmetric Ion Mobility Spectrometer, array of the semiconductor gas sensors and is installed on multicopter. The system was developed based on the commercially available DJI Matrix 100 platform. For data collection and communication with operator, the special compact computer (Intel Compute Stick) was installed onboard. The total weight of the system was 3.3 kg. The system allows the 15-minute flight and provides the remote access to the obtained data. The developed system can be effectively used for the detection of impurities in the air, ecology monitoring, detection of chemical warfare agents, and explosives, what is especially important in light of recent terroristic attacks. The capabilities of the system were tested on the several explosives such as trinitrotoluene and nitro powder. Copyright © 2017 John Wiley & Sons, Ltd.

Transcriptional Inducers of Acetylcholinesterase Expression as Novel Antidotes for Protection Against Chemical Warfare Agents

DTIC Science & Technology

2005-10-01

neuroblastoma cell line , P19 and a human neuroblastoma cell line SH - SY5Y (data not shown). Effect of trichostatin A on...mouse neuroblastoma P19 cell line and a human neuroblastoma cell line SH - SY5Y . More experiments are needed to prove the potential of AChE expression in...treatment of nerve agent exposure. MATERIALS AND METHODS Neuronal cell lines and

Technical and Associated R&D Laboratory/Project Support to AFRL/RXQL Airbase Sciences Branch

DTIC Science & Technology

2011-10-01

the organophosphorus nerve agents . The coupons were allowed to sit overnight at room temperature to allow the phosphoric acid to adsorb into the...of chlorine and of ammonia across samples of several soil types; measurements of adsorption of two chemical agent surrogates (dimethyl...methylphosphonate and diisopropyl fluorophosphate) on cellulose and silica gel surfaces by inverse gas chromatography, to infer enthalpies of adsorption. Reactive

Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

DTIC Science & Technology

2010-04-01

target for oganophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence GlyXSerXGly of acetylcholinesterase. By...human plasma. Task 6. Use a second method, for example enzyme activity assays or immunoprecipitation, to confirm the identity of soman-labeled proteins...spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin: a potential

Polysaccharide-thickened aqueous fluoride solutions for rapid destruction of the nerve agent VX. Introducing the opportunity for extensive decontamination scenarios.

PubMed

Elias, Shlomi; Saphier, Sigal; Columbus, Ishay; Zafrani, Yossi

2014-01-01

Among the chemical warfare agents, the extremely toxic nerve agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) is a target of high importance in the development of decontamination methods, due to its indefinite persistence on common environmental surfaces. Liquid decontaminants are mostly characterized by high corrosivity, usually offer poor coverage, and tend to flow and accumulate in low areas. Therefore, the development of a noncorrosive decontaminant, sufficiently viscous to resist dripping from the contaminated surface, is necessary. In the present paper we studied different polysaccharides-thickened fluoride aqueous solutions as noncorrosive decontaminants for rapid and efficient VX degradation to the nontoxic product EMPA (ethyl methylphosphonic acid). Polysaccharides are environmentally benign, natural, and inexpensive. Other known decontaminants cannot be thickened by polysaccharides, due to the sensitivity of the latter toward basic or oxidizing agents. We found that the efficiency of VX degradation in these viscous solutions in terms of kinetics and product identity is similar to that of KF aqueous solutions. Guar gum (1.5 wt %) with 4 wt % KF was chosen for further evaluation. The benign nature, rheological properties, adhering capabilities to different surfaces, and decontamination from a porous matrix were examined. This formulation showed promising properties for implementation as a spray decontaminant for common and sensitive environmental surfaces.

Genipin-Cross-Linked Chitosan Nerve Conduits Containing TNF-α Inhibitors for Peripheral Nerve Repair.

PubMed

Zhang, Li; Zhao, Weijia; Niu, Changmei; Zhou, Yujie; Shi, Haiyan; Wang, Yalin; Yang, Yumin; Tang, Xin

2018-07-01

Tissue engineered nerve grafts (TENGs) are considered a promising alternative to autologous nerve grafting, which is considered the "gold standard" clinical strategy for peripheral nerve repair. Here, we immobilized tumor necrosis factor-α (TNF-α) inhibitors onto a nerve conduit, which was introduced into a chitosan (CS) matrix scaffold utilizing genipin (GP) as the crosslinking agent, to fabricate CS-GP-TNF-α inhibitor nerve conduits. The in vitro release kinetics of TNF-α inhibitors from the CS-GP-TNF-α inhibitor nerve conduits were investigated using high-performance liquid chromatography. The in vivo continuous release profile of the TNF-α inhibitors released from the CS-GP-TNF-α inhibitor nerve conduits was measured using an enzyme-linked immunosorbent assay over 14 days. We found that the amount of TNF-α inhibitors released decreased with time after the bridging of the sciatic nerve defects in rats. Moreover, 4 and 12 weeks after surgery, histological analyses and functional evaluations were carried out to assess the influence of the TENG on regeneration. Immunochemistry performed 4 weeks after grafting to assess early regeneration outcomes revealed that the TENG strikingly promoted axonal outgrowth. Twelve weeks after grafting, the TENG accelerated myelin sheath formation, as well as functional restoration. In general, the regenerative outcomes following TENG more closely paralleled findings observed with autologous grafting than the use of the CS matrix scaffold. Collectively, our data indicate that the CS-GP-TNF-α inhibitor nerve conduits comprised an elaborate system for sustained release of TNF-α inhibitors in vitro, while studies in vivo demonstrated that the TENG could accelerate regenerating axonal outgrowth and functional restoration. The introduction of CS-GP-TNF-α-inhibitor nerve conduits into a scaffold may contribute to an efficient and adaptive immune microenvironment that can be used to facilitate peripheral nerve repair.

Sex and Violence in Neuroscience.

ERIC Educational Resources Information Center

Barnes, Deborah M.

1988-01-01

Describes advances made in the understanding of how sex hormones may modify various cognitive skills, how normal brain signaling mechanisms may cause nerve cell death, and how many cells appear to hold genetic agents which determine their own destruction. (RT)

A Comparative Toxidrome Analysis of Human Organophosphate and Nerve Agent Poisonings Using Social Media

PubMed Central

Colman, E

2017-01-01

Here we utilized social media to compare the toxidrome of three lethal chemical exposures worldwide. YouTube videos were the main source from which the data were collected, but published reports and news were also utilized to fill in some gaps. All videos were organized in a database detailing symptoms and severity of each victim, along with demographics such as approximate age and gender. Each symptom was rated as mild, moderate, or severe and corresponding pie graphs for each incident were compared. The videos displayed symptoms ranging from mild to severe cholinergic toxicity and life‐threatening convulsions. Social media may represent an important resource in developing a viable approach to the early detection and identification of chemical exposure, reinforce our preparedness for better antidotes, long‐term follow up, and training about deadly chemical nerve agent attacks. PMID:28238224

Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

PubMed

Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

2018-01-30

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

Modeling and simulation of explosion effectiveness as a function of blast and crowd characteristics

NASA Astrophysics Data System (ADS)

