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Sample records for agents nerve agents

  1. Inhalational exposure to nerve agents.

    PubMed

    Niven, Alexander S; Roop, Stuart A

    2004-03-01

    The respiratory system plays a major role in the pathogenesis of nerve agent toxicity. It is the major route of entry and absorption of nerve agent vapor, and respiratory failure is the most common cause of death follow-ing exposure. Respiratory symptoms are mediated by chemical irritation,muscarinic and nicotinic receptor overstimulation, and central nervous system effects. Recent attacks have demonstrated that most patients with an isolated vapor exposure developed respiratory symptoms almost immediately. Most patients had only mild and transient respiratory effects, and those that did develop significant respiratory compromise did so rapidly. These observations have significant ramifications on triage of patients in a mass-casualty situation, because patients with mild-to-moderate exposure to nerve agent vapor alone do not require decontamination and are less likely to develop progressive symptoms following initial antidote therapy. Limited data do not demonstrate significant long-term respiratory effects following nerve agent exposure and treatment. Provisions for effective respiratory protection against nerve agents is a vital consideration in any emergency preparedness or health care response plan against a chemical attack. PMID:15062227

  2. Chemical warfare. Nerve agent poisoning.

    PubMed

    Holstege, C P; Kirk, M; Sidell, F R

    1997-10-01

    The threat of civilian and military casualties from nerve agent exposure has become a greater concern over the past decade. After rapidly assessing that a nerve agent attack has occurred, emphasis must be placed on decontamination and protection of both rescuers and medical personnel from exposure. The medical system can become rapidly overwhelmed and strong emotional reactions can confuse the clinical picture. Initially, care should first be focused on supportive care, with emphasis toward aggressive airway maintenance and decontamination. Atropine should be titrated, with the goal of therapy being drying of secretions and the resolution of bronchoconstriction and bradycardia. Early administration of pralidoxime chloride maximizes antidotal efficacy. Benzodiazepines, in addition to atropine, should be administered if seizures develop. Early, aggressive medical therapy is the key to prevention of the morbidity and mortality associated with nerve agent poisoning. PMID:9330846

  3. Nerve agents: implications for anesthesia providers.

    PubMed

    Hrobak, Paula Kay

    2008-04-01

    Anesthesia providers may be called to treat injuries from chemical weapons or spills, for which prompt treatment is vital. It is therefore important to understand the mechanism of action of nerve agents and the resultant pathophysiology and to be able to quickly recognize the signs and symptoms of nerve agent exposure. This review article addresses the different types of nerve agents that are currently being manufactured as well as the symptomatic and definitive treatment of the patient who presents with acute nerve agent toxicity. This article also reviews the physiology of the neuromuscular junction and the autonomic nervous system receptors that nerve agent toxicity affects. PMID:18478812

  4. Emergency department management of nerve agent exposure.

    PubMed

    Pfaff, B L

    1998-01-01

    Nerve agents are toxic chemicals developed for use by the military, but used by terrorists against civilian populations. As threats of terrorism increase, it is possible that health care providers will be confronted with multiple victims of nerve agent exposure. Nerve agents are highly toxic forms of organophosphate poisons that potentially could cause harm to anyone who comes in contact. Emergency personnel need to be familiar with the agents, know how to prepare for encountering and treating victims, and know how to protect all people involved from further poisoning. PMID:9855972

  5. Resuscitative challenges in nerve agent poisoning.

    PubMed

    Ben Abraham, Ron; Weinbroum, Avi A

    2003-09-01

    The threat of weapons of mass destruction such as nerve agents has become real since last year. The medical community has established protocols for the rapid evacuation and decontamination of affected civilians. However, protocols for resuscitative measures or acute perioperative care in cases of life-saving surgical interventions in toxic-traumatized casualties are still lacking. The database concerning the effects of nerve agent poisoning in humans is limited, and is largely based on reports of unintentional exposures to pesticide organophosphate poisoning and similar chemical substances. In this review, we summarize the knowledge on the possible pharmacological interactions between nerve agents and acute care. PMID:12972890

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

    SciTech Connect

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika; Edwards, Carol C.; Fleming, Christopher D.; MacDonald, Mary; Cashman, John R.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

    2010-10-28

    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 with 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.

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

    PubMed Central

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika; Edwards, Carol C.; Fleming, Christopher D.; MacDonald, Mary; Cashman, John R.; Potter, Philip M.; Cerasoli, Douglas M.

    2010-01-01

    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 with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the PR enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the PS 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 PS 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. PMID:20051531

  8. Fluorescent sensors for organophosphorus nerve agent mimics.

    PubMed

    Dale, Trevor J; Rebek, Julius

    2006-04-12

    We present a small molecule sensor that provides an optical response to the presence of an organophosphorus (OP)-containing nerve agent mimic. The design contains three key features: a primary alcohol, a tertiary amine in close proximity to the alcohol, and a fluorescent group used as the optical readout. In the sensor's rest state, the lone pair of electrons of the basic amine quenches the fluorescence of the nearby fluorophore through photoinduced electron transfer (PET). Exposure to an OP nerve agent mimic triggers phosphorylation of the primary alcohol followed rapidly by an intramolecular substitution reaction as the amine displaces the created phosphate. The quaternized ammonium salt produced by this cyclization reaction no longer possesses a lone pair of electrons, and a fluorescence readout is observed as the nonradiative PET quenching pathway of the fluorophore is shut down. PMID:16594648

  9. An anesthesiological approach to nerve agent victims.

    PubMed

    Cosar, Ahmet; Kenar, Levent

    2006-01-01

    The potential use of weapons of mass destruction has recently become a real threat even in the areas of ongoing armed conflicts. Mass casualty victims can suffer from psychological and physical trauma. The exposure of physically injured patients to a toxic substance, in a scenario of mass injury, has recently gained major attention among planners of future protocols for emergency medical services. Because rapid deterioration and multiorgan involvement are to be expected after physical injuries, proper organization and complex but efficient acute medical care systems must be organized and deployed to ensure a maximal number of saved lives. These victims will inevitably require urgent surgical intervention and prolonged perioperative care. Understanding the interdependence between the toxic and traumatic occurrences and the drugs used to prevent or treat nerve agent intoxication (pyridostigmine bromide, a reversible inhibitor of acetylcholinesterase; atropine, a muscarinic receptor antagonist that is one of the on-site, first aid, pharmacological resuscitation drugs; and oxime-like pralidoxime chloride or obidoxime chloride, acetylcholinesterase reactivators) is vital. In addition, the administration of anesthesia and emergency surgery pose further unpredictable threats to the central nervous system, the cardiovascular system, and respiratory function, all of which may be compromised after chemical intoxication and physical trauma. It is noteworthy that information concerning the effects of nerve agent intoxication among human subjects is derived largely from reports of incidents of intentional terrorist attacks or of accidental exposure to organophosphate pesticides, compounds that are chemically related to nerve agents. PMID:16532866

  10. Organophosphate nerve agent toxicity in Hydra attenuata.

    PubMed

    Lum, Karin T; Huebner, Henry J; Li, Yingchun; Phillips, Timothy D; Raushel, Frank M

    2003-08-01

    The toxicity for analogues of sarin (GB), soman (GD), and VX was evaluated using Hydra attenuata as a model organism. The organophosphate nerve agent analogue simulants used in this investigation included the following: isopropyl p-nitrophenyl methylphosphonate (for GB); pinacolyl p-nitrophenyl methylphosphonate (for GD); and diisopropyl S-(2-diisopropylaminoethyl)phosphorothioate, diethyl S-(2-diisopropylaminoethyl)phosphorothioate, and diethyl S-(2-trimethylaminoethyl)phosphorothioate (for VX). The toxicity of each organophosphate nerve agent was assessed quantitatively by measuring the minimal effective concentration within 92 h in H. attenuata. There is a positive correlation between the molecular hydrophobicity of the compound and its ability to cause toxicity. Results from this study indicate the potential for application of this assay in the field of organophosphate chemical warfare agent detection, as well as for the prediction of toxicity of structurally similar organophosphate compounds. The minimal effective concentration for two of the VX analogues was 2 orders of magnitude more toxic than the analogue for GD and 4 orders of magnitude more toxic than the analogue for GB. PMID:12924922

  11. Detection of nerve agent via perturbation of supramolecular gel formation.

    PubMed

    Hiscock, Jennifer R; Piana, Francesca; Sambrook, Mark R; Wells, Neil J; Clark, Alistair J; Vincent, Jack C; Busschaert, Nathalie; Brown, Richard C D; Gale, Philip A

    2013-10-14

    The formation of tren-based tris-urea supramolecular gels in organic solvents is perturbed by the presence of the nerve agent soman providing a new method of sensing the presence of organophosphorus warfare agents. PMID:23994877

  12. Nanomotors responsive to nerve-agent vapor plumes.

    PubMed

    Singh, Virendra V; Kaufmann, Kevin; Esteban-Fernández de Ávila, Berta; Uygun, Murat; Wang, Joseph

    2016-02-25

    Enzyme-powered nanomotors responsive to the presence of nerve agents in the surrounding atmosphere are employed for remote detection of chemical vapor threats. Distinct changes in the propulsion behavior, associated with the partition of the sarin simulant diethyl chlorophosphate (DCP), offer reliable and rapid detection of the nerve-agent vapor threat. PMID:26824395

  13. Analysis of Nerve Agent Metabolites from Hair for Long-Term Verification of Nerve Agent Exposure.

    PubMed

    Appel, Amanda S; McDonough, John H; McMonagle, Joseph D; Logue, Brian A

    2016-06-21

    Several methods for the bioanalysis of nerve agents or their metabolites have been developed for the verification of nerve agent exposure. However, parent nerve agents and known metabolites are generally rapidly excreted from biological matrixes typically used for analysis (i.e., blood, urine, and tissues), limiting the amount of time after an exposure that verification is feasible. In this study, hair was evaluated as a long-term repository of nerve agent hydrolysis products. Pinacolyl methylphosphonic acid (PMPA; hydrolysis product of soman) and isopropyl methylphosphonic acid (IMPA; hydrolysis product of sarin) were extracted from hair samples with N,N-dimethylformamide and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Limits of detection for PMPA and IMPA were 0.15 μg/kg and 7.5 μg/kg and linear ranges were 0.3-150 μg/kg and 7.5-750 μg/kg, respectively. To evaluate the applicability of the method to verify nerve agent exposure well after the exposure event, rats were exposed to soman, hair was collected after approximately 30 days, and stored for up to 3.5 years prior to initial analysis. PMPA was positively identified in 100% of the soman-exposed rats (N = 8) and was not detected in any of the saline treated animals (N = 6). The hair was reanalyzed 5.5 years after exposure and PMPA was detected in 6 of the 7 (one of the soman-exposed hair samples was completely consumed in the analysis at 3.5 years) rat hair samples (with no PMPA detected in the saline exposed animals). Although analysis of CWA metabolites from hair via this technique is not appropriate as a universal method to determine exposure (i.e., it takes time for the hair to grow above the surface of the skin and typical analysis times are >24 h), it complements existing methods and could become the preferred method for verification of exposure if 10 or more days have elapsed after a suspected exposure. PMID:27161086

  14. Fighting nerve agent chemical weapons with enzyme technology.

    PubMed

    LeJeune, K E; Dravis, B C; Yang, F; Hetro, A D; Doctor, B P; Russell, A J

    1998-12-13

    The extreme toxicity of organophosphorous-based compounds has been known since the late 1930s. Starting in the mid-1940s, many nations throughout the world have been producing large quantities of organophosphorous (OP) nerve agents. Huge stockpiles of nerve agents have since developed. There are reportedly more than 200,000 tons of nerve agents in existence worldwide. There is an obvious need for protective clothing capable of guarding an individual from exposure to OP chemical weapons. Also, chemical processes that can effectively demilitarize and detoxify stored nerve agents are in great demand. The new and widely publicized Chemical Weapons Treaty requires such processes to soon be in place throughout the world. Biotechnology may provide the tools necessary to make such processes not only possible, but quite efficient in reducing the nerve agent dilemma. The following paper discusses some of the history in developing enzyme technology against nerve agents. Our laboratory has interest in enhancing the productivity and potential utility of these systems in both demilitarization and decontamination applications. Freeze-dried nerve agent-hydrolyzing enzyme preparations have been shown to be effective in decontaminating gaseous nerve agents. The direct incorporation of nerve agent-hydrolyzing enzymes within cross-linked polyurethane foam matrices during polymer synthesis has been shown to dramatically enhance the productivity of two different enzyme systems. The future goal of such work lies in building a bridge between the clinical application of nerve agent-hydrolyzing enzymes and practical processing techniques that may take advantage of the initial results already achieved in the laboratory. PMID:9928090