Usmani, Zeeshan-Ul-Hassan

Suicide bombing has become one of the most lethal and favorite modus operandi of terrorist organizations around the world. On average, there is a suicide bombing attack every six days somewhere in the world. While various attempts have been made to assess the impact of explosions on structures and military personnel, little has been done on modeling the impact of a blast wave on a crowd in civilian settings. The assessment of an explosion's effect on a crowd can lead to better management of disasters, triage of patients, locating blast victims under the debris, development of protective gear, and safe distance recommendations to reduce the casualties. The overall goal of this work is to predict the magnitude of injuries and lethality on humans from a blast-wave with various explosive and crowd characteristics, and to compare, contrast, and analyze the performance of explosive and injury models against the real-life data of suicide bombing incidents. This thesis introduces BlastSim---a physics based stationary multi-agent simulation platform to model and simulate a suicide bombing event. The agents are constrained by the physical characteristics and mechanics of the blast wave. The BlastSim is programmed to test, analyze, and validate the results of different model combinations under various conditions with different sets of parameters, such as the crowd and explosive characteristics, blockage and human shields, fragmentation and the bomber's position, in 2-dimensional and 3-dimensional environments. The suicide bombing event can be re-created for forensic analysis. The proposed model combinations show a significant performance---the Harold Brode explosive model with Catherine Lee injury model using the blockage stands out consistently to be the best with an overall cumulative accuracy of 87.6%. When comparing against actual data, overall, prediction accuracy can be increased by 71% using this model combination. The J. Clutter with Reflection explosive model using Charles Stewart injury model with blockage works best for confined-space incidents with an accuracy of 80%. Blockage in a crowd can increase the accuracy by 17% for all models. Line-of-sight with an attacker, rushing towards an exit, announcing the threat of a suicide bombing, sitting inside a vehicle or building, and standing closer to a wall or a rigid surface were found to be the most lethal choices both during and after an attack. The findings can have implications for emergency response and counter terrorism.

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

High-Resolution Nerve Ultrasound and Electrophysiological Findings in Restless Legs Syndrome.

PubMed

Pitarokoili, K; Fels, M; Kerasnoudis, A; Toenges, L; Gold, R; Yoon, M-S

2018-05-11

Restless legs syndrome (RLS) is a multifactorial network disorder of a sensorimotor system extending from dopaminergic and glutamatergic cerebral structures to the spinal neurons and peripheral nerves. The role of peripheral nerve damage in the causality and severity progression for RLS patients remains unclear. We performed a clinical and epidemiological study on a cohort of 34 RLS patients focusing on RLS risk factors and disease severity. We investigated the peripheral nerves with nerve conduction studies and with high-resolution nerve ultrasound (HRUS). In 18 of the 34 patients (mean age 67.4 ± 15 years old), a sensorimotor axonal neuropathy was diagnosed. These patients presented with late-onset RLS were treated with membrane stabilizing agents, whereas no neuropathy predisposing comorbidity could be identified for the majority of them. We could show an inverse correlation between the amplitudes of the tibial nerve for the patients with polyneuropathy and the RLS severity index. Neuropathy patients were characterized by an increase of the cross-sectional area (CSA) of the tibial nerve in the popliteal fossa and by increased intranerve and internerve variability values showing an asymmetry of CSA distribution. This pattern resembles previous studies on diabetic neuropathy. Early diagnosis, characterization, and treatment of neuropathy are increasingly relevant for RLS patients as it correlates with disease severity. HRUS revealed a pattern resembling diabetic neuropathy, which implies a similar pathophysiology with metabolic and ischemic origin of RLS-related axonal neuropathy. Copyright © 2018 by the American Society of Neuroimaging.

Gas chromatography/ion mobility spectrometry as a hyphenated technique for improved explosives detection and analysis

NASA Technical Reports Server (NTRS)

Mercado, AL; Marsden, Paul

1995-01-01

Ion Mobility Spectrometry (IMS) is currently being successfully applied to the problem of on-line trace detection of plastic and other explosives in airports and other facilities. The methods of sample retrieval primarily consist of batch sampling for particulate residue on a filter card for introduction into the IMS. The sample is desorbed into the IMS using air as the carrier and negative ions of the explosives are detected, some as an adduct with a reagent ion such as Cl(-). Based on studies and tests conducted by different airport authorities, this method seems to work well for low vapor pressure explosives such as RDX and PETN, as well as TNT that are highly adsorptive and can be found in nanogram quantities on contaminated surfaces. Recently, the changing terrorist threat and the adoption of new marking agents for plastic explosives has meant that the sample introduction and analysis capabilities of the IMS must be enhanced in order to keep up with other detector developments. The IMS has sufficient analytical resolution for a few threat compounds but the IMS Plasmogram becomes increasingly more difficult to interpret when the sample mixture gets more complex.

Effect of W/O Emulsion Fuel Properties on Spray Combustion

NASA Astrophysics Data System (ADS)

Ida, Tamio; Fuchihata, Manabu; Takeda, Shuuco

This study proposes a realizable technology for an emulsion combustion method that can reduce environmental loading. This paper discusses the effect on spray combustion for W/O emulsion fuel properties with an added agent, and the ratio between water and emulsifier added to a liquid fuel. The addition of water or emulsifier to a liquid fuel affected the spray combustion by causing micro-explosions in the flame due to geometric changes in the sprayed flame and changes to the temperature distribution. Experimental results revealed that the flame length shortened by almost 40% upon the addition of the water. Furthermore, it was found that water was effective in enhancing combustion due to its promoting micro-explosions. Results also showed that when the emulsifier was added to the spray flame, the additive burned in the flame's wake, producing a bright red flame. The flame length was observed to be long as a result. The micro-explosion phenomenon, caused by emulsifier dosage differences, was observed using time-dependent images at a generated frequency and an explosion scale with a high-speed photography method. Results indicated that the micro-explosion phenomenon in the W/O emulsion combustion method effectively promoted the combustion reaction and suppressed soot formation.

Recent Advances in the Treatment of Organophosphorous Poisonings

PubMed Central

Balali-Mood, Mahdi; Saber, Hamidreza

2012-01-01

Organophosphorous compounds have been employed as pesticides and chemical warfare nerve agents. Toxicity of organophosphorous compounds is a result of excessive cholinergic stimulation through inhibition of acetyl cholinesterase. Clinical manifestations include cholinergic syndromes, central nervous system and cardiovascular disorders. Organophosphorous pesticide poisonings are common in developing worlds including Iran and Sri Lanka. Nerve agents were used during the Iraq-Iran war in 1983-1988 and in a terrorist attack in Japan in 1994-1995. Following decontamination, depending on the severity of intoxication the administration of atropine to counteract muscarinic over-stimulation, and an oxime to reactivate acetyl cholinesterase are indicated. Supportive and intensive care therapy including diazepam to control convulsions and mechanical respiration may be required. Recent investigations have revealed that intravenous infusion of sodium bicarbonate to produce mild to moderate alkalinization is effective. Gacyclidine; an antiglutamatergic compound, was also proved to be beneficial in conjunction with atropine, pralidoxime, and diazepam in nerve agent poisoning. Intravenous magnesium sulfate decreased hospitalization duration and improved outcomes in patients with organophosphorous poisoning. Bio-scavengers including fresh frozen plasma or albumin have recently been suggested as a useful therapy through clearing of free organophosphates. Hemofiltration and antioxidants are also suggested for organophosphorous poisoning. Recombinant bacterial phosphotriesterases and hydrolases that are able to transfer organophosphorous-degrading enzymes are very promising in delayed treatment of organophosphorous poisoning. Recently, encapsulation of drugs or enzymes in nanocarriers has also been proposed. Given the signs and symptoms of organophosphorous poisoning, health professionals should remain updated about the recent advances in treatment of organophosphorous poisoning poisonings. PMID:23115436

Breeding system and bumblebee drone pollination of an explosively pollen-releasing plant, Meliosma tenuis (Sabiaceae).