  15. Catalytic bioscavengers in nerve agent poisoning: A promising approach?

    PubMed

    Worek, Franz; Thiermann, Horst; Wille, Timo

    2016-02-26

    The repeated use of the nerve agent sarin against civilians in Syria in 2013 emphasizes the continuing threat by chemical warfare agents. Multiple studies demonstrated a limited efficacy of standard atropine-oxime treatment in nerve agent poisoning and called for the development of alternative and more effective treatment strategies. A novel approach is the use of stoichiometric or catalytic bioscavengers for detoxification of nerve agents in the systemic circulation prior to distribution into target tissues. Recent progress in the design of enzyme mutants with reversed stereo selectivity resulting in improved catalytic activity and their use in in vivo studies supports the concept of catalytic bioscavengers. Yet, further research is necessary to improve the catalytic activity, substrate spectrum and in vivo biological stability of enzyme mutants. The pros and cons of catalytic bioscavengers will be discussed in detail and future requirements for the development of catalytic bioscavengers will be proposed. PMID:26200600

  16. Assessment of nerve agent exposure: existing and emerging methods.

    PubMed

    Langenberg, Jan P; van der Schans, Marcel J; Noort, Daan

    2009-07-01

    The perceived threat of the use of nerve agents by terrorists against civilian targets implies the need for methods for point-of-care (POC) diagnosis. This review presents an overview of methods that are currently available for the assessment of exposure to nerve agents. Since these methods are mostly MS based, they require complex and expensive equipment and well-trained personnel and, consequently, they are not very suitable for rapid POC diagnosis. However, new technologies are emerging that allow, among others, immunochemical detection of acetylcholinesterase inhibited by nerve agents. Also, lab-on-a-chip methodologies are under development. It is anticipated that MS methods will be suitable for POC diagnosis within a few years, due to the miniaturization of equipment and the emergence of methodologies that enable mass spectrometric analysis with little sample pretreatment and that are potentially fieldable, such as direct analysis in real time and desorption electrospray ionization MS. PMID:21083135

  17. Bionanoconjugate-based composites for decontamination of nerve agents.

    PubMed

    Borkar, Indrakant V; Dinu, Cerasela Zoica; Zhu, Guangyu; Kane, Ravi S; Dordick, Jonathan S

    2010-01-01

    We have developed enzyme-based composites that rapidly and effectively detoxify simulants of V- and G-type chemical warfare nerve agents. The approach was based on the efficient immobilization of organophosphorus hydrolase onto carbon nanotubes to form active and stable conjugates that were easily entrapped in commercially available paints. The resulting catalytic-based composites showed no enzyme leaching and rendered >99% decontamination of 10 g/m(2) paraoxon, a simulant of the V-type nerve agent, in 30 minutes and >95% decontamination of diisopropylfluorophosphate, a simulant of G-type nerve agent, in 45 minutes. The formulations are expected to be environmentally friendly and to offer an easy to use, on demand, decontamination alternative to chemical approaches for sustainable material self-decontamination. PMID:20859933

  18. 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.

  19. Nerve agent-induced seizures and their pharmacological modulation

    SciTech Connect

    McDonough, J.H.; Shih, T.M.; Adams, N.L.; Koviak, T.A.; Cook, L.A.

    1993-05-13

    Intoxication with nerve agents produces prolonged central nervous system seizures (status epilepticus) that can produce irreversible brain pathology (15). This report summarizes our recent findings regarding the neurotransmitter changes that occur in discrete brain regions as a function of seizure duration and the differential effectiveness of anticholinergic, benzodiazepine and excitatory amino acid (EAA) antagonist drugs in terminating soman-induced seizures when given at different times after seizure onset. These results are discussed in relation to a model we have proposed to explain the sequence of electrophysiological, biochemical and neurochemical events and mechanisms controlling nerve agent-induced seizures.

  20. 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...

  1. Stereoselective Hydrolysis of Organophosphate Nerve Agents by the Bacterial Phosphotriesterase†

    PubMed Central

    Tsai, Ping-Chuan; Bigley, Andrew; Li, Yingchun; Ghanem, Eman; Cadieux, C. Linn; Kasten, Shane A.; Reeves, Tony E.; Cerasoli, Douglas M.; Raushel, Frank M.

    2010-01-01

    Organophosphorus compounds include many synthetic, neurotoxic substances that are commonly used as insecticides. The toxicity of these compounds is due to their ability to inhibit the enzyme acetylcholine esterase. Some of the most toxic organophosphates have been adapted for use as chemical warfare agents; the most well known are GA, GB, GD, GF, VX and VR. All of these compounds contain a chiral phosphorus center with the SP-enantiomers being significantly more toxic than the RP-enantiomers. Phosphotriesterase (PTE) is an enzyme capable of detoxifying these agents, but the stereochemical preference of the wild-type enzyme is for the RP-enantiomers. A series of enantiomerically pure chiral nerve agent analogues has been developed containing the relevant phosphoryl centers found in GB, GD, GF, VX and VR. Wild-type and mutant forms of PTE have been tested for their ability to hydrolyze this series of compounds. Mutant forms of PTE with significantly enhanced, as well as relaxed or reversed stereoselectivity, have been identified. A number of variants showed dramatically improved kinetic constants for the catalytic hydrolysis of the more toxic SP-enantiomers. Improvements of up to three orders of magnitude relative to the wild type enzyme were observed. Some of these mutants were tested against racemic mixtures of GB and GD. The kinetic constants obtained with the chiral nerve agent analogues accurately predict the improved activity and stereoselectivity against the authentic nerve agents used in this study. PMID:20701311

  2. Detoxification of organophosphate nerve agents by bacterial phosphotriesterase

    SciTech Connect

    Ghanem, Eman; Raushel, Frank M. . E-mail: raushel@tamu.edu

    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 utilized 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.

  3. Chemical approaches for detection and destruction of nerve agents.

    PubMed

    Ajami, Dariush; Rebek, Julius

    2013-06-28

    Since the introduction of organophosphorus (OP) compounds as nerve agents and pesticides, methods of dealing with their toxicity to humans have been intensely researched. There are studies on sensing, pretreatments, prophylactics, antidotes and therapies. There is some overlap in all of these endeavors because they have to deal with the reactivity of the phosphorus atom in various contexts. The contexts range from large spaces, the thinly spread vapors in the air, to very small spaces in the active sites of enzymes - acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) - that have reacted with the OP agent. PMID:23604461

  4. A review of nerve agent exposure for the critical care physician.

    PubMed

    Leikin, Jerrold B; Thomas, Richard G; Walter, Frank G; Klein, Raymond; Meislin, Harvey W

    2002-10-01

    Nerve agents are discussed. The article discusses their properties, routes of exposure, toxicodynamics, targets of toxicity, and treatment. It is concluded that a focused organized approach to the treatment of nerve agents is key to its successful management. PMID:12394966

  5. Multidimensional conducting polymer nanotubes for ultrasensitive chemical nerve agent sensing.

    PubMed

    Kwon, Oh Seok; Park, Seon Joo; Lee, Jun Seop; Park, Eunyu; Kim, Taejoon; Park, Hyun-Woo; You, Sun Ah; Yoon, Hyeonseok; Jang, Jyongsik

    2012-06-13

    Tailoring the morphology of materials in the nanometer regime is vital to realizing enhanced device performance. Here, we demonstrate flexible nerve agent sensors, based on hydroxylated poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes (HPNTs) with surface substructures such as nanonodules (NNs) and nanorods (NRs). The surface substructures can be grown on a nanofiber surface by controlling critical synthetic conditions during vapor deposition polymerization (VDP) on the polymer nanotemplate, leading to the formation of multidimensional conducting polymer nanostructures. Hydroxyl groups are found to interact with the nerve agents. Representatively, the sensing response of dimethyl methylphosphonate (DMMP) as a simulant for sarin is highly sensitive and reversible from the aligned nanotubes. The minimum detection limit is as low as 10 ppt. Additionally, the sensor had excellent mechanical bendability and durability. PMID:22545863

  6. 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. PMID:16808484

  7. New Chemically Functionalized Nanomaterials for Electrical Nerve Agents Sensors

    NASA Astrophysics Data System (ADS)

    Simonato, Jean-Pierre; Clavaguera, Simon; Carella, Alexandre; Delalande, Michael; Raoul, Nicolas; Lenfant, Stephane; Vuillaume, Dominique; Dubois, Emmanuel

    2011-08-01

    A chemical receptor specific to traces of organophosphorus nerve agents (OPs) has been synthesized and grafted to carbon nanotubes and silicon nanowires in order to make electrical sensors. Our results show that it is possible to detect efficiently sub-ppm traces of OPs with excellent selectivity notably with the use of silicon nanowires by monitoring the Drain-Source current of the SiNW-FET at an optimum back Gate voltage as a function of time. First developments of a prototype have also been realized.

  8. Modifications to the organophosphorus nerve agent-protein adduct refluoridation method for retrospective analysis of nerve agent exposures.

    PubMed

    Holland, Kerry E; Solano, Maria I; Johnson, Rudolph C; Maggio, Vincent L; Barr, John R

    2008-01-01

    Organophosphorus nerve agents (OPNAs) continue to pose a threat to military personnel and the general public because of their toxicity and their potential use as weapons of mass destruction. An effective method for the detection of human exposure to OPNAs involves the refluoridation of nerve agents adducted to the serum protein butyrylcholinesterase. The regenerated agents are then enriched by solid-phase extraction and quantified by isotope-dilution gas chromatography-mass spectrometry. We have previously reported improvements that resulted in a 10-fold increase in sensitivity. We have now made further changes to the method that include the addition of confirmation ions, the addition of soman (GD) to the assay, the expansion of the linear range, and the elimination of high-volume injection to decrease background noise and run time while improving sensitivity. This report includes the standard operating procedures for this method for tabun, sarin, soman, cyclohexylsarin, and VX and validation studies. The method's limits of detection ranged from 5.5 to 16.5 pg/mL for the G analogue of VX and GD, respectively. Characterization of quality control (QC) materials resulted in an average coefficient of variation of 15.1% for the five analytes in low QC pools and 11.7% in high QC pools. PMID:18269803

  9. Cyclodextrines as functional agents for decontamination of the skin contaminated by nerve agents.

    PubMed

    Cabal, Jirí; Kuca, Kamil; Sevelová-Bartosová, Lucie; Dohnal, Vlastimil

    2004-01-01

    Three decontamination solutions of beta-cyclodextrines were prepared. Their abilities to decontamine rat skin contamined with nerve agent soman were tested. Decontamination efficacy of the tested cyclodextrine solutions was compared with the same decontamination means but without the cyclodextrines. The efficacy of tested decontaminants was evaluated by the assessment of the ID50 values. Two decontamination prescriptions with cyclodextrines (tetraborate buffer and tetraborate buffer with acetone) do not show significantly better decontamination efficacies in comparison with prescriptions without cyclodextrines. Only in case of aqueous solution of 2-aminoethanol the addition of beta-cyclodextrine resulted in significant increase (32%) in decontamination efficacy. PMID:15446361

  10. Screening of carbonaceous nanoporous materials for capture of nerve agents.

    PubMed

    Kowalczyk, Piotr; Gauden, Piotr A; Terzyk, Artur P; Neimark, Alexander V

    2013-01-01

    A strategy for combined experimental and computational screening of candidate carbonaceous materials for capturing highly volatile nerve agents at ambient temperature using physisorption. Based on theoretical calculations of Henry constants and zero-coverage adsorption enthalpies for sarin and DMMP (its common stimulant) adsorbed in model slit-shaped carbon pores at 298 K, we found the following. Slit-shaped carbon pores with pore width ~0.5 nm are optimal for agent adsorption due to strong confinement of adsorbed molecules. Agent adsorption enthalpy at zero coverage computed for optimal pore width is very high and reaches ~83 kJ mol(-1). Widening of pore width above ~1 nm results in a significant decrease of the Henry constant and zero-coverage adsorption enthalpy (~44 kJ mol(-1)). Polydispersity of studied candidate carbonaceous materials strongly affects adsorption capacity for DMMP under the operating conditions. The optimal carbonaceous adsorbent, pitch-based P7 activated carbon fiber, adsorbed ~100 μg g(-1) DMMP at 0.03 μg m(-3). Commercial Norit activated carbon adsorbed only ~20 μg g(-1) DMMP at 0.03 μg m(-3). Surprisingly, a small shift of the pore size distribution towards wider micropores has a great impact on agent adsorption. Because the adsorption enthalpies computed at zero coverage weakly dependent on pore size, the heat released during agent adsorption is similar for all studied candidate adsorbents (i.e.~55-60 kJ mol(-1)). PMID:23165364

  11. Recent advances toward a fiber optic sensor for nerve agent

    NASA Astrophysics Data System (ADS)

    Beshay, Manal; Cordero, Steven R.; Mukamal, Harold; Ruiz, David; Lieberman, Robert A.

    2008-04-01

    We report advances made on the development of a fiber optic nerve agent sensor having its entire length as the sensing element. Upon exposure to sarin gas or its simulant, diisopropyl fluorophosphate, the cladding changes color resulting in an alteration of the light intensity throughput. The optical fiber is multimode and consists of a fused-silica core and a nerve agent sensitive cladding. The absorption characteristics of the cladding affect the fiber's spectral attenuation and limit the length of light guiding fiber that can be deployed continuously. The absorption of the cladding is also dependent on the sensor formulation, which in turn influences the sensitivity of the fiber. In this paper, data related to the trade-off of sensitivity, spectral attenuation, and length of fiber challenged will be reported. The fiber is mass produced using a conventional fiber optic draw tower. This technology could be used to protect human resources and buildings from dangerous chemical attacks, particularly when large areas or perimeters must be covered. It may also be used passively to determine how well such areas have been decontaminated.

  12. Quantification of nerve agent biomarkers in human serum and urine.

    PubMed

    Røen, Bent Tore; Sellevåg, Stig Rune; Lundanes, Elsa

    2014-12-01

    A novel method for rapid and sensitive quantification of the nerve agent metabolites ethyl, isopropyl, isobutyl, cyclohexyl, and pinacolyl methylphosphonic acid has been established by combining salting-out assisted liquid-liquid extraction (SALLE) and online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). The procedure allows confirmation of nerve agent exposure within 30 min from receiving a sample, with very low detection limits for the biomarkers of 0.04-0.12 ng/mL. Sample preparation by SALLE was performed in less than 10 min, with a common procedure for both serum and urine. Analyte recoveries of 70-100% were obtained using tetrahydrofuran as extraction solvent and Na2SO4 to achieve phase separation. After SALLE, selective analyte retention was obtained on a ZrO2 column by Lewis acid-base and hydrophilic interactions with acetonitrile/1% CH3COOH (82/18) as the loading mobile phase. The phosphonic acids were backflush-desorbed onto a polymeric zwitterionic column at pH 9.8 and separated by hydrophilic interaction liquid chromatography. The method was linear (R(2) ≥ 0.995) from the limits of quantification to 50 ng/mL, and the within- and between-assay repeatability at 20 ng/mL were below 5% and 10% relative standard deviation, respectively. PMID:25371246

  13. Multi-encoded rugate porous silicon as nerve agents sensors.

    PubMed

    Jang, Seunghyun; Kim, Jihoon; Koh, Youngdae; Ko, Young Chun; Woo, Hee-Gweon; Sohn, Honglae

    2007-11-01

    The nanostructured rugate porous silicons (PSi) containing multiple photonic band gaps have been generated by an electrochemical etching through applying a composite waveform summed three computer-generated pseudo-sinusoidal current waveforms. They exhibit three sharp photonic band gaps in the optical reflectivity spectrum, corresponding to the each of the sine components varied from 0.42, 0.36, and 0.30 Hz, with a spacing of 0.06 Hz between each sine component. The sensing experiments using multi-encoded rugate PSi for the detection of nerve agents such as triethyl phosphate (TEP), diethyl chlorophosphate (DCP), dimethyl methylphosphonate (DMMP), and diethyl ethylphosphonate (DEEP) have been achieved. Capillary condensation in the pores causes the reflectivity of rugate PSi to shift to longer wavelengths due to an increase in refractive indices of the porous medium. PMID:18047116

  14. Field deployable EEG monitor for nerve agent casualties.

    PubMed

    McDonnall, Daniel; Hiatt, Scott; Yatsenko, Dimitri; Guillory, K Shane

    2009-01-01

    Early recognition and aggressive management of seizure activity is important in the treatment of patients with nerve agent exposure. However, these patients can experience non-convulsive seizures that are difficult to identify without EEG monitoring. In this paper, we discuss the development and testing of a low-cost, field-deployable device that records and displays patient EEG trends over time. The device is optimized for early levels of care for military and mass casualty patients until they can be relocated to medical facilities with more comprehensive monitoring. The device also records pulse oximetry and acceleration information, and patient data are available for later analysis and improvement of treatment protocols. PMID:19964118

  15. 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. PMID:10068213

  16. Flexible carbon nanotube sensors for nerve agent simulants

    NASA Astrophysics Data System (ADS)

    Cattanach, Kyle; Kulkarni, Rashmi D.; Kozlov, Mikhail; Manohar, Sanjeev K.

    2006-08-01

    Chemiresistor-based vapour sensors made from network films of single-walled carbon nanotube (SWNT) bundles on flexible plastic substrates (polyethylene terephthalate, PET) can be used to detect chemical warfare agent simulants for the nerve agents Sarin (diisopropyl methylphosphonate, DIMP) and Soman (dimethyl methylphosphonate, DMMP). Large, reproducible resistance changes (75-150%), are observed upon exposure to DIMP or DMMP vapours, and concentrations as low as 25 ppm can be detected. Robust sensor response to simulant vapours is observed even in the presence of large equilibrium concentrations of interferent vapours commonly found in battle-space environments, such as hexane, xylene and water (10 000 ppm each), suggesting that both DIMP and DMMP vapours are capable of selectively displacing other vapours from the walls of the SWNTs. Response to these interferent vapours can be effectively filtered out by using a 2 µm thick barrier film of the chemoselective polymer polyisobutylene (PIB) on the SWNT surface. These network films are composed of a 1-2 µm thick non-woven mesh of SWNT bundles (15-30 nm diameter), whose sensor response is qualitatively and quantitatively different from previous studies on individual SWNTs, or a network of individual SWNTs, suggesting that vapour sorption at interbundle sites could be playing an important role. This study also shows that the line patterning method used in device fabrication to obtain any desired pattern of films of SWNTs on flexible substrates can be used to rapidly screen simulants at high concentrations before developing more complicated sensor systems.

  17. [The nerve agent sarin: history, clinical manifestations, and treatment].

    PubMed

    Yanagisawa, Nobuo

    2014-05-01

    Organic phosphate pesticides were used worldwide after World War II and experiences on poisoning and treatment have been accumulated. An organic phosphate "nerve agent" Sarin was used in two terrorist attacks in Japan in the 1990s. Sarin effects on humans were well documented in these two incidents. Sarin gas inhalation caused instantaneous death by respiratory arrest in several victims in Matsumoto. Severely injured victims presenting with coma and generalized convulsion were resuscitated and recovered rapidly without sequelae. Miosis and blurred-dark vision, ocular pain, copious secretions from respiratory and gastrointestinal tract (muscarinic effects), and headache were common in severely to slightly affected victims. Plasma cholinesterase (ChE) activity decreased in parallel with the severity of signs and symptoms in victims. Oximes, atropine sulphate, diazepam, and ample intravenous infusion were effective treatments. Follow-up examinations on victims were conducted up to 10 years in Matsumoto, and 5 years in Tokyo. No neurological sequelae or abnormalities were observed after 1 year, except for a few EEG abnormalities or delay in sensory nerve conduction velocity. Posttraumatic stress disorder (PTSD) was observed in several of the victims in the 5-year follow up, irrespective of the severity of poisoning at Matsumoto. Psychological symptoms continue in victims of both incidents. PMID:24807372

  18. Cholinergic symptoms due to nerve agent attack: a strategy for management.

    PubMed

    Schecter, William P

    2004-09-01

    This article provides a brief history of nerve agent development and use and discusses the pharmacology, symptoms, signs, and treatment of nerve agent exposure. In addition, this article discusses the challenges of mass-casualty triage, decontamination, resuscitation, and intensive care. PMID:15325720

  19. Novel reversible and selective nerve agent simulant detection in conjunction with superoxide "turn-on" probing.

    PubMed

    Jang, Yoon Jeong; Murale, Dhiraj P; Churchill, David G

    2014-04-01

    Herein, we present fluorescein as a reversible fluorescent sensor for nerve agent simulants diethylchlorophosphate (DCP), diethyl methylphosphonate (DEMP), and diethyl cyanophosphonate (DECP). The superoxide allows for an "off-on" mechanism to regenerate fluorescein. The order of decrease in fluorescence intensity for nerve agent simulants is DCP > DEMP ≫ DECP. PMID:24558644

  20. Behavioral efficacy of diazepam against nerve agent exposure in rhesus monkeys. (Reannouncement with new availability information)

    SciTech Connect

    Castro, C.A.; Larsen, T.; Finger, A.V.; Solana, R.P.; McMaster, S.B.

    1991-12-31

    The possibility that nerve agents will be used on the battlefield is real. The traditional therapy against nerve agent exposure consists of pyridostigmine pretreatment and atropine-pralidoxime chloride therapy administered after nerve agent exposure. This therapy regimen is extremely effective in preventing mortality in laboratory animals exposed to multilethal concentrations of nerve agent, yet these animals often display convulsions, brain damage, and behavioral incapacitation. We report here that the addition of diazepam to the traditional therapy for nerve agent (soman) exposure not only decreases the incidence of convulsions, but also attenuates the cognitive impairments of rhesus monkeys trained on a Serial Probe Recognition (SPR) task. Monkeys which received diazepam treatment required only 6 days before their performance on the SPR task returned to presoman exposure levels, compared to nondiazepamtreated monkeys which required 15 days. Moreover, only 1 out of the 5 monkeys which received diazepain treatment suffered tonic-clonic convulsions; in contrast all 5 monkeys which did not receive diazepam treatment experienced severe convulsive episodes. These results suggest that diazepam would be an excellent adjunct to traditional nerve agent therapy to facilitate behavioral recovery from nerve agent intoxication that might be encountered by US military personnel on the battlefield or accidental organophosphate poisoning encountered in industrial or agricultural accidents. Serial probe recognition task, diazepam, nerve agents, soman convulsions, rhesus monkeys, cognition, organophosphate.

  1. Nerve agent hydrolysis activity designed into a human drug metabolism enzyme.

    PubMed

    Hemmert, Andrew C; Otto, Tamara C; Chica, Roberto A; Wierdl, Monika; Edwards, Jonathan S; Lewis, Steven M; Lewis, Steven L; Edwards, Carol C; Tsurkan, Lyudmila; Cadieux, C Linn; Kasten, Shane A; Cashman, John R; Mayo, Stephen L; Potter, Philip M; Cerasoli, Douglas M; Redinbo, Matthew R

    2011-01-01

    Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning. PMID:21445272

  2. Nerve Agent Hydrolysis Activity Designed into a Human Drug Metabolism Enzyme

    PubMed Central

    Hemmert, Andrew C.; Otto, Tamara C.; Chica, Roberto A.; Wierdl, Monika; Edwards, Jonathan S.; Lewis, Steven L.; Edwards, Carol C.; Tsurkan, Lyudmila; Cadieux, C. Linn; Kasten, Shane A.; Cashman, John R.; Mayo, Stephen L.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

    2011-01-01

    Organophosphorus (OP) nerve agents are potent suicide inhibitors of the essential neurotransmitter-regulating enzyme acetylcholinesterase. Due to their acute toxicity, there is significant interest in developing effective countermeasures to OP poisoning. Here we impart nerve agent hydrolysis activity into the human drug metabolism enzyme carboxylesterase 1. Using crystal structures of the target enzyme in complex with nerve agent as a guide, a pair of histidine and glutamic acid residues were designed proximal to the enzyme's native catalytic triad. The resultant variant protein demonstrated significantly increased rates of reactivation following exposure to sarin, soman, and cyclosarin. Importantly, the addition of these residues did not alter the high affinity binding of nerve agents to this protein. Thus, using two amino acid substitutions, a novel enzyme was created that efficiently converted a group of hemisubstrates, compounds that can start but not complete a reaction cycle, into bona fide substrates. Such approaches may lead to novel countermeasures for nerve agent poisoning. PMID:21445272

  3. Flexible carbon nanotube sensors for nerve agent simulants.

    PubMed

    Cattanach, Kyle; Kulkarni, Rashmi D; Kozlov, Mikhail; Manohar, Sanjeev K

    2006-08-28

    Chemiresistor-based vapour sensors made from network films of single-walled carbon nanotube (SWNT) bundles on flexible plastic substrates (polyethylene terephthalate, PET) can be used to detect chemical warfare agent simulants for the nerve agents Sarin (diisopropyl methylphosphonate, DIMP) and Soman (dimethyl methylphosphonate, DMMP). Large, reproducible resistance changes (75-150%), are observed upon exposure to DIMP or DMMP vapours, and concentrations as low as 25 ppm can be detected. Robust sensor response to simulant vapours is observed even in the presence of large equilibrium concentrations of interferent vapours commonly found in battle-space environments, such as hexane, xylene and water (10 000 ppm each), suggesting that both DIMP and DMMP vapours are capable of selectively displacing other vapours from the walls of the SWNTs. Response to these interferent vapours can be effectively filtered out by using a 2 µm thick barrier film of the chemoselective polymer polyisobutylene (PIB) on the SWNT surface. These network films are composed of a 1-2 µm thick non-woven mesh of SWNT bundles (15-30 nm diameter), whose sensor response is qualitatively and quantitatively different from previous studies on individual SWNTs, or a network of individual SWNTs, suggesting that vapour sorption at interbundle sites could be playing an important role. This study also shows that the line patterning method used in device fabrication to obtain any desired pattern of films of SWNTs on flexible substrates can be used to rapidly screen simulants at high concentrations before developing more complicated sensor systems. PMID:21727548

  4. In vitro kinetics of nerve agent degradation by fresh frozen plasma (FFP).

    PubMed

    Wille, Timo; Thiermann, Horst; Worek, Franz

    2014-02-01

    Great efforts have been undertaken in the last decades to develop new oximes to reactivate acetylcholinesterase inhibited by organophosphorus compounds (OP). So far, a broad-spectrum oxime effective against structurally diverse OP is still missing, and alternative approaches, e.g. stoichiometric and catalytic scavengers, are under investigation. Fresh frozen plasma (FFP) has been used in human OP pesticide poisoning which prompted us to investigate the in vitro kinetics of OP nerve agent degradation by FFP. Degradation was rapid and calcium-dependent with the G-type nerve agents tabun, sarin, soman and cyclosarin with half-lives from 5 to 28 min. Substantially longer and calcium-independent degradation half-lives of 23-33 h were determined with the V-type nerve agents CVX, VR and VX. However, at all the tested conditions, the degradation of V-type nerve agents was several-fold faster than spontaneous hydrolysis. Albumin did not accelerate the degradation of nerve agents. In conclusion, the fast degradation of G-type nerve agents by FFP might be a promising tool, but would require transfusion shortly after poisoning. FFP does not seem to be suitable for detoxifying relevant agent concentrations in case of human poisoning by V-type nerve agents. PMID:24057572

  5. Role of glutamatergic system in nerve agent intoxication

    SciTech Connect

    Blanchet, G.; Lallement, G.; Carpentier, P.; De Groot, D.; Bodjarian, N.