PubMed

Wong Sato, A A; Kato, M

2018-05-01

Explosive pollen release is a mechanism used by some angiosperms that serves to attach pollen to a pollinator's body. It is usually adopted by species with zygomorphic tubular flowers and pollinated by birds and bees. The tree genus Meliosma (Sabiaceae, Proteales) has unique disc-like flowers that are externally actinomorphic, but internally zygomorphic, and release pollen explosively. To elucidate the adaptive significance of explosive pollen release, we observed flowering behaviour, the breeding system and pollinator visits to flowers of the Japanese species Meliosma tenuis in a temperate forest. Flowers bloomed in June and were nectariferous and protandrous. Explosive pollen release was triggered by slight tactile stimuli to anther filaments or staminodes in male-stage flowers. Because pollen cannot come into contact with the pistils enclosed by staminodes, M. tenuis is functionally protandrous. Artificial pollination treatments revealed that M. tenuis is allogamous. The dominant flower visitors were nectar-seeking drones of the bumblebee species Bombus ardens (Apidae). The drones' behaviour, pollen attachment on their bodies and fruit set of visit-restricted flowers suggest that they are the only agent triggering the explosive pollen release mechanism, and are the main pollinator of M. tenuis. The finding that bumblebee workers rarely visit these flowers suggests that the explosive pollen release has another function, namely to discourage pollen-harvesting bumblebee workers. © 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

Esterase metabolism of cholinesterase inhibitors using rat liver in vitro

EPA Science Inventory

A variety of chemicals, such as organophosphate (OP) and carbamate pesticides, nerve agents, and industrial chemicals, inhibit acetylcholinesterase (AChE) leading to overstimulation of the cholinergic nervous system. The resultant neurotoxicity is similar across mammalian species...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2011 CFR

2011-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

40 CFR 272.2251 - Utah State-Administered program: Final authorization.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: nerve, military, and chemical agents) as more stringent than the Federal rule. To the extent that unused... Wastewaters, Carbamate Wastes, and Spent Potliners (Revision Checklist 151) 61 FR 15566;61 FR 15660; 4/8/96;4...

Wearable Flexible and Stretchable Glove Biosensor for On-Site Detection of Organophosphorus Chemical Threats

DTIC Science & Technology

2017-03-03

finger enables rapid on-site detection of organophosphate (OP) nerve-agent compounds on suspicious surfaces and agricultural products following their...used as pesticides in agricultural and domestic settings.21,22 These OP neurotoxins severely affect the nervous system and lead to rapid death. Due to...The “on-hand” detection of different OP chemical agents on a variety of surfaces and agricultural foodstuffs demonstrate that the new wireless glove

Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

DTIC Science & Technology

2010-09-01

or VX. Guinea pigs chronically instrumented for concurrent recordings of EEG, cardiorespiratory activities , diaphragm and skeletal muscle EMG were... activities , or any debilitating effects. The animals were asymptomatic within 30 min following therapy and survived the agent challenge 24 hr later. In...For a thorough efficacy evaluation, the animals were chronically instrumented to permit concurrent recordings of central nervous system activity

Structural Analysis and Bioengineering of Thermostable Pyrococcus furiosus Prolidase for the Optimization of Organophosphorus Nerve Agent Detoxification

DTIC Science & Technology

2012-04-26

in the following categories: PaperReceived TOTAL: (b) Papers published in non-peer-reviewed journals (N/A for none) Number of ... biodegradable , yet they are extremely toxic to mammals because they bind to acetyl cholinesterase and render it inactive leading to a buildup of the ...respiratory complications, respiratory failure, coma and death. OP compounds exist mainly in the form of pesticides and chemical warfare agents

Immunohistopathology in the Guinea Pig Following Chronic Low-Level Exposure to Chemical Warfare Agents

DTIC Science & Technology

2005-11-01

U.S. Army Medical Research Institute of Chemical Defense USAMRICD-TR-05-09 Immunohistopathology in the Guinea Pig Following Chronic Low...2005 2. REPORT TYPE Technical Report 3. DATES COVERED (From - To) May 2003 to April 2005 4. TITLE AND SUBTITLE Immunohistopathology in the Guinea Pig Following...release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Guinea pigs exposed repeatedly to low levels of chemical warfare nerve agents

Mapping auditory nerve firing density using high-level compound action potentials and high-pass noise masking a

PubMed Central

Earl, Brian R.; Chertoff, Mark E.

2012-01-01

Future implementation of regenerative treatments for sensorineural hearing loss may be hindered by the lack of diagnostic tools that specify the target(s) within the cochlea and auditory nerve for delivery of therapeutic agents. Recent research has indicated that the amplitude of high-level compound action potentials (CAPs) is a good predictor of overall auditory nerve survival, but does not pinpoint the location of neural damage. A location-specific estimate of nerve pathology may be possible by using a masking paradigm and high-level CAPs to map auditory nerve firing density throughout the cochlea. This initial study in gerbil utilized a high-pass masking paradigm to determine normative ranges for CAP-derived neural firing density functions using broadband chirp stimuli and low-frequency tonebursts, and to determine if cochlear outer hair cell (OHC) pathology alters the distribution of neural firing in the cochlea. Neural firing distributions for moderate-intensity (60 dB pSPL) chirps were affected by OHC pathology whereas those derived with high-level (90 dB pSPL) chirps were not. These results suggest that CAP-derived neural firing distributions for high-level chirps may provide an estimate of auditory nerve survival that is independent of OHC pathology. PMID:22280596

Pathogenesis of Borna disease in rats: evidence that intra-axonal spread is the major route for virus dissemination and the determinant for disease incubation.