    1993-05-13

    Our recent studies concerning soman-induced seizures mechanisms and subsequent brain damage are reviewed. (1) Seizure activity was associated with transient increases of extracellular concentrations of acetylcholine (ACh) and with long-lasting releases of glutamate (Glu) in all limbic areas studied. (2) Preventive intraseptal application of atropine abolished the hippocampal increases of extracellular AChi and Glu indicating a key role of septum in triggering seizure activity. (3) Early increases of hippocampal AMPA receptor binding occurred before activation of NMDA receptors. (4) Pretreatment with NBQX, an antagonist of AMPA receptor, prevented convulsions and brain damage even without atropine. In the same conditions, no protection was afforded by TCP, a non-competitive antagonist of the NMDA receptor. (5) On the contrary, in the presence of pyridostigmine and atropine, TCP blocked the seizures induced by 2 x LD50 of soman. The anticonvulsant potency of TCP was particularly obvious when administered curatively. (6) Mossy fibers sprouting takes place in the supragranular-molecular layers of rat hippocampus long after brain injury associated with abnormal neuronal excitability. (7) Altogether, it appears that an AMPA component is involved in combination with cholinergic mechanisms in initiating seizures. A subsequent and long-lasting recruitment of NMDA receptors is then essential in sustaining the seizures. New anticonvulsant and neuroprotective approaches using Glu antagonists against nerve agents intoxication are discussed.

  6. Evidence of VX nerve agent use from contaminated white mustard plants.

    PubMed

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

    2014-08-01

    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

  7. 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

  8. Pyridostigmine used as a nerve agent pretreatment under wartime conditions. (Reannouncement with new availability information)

    SciTech Connect

    Keeler, J.R.; Hurst, C.G.; Dunn, M.A.

    1991-08-07

    During Operation Desert Storm there was a credible threat of chemical warfare even though there was never actual use of chemical agents. Intelligence reports indicated that the Iraqi chemical arsenal contained nerve, vesicant, and blood agents. Nerve agents are organophosphorus inhibitors of acetylcholinesterase, such as sarin and tabun. The vesicants are skin blistering compounds, such as mustards and arsenicals, while blood agents are the cyanides, inhibitors of cytochrome oxidase. The US Armed Force`s approach to the medical management of actual or anticipated nerve agent injuries employs a regimen that consists of pretreatment with pyridostigmine bromide tablets prior to nerve agent exposure followed by atropine citrate and pralidoxime chloride by autoinjector intramuscularly on actual exposure. Proper administration of this drug combination provides significantly increased survival after lethal exposures to nerve agents above that provided by atropine and pralidoxime therapy alone. The recent addition of pyridostigmine to the US therapeutic regimen for nerve agent poisoning was based on efficacy data in animals and safety studies in humans.

  9. Analysis of nerve agents using capillary electrophoresis and laboratory-on-a-chip technology.

    PubMed

    Pumera, Martin

    2006-04-28

    The nerve agents belong among the most toxic compounds produced by human kind. While they have been used very sporadically until now, typically in local conflicts or by local terrorists groups, the global increase in terrorist activity in the recent years has generated tremendous demand for innovative tools capable of detecting nerve agents. Fast, sensitive and reliable detection of nerve agents in the field is very important issue in present days. Capillary electrophoresis (CE) offers great possibilities for sensitive detection of these harmful compounds as well as incorporation in mobile laboratory and it proved to have capability to detect nerve agent breakdown products in real environmental samples. Laboratory-on-a-chip format offers great possibilities to create portable, field deployable, rapidly responding and potentially disposable device, allowing security forces to make the important decision regarding the safety of civilians. This article overviews the conventional capillary electrophoretic and laboratory-on-a-chip techniques for analysis of degradation products of G-type and V-type nerve agents. It discusses diverse strategies of detection of different nerve agents breakdown products, which are corresponding to their parental nerve agents. It also overviews possibilities and challenges for analysis of the real samples. PMID:16530776

  10. Theoretical proton affinity and fluoride affinity of nerve agent VX.

    PubMed

    Bera, Narayan C; Maeda, Satoshi; Morokuma, Keiji; Viggiano, Al A

    2010-12-23

    Proton affinity and fluoride affinity of nerve agent VX at all of its possible sites were calculated at the RI-MP2/cc-pVTZ//B3LYP/6-31G* and RI-MP2/aug-cc-pVTZ//B3LYP/6-31+G* levels, respectively. The protonation leads to various unique structures, with H(+) attached to oxygen, nitrogen, and sulfur atoms; among which the nitrogen site possesses the highest proton affinity of -ΔE ∼ 251 kcal/mol, suggesting that this is likely to be the major product. In addition some H(2), CH(4) dissociation as well as destruction channels have been found, among which the CH(4) + [Et-O-P(═O)(Me)-S-(CH(2))(2)-N(+)(iPr)═CHMe] product and the destruction product forming Et-O-P(═O)(Me)-SMe + CH(2)═N(+)(iPr)(2) are only 9 kcal/mol less stable than the most stable N-protonated product. For fluoridization, the S-P destruction channel to give Et-O-P(═O)(Me)(F) + [S-(CH(2))(2)-N-(iPr)(2)](-) is energetically the most favorable, with a fluoride affinity of -ΔE ∼ 44 kcal. Various F(-) ion-molecule complexes are also found, with the one having F(-) interacting with two hydrogen atoms in different alkyl groups to be only 9 kcal/mol higher than the above destruction product. These results suggest VX behaves quite differently from surrogate systems. PMID:21117653

  11. 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...

  12. Chromo-fluorogenic BODIPY-complexes for selective detection of V-type nerve agent surrogates.

    PubMed

    Barba-Bon, Andrea; Costero, Ana María; Gil, Salvador; Sancenón, Félix; Martínez-Máñez, Ramón

    2014-11-11

    Two new Eu(3+) and Au(3+) BODIPY-complexes capable of chromo-fluorogenically detecting micromolar concentrations of V-type nerve agent surrogates by a simple displacement assay are described. PMID:25233370

  13. Chromogenic and fluorogenic detection of a nerve agent simulant with a rhodamine-deoxylactam based sensor.

    PubMed

    Wu, Xuanjun; Wu, Zhisheng; Han, Shoufa

    2011-11-01

    A chromogenic and fluorogenic detection of a nerve agent simulant was developed based on diethyl chlorophosphate triggered tandem phosphorylation and intramolecular cyclization of N-(rhodamine B)-deoxylactam-2-aminoethanol. PMID:21952323

  14. 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. PMID:15136687

  15. Nerve agent detection using networks of single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Novak, J. P.; Snow, E. S.; Houser, E. J.; Park, D.; Stepnowski, J. L.; McGill, R. A.

    2003-11-01

    We report the use of carbon nanotubes as a sensor for chemical nerve agents. Thin-film transistors constructed from random networks of single-walled carbon nanotubes were used to detect dimethyl methylphosphonate (DMMP), a simulant for the nerve agent sarin. These sensors are reversible and capable of detecting DMMP at sub-ppb concentration levels, and they are intrinsically selective against interferent signals from hydrocarbon vapors and humidity. We provide additional chemical specificity by the use of filters coated with chemoselective polymer films. These results indicate that the electronic detection of sub-ppb concentrations of nerve agents and potentially other chemical warfare agents is possible with simple-to-fabricate carbon nanotube devices.

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

    SciTech Connect

    Collombet, Jean-Marc

    2011-09-15

    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 increased 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.

  17. Analysis of nerve agent metabolites from nail clippings by liquid chromatography tandem mass spectrometry.

    PubMed

    Appel, Amanda S; Logue, Brian A

    2016-09-15

    While several methods for the bioanalysis of nerve agents or their metabolites have been developed for the verification of nerve agent exposure, these methods are generally limited in the amount of time after an exposure that markers of exposure can be detected (due to rapid metabolism from biological matrices). In this study, a method for the analysis of nerve agent hydrolysis products from nail clippings was developed to allow evaluation of nails as a long-term repository of these markers. Pinacolyl methylphosphonic acid (PMPA) and isopropyl methylphosphonic acid (IMPA) were extracted from nail samples with N,N-dimethylformamide and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Limits of detection for PMPA and IMPA were 0.3μg/kg and 7.5μg/kg and linear ranges were 0.75-300μg/kg and 30-1500μg/kg, respectively. Precision was within 10% and 8% for PMPA and IMPA, respectively, and accuracy was 100±12% for both analytes. The approach presented here is complementary to current methods for nerve agent exposure verification, and should allow for long-term determination of nerve agent poisoning. PMID:27474780

  18. Anticonvulsants for nerve agent-induced seizures: The influence of the therapeutic dose of atropine.

    PubMed

    Shih, Tsung-Ming; Rowland, Tami C; McDonough, John H

    2007-01-01

    Two guinea pig models were used to study the anticonvulsant potency of diazepam, midazolam, and scopolamine against seizures induced by the nerve agents tabun, sarin, soman, cyclosarin, O-ethyl S-(2-(diisopropylamino)ethyl)methylphosphonothioate (VX), and O-isobutyl S-(2-diethylamino)ethyl)-methyl phosphonothioate (VR). Animals instrumented for electroencephalogram recording were pretreated with pyridostigmine bromide (0.026 mg/kg i.m.) 30 min before challenge with 2 x LD50 (s.c.) of a nerve agent. In model A, atropine sulfate (2.0 mg/kg i.m.) and pyridine-2-aldoxime methylchloride (2-PAM; 25.0 mg/kg i.m.) were given 1 min after nerve agent challenge, and the tested anticonvulsant was given (i.m.) 5 min after seizure onset. In model B, a lower dose of atropine sulfate (0.1 mg/kg i.m.) was given along with 2-PAM 1 min after nerve agent challenge, and the anticonvulsant was given at seizure onset. With the lower dose of atropine, seizure occurrence increased to virtually 100% for all agents; the time to seizure onset decreased for sarin, cyclosarin, and VX; the signs of nerve agent intoxication were more severe; and coma resulted frequently with cyclosarin. The anticonvulsant ED50 doses for scopolamine or diazepam were, in general, not different between the two models, whereas the anticonvulsant ED50 values of midazolam increased 3- to 17-fold with the lower atropine dose. Seizure termination times were not systematically effected by the different doses of atropine. The order of anticonvulsant effectiveness within each model was scopolamine > or = midazolam > diazepam. The findings indicate that the dose of atropine given as antidotal therapy can significantly influence measures of nerve agent toxicity and responsiveness to anticonvulsant therapy. PMID:17015638

  19. [The VR, the Russian version of the nerve agent VX].

    PubMed

    Cuquel, A-C; Dorandeu, F; Ceppa, F; Renard, C; Burnat, P

    2015-05-01

    A product of the arms race during the Cold War, the Russian VX, or VR, is an organophosphorus compound that is a structural isomer of the western VX compound (or A4), with which it shares a very high toxicity. It is much less studied and known than VX because the knowledge of its existence is relatively recent. A very low volatility and high resistance in the environment make it a persistent agent. Poisoning occurs mainly following penetration through skin and mucosa but vapour inhalation is a credible risk in some circumstances. The clinical presentation may be differed by several hours and despite the absence of signs and symptoms, the casualty should not be considered as contamination or intoxication-free. This agent has a long residence time in blood, a characteristics that clearly differentiates it from other compounds such as sarin. The protocols for antidote administration may thus have to be changed accordingly. The fact that VR poisoned individuals will less respond to the current oxime therapy used in France, the 2-PAM and that VR represents a higher threat than VX, being probably possessed by some proliferating states, justify the interest for this toxic product. PMID:25592653

  20. Engineering V-type nerve agents detoxifying enzymes using computationally focused libraries.

    PubMed

    Cherny, Izhack; Greisen, Per; Ashani, Yacov; Khare, Sagar D; Oberdorfer, Gustav; Leader, Haim; Baker, David; Tawfik, Dan S

    2013-11-15

    VX and its Russian (RVX) and Chinese (CVX) analogues rapidly inactivate acetylcholinesterase and are the most toxic stockpile nerve agents. These organophosphates have a thiol leaving group with a choline-like moiety and are hydrolyzed very slowly by natural enzymes. We used an integrated computational and experimental approach to increase Brevundimonas diminuta phosphotriesterase's (PTE) detoxification rate of V-agents by 5000-fold. Computational models were built of the complex between PTE and V-agents. On the basis of these models, the active site was redesigned to be complementary in shape to VX and RVX and to include favorable electrostatic interactions with their choline-like leaving group. Small libraries based on designed sequences were constructed. The libraries were screened by a direct assay for V-agent detoxification, as our initial studies showed that colorimetric surrogates fail to report the detoxification rates of the actual agents. The experimental results were fed back to improve the computational models. Overall, five rounds of iterating between experiment and model refinement led to variants that hydrolyze the toxic SP isomers of all three V-agents with kcat/KM values of up to 5 × 10(6) M(-1) min(-1) and also efficiently detoxify G-agents. These new catalysts provide the basis for broad spectrum nerve agent detoxification. PMID:24041203

  1. Fiber-optic-based surface plasmon resonance (SPR) sensors for the detection of toxic nerve agents

    NASA Astrophysics Data System (ADS)

    Prakash, Anna M. C.; Kim, Yoon-Chang; Banerji, Soame; Masson, Jean-Francois; Booksh, Karl S.

    2004-03-01

    Analytical instruments capable of detecting nerve agents in battlefield conditions where speed, accuracy and ease of operation are a must in today's military. Fast detection and decontamination of nerve agents in very low concentrations is the primary focus of our research. The method presented here focuses on optimizing polymer stabilized sensing elements on the surface of SPR fiber-optic probes. A number of polymers & polymer supported metal complexes capable of reversibly binding to the species of interest & which have robust operation in hostile environments are incorporated with the fiber optic sensing elements. An optical technique, such as Surface Plasmon Resonance (SPR), better suited to rapid data collection without sample pretreatment is employed. The approach using polymer-based optical fibers with off-the-shelf SPR system components has been tested for the detection of Pinacolyl methylphosphonate (PMP), a simulant for nerve agent Soman. Surface initiated polymeric sensors have higher sensitivity toward detecting PMP than bulk-polymerized sensors.

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

    PubMed Central

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

    2009-01-01

    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 analog at pH 7.4 for 17 h at 21°C. The protein was denatured by boiling and digested with trypsin. Aged and non-aged active site peptide adducts were quantified by 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 analog were found to be suitable substitutes for true soman, sarin, tabun, and GF in terms of the adduct they produced with human butyrylcholinesterase. However, the soman and sarin thiomethyl compounds yielded two types of adducts, one of which was thiomethyl phosphonate, a

  3. Rapid and highly selective chromogenic detection of nerve agents with a cleft-shaped host.

    PubMed

    Kumar, Vinod; Kaushik, Mahabir Parshad

    2011-12-21

    A new chromogenic protocol has been developed for rapid and selective detection of nerve agents like tabun. The chemsensor displayed a drastic color change from its colorless solution to yellow instantaneously with an 89 nm bathochromic shift. No inference of other chemical warfare agents and its mimics was observed either with the naked-eye or by UV-Vis spectroscopy. The development of a portable chemosensor kit for tabun demonstrates its practical application in real-time monitoring. PMID:22013586

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

    SciTech Connect

    Worek, F. . E-mail: FranzWorek@Bundeswehr.org; Eyer, P.; Aurbek, N.; Szinicz, L.; Thiermann, H.

    2007-03-15

    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.

  5. Evaluation of oxime efficacy in nerve agent poisoning: Development of a kinetic-based dynamic model

    SciTech Connect

    Worek, Franz . E-mail: FranzWorek@Bundeswehr.org; Szinicz, Ladislaus; Eyer, Peter; Thiermann, Horst

    2005-12-15

    The widespread use of organophosphorus compounds (OP) as pesticides and the repeated misuse of highly toxic OP as chemical warfare agents (nerve agents) emphasize the necessity for the development of effective medical countermeasures. Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. From obvious ethical reasons only animal experiments can be used to evaluate new oximes as nerve agent antidotes. However, the extrapolation of data from animal to humans is hampered by marked species differences. Since reactivation of OP-inhibited AChE is considered to be the main mechanism of action of oximes, human erythrocyte AChE can be exploited to test the efficacy of new oximes. By combining enzyme kinetics (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics a dynamic in vitro model was developed which allows the calculation of AChE activities at different scenarios. This model was validated with data from pesticide-poisoned patients and simulations were performed for intravenous and percutaneous nerve agent exposure and intramuscular oxime treatment using published data. The model presented may serve as a tool for defining effective oxime concentrations and for optimizing oxime treatment. In addition, this model can be useful for the development of meaningful therapeutic animal models.

  6. Detoxification of nerve agents by a substituted beta-cyclodextrin: application of a modified biological assay.

    PubMed

    Wille, T; Tenberken, O; Reiter, G; Müller, S; Le Provost, R; Lafont, O; Estour, F; Thiermann, H; Worek, F

    2009-11-30

    Chemical warfare agents (nerve agents) are still available and present a real threat to the population. Numerous in vitro and in vivo studies showed that various nerve agents, e.g. tabun and cyclosarin, are resistant towards standard therapy with atropine and oxime. Based on these facts we applied a modified biological assay for the easy, semi-quantitative testing of the detoxifying properties of the beta-cyclodextrin derivative CD-IBA. Cyclosarin, sarin, tabun and VX were incubated with CD-IBA for 1-50 min at 37 degrees C, then an aliquot was added to erythrocyte acetylcholinesterase (AChE) and the percentage of AChE inhibition was determined. The validity of the assay was confirmed by concomitant quantification of tabun by GC-MS. Different concentrations of cyclosarin were detoxified by CD-IBA in a concentration-dependent velocity. The ability to detoxify various nerve agents decreased in the order cyclosarin>sarin>tabun>VX. Hereby, no detoxification of VX could be detected. Sarin was detoxified in a biphasic reaction with a fast reduction of inhibitory potential in the first phase and a slower detoxification in the second phase. CD-IBA detoxified tabun in a one phase decay and, compared to cyclosarin and sarin, a longer half-life was determined with tabun. The modified biological assay is appropriate for the initial semi-quantitative screening of candidate compounds for the detoxification of nerve agents. The beta-cyclodextrin derivative CD-IBA demonstrated its ability to detoxify different nerve agents. PMID:19800384

  7. Long-term neuropathological and behavioral impairments after exposure to nerve agents.

    PubMed

    Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Apland, James P; Prager, Eric M; Pidoplichko, Volodymyr I; Miller, Steven L; Braga, Maria F M

    2016-06-01

    One of the deleterious effects of acute nerve agent exposure is the induction of status epilepticus (SE). If SE is not controlled effectively, it causes extensive brain damage. Here, we review the neuropathology observed after nerve agent-induced SE, as well as the ensuing pathophysiological, neurological, and behavioral alterations, with an emphasis on their time course and longevity. Limbic structures are particularly vulnerable to damage by nerve agent exposure. The basolateral amygdala (BLA), which appears to be a key site for seizure initiation upon exposure, suffers severe neuronal loss; however, GABAergic BLA interneurons display a delayed death, perhaps providing a window of opportunity for rescuing intervention. The end result is a long-term reduction of GABAergic activity in the BLA, with a concomitant increase in spontaneous excitatory activity; such pathophysiological alterations are not observed in the CA1 hippocampal area, despite the extensive neuronal loss. Hyperexcitability in the BLA may be at least in part responsible for the development of recurrent seizures and increased anxiety, while hippocampal damage may underlie the long-term memory impairments. Effective control of SE after nerve agent exposure, such that brain damage is also minimized, is paramount for preventing lasting neurological and behavioral deficits. PMID:27002925

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  9. Fluorogenic and chromogenic probe for rapid detection of a nerve agent simulant DCP.

    PubMed

    Wu, Wei-hui; Dong, Jun-jun; Wang, Xin; Li, Jian; Sui, Shao-hui; Chen, Gao-yun; Liu, Ji-wei; Zhang, Ming

    2012-07-21

    A fluorogenic and visual probe was devised to detect diethyl chlorophosphate (DCP), a nerve agent simulant. The probe, N-(rhodamine B)-lactam-2-aminoethanol (RB-AE), undergoes oxazoline formation following phosphorylation in the presence of DCP, which gives rapid and clear fluorescence and color change in the assay solutions. PMID:22624148

  10. 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 ...

  11. Polynorbornene derived 8-hydroxyquinoline paper strips for ultrasensitive chemical nerve agent surrogate sensing.

    PubMed

    Sarkar, Santu; Shunmugam, Raja

    2014-08-11

    The detection of nerve agent simulants is achieved by the photoinduced electron transfer (PET) mechanism. A "turn-on" fluorescence response upon phosphorylation at 8-hydroxyquinoline of norbornene-based triazolyl functionalized 8-hydroxyquinoline () followed by intramolecular rearrangement provides very intense green emission. The detection limit of polymer () coated paper strips is 25 ppb with instantaneous response. PMID:24948420

  12. 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....

  13. Organophosphate hydrolases as catalytic bioscavengers of organophosphorus nerve agents.

    PubMed

    Trovaslet-Leroy, Marie; Musilova, Lucie; Renault, Frédérique; Brazzolotto, Xavier; Misik, Jan; Novotny, Ladislav; Froment, Marie-Thérèse; Gillon, Emilie; Loiodice, Mélanie; Verdier, Laurent; Masson, Patrick; Rochu, Daniel; Jun, Daniel; Nachon, Florian

    2011-09-25

    Bioscavengers are molecules able to neutralize neurotoxic organophosphorus compounds (OP) before they can reach their biological target. Human butyrylcholinesterase (hBChE) is a natural bioscavenger each molecule of enzyme neutralizing one molecule of OP. The amount of natural enzyme is insufficient to achieve good protection. Thus, different strategies have been envisioned. The most straightforward consists in injecting a large dose of highly purified natural hBChE to increase the amount of bioscavenger in the bloodstream. This proved to be successful for protection against lethal doses of soman and VX but remains expensive. An improved strategy is to regenerate prophylactic cholinesterases (ChE) by administration of reactivators after exposure. But broad-spectrum efficient reactivators are still lacking, especially for inhibited hBChE. Cholinesterase mutants capable of reactivating spontaneously are another option. The G117H hBChE mutant has been a prototype. We present here the Y124H/Y72D mutant of human acetylcholinesterase; its spontaneous reactivation rate after V-agent inhibition is increased up to 110 fold. Catalytic bioscavengers, enzymes capable of hydrolyzing OP, present the best alternative. Mesophilic bacterial phosphotriesterase (PTE) is a candidate with good catalytic efficiency. Its enantioselectivity has been enhanced against the most potent OP isomers by rational design. We show that PEGylation of this enzyme improves its mean residence time in the rat blood stream 24-fold and its bioavailability 120-fold. Immunogenic issues remain to be solved. Human paraoxonase 1 (hPON1) is another promising candidate. However, its main drawback is that its phosphotriesterase activity is highly dependent on its environment. Recent progress has been made using a mammalian chimera of PON1, but we provide here additional data showing that this chimera is biochemically different from hPON1. Besides, the chimera is expected to suffer from immunogenic issues. Thus, we

  14. Evaluation of Multiple Blood Matrices for Assessment of Human Exposure to Nerve Agents.

    PubMed

    Schulze, Nicholas D; Hamelin, Elizabeth I; Winkeljohn, W Rucks; Shaner, Rebecca L; Basden, Brian J; deCastro, B Rey; Pantazides, Brooke G; Thomas, Jerry D; Johnson, Rudolph C

    2016-04-01

    Biomedical samples may be used to determine human exposure to nerve agents through the analysis of specific biomarkers. Samples received may include serum, plasma, whole blood, lysed blood and, due to the toxicity of these compounds, postmortem blood. To quantitate metabolites resulting from exposure to sarin (GB), soman (GD), cyclosarin (GF), VX and VR, these blood matrices were evaluated individually for precision, accuracy, sensitivity and specificity. Accuracies for these metabolites ranged from 100 to 113% with coefficients of variation ranging from 2.31 to 13.5% across a reportable range of 1-100 ng/mL meeting FDA recommended guidelines for bioanalytical methods in all five matrices. Limits of detection were calculated to be 0.09-0.043 ng/mL, and no interferences were detected in unexposed matrix samples. The use of serum calibrators was also determined to be a suitable alternative to matrix-matched calibrators. Finally, to provide a comparative value between whole blood and plasma, the ratio of the five nerve agent metabolites measured in whole blood versus plasma was determined. Analysis of individual whole blood samples (n = 40), fortified with nerve agent metabolites across the reportable range, resulted in average nerve agent metabolite blood to plasma ratios ranging from 0.53 to 0.56. This study demonstrates the accurate and precise quantitation of nerve agent metabolites in serum, plasma, whole blood, lysed blood and postmortem blood. It also provides a comparative value between whole blood and plasma samples, which can assist epidemiologists and physicians with interpretation of test results from blood specimens obtained under variable conditions. PMID:26861671

  15. 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.

  16. 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

  17. General guidelines for medically screening mixed population groups potentially exposed to nerve or vesicant agents

    SciTech Connect

    Watson, A.P.; Munro, N.B.; Sidell, F.R.; Leffingwell, S.S.

    1992-01-01

    A number of state and local planners have requested guidance on screening protocols and have expressed interest in sampling body fluids from exposed or potentially exposed individuals as a means of estimating agent dose. These guidelines have been developed to provide a clear statement that could be used by state and local emergency response personnel in the event of a nerve or vesicant agent incident resulting in off-post contamination; maximum protection from harm is the goal. The assumption is that any population group so exposed would be heterogeneous for age, gender, reproductive status, and state of health.