PubMed

Carbone, K M; Duchala, C S; Griffin, J W; Kincaid, A L; Narayan, O

1987-11-01

Borna disease virus is an uncharacterized agent that causes sporadic but fatal neurological disease in horses and sheep in Europe. Studies of the infection in rats have shown that the agent has a strict tropism for neural tissues, in which it persists indefinitely. Inoculated rats developed encephalitis after an incubation period of 17 to 90 days. This report shows that the incubation period is the time required for transport of the agent in dendritic-axonal processes from the site of inoculation to the hippocampus. The immune responses to the agent had no effect on replication or transport of the virus. The neural conduit to the brain was proven by intranasal inoculation of virus that resulted in rapid transport of the agent via olfactory nerves to the hippocampus and in development of disease in 20 days. Virus inoculation into the feet resulted in spread along nerve fibers from neuron to neuron. There was sequential replication in neurons of the dorsal root ganglia adjacent to the lumbar spinal cord, the gracilis nucleus in the medulla, and pyramidal cells in the cerebral cortex, followed by infection of the hippocampal neurons and onset of disease. This progression required 50 to 60 days. The exclusiveness of the neural conduit was proven by failure to cause infection after injection of the virus intravenously or into the feet of neurectomized rats.

Neuroprotection trek--the next generation: neuromodulation II. Applications--epilepsy, nerve regeneration, neurotrophins

NASA Technical Reports Server (NTRS)

Andrews, Russell J.

2003-01-01

Three examples of neuroprotective applications of electrical stimulation-neuromodulation-are considered: (1) the diagnosis and treatment of epilepsy, (2) the augmentation of peripheral nerve regeneration after transection, and (3) the interaction between electrical stimulation and neurotrophins (notably brain derived neurotrophic factor [BDNF]) in various neuroprotective situations. The research cited demonstrates clear benefit from appropriate electrical stimulation in the treatment of (1) certain patients with medication-refractory epilepsy, and (2) the functional regeneration of peripheral nerves after transection and surgical repair. Furthermore, neuromodulation of peripheral nerve regeneration has been associated with an increase in the neurotrophin BDNF. The roles of BDNF and other neurotrophins in several disorders of the nervous system are discussed in the context of neuromodulation and its augmentation of neurotrophins. Neuromodulation-at least in part through its effect on BDNF and other neurotrophins-will likely play a major role in the treatment (and possibly prevention) of disorders of the nervous system for which neuroproteive pharmacologic agents have traditionally been sought.

Neuroprotection trek--the next generation: neuromodulation II. Applications--epilepsy, nerve regeneration, neurotrophins.

PubMed

Andrews, Russell J

2003-05-01

Three examples of neuroprotective applications of electrical stimulation-neuromodulation-are considered: (1) the diagnosis and treatment of epilepsy, (2) the augmentation of peripheral nerve regeneration after transection, and (3) the interaction between electrical stimulation and neurotrophins (notably brain derived neurotrophic factor [BDNF]) in various neuroprotective situations. The research cited demonstrates clear benefit from appropriate electrical stimulation in the treatment of (1) certain patients with medication-refractory epilepsy, and (2) the functional regeneration of peripheral nerves after transection and surgical repair. Furthermore, neuromodulation of peripheral nerve regeneration has been associated with an increase in the neurotrophin BDNF. The roles of BDNF and other neurotrophins in several disorders of the nervous system are discussed in the context of neuromodulation and its augmentation of neurotrophins. Neuromodulation-at least in part through its effect on BDNF and other neurotrophins-will likely play a major role in the treatment (and possibly prevention) of disorders of the nervous system for which neuroproteive pharmacologic agents have traditionally been sought.

Integration of multi-array sensors and support vector machines for the detection and classification of organophosphate nerve agents

NASA Astrophysics Data System (ADS)

Land, Walker H., Jr.; Sadik, Omowunmi A.; Embrechts, Mark J.; Leibensperger, Dale; Wong, Lut; Wanekaya, Adam; Uematsu, Michiko

2003-08-01

Due to the increased threats of chemical and biological weapons of mass destruction (WMD) by international terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat biochemical warfare. Furthermore, recent events have highlighted awareness that chemical and biological agents (CBAs) may become the preferred, cheap alternative WMD, because these agents can effectively attack large populations while leaving infrastructures intact. Despite the availability of numerous sensing devices, intelligent hybrid sensors that can detect and degrade CBAs are virtually nonexistent. This paper reports the integration of multi-array sensors with Support Vector Machines (SVMs) for the detection of organophosphates nerve agents using parathion and dichlorvos as model stimulants compounds. SVMs were used for the design and evaluation of new and more accurate data extraction, preprocessing and classification. Experimental results for the paradigms developed using Structural Risk Minimization, show a significant increase in classification accuracy when compared to the existing AromaScan baseline system. Specifically, the results of this research has demonstrated that, for the Parathion versus Dichlorvos pair, when compared to the AromaScan baseline system: (1) a 23% improvement in the overall ROC Az index using the S2000 kernel, with similar improvements with the Gaussian and polynomial (of degree 2) kernels, (2) a significant 173% improvement in specificity with the S2000 kernel. This means that the number of false negative errors were reduced by 173%, while making no false positive errors, when compared to the AromaScan base line performance. (3) The Gaussian and polynomial kernels demonstrated similar specificity at 100% sensitivity. All SVM classifiers provided essentially perfect classification performance for the Dichlorvos versus Trichlorfon pair. For the most difficult classification task, the Parathion versus Paraoxon pair, the following results were achieved (using the three SVM kernels: (1) ROC Az indices from approximately 93% to greater than 99%, (2) partial Az values from ~79% to 93%, (3) specificities from 76% to ~84% at 100 and 98% sensitivity, and (4) PPVs from 73% to ~84% at 100% and 98% sensitivities. These are excellent results, considering only one atom differentiates these nerve agents.

Comparison of the efficacy of articaine and prilocaine local anaesthesia for pulpotomy of maxillary and mandibular primary molars.

PubMed

Yilmaz, Y; Eyuboglu, O; Keles, S

2011-06-01

The aim of this study was to compare the local anaesthetic efficacy of articaine HCl and prilocaine HCl during an operative procedure after their administration by either mandibular nerve block or maxillary infiltration. The study was a double-blind clinical study which comprised 162 children (81 boys and 81 girls), who required a pulpotomy on their primary molars. Pain-related behaviours were used to assess the severity of pain during the injection of either prilocaine HCl or articaine HCl and the operative procedures following either a maxillary infiltration or mandibular nerve block of the two local anaesthetic agents. The frequencies of post-procedural adverse events in the prilocaine and articaine anaesthetised groups were also determined. Significantly more discomfort (p<0.05) was observed following maxillary infiltration compared to mandibular nerve block. There were no significant differences in the pain-related behaviours scores between the two local anaesthetic agents administered during the dental operative procedures, except for the removal of the coronal pulp. For this latter procedure, the pain-related behaviour score was 1.5- times higher in the prilocain-anaesthetised children than in the articaine-anaesthetised children. The frequencies of post- procedural adverse events in the prilocaine-treated children were similar to those found in the articaine-treated children. We concluded that local anaesthesia following mandibular nerve block is more effective than that following maxillary infiltration in 6-8-year-old children. However, the intensity of pain that was experienced by the children during administration of either prilocaine or articaine and some of the dental procedures after their administration were similar.