  18. Solid supported in situ derivatization extraction of acidic degradation products of nerve agents from aqueous samples.

    PubMed

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Dubey, D K; Pardasani, Deepak

    2014-09-12

    This study deals with the solid supported in situ derivatization extraction of acidic degradation products of nerve agents present in aqueous samples. Target analytes were alkyl alkylphosphonic acids and alkylphosphonic acids, which are important environmental signatures of nerve agents. The method involved tert-butyldimethylchlorosilane mediated in situ silylation of analytes on commercially available diatomaceous solid phase extraction cartridges. Various parameters such as derivatizing reagent, its concentration, reaction time, temperature and eluting solvent were optimized. Recoveries of the analytes were determined by GC-MS which ranged from 60% to 86%. The limits of detection (LOD) and limit of quantification (LOQ) with selected analytes were achieved down to 78 and 213ngmL(-1) respectively, in selected ion monitoring mode. The successful applicability of method was also demonstrated on samples of biological origin such as plasma and to the samples received in 34th official proficiency test conducted by the Organization for Prohibition the of Chemical Weapons. PMID:25103280

  19. Synthesis and in vitro and in vivo inhibition potencies of highly relevant nerve agent surrogates.

    PubMed

    Meek, Edward C; Chambers, Howard W; Coban, Alper; Funck, Kristen E; Pringle, Ronald B; Ross, Matthew K; Chambers, Janice E

    2012-04-01

    Four nonvolatile nerve agent surrogates, 4-nitrophenyl ethyl dimethylphosphoramidate (NEDPA, a tabun surrogate), 4-nitrophenyl ethyl methylphosphonate (NEMP, a VX surrogate), and two sarin surrogates, phthalimidyl isopropyl methylphosphonate (PIMP) and 4-nitrophenyl isopropyl methylphosphonate (NIMP), were synthesized and tested as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. These surrogates were designed to phosphorylate cholinesterases with the same moiety as their respective nerve agents, making them highly relevant for the study of cholinesterase reactivators. Surrogates were characterized by liquid chromatography-mass spectrometry and nuclear magnetic resonance. NEMP, PIMP, and NIMP were potent inhibitors of rat brain, skeletal muscle, diaphragm, and serum AChE as well as human erythrocyte AChE and serum BuChE in vitro. PIMP was determined to degrade quickly in aqueous solution, making it useful for in vitro assays only, and NEDPA was not a potent inhibitor of AChE or BuChE in vitro; therefore, these two surrogates were not tested in subsequent in vivo studies. Sublethal dosages (yielding about 80% brain AChE inhibition) were determined for both the stable sarin surrogate, NIMP (0.325 mg/kg ip), and the VX surrogate, NEMP (0.4 mg/kg ip), in adult male rats. Time course studies indicated the time to peak brain AChE inhibition for both NIMP and NEMP to be 1 h postexposure. Both surrogates yielded severe cholinergic signs. These dosages did not require the addition of atropine to prevent lethality, and the rate of AChE aging was slow, making these surrogates useful for reactivation studies both in vitro and in vivo. The surrogates synthesized in this study are potent yet safer to test than nerve agents and are useful tools for initial screening of nerve agent oxime therapeutics. PMID:22247004

  20. A rhodamine-deoxylactam based sensor for chromo-fluorogenic detection of nerve agent simulant.

    PubMed

    Wu, Zhisheng; Wu, Xuanjun; Yang, Yuhui; Wen, Ting-bin; Han, Shoufa

    2012-10-15

    N-(rhodamine B)-deoxylactam-5-amino-1-pentanol (dRB-APOH) was designed and prepared as the chromo-fluorogenic sensor for detection of a nerve agent simulant via analyte triggered tandem phosphorylation and opening of the intramolecular deoxylactam. The successful detection of diethyl chlorophosphate suggests the utility of rhodamine-deoxylactams as the chromo-fluorogenic signal reporting platform for design of sensors targeting reactive chemical species via various chemistries. PMID:22995618

  1. A near infrared colorimetric and fluorometric probe for organophosphorus nerve agent mimics by intramolecular amidation.

    PubMed

    Hu, Xiao-Xiao; Su, Yue-Ting; Ma, Yun-Wei; Zhan, Xin-Qi; Zheng, Hong; Jiang, Yun-Bao

    2015-10-21

    A near infrared probe for sensitive colorimetric and fluorimetric detection of nerve agent mimics, DCP and DCNP, was reported based on the activation of a carboxylic acid group by the mimics to conduct an intramolecular amidation reaction in the heptamethine chromophore, where its absorption or excitation maximum wavelength could be greatly red-shifted by attenuating the electron-donating ability of the amine group in the bridgehead site of heptamethine cyanine. PMID:26323249

  2. Highly selective detection of nerve-agent simulants with BODIPY dyes.

    PubMed

    Barba-Bon, Andrea; Costero, Ana M; Gil, Salvador; Harriman, Anthony; Sancenón, Félix

    2014-05-19

    Two chromo-fluorogenic probes, each based on the boron dipyrromethene core, have been developed for the detection of nerve-agent mimics. These chemosensors display both a color change and a significant enhancement of fluorescence in the presence of diethylcyanophosphonate (DCNP) and diisopropylfluorophosphate (DFP). No interference from other organophosphorus compounds or acids has been observed. Two portable chemosensor kits have been developed and tested to demonstrate its practical application in real-time monitoring. PMID:24700454

  3. Chromogenic and fluorogenic detection and discrimination of nerve agents Tabun and Vx.

    PubMed

    Kumar, Vinod; Rana, Hemlata

    2015-11-28

    Our approach uses squaraine (SQ) as the molecular-receptor as well as an indicator for the chromogenic and fluorogenic detection and discrimination of nerve agents Tabun and Vx. To mimic a real-life scenario, the protocols were implemented in spiked water and soil samples, on surfaces, and in the gas phase. The lower detection limit will be useful to protect human health and national security. PMID:26394304

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

    SciTech Connect

    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.

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

    PubMed

    Maxwell, Donald M; Koplovitz, Irwin; Worek, Franz; Sweeney, Richard E

    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(r2)) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and in vitro k(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(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(r2)[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. PMID:18508103

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

    SciTech Connect

    Maxwell, Donald M. Koplovitz, Irwin; Worek, Franz; Sweeney, Richard E.

    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 in 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.

  7. Ultraviolet Raman spectra and cross-sections of the G-series nerve agents.

    PubMed

    Christesen, Steven D; Pendell Jones, Jay; Lochner, Joseph M; Hyre, Aaron M

    2008-10-01

    Ultraviolet (UV) Raman spectroscopy is being applied to the detection of chemical agent contamination of natural and man-made surfaces. In support of these efforts, we have measured the UV Raman signatures of the G-series nerve agents GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), and the agent simulant diisopropyl methylphosphonate (DIMP) at 248 nm and 262 nm, as well as taking their UV Raman and UV absorption cross-sections. Of these chemicals, only GA exhibits any significant pre-resonance enhancement. We also show that reduction of the excitation wavelength from 262 nm to 248 nm effectively shifts the Raman spectrum away from a substantial sample fluorescence background, implying a significant improvement in detection capability. PMID:18926015

  8. Nerve agent intoxication: recent neuropathophysiological findings and subsequent impact on medical management prospects.

    PubMed

    Collombet, Jean-Marc

    2011-09-15

    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 3months after soman poisoning. Indeed, an increased 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. PMID:21791221

  9. Choice of approaches in developing novel medical countermeasures for nerve agent poisoning.

    PubMed

    Myhrer, Trond; Aas, Pål

    2014-09-01

    During the establishment of a research branch, all relevant matters encountered will be of interest to study. After having acquired a body of basal knowledge, it becomes possible to derive ideas or hypotheses for further elaboration of information. The purpose of the present study was to show that therapies for nerve agent poisoning based on specific neuropharmacological approaches can have greater probability for being successful than treatment regimens based on fragmental research or serendipitous discoveries. By following the guidelines for research in experimental epilepsy, neuronal target areas for nerve agents have been identified through lesion studies, and critical receptors for pharmacological treatment have been specified through microinfusion studies of rats. Subsequent experimentations have shown that the results achieved from microinfusion studies are transferable to systemic administration. It is demonstrated that a treatment regimen developed through the novel approach is more efficacious than regimens derived from conventional research on countermeasures. A therapy consisting of HI-6, levetiracetam, and procyclidine that has been worked out along the new lines, exerts powerful anticonvulsant capacity and appears to have universal utility as a stand-alone therapy against soman intoxication in rats. It would be of great interest to examine whether the latter findings can be expanded to other animal species than rats and other classical nerve agents than soman. PMID:24820435

  10. Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication.

    PubMed

    Bajgar, Jirí

    2010-01-01

    The studies dealing with mechanism of organophosphates (OP)/nerve agent action, prophylaxis and treatment of intoxications is a very hot topic at present. Though the research is very intensive, unfortunately, up to now, there is not universal or significantly better reactivator sufficiently effective against all nerve agents/OP when compared with presently available oximes (pralidoxime, methoxime, obidoxime, trimedoxime, HI-6). The use of the most effective reactivator (HI-6) using simple type of autoinjector (e.g. ComboPen) is strictly limited because of decomposition of HI-6 in solution. Thanks to better solubility it is clear that another salt of HI-6 (dimethanesulfonate, HI-6 DMS) is more convenient for the use as antidote against nerve agents in the autoinjector than HI-6 chloride (Cl). It was clearly demonstrated that reactivation potency of HI-6 DMS in comparison with HI-6 Cl in vivo was the same and bioavailability of HI-6 DMS is better than that of HI-6 Cl. Three chambered autoinjector allows administration of all three antidotes (atropine, reactivator, diazepam) simultaneously. Moreover, the content of chambers can be changed according to proposed requirements. Possible way to solve the problem of universal reactivator could be the use of two reactivators. Three chambered autoinjector is an ideal device for this purpose. PMID:21400978

  11. Identification and characterization of novel catalytic bioscavengers of organophosphorus nerve agents.

    PubMed

    Otto, Tamara C; Scott, Jennifer R; Kauffman, Monika A; Hodgins, Sean M; Ditargiani, Robert C; Hughes, James H; Sarricks, Erin P; Saturday, Greg A; Hamilton, Tracey A; Cerasoli, Douglas M

    2013-03-25

    In an effort to discover novel catalytic bioscavengers of organophosphorus (OP) nerve agents, cell lysates from a diverse set of bacterial strains were screened for their capacity to hydrolyze the OP nerve agents VX, VR, and soman (GD). The library of bacterial strains was identified using both random and rational approaches. Specifically, two representative strains from eight categories of extremophiles were chosen at random. For the rational approach, the protein sequence of organophosphorus hydrolase (OPH) from Brevundimonas diminuta was searched against a non-redundant protein database using the Basic Local Alignment Search Tool to find regions of local similarity between sequences. Over 15 protein sequences with significant sequence similarity to OPH were identified from a variety of bacterial strains. Some of these matches were based on predicted protein structures derived from bacterial genome sequences rather than from bona fide proteins isolated from bacteria. Of the 25 strains selected for nerve agent testing, three bacterial strains had measurable levels of OP hydrolase activity. These strains are Ammoniphilus oxalaticus, Haloarcula sp., and Micromonospora aurantiaca. Lysates from A. oxalaticus had detectable hydrolysis of VR; Haloarcula sp. had appreciable hydrolysis of VX and VR, whereas lysates from M. aurantiaca had detectable hydrolysis of VR and GD. PMID:23041042

  12. Anticholinesterase (DFP) toxicity antagonism by chronic donepezil: a potential nerve agent treatment.

    PubMed

    Janowsky, David S; Davis, John M; Overstreet, David H

    2005-08-01

    Animal studies exploring the antagonism of irreversible cholinesterase inhibitors (i.e. nerve agents) such as soman and sarin have shown that pretreatment with the reversible centrally acting cholinesterase inhibitor, physostigmine, alone or in conjunction with the centrally acting anticholinergic drug, scopolamine, antagonizes the lethality and toxicity of these agents. This study evaluated the effects of pretreatment with the oral cholinesterase inhibitor and anti-Alzheimer's agent, donepezil (Aricept) on the hypokinetic, hypothermic and diarrhea-inducing effects of the irreversible long-acting cholinesterase inhibitor, diisopropylfluorophosphate (DFP) in adult Sprague-Dawley rats. Donepezil (2 mg/kg), given acutely (30 min pretreatment) or chronically (10 daily treatments), significantly antagonized the hypothermia, hypoactivity and diarrhea induced by DFP (1.25 mg/kg) administration. The effects were most prominent 4 and 6 h after the injection of DFP and some protection was observed even when the last treatment of the chronic donepezil protocol was given 24 h before the DFP injection. Although these phenomena are not the same as lethality, they may be parallel phenomena, and our results may have therapeutic implications for the treatment of nerve agent toxicity. PMID:16054679

  13. Chemical synthesis of two series of nerve agent model compounds and their stereoselective interaction with human acetylcholinesterase and human butyrylcholinesterase

    PubMed Central

    Barakat, Nora H.; Zheng, Xueying; Gilley, Cynthia B.; MacDonald, Mary; Okolotowicz, Karl; Cashman, John R.; Vyas, Shubham; Beck, Jeremy M.; Hadad, Christopher M.; Zhang, Jun

    2009-01-01

    Both G- and V-type nerve agents possess a center of chirality about phosphorus. The Sp-enantiomers are generally more potent inhibitors than their Rp-counterparts toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). To develop model compounds with defined centers of chirality that mimic the target nerve agent structures, we synthesized both the Sp and Rp stereoisomers of two series of G-type nerve agent model compounds in enantiomerically enriched form. The two series of model compounds contained identical substituents on the phosphorus as the G-type agents, except that thiomethyl (CH3-S-) and thiocholine ((CH3)3NCH2CH2-S-) groups were used to replace the traditional nerve agent leaving groups (i.e., fluoro for GB, GF, and GD; and cyano for GA). Inhibition kinetic studies of the thiomethyl- and thiocholine-substituted series of nerve agent model compounds revealed that the Sp enantiomers of both series of compounds showed greater inhibition potency toward AChE and BChE. The level of stereoselectivity, as indicated by the ratio of the bimolecular inhibition rate constants between Sp and Rp enantiomers, was greatest for the GF model compounds in both series. The thiocholine analogs were much more potent than the corresponding thiomethyl analogs. With the exception of the GA model compounds, both series showed greater potency against AChE than BChE. The stereoselectivity (i.e., Sp > Rp), enzyme selectivity, and dynamic range of inhibition potency contributed from these two series of compounds suggest that the combined application of these model compounds will provide useful research tools for understanding interactions of nerve agents with cholinesterase and other enzymes involved in nerve agent and organophosphate pharmacology. The potential of and limitations for using these model compounds in the development of biological therapeutics against nerve agent toxicity are also discussed. PMID:19715346

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

    SciTech Connect

    Liu, Guodong; Wang, Jun; Barry, Richard C.; Petersen, Catherine E.; Timchalk, Charles; Gassman, Paul L.; Lin, Yuehe

    2008-11-01

    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 electrochemical 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.

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

    SciTech Connect

    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 to 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.

  16. Selective opening of nanoscopic capped mesoporous inorganic materials with nerve agent simulants; an application to design chromo-fluorogenic probes.

    PubMed

    Candel, Inmaculada; Bernardos, Andrea; Climent, Estela; Marcos, M Dolores; Martínez-Máñez, Ramón; Sancenón, Félix; Soto, Juan; Costero, Ana; Gil, Salvador; Parra, Margarita

    2011-08-01

    A hybrid nanoscopic capped mesoporous material, that is selectively opened in the presence of nerve agent simulants, has been prepared and used as a probe for the chromo-fluorogenic detection of these chemicals. PMID:21691625

  17. Detection of nerve agents using proton transfer reaction mass spectrometry with ammonia as reagent gas.

    PubMed

    Ringer, Joachim M

    2013-01-01

    The chemical warfare agents (CWA) Sarin, Soman, Cyclosarin and Tabun were characterised by proton transfer mass spectrometry (PTRMS). It was found that PTRMS is a suitable technique to detect nerve agents highly sensitively, highly selectively and in near real-time. Methods were found to suppress molecule fragmentation which is significant under PTRMS hollow cathode ionisation conditions. In this context, the drift voltage (as one of the most important system parameters) was varied and ammonia was introduced as an additional chemical reagent gas. Auxiliary chemicals such as ammonia affect ionisation processes and are quite common in context with detectors for CWAs based on ion mobility spectrometry (IMS). With both, variation of drift voltage and ammonia as the reagent gas, fragmentation can be suppressed effectively. Suppression of fragmentation is crucial particularly concerning the implementation of an algorithm for automated agent identification in field applications. On the other hand, appearance of particular fragments might deliver additional information. Degradation and rearrangement products of nerve agents are not distinctive for the particular agent but for the chemical class they belong to. It was found that switching between ammonia doped and ordinary water ionisation chemistry can easily be performed within a few seconds. Making use of this effect it is possible to switch between fragment and molecular ion peak spectra. Thus, targeted fragmentation can be used to confirm identification based only on single peak detection. PTRMS turned out to be a promising technique for future CWA detectors. In terms of sensitivity, response time and selectivity (or confidence of identification, respectively) PTRMS performs as a bridging technique between IMS and GC-MS. PMID:24308198

  18. A FRET-based ratiometric fluorescent and colorimetric probe for the facile detection of organophosphonate nerve agent mimic DCP.

    PubMed

    Xuan, Weimin; Cao, Yanting; Zhou, Jiahong; Wang, Wei

    2013-11-18

    A FRET ratiometric fluorescent probe enabling a fast and highly sensitive response to OP nerve agent mimic DCP within 1 min and with as low as 0.17 ppm concentration detection limit has been developed. Moreover, the probe exhibits noticeable color changes under UV light and even with the naked eye. It is also demonstrated that it can detect both liquid and gas nerve agents. PMID:24080856

  19. Detrimental influences of intraluminally-administered sclerotic agents on surrounding tissues and peripheral nerves: An experimental study

    PubMed Central

    Fujiki, Masahide; Kurita, Masakazu; Ozaki, Mine; Kawakami, Hayato; Kaji, Nobuyuki; Takushima, Akihiko; Harii, Kiyonori

    2012-01-01

    The minimally-invasive nature of sclerotherapy makes it one of the first treatment options for venous malformations, although treatment-related complications, such as peripheral nerve paralysis, have been reported in some clinical cases. However, no studies of the aetiology of the detrimental effects of intraluminally-administered sclerotic agents on the surrounding tissues, including the peripheral nerves, have yet been published. This study therefore investigated the influences of intraluminally-administered sclerotic agents on the tissues surrounding the injection site using a newly-developed rat femoral vein model. Using this model, the effects of absolute ethanol, 5% ethanolamine oleate, and 1% polidocanol were compared histologically with those of normal saline controls. Fluorescein isothiocyanate-conjugated agents were administered and the leakage of sclerotic agents through the venous wall was evaluated by fluorescence microscopy. Damage to the adjacent femoral nerve was quantitatively evaluated by counting the numbers of axons in cross-sections. All the sclerotic agents caused vascular wall injuries and leakage into the surrounding tissues. The number of axons in the femoral nerve was significantly reduced following administration of absolute ethanol or 5% ethanolamine oleate, compared with normal saline. The results of this study suggest that sclerotic agents commonly leak out the vascular lumen, and some agents can cause adjacent nerve injury. It is important to be aware of this type of complication of sclerotherapy for venous malformations when selecting appropriate therapeutic interventions. PMID:22686430

  20. Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin.

    PubMed

    Tan, Hsih Yin; Loke, Weng Keong; Nguyen, Nam-Trung; Tan, Swee Ngin; Tay, Nam Beng; Wang, Wei; Ng, Sum Huan

    2014-04-01

    This paper reports a lab-on-a-chip for the detection of Sarin nerve agent based on rapid electrochemical detection. The chemical warfare agent Sarin (C₄H₁₀FO₂P, O-isopropyl methylphosphonofluoridate) is a highly toxic organophosphate that induces rapid respiratory depression, seizures and death within minutes of inhalation. As purified Sarin is colourless, odourless, water soluble and a easily disseminated nerve agent, it has been used as a weapon in terrorist or military attacks. To ascertain whether potable water supplies have been adulterated with this extremely potent poison, an inexpensive, sensitive and easy to use portable test kit would be of interest to first responders investigating such attacks. We report here an amperometric-based approach for detecting trace amounts of Sarin in water samples using a screen-printed electrode (SPE) integrated in a microfluidic chip. Enzymatic inhibition was obtained by exposing the immobilised biosensor in the microfluidic platform to Sarin in water samples. With the aid of cobalt phthalocyanine modified SPE, the device could detect Sarin at part-per-billion levels with concentration as low as 1 nM. The detection method reported here represents a significant improvement over the authors'previous optical-based detection method. PMID:24288016

  1. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

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

    PubMed

    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 routes 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. PMID:1376237

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

    SciTech Connect

    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 routes 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.

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

    SciTech Connect

    Lin, Yuehe; Wang, Jun; Liu, Guodong; Timchalk, Chuck

    2009-12-01

    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-based 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.

  5. Detection of nerve agents and biological molecules using embedded piezoresistive microcantilever sensors.

    NASA Astrophysics Data System (ADS)

    Porter, Timothy; Vail, Tim; Wooley, Amanda

    2008-03-01

    Embedded piezoresistive microcantilever (EPM) sensors have been used in the detection of a variety of analyte species. EPM sensors utilize a tiny piezoresistive microcantilever partially embedded into a sensing material to produce a sensing element that is compact, simple, resistant to movement and shock, and suitable for remote sensing applications. In the current project, we have used sensing materials comprised of an immobilizing polymer functionalized with either target enzymes or antibodies to detect two biological agents, bacillus globigi (BG) and Diisopropyl fluorophosphate (DFP). DFP is an organophosphate used as a simulant for organophosphate nerve agents, while BG is a large bacterial spore used as a simulant for other bacterial spores such as bacillus anthracis. Sensing results are presented for both types of EPM sensors.

  6. Molecular Dynamics of Organophosphorous Hydrolases Bound to the Nerve Agent Soman

    SciTech Connect

    Soares, Thereza A.; Osman, Mohamed A.; Straatsma, TP

    2007-07-01

    The organophosphorous hydrolase (OPH) from Pseudomonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. The potential use of this enzyme for the detection and detoxification of warfare nerve agents has spurred efforts to engineer mutants of enhanced catalytic activity and modified stereospecificity towards the most toxic forms of organophosphate nerve agents. Molecular dynamics simulations of the wild-type OPH and the complexes between the wild-type and the triple-mutant H254G/H257W/L303R forms and the substrate SpSc-soman have been carried out to enhance our molecular level understanding of its reaction mechanism. Comparison of the three simulations indicate that substrate binding induces conformational changes of the loops near the active site, suggesting an induced-fit mechanism. Likewise, the coordination of the zinc cations in the active site of the enzyme differs between the free enzyme and the complexes. In the absence of the substrate, the more exposed b-zinc is hexa-coordinated and the less exposed a-zinc is penta-coordinated. In the presence of the substrate, the b- zinc atom can be both penta- or hexa-coordinated while the a-zinc atom is tetra-coordinated. In addition, binding energies were calculated from electrostatic properties obtained by solution of the Poisson-Boltzmann equation combined with a surface area-dependent apolar contribution. The calculations indicate that the binding of SpSc-soman to OPH is driven by nonpolar interactions while electrostatic interactions determine binding specificity. These results provide a qualitative, molecular-level explanation for 2 the three-fold increase in catalytic efficiency of the triple-mutant towards SpSc-soman. Keywords: organophosphorous hydrolase, phosphotriesterase, nerve agents, soman, molecular dynamics, Poisson-Boltzmann equation, continuum electrostatics, metalloprotein.

  7. Novel dual-mode immunomagnetic method for studying reactivation of nerve agent-inhibited butyrylcholinesterase.

    PubMed

    Abney, Carter W; Knaack, Jennifer L S; Ali, Ahmed A I; Johnson, Rudolph C

    2013-05-20

    A novel immunomagnetic method has been developed for the simultaneous measurement of organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BuChE) and free OPNAs in serum. This new approach, deemed dual-mode immunomagnetic analysis (Dual-Mode IMA), combines immunomagnetic separation (IMS) and immunomagnetic scavenging (IMSc) and has been used to measure the effectiveness of cholinesterase reactivators on OPNA-inhibited BuChE in serum. BuChE inhibited by the nerve agent VX, uninhibited BuChE, and unbound VX were measured up to 1 h after the addition of oxime reactivators pralidoxime (2-PAM) and obidoxime. IMS experiments consisted of extracting BuChE and VX-BuChE serum adducts using antibutyrylcholinesterase monoclonal antibodies conjugated to protein-G ferromagnetic particles. In a parallel set of experiments using IMSc, BuChE-coated magnetic beads were used to extract free VX from protein-depleted serum. Adducts from both IMS and IMSc were analyzed using a published IMS liquid chromatography tandem mass spectrometry (IMS-LC-MS/MS) protocol, which has also been demonstrated with other OPNAs. By applying this Dual-Mode IMA approach, 2-PAM was observed to be more potent than obidoxime in reactivating VX-adducted BuChE. VX-BuChE peptide concentrations initially measured at 19.7 ± 0.7 ng/mL decreased over 1 h to 10.6 ± 0.6 ng/mL when reactivated with 2-PAM and 14.4 ± 1.2 ng/mL when reactivated with obidoxime. These experiments also show that previously published IMS-LC-MS/MS analyses are compatible with serum treated with oximes. Dual-Mode IMA is the first immunoaffinity method developed for the simultaneous measurement of OPNA adducted BuChE, unadducted BuChE, and free nerve agent in serum and is a promising new tool for studying reactivator effectiveness on cholinesterases inhibited by nerve agents. PMID:23656164

  8. Nonconventional terror--the anesthesiologist's role in a nerve agent event.

    PubMed

    Talmor, Daniel

    2007-03-01

    The structure and biologic action of nerve agents is similar to organophosphates, commonly used as insecticides. Acetylcholine accumulation and binding to the cholinergic receptor site stimulates the affected organs producing a predictable set of clinical symptoms. Treatment of the affected patients will include decontamination, respiratory and hemodynamic support, as well as specific antidotes. The multiple casualties that may be expected present additional logistical and organizational problems. The specific skills of anesthesiologists will make them invaluable members of the care team in such a chemical mass casualty event. PMID:17400165

  9. Integration of metal oxide nanobelts with microsystems for nerve agent detection

    NASA Astrophysics Data System (ADS)

    Yu, Choongho; Hao, Qing; Saha, Sanjoy; Shi, Li; Kong, Xiangyang; Wang, Z. L.