IN VITRO RESEARCH OF THE ALTERATION OF NEURONS IN VAGAL CORE IN MEDULLA OBLONGATA AT ASPHYXIC DEATHS

PubMed Central

Haliti, Naim; Islami, Hilmi; Elezi, Nevzat; Shabani, Ragip; Abdullahu, Bedri; Dragusha, Gani

2010-01-01

The aim of this study was to research the morphological changes of neurons in the vagus nerve nuclei in medulla oblongata in asphyxia related death cases. Morphological changes that were investigated were mainly in the dorsal motor respiratory center (DMRC), nucleus tractus solitarius (nTS) and nucleus ambigus (nA) in the medulla oblongata. In our research, the autopsy material from asphyxia related death cases was used from various etiologies: monoxide carbon (CO), liquid drowning, strangulation, electricity, clinical-pathological death, firing weapon, explosive weapon, sharp and blunt objects and death cases due to accident. The material selected for research was taken from medulla oblongata and lungs from all lobes. The material from the medulla oblongata and lungs was fixed in a 10% solution of buffered formalin. Special histochemical methods for central nervous system (CNS) were employed like: Cresyl echt violet, toluidin blue, Sevier-Munger modification and Grimelius. For stereometrical analysis of the quantitative density of the neurons the universal testing system Weibel M42 was used. The acquired results show that in sudden asphyxia related death cases, there are alterations in the nuclei of vagal nerve in form of: central chromatolysis, axonal retraction, axonal fragmentation, intranuclear vacuolization, cytoplasmic vacuolization, edema, condensation and dispersion of substance of Nissl, proliferation of oligodendrocytes, astrocytes and microglia. The altered population of vagus nerve neurons does not show an important statistica! significarne compared to the overall quantity of the neurons in the nuclei of the vagus nerve (p<0,05). PMID:20846134

Somatosensory Neurotoxicity: Agents and Assessment Methodology.

EPA Science Inventory

The somatosensory system is comprised of a variety of sensory receptors located in the skin, muscle tendons, and visceral organs that are innervated by myelinated and nonmyelinated axons of the peripheral nervous system. These peripheral sensory nerve fibers in tum communicate so...

Somatosensory Neurotoxicity: Agents and Assessment Methodology

EPA Science Inventory

The somatosensory system is comprised of a variety of sensory receptors located in the skin, muscle tendons, and visceral organs that are innervated by myelinated and nonmyelinated axons of the peripheral nervous system. These peripheral sensory nerve fibers in turn communicate s...

Micromotor-based on-off fluorescence detection of sarin and soman simulants.

PubMed

Singh, Virendra V; Kaufmann, Kevin; Orozco, Jahir; Li, Jinxing; Galarnyk, Michael; Arya, Gaurav; Wang, Joseph

2015-06-30

Self-propelled micromotor-based fluorescent "On-Off" detection of nerve agents is described. The motion-based assay utilizes Si/Pt Janus micromotors coated with fluoresceinamine toward real-time "on-the-fly" field detection of sarin and soman simulants.

Acetylcholinesterases of Blood-feeding Flies and Ticks

USDA-ARS?s Scientific Manuscript database

Acetylcholinesterase (AChE) is the biochemical target of organophosphate (OP) and carbamate pesticides for invertebrates, vertebrate nerve agents, and AChE inhibitors used to reduce effects of Alzheimer’s disease. Organophosphate pesticides (OPs) are widely used to control blood-feeding arthropods, ...

Complexity of acetylcholinesterases in biting flies and ticks

USDA-ARS?s Scientific Manuscript database

Acetylcholinesterase (AChE) inhibitors function as pesticides for invertebrates, vertebrate nerve agents, and medicine to reduce cognitive effects of Alzheimer’s disease. Organophosphate (OP) pesticides have been widely used to control biting flies and ticks, however, OP-resistance has compromised c...

Biocatalytic nerve agent detoxification in fire fighting foams.

PubMed

LeJeune, K E; Russell, A J

1999-03-20

Current events across the globe necessitate rapid technological advances to combat the epidemic of nerve agent chemical weapons. Biocatalysis has emerged as a viable tool in the detoxification of organophosphorus neurotoxins, such as the chemical weapons VX and sarin. Efficient detoxification of contaminated equipment, machinery, and soils are of principal concern. This study describes the incorporation of a biocatalyst (organophosphorus hydrolase, E.C. 3.1.8.1) into conventional formulations of fire fighting foam. The capacity of fire fighting foams to decrease volatilization of contained contaminants, increase surface wettability, and control the rate of enzyme delivery to large areas makes them useful vehicles for enzyme application at surfaces. The performance of enzyme containing foams has been shown to be not only reproducible but also predictable. An empirical model provides reasonable estimations for the amounts of achievable surface decontamination as a function of the important parameters of the system. Theoretical modeling illustrates that the enzyme-containing foam is capable of extracting agent from the surface and is catalytically active at the foam-surface interface and throughout the foam itself. Biocatalytic foam has proven to be an effective, "environmentally friendly" means of surface and soil decontamination.

Study of the n-methyl-d-aspartate antagonistic properties of anticholinergic drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonough, J.H.; Shih, T.M.

1995-12-31

A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs. PHARMACOL BIOCHEM BEHAV. 51(2/3) 249-253, 1995. Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex have the ability to terminate nerve agent-induced seizures and modulate the neuropathologic consequences of agent exposure. Drugs with mixed anticholinergic and anti-NMDA properties potentially provide an ideal class of compounds for development as anticonvulsant treatments for nerve agent casualties. The present experiment evaluated the potential NMDA antagonist activity of 11 anticholinergic drugs by determining whether pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antagonizedmore » NMDA lethality and are ranked according to their potency: mecamylamine > procyclidine = benactyzine > biperiden > tribexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinudidinyl benzilate (QNB), and scopolamine failed to show NMDA antagonist properties. In addition, and unexpectedly, diazepam, ethanol, and pentobarbital were also shown to be capable of antagonizing NMDA lethality over a certain range of doses. The advantages and limitations of using antagonism of NMDA lethality in mice as a bioassay for determining the NMDA antagonist properties of drugs are also discussed.« less

Polymer-based lanthanide luminescent sensor for detection of the hydrolysis product of the nerve agent Soman in water.

PubMed

Jenkins, A L; Uy, O M; Murray, G M

1999-01-15

The techniques of molecular imprinting and sensitized lanthanide luminescence have been combined to create the basis for a sensor that can selectively measure the hydrolysis product of the nerve agent Soman in water. The sensor functions by selectively and reversibly binding the phosphonate hydrolysis product of this agent to a functionality-imprinted copolymer possessing a coordinatively bound luminescent lanthanide ion, Eu3+. Instrumental support for this device is designed to monitor the appearance of a narrow luminescence band in the 610-nm region of the Eu3+ spectrum that results when the analyte is coordinated to the copolymer. The ligand field shifted luminescence was excited using 1 mW of the 465.8-nm line of an argon ion laser and monitored via an optical fiber using a miniature spectrometer. For this configuration, the limit of detection for the hydrolysis product is 7 parts per trillion (ppt) in solution with a linear range from 10 ppt to 10 ppm. Chemical and spectroscopic selectivities have been combined to reduce the likelihood of false positive analyses. Chemically analogous organophosphorus pesticides tested against the sensor have been shown to not interfere with determination.

Deficit, recovery and the vis nervosa.

PubMed

McDonald, Ian

2006-01-01

Physicians have long sought to explain neurological deficit and recovery on the basis of alterations in the agent of nervous action. The ancient Greeks knew that the brain influences muscles and they showed experimentally that the effects were mediated by nerves. Galen believed that the agent of action was the animal spirits. Ideas began to change with a new approach to knowledge and the revival of experimentation that followed the arrival in Venice of ancient Greek manuscripts after the fall of Constantinople in 1453. In the mid-18th century the notion of animal spirits was replaced by that of the vis nervosa and speculation began that the agent might be electrical. This was established by the mid-19th century. The nature of conduction in nerve was clearly different from that in a wire but how it took place remained uncertain until Hodgkin and Huxley proved the ionic hypothesis in the mid-20th century. In the following decades the membrane mechanisms of conduction failure and restoration were elucidated, with practical consequences in the form of improved diagnostic methods and the potential for more rational approaches to treatment. The demonstration that adaptive cortical plasticity contributes to recovery raises the possibility of new strategies for neurological rehabilitation.

33 CFR 160.204 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Definitions. 160.204 Section 160... Certain Dangerous Cargos § 160.204 Definitions. As used in this subpart: Agent means any person..., explosion, grounding, leaking, damage, injury or illness of a person aboard, or manning-shortage...

N,N-Dihaloamine Explosives as Harmful Agent Defeat Materials

DTIC Science & Technology

2014-06-01

hexachloromelamine detonations .......................32 List of Figures Figure 1. Stainless steel detonation chamber...12 Figure 10. Stainless steel coupons for spore samples ....................................................................14... Stainless steel mesh (2 cm × 2 cm), as used; tube containing the screen rolled into a cone, inserted in the tube

How Can We Use Bioinformatics to Predict Which Agents Will Cause Birth Defects?

EPA Science Inventory

The availability of genomic sequences from a growing number of human and model organisms has provided an explosion of data, information, and knowledge regarding biological systems and disease processes. High-throughput technologies such as DNA and protein microarray biochips are ...

Vertically Integrated MEMS SOI Composite Porous Silicon-Crystalline Silicon Cantilever-Array Sensors: Concept for Continuous Sensing of Explosives and Warfare Agents

NASA Astrophysics Data System (ADS)

Stolyarova, Sara; Shemesh, Ariel; Aharon, Oren; Cohen, Omer; Gal, Lior; Eichen, Yoav; Nemirovsky, Yael

This study focuses on arrays of cantilevers made of crystalline silicon (c-Si), using SOI wafers as the starting material and using bulk micromachining. The arrays are subsequently transformed into composite porous silicon-crystalline silicon cantilevers, using a unique vapor phase process tailored for providing a thin surface layer of porous silicon on one side only. This results in asymmetric cantilever arrays, with one side providing nano-structured porous large surface, which can be further coated with polymers, thus providing additional sensing capabilities and enhanced sensing. The c-Si cantilevers are vertically integrated with a bottom silicon die with electrodes allowing electrostatic actuation. Flip Chip bonding is used for the vertical integration. The readout is provided by a sensitive Capacitance to Digital Converter. The fabrication, processing and characterization results are reported. The reported study is aimed towards achieving miniature cantilever chips with integrated readout for sensing explosives and chemical warfare agents in the field.

Thoracoscopic patch insulation to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy.

PubMed

Mediratta, Neeraj; Barker, Diane; McKevith, James; Davies, Peter; Belchambers, Sandra; Rao, Archana

2012-07-01

Cardiac resynchronization therapy is an established therapy for heart failure, improving quality of life and prognosis. Despite advances in technique, available leads and delivery systems, trans-venous left ventricular (LV) lead positioning remains dependent on the patient's underlying venous anatomy. The left phrenic nerve courses over the surface of the pericardium laterally and may be stimulated by the LV pacing lead, causing uncomfortable diaphragmatic twitch. This paper describes a video-assisted thoracoscopic (VATS) procedure to correct phrenic nerve stimulation secondary to cardiac resynchronization therapy. Most current ways of avoiding phrenic stimulation involve either electronic reprogramming to distance the phrenic nerve from the stimulation circuit or repositioning the lead. We describe a case where the phrenic nerve was surgically insulated from the stimulating current by insinuating a patch of bovine pericardium between the epicardium and native pericardium of the heart thus completely resolving previously intolerable and incessant diaphragmatic twitch. The procedure was performed under general anaesthesia with single-lung ventilation and minimal use of neuromuscular blocking agents. Surgical patch insulation of the phrenic nerve was performed using minimally invasive VATS surgery, as a short-stay procedure, with no complications. No diaphragmatic twitch occurred post-surgery and the patient continued to gain symptomatic benefit from cardiac synchronization therapy (New York Heart Association Class III to II), enabling return to work. In cases where the trans-venous position of a LV lead is limited by troublesome phrenic nerve stimulation, thoracoscopic surgical patch insulation of the phrenic nerve could be considered to allow beneficial cardiac resynchronization therapy.

Modelling and Testing of Blast Effect On the Structures

NASA Astrophysics Data System (ADS)

Figuli, Lucia; Jangl, Štefan; Papán, Daniel

2016-10-01

As a blasting agent in the blasting and mining engineering, has been using one of so called new generation of explosives which offer greater flexibility in their range and application, and such explosive is ANFO. It is type of explosive consists of an oxidiser and a fuel (ammonium nitrate and fuel oil). One of such ANFO explosives which are industrially made in Slovakia is POLONIT. The explosive is a mixture of ammonium nitrate, methyl esters of higher fatty acids, vegetable oil and red dye. The paper deals with the analysis of structure subjected to the blast load created by the explosion of POLONIT charge. First part of paper is describing behaviour and characteristic of blast wave generated from the blast (detonation characteristics, physical characteristics, time-history diagram etc.) and the second part presents the behaviour of such loaded structures, because of the analysis of such dynamical loaded structure is required knowing the parameters of blast wave, its effect on structure and the tools for the solution of dynamic analysis. The real field tests of three different weight of charges and two different structures were done. The explosive POLONIT was used together with 25 g of ignition explosive PLNp10. Analytical and numerical model of blast loaded structure is compared with the results obtained from the field tests (is compared with the corresponding experimental accelerations). For the modelling structures were approximated as a one-degree system of freedom (SDOF), where the blast wave was estimated with linear decay and exponential decay using positive and negative phase of blast wave. Numerical solution of the steel beam dynamic response was performed via FEM (Finite Element Method) using standard software Visual FEA.

Comparative Kinetics and Distribution to Target Tissues of Organophosphates Using Physiologically - Based Pharmacokinetic Modeling

DTIC Science & Technology

2008-03-01

throughout history where nerve agents have been used on human populations, such as the subway bombing in Tokyo and Matsumoto, Japan. Data can be...kidney, fat, diaphragm, arterial blood, venous blood, bronchial passages, and the skin. The remaining tissues will be lumped together as either slowly...were then further developed as a weapon, whose primary effect is on the central nervous system. These agents are tabun, sarin, soman, and VX. They

Spectroscopic and Computational Investigation of Room-Temperature Decomposition of a Chemical Warfare Agent Simulant on Polycrystalline Cupric Oxide

DOE PAGES

Trotochaud, Lena; Tsyshevsky, Roman; Holdren, Scott; ...

2017-08-21

Certain organophosphorus molecules are infamous due to their use as highly toxic nerve agents. The filtration materials currently in common use for protection against chemical warfare agents were designed before organophosphorus compounds were used as chemical weapons. A better understanding of the surface chemistry between simulant molecules and the individual filtration-material components is a critical precursor to the development of more effective materials for filtration, destruction, decontamination, and/or sensing of nerve agents. Here, we report on the surface adsorption and reactions of a sarin simulant molecule, dimethyl methylphosphonate (DMMP), with cupric oxide surfaces. In situ ambient pressure X-ray photoelectron andmore » infrared spectroscopies are coupled with density functional calculations to propose mechanisms for DMMP decomposition on CuO. We find extensive room temperature decomposition of DMMP on CuO, with the majority of decomposition fragments bound to the CuO surface. We observe breaking of PO-CH3, P-OCH3, and P-CH3bonds at room temperature. On the basis of these results, we identify specific DMMP decomposition mechanisms not seen on other metal oxides. Participation of lattice oxygen in the decomposition mechanism leads to significant changes in chemical and electronic surface environment, which are manifest in the spectroscopic and computational data. This study establishes a computational baseline for the study of highly toxic organophosphorous compounds on metal oxide surfaces.« less

Using Metal Complex Ion-Molecule Reactions in a Miniature Rectilinear Ion Trap Mass Spectrometer to Detect Chemical Warfare Agents

NASA Astrophysics Data System (ADS)

Graichen, Adam M.; Vachet, Richard W.

2013-06-01

The gas-phase reactions of a series of coordinatively unsaturated [Ni(L)n]y+ complexes, where L is a nitrogen-containing ligand, with chemical warfare agent (CWA) simulants in a miniature rectilinear ion trap mass spectrometer were investigated as part of a new approach to detect CWAs. Results show that upon entering the vacuum system via a poly(dimethylsiloxane) (PDMS) membrane introduction, low concentrations of several CWA simulants, including dipropyl sulfide (simulant for mustard gas), acetonitrile (simulant for the nerve agent tabun), and diethyl phosphite (simulant for nerve agents sarin, soman, tabun, and VX), can react with metal complex ions generated by electrospray ionization (ESI), thereby providing a sensitive means of detecting these compounds. The [Ni(L)n]2+ complexes are found to be particularly reactive with the simulants of mustard gas and tabun, allowing their detection at low parts-per-billion (ppb) levels. These detection limits are well below reported exposure limits for these CWAs, which indicates the applicability of this new approach, and are about two orders of magnitude lower than electron ionization detection limits on the same mass spectrometer. The use of coordinatively unsaturated metal complexes as reagent ions offers the possibility of further tuning the ion-molecule chemistry so that desired compounds can be detected selectively or at even lower concentrations.

Spectroscopic and Computational Investigation of Room-Temperature Decomposition of a Chemical Warfare Agent Simulant on Polycrystalline Cupric Oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trotochaud, Lena; Tsyshevsky, Roman; Holdren, Scott

Certain organophosphorus molecules are infamous due to their use as highly toxic nerve agents. The filtration materials currently in common use for protection against chemical warfare agents were designed before organophosphorus compounds were used as chemical weapons. A better understanding of the surface chemistry between simulant molecules and the individual filtration-material components is a critical precursor to the development of more effective materials for filtration, destruction, decontamination, and/or sensing of nerve agents. Here, we report on the surface adsorption and reactions of a sarin simulant molecule, dimethyl methylphosphonate (DMMP), with cupric oxide surfaces. In situ ambient pressure X-ray photoelectron andmore » infrared spectroscopies are coupled with density functional calculations to propose mechanisms for DMMP decomposition on CuO. We find extensive room temperature decomposition of DMMP on CuO, with the majority of decomposition fragments bound to the CuO surface. We observe breaking of PO-CH3, P-OCH3, and P-CH3bonds at room temperature. On the basis of these results, we identify specific DMMP decomposition mechanisms not seen on other metal oxides. Participation of lattice oxygen in the decomposition mechanism leads to significant changes in chemical and electronic surface environment, which are manifest in the spectroscopic and computational data. This study establishes a computational baseline for the study of highly toxic organophosphorous compounds on metal oxide surfaces.« less

[Chemical weapons and chemical terrorism].

PubMed

Nakamura, Katsumi

2005-10-01

Chemical Weapons are kind of Weapons of Mass Destruction (WMD). They were used large quantities in WWI. Historically, large quantities usage like WWI was not recorded, but small usage has appeared now and then. Chemical weapons are so called "Nuclear weapon for poor countrys" because it's very easy to produce/possession being possible. They are categorized (1) Nerve Agents, (2) Blister Agents, (3) Cyanide (blood) Agents, (4) Pulmonary Agents, (5) Incapacitating Agents (6) Tear Agents from the viewpoint of human body interaction. In 1997 the Chemical Weapons Convention has taken effect. It prohibits chemical weapons development/production, and Organization for the Prohibition of Chemical Weapons (OPCW) verification regime contributes to the chemical weapons disposal. But possibility of possession/use of weapons of mass destruction by terrorist group represented in one by Matsumoto and Tokyo Subway Sarin Attack, So new chemical terrorism countermeasures are necessary.

Measurement of drug facilitated sexual assault agents in simulated sweat by ion mobility spectrometry.

PubMed

Demoranville, Leonard T; Verkouteren, Jennifer R

2013-03-15

Ion mobility spectrometry has found widespread use for the detection of explosives and illicit drugs. The technique offers rapid results with high sensitivity and little sample preparation. As such, it is well suited for field deployed screening settings. Here the response of ion mobility spectrometers for three drug-facilitated sexual assault (DFSA) agents - flunitrazepam, ketamine, and MDMA - and related metabolites has been studied in the presence of a simulated sweat. While all three DFSA agents present certain challenges for qualitative identification, IMS can provide useful information to guide the early treatment and investigation of sexual assault cases. Used as a presumptive test, the identification of DFSA agents would later require confirmatory analysis by other techniques. Published by Elsevier B.V.

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2011-08-01

evaluated alone and in combination (i.e. pyridostigmine bromide (PB), diethyl-m-toluamide (DEET), 5 lipopolysaccharide (LPS), corticosterone (CORT) and...acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These combined

Nerve-gas destruction with metal organic frameworks

EPA Science Inventory

Chemical warfare agents (CWAs) such as saran, soman, and tabun have been developed since World War I. Their mode of action involves the rapid formation of phosphate ester bonds with acetylcholinesterase to attenuate activity. The cumulative result of this activity loss leads to a...

[Orbital apex syndrome of the aspergillus etiology--a case report].

PubMed

Fric, E; Rehák, M; Vlcková, I; Burval, S; Chrapek, O; Rehák, J

2007-04-01

The authors present a case report of a patient, in whom after a head injury the monolateral blindness occurred. Because of autoimmune thrombocytopeny the patient was treated with long-term corticosteroids. The clinical findings corresponded with the orbital apex syndrome. According to the results of the CT and MRI examinations, the sphenoidotomy was indicated, and the histological findings verified fragments of paranasal sinuses' aspergiloma. During the next course of the disease, despite antimycotic therapy, the progression of the aspergiloma in to the anterior cranial fossa occurred. Invasive sino-orbital aspergilosis, after the penetration of the infectious agent across the wall of the sinus, may cause the orbital apex syndrome with paralysis of all three cranial nerves innervating the extraocular muscles, sensoric defect in the area of the ophthalmic nerve and the involvement of the optic nerve.

Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans.

PubMed

Yi, Sang-Wook; Ohrr, Heechoul; Hong, Jae-Seok; Yi, Jee-Jeon

2013-09-01

The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.

Thin-layer chromatography and colorimetric analysis of multi-component explosive mixtures

DOEpatents

Pagoria, Philip F.; Mitchell, Alexander R.; Whipple, Richard E.; Carman, M. Leslie

2014-08-26

A thin-layer chromatography method for detection and identification of common military and peroxide explosives in samples includes the steps of provide a reverse-phase thin-layer chromatography plate; prepare the plate by marking spots on which to deposit the samples by touching the plate with a marker; spot one micro liter of a first standard onto one of the spots, spot one micro liter of a second standard onto another of the spots, and spot samples onto other of spots producing a spotted plate; add eluent to a developing chamber; add the spotted plate to the developing chamber; remove the spotted plate from the developing chamber producing a developed plate; place the developed plate in an ultraviolet light box; add a visualization agent to a dip tank; dip the developed plate in the dip tank and remove the developed plate quickly; and detect explosives by viewing said developed plate.

The clinical consequences of an industrial aerosol plant explosion.

PubMed

Hull, D; Grindlinger, G A; Hirsch, E F; Petrone, S; Burke, J

1985-04-01

The factors relating to the clinical outcome of an industrial aerosol plant explosion are reviewed. Eighteen of 24 workers inside the plant required hospitalization and five died. Proximity to the blast was associated with extensive injuries unless workers were shielded by physical barriers or partitions. Burn severity and mortality were increased in those wearing synthetic garments compared to their counterparts wearing fiber clothing. Facial burns occurred in all unprotected workers. Forearm and hand burns in 11 patients required decompressive escharotomies. Topical treatment with silver sulfadiazine was associated with more significant leukopenia and neutropenia than treatment with silver nitrate. We conclude that industrial design should include safeguards which isolate workers from flammable materials, including isolation of explosive materials from working areas, alarm systems to detect leakage of flammable agents, protective barriers and shields, and the regulation and institution of flame and flash-resistant clothing.

[Ion mobility spectrometer (IMS): a novel online monitor of trace volatile organic compounds].

PubMed

Li, Fang; Xie, Zhi-yong; Schmidt, H; Sielemann, S; Baumbach, J I

2002-12-01

The principle, character and developments of the instrument of ion mobility spectrometry are introduced, the applications of IMS to chemical warfare agents, explosives, drugs, environments monitoring and on-site industrial sensing are discussed, and some work on IMS in ISAS is represented.

Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nambiar, Madhusoodana P.; Gordon, Richard K.; Rezk, Peter E.

2007-03-15

To develop therapeutics against lung injury and respiratory toxicity following nerve agent VX exposure, we evaluated the protective efficacy of a number of potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m{sup 3} of VX or saline using a microinstillation inhalation exposure technique for 4 min and then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h survival rate of 52%. There was a significant increase in bronchoalveolar lavage (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti-sense syk oligonucleotides 2 min post-exposure didmore » not significantly increase the survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway, and bronchioles, VX-induced viscous mucous secretions were exacerbated by these aerosolized treatments. To overcome these events, we developed a strategy to protect the animals by treatment with atropine. Atropine inhibits muscarinic stimulation and markedly reduces the copious airway secretion following nerve agent exposure. Indeed, post-exposure treatment with atropine methyl bromide, which does not cross the blood-brain barrier, resulted in 100% survival of VX-exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated animals exhibited lower protein levels, cell number, and cell death compared to VX-exposed controls, indicating less lung injury. When pulmonary therapeutics were combined with atropine, significant protection to VX-exposure was observed. These results indicate that combinations of pulmonary therapeutics with atropine or drugs that inhibit mucous secretion are important for the treatment of respiratory toxicity and lung injury following VX exposure.« less

Simultaneous Measurement of Tabun, Sarin, Soman, Cyclosarin, VR, VX, and VM Adducts to Tyrosine in Blood Products by Isotope Dilution UHPLC-MS/MS

PubMed Central

Crow, Brian S.; Pantazides, Brooke G.; Quiñones-González, Jennifer; Garton, Joshua W.; Carter, Melissa D.; Perez, Jonas W.; Watson, Caroline M.; Tomcik, Dennis J.; Crenshaw, Michael D.; Brewer, Bobby N.; Riches, James R.; Stubbs, Sarah J.; Read, Robert W.; Evans, Ronald A.; Thomas, Jerry D.; Blake, Thomas A.; Johnson, Rudolph C.

2015-01-01

This work describes a new specific, sensitive, and rapid stable isotope dilution method for the simultaneous detection of the organophosphorus nerve agents (OPNAs) tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VR, VX, and VM adducts to tyrosine (Tyr). Serum, plasma, and lysed whole blood samples (50 µL) were prepared by protein precipitation followed by digestion with Pronase. Specific Tyr adducts were isolated from the digest by a single solid phase extraction (SPE) step, and the analytes were separated by reversed-phase ultra high performance liquid chromatography (UHPLC) gradient elution in less than 2 min. Detection was performed on a triple quadrupole tandem mass spectrometer using time-triggered selected reaction monitoring (SRM) in positive electrospray ionization (ESI) mode. The calibration range was characterized from 0.100–50.0 ng/mL for GB– and VR– Tyr and 0.250–50.0 ng/mL for GA–, GD–, GF–, and VX/VM–Tyr (R2 ≥ 0.995). Inter- and intra-assay precision had coefficients of variation of ≤17 and ≤10%, respectively, and the measured concentration accuracies of spiked samples were within 15% of the targeted value for multiple spiking levels. The limit of detection was calculated to be 0.097, 0.027, 0.018, 0.074, 0.023, and 0.083 ng/mL for GA–, GB–, GD–, GF–, VR–, and VX/VM–Tyr, respectively. A convenience set of 96 serum samples with no known nerve agent exposure was screened and revealed no baseline values or potential interferences. This method provides a simple and highly specific diagnostic tool that may extend the time postevent that a confirmation of nerve agent exposure can be made with confidence. PMID:25286390