    2005-02-01

    We have assembled tin dioxide nanobelts with low-power microheaters for detecting dimethyl methylphosphonate (DMMP), a nerve agent simulant. The electrical conductance of a heated nanobelt increased for 5% upon exposure to 78 parts per billion DMMP in air. The nanobelt conductance recovered fully quickly after the DMMP was shut off, suggesting that the single-crystal nanobelt was not subject to poisoning often observed in polycrystalline metal oxide sensors. While the sensitivity can be improved via doping nanobelts with catalytic additives, directed assembly or growth of nanobelts on microsystems will potentially allow for the large-scale fabrication of nanosensor arrays.

  10. Low-power microsensors for explosives and nerve warfare agents using silicon nanodots and nanowires

    NASA Astrophysics Data System (ADS)

    Sailor, Michael J.; Trogler, William C.; Letant, Sonia; Sohn, Honglae; Content, Stephane; Schmedake, Thomas A.; Gao, Jun; Zmolek, Peter; Link, Jamie R.; Fainman, Yeshaiahu; Xu, Fang; Shames, Paul E.

    2001-09-01

    Nanocrystalline porous silicon films (nanodots) and polymeric silicon wires (nanowires) have been used to detect chemicals in gas and liquid phase. Transduction mechanisms using quantum confinement derived photoluminescence and optical reflectivity have been used. Photoluminescence intensity is modulated by energy or electron transfer induced quenching, and a shift of the Fabry-Perot reflectivity fringes from thin nanocrystalline films occurs upon molecular absorption. Examples of irreversible detection and reversible sensing modes for explosives, nerve warfare agents, and various odors of commercial interest will be provided. A catalyst can be incorporated into the nanomaterials to provide specificity for the analyte of interest.

  11. An attempt to assess functionally minimal acetylcholinesterase activity necessary for survival of rats intoxicated with nerve agents.

    PubMed

    Bajgar, Jiri; Fusek, Josef; Kassa, Jiri; Jun, Daniel; Kuca, Kamil; Hajek, Petr

    2008-09-25

    Acetylcholinesterase (AChE, EC 3.1.1.7) is an important enzyme for cholinergic nerve transmission. The action of toxic organophosphates such as nerve agents is based on AChE inhibition. The death following acute nerve agent poisoning is due to central or peripheral respiratory/cardiac failure. Therefore, the changes in AChE activity following nerve agents acting predominantly on the central (sarin, soman) or peripheral (VX) level were studied. It is known that AChE activity in different structures exists in relative excess. Female Wistar rats intoxicated with sarin, soman, and VX in different doses (0.5-2.0 x LD(50)) were divided into groups of survived and died animals. AChE activities in diaphragm, brain parts (pontomedullar area, frontal cortex, basal ganglia, in some cases other parts of the brain) were determined and the rest of activity (in %) was correlated with survival/death of animals. More precise elucidation of action of nerve agents and the assessment of minimal AChE activity in different organs compatible with the survival of organism poisoned with nerve agents were the aims of this study. PMID:18579126

  12. 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

  13. An acetylcholinesterase-based chronoamperometric biosensor for fast and reliable assay of nerve agents.

    PubMed

    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

  14. 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. PMID:18269796

  15. Behavioral side effects in rats treated with acetylcholinesterase inhibitors suggested used as prophylactics against nerve agents.

    PubMed

    Myhrer, Trond; Enger, Siri; Aas, Pål

    2010-05-01

    Acetylcholinesterase inhibitors in combination with an anticholinergic, particularly anticholinergics with antiglutamatergic properties, can effectively protect against nerve agent-induced seizures and lethality. The objective of the present study was to examine potential behavioral side effects of the anticholinesterases physostigmine (0.1mg/kg), galantamine (3mg/kg), huperzine (0.5mg/kg), and donepezil (2.5mg/kg) alone or each drug in combination with anticholinergic procyclidine (3mg/kg). The results showed that rats injected intraperitoneally with galantamine displayed a mild cognitive deficit in terms of reduced preference for novelty that was similarly found among animals treated with procyclidine combined with either galantamine or donepezil. Locomotor activity and rearing were radically depressed in all groups treated with anticholinesterases as well as in combination with procyclidine. Reductions in activity were most prominent for rats injected with galantamine alone. Equalizing effects of cholinesterase inhibitors and anticholinergics were absent in the present context. Findings from previous studies that both systemic and local (amygdala) application of physostigmine cause increased fear-motivated freezing response in rats, may explain the marked reductions in activity among the present rats. In view of these findings, use of anticholinesterases (crossing the blood-brain barrier) as prophylactics against nerve agents must be carefully examined to avoid severe side effects. PMID:20184916

  16. 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

  17. A lab-on-a-chip for detection of nerve agent sarin in blood.

    PubMed

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

    2008-06-01

    Sarin (C(4)H(10)FO(2)P,O-isopropyl methylphosphonofluoridate) is a colourless, odourless and highly toxic phosphonate that acts as a cholinesterase inhibitor and disrupts neuromuscular transmission. Sarin and related phosphonates are chemical warfare agents, and there is a possibility of their application in a military or terrorist attack. This paper reports a lab-on-a-chip device for detecting a trace amount of sarin in a small volume of blood. The device should allow early detection of sarin exposure during medical triage to differentiate between those requiring medical treatment from mass psychogenic illness cases. The device is based on continuous-flow microfluidics with sequential stages for lysis of whole blood, regeneration of free nerve agent from its complex with blood cholinesterase, protein precipitation, filtration, enzyme-assisted reaction and optical detection. Whole blood was first mixed with a nerve gas regeneration agent, followed by a protein precipitation step. Subsequently, the lysed product was filtered on the chip in two steps to remove particulates and fluoride ions. The filtered blood sample was then tested for trace levels of regenerated sarin using immobilised cholinesterase on the chip. Activity of immobilised cholinesterase was monitored by the enzyme-assisted reaction of a substrate and reaction of the end-product with a chromophore. Resultant changes in chromophore-induced absorbance were recorded on the chip using a Z-shaped optical window. Loss of enzyme activity obtained prior and after passage of the treated blood sample, as shown by a decrease in recorded absorbance values, indicates the presence of either free or regenerated sarin in the blood sample. The device was fabricated in PMMA (polymethylmethacrylate) using CO(2)-laser micromachining. This paper reports the testing results of the different stages, as well as the whole device with all stages in the required assay sequence. The results demonstrate the potential use of a

  18. The noncontact detection of nerve agent simulants on U.S. military CARC

    NASA Astrophysics Data System (ADS)

    Petryk, Michael W. P.

    2009-05-01

    The non-contact detection of chemical warfare agent simulants is achieved in the condensed phase using polarization modulation infrared reflection-absorption spectroscopy (PMIRRAS). The G-series nerve agent simulants, trimethyl phosphate (TMP) and triethyl phosphate (TEP), are detected on US military chemical agent resistant coating (CARC) using PMIRRAS. Optimal detector angles for PMIRRAS are determined, as are absorption features which can be used to distinguish between the spectral contributions of the substrate (CARC) and the analyte (TMP or TEP). Ab initio calculations carried out at the B3LYP / 6-31G(d,p) level of theory and basis set are used to predict the most stable simulant conformations, and their harmonic (unscaled) vibrational frequencies. Ab initio vibrational frequency data is used to explain the existence of both upward-oriented and downward-oriented PMIRRAS absorption features in terms of molecular orientation at a surface and the orientation of the dipole derivative vector of a given vibrational mode.

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

    PubMed

    Halbrook, R S; Shugart, L R; Watson, A P; Munro, N B; Linnabary, R D

    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. A 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. PMID:1399773

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

    SciTech Connect

    Halbrook, R.S.; Shugart, L.R.; Watson, A.P.; Munro, N.B.; Linnabary, R.D. )

    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. A 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.

  1. Tailoring the Pore Size and Functionality of UiO-Type Metal-Organic Frameworks for Optimal Nerve Agent Destruction.

    PubMed

    Peterson, Gregory W; Moon, Su-Young; Wagner, George W; Hall, Morgan G; DeCoste, Jared B; Hupp, Joseph T; Farha, Omar K

    2015-10-19

    Evaluation of UiO-66 and UiO-67 metal-organic framework derivatives as catalysts for the degradation of soman, a chemical warfare agent, showed the importance of both the linker size and functionality. The best catalysts yielded half-lives of less than 1 min. Further testing with a nerve agent simulant established that different rate-assessment techniques yield similar values for degradation half-lives. PMID:26431370

  2. 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). PMID:20061191

  3. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  4. Showering effectiveness for human hair decontamination of the nerve agent VX.

    PubMed

    Josse, Denis; Wartelle, Julien; Cruz, Catherine

    2015-05-01

    In this work, our goals were to establish whether hair decontamination by showering one hour post-exposure to the highly toxic organophosphate nerve agent VX was effective, whether it required the addition of a detergent to water and, if it could be improved by using the adsorbent Fuller's Earth (FE) or the Reactive Skin Decontamination Lotion (RSDL) 30 min prior to showering. Hair exposure to VX and decontamination was performed by using an in vitro model. Hair showering led to 72% reduction of contamination. Addition of detergent to water slightly increased the decontamination effectiveness. Hair treatment with FE or RSDL improved the decontamination rate. Combination of FE use and showering, which yielded a decontamination factor of 41, was demonstrated to be the most effective hair decontamination procedure. Hair wiping after showering was shown to contribute to hair decontamination. Altogether, our results highlighted the importance of considering hair decontamination as an important part of body surface decontamination protocols. PMID:25791764

  5. Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.

    PubMed

    McCarren, Hilary S; McDonough, John H

    2016-06-01

    Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit. PMID:27258770

  6. Impurity Profiling to Match a Nerve Agent to Its Precursor Source for Chemical Forensics Applications

    SciTech Connect

    Fraga, Carlos G.; Perez Acosta, Gabriel A.; Crenshaw, Michael D.; Wallace, Krys; Mong, Gary M.; Colburn, Heather A.

    2011-10-31

    Chemical forensics is an emerging field in homeland security that aims to attribute a weaponized toxic chemical or related material to its source. Herein, for the first time, trace impurities originating from a chemical precursor were used to match a synthesized nerve agent to its precursor source. Specifically, multiple batches of sarin and its intermediate were synthesized from two commercial stocks of methylphosphonic dichloride (DC) and were then matched by impurity profiling to their DC stocks from out of five possible stocks. This was possible because each DC stock had a unique impurity profile that, for the tested stocks, persisted through synthesis, decontamination, and sample preparation. This work may form a basis for using impurity profiling to help find and prosecute perpetrators of chemical attacks.

  7. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    PubMed

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. PMID:26621540

  8. Trapping of organophosphorus chemical nerve agents in water with amino acid functionalized baskets.

    PubMed

    Ruan, Yian; Dalkiliç, Erdin; Peterson, Paul W; Pandit, Aroh; Dastan, Arif; Brown, Jason D; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D

    2014-04-01

    We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future. PMID:24616086

  9. Synthesis and biodegradation of the VX nerve agent derivative 2-DIISO-propylaminoethylsulfonic acid

    SciTech Connect

    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 degraded by Rhodococcus dp. strain IGTS8 as evidenced by an increase in the optical density at 600 nm.

  10. Nucleotide sequence of a gene encoding an organophosphorus nerve agent degrading enzyme from Alteromonas haloplanktis.

    PubMed

    Cheng, T; Liu, L; Wang, B; Wu, J; DeFrank, J J; Anderson, D M; Rastogi, V K; Hamilton, A B

    1997-01-01

    Organophosphorus acid anhydrolases (OPAA) catalyzing the hydrolysis of a variety of toxic organophosphorus cholinesterase inhibitors offer potential for decontamination of G-type nerve agents and pesticides. The gene (opa) encoding an OPAA was cloned from the chromosomal DNA of Alteromonas haloplanktis ATCC 23821. The nucleotide sequence of the 1.7 -kb DNA fragment contained the opa gene (1.3 kb) and its flanking region. We report structural and functional similarity of OPAAs from A. haloplanktis and Alteromonas sp JD6.5 with the enzyme prolidase that hydrolyzes dipeptides with a prolyl residue in the carboxyl-terminal position. These results corroborate the earlier conclusion that the OPAA is a type of X-Pro dipeptidase, and that X-Pro could be the native substrate for such an enzyme in Alteromonas cells. PMID:9079288

  11. Gas sensor based on nano ZSM-5 zeolite films for the nerve agent simulant dimethylmethylphosphonate detection

    NASA Astrophysics Data System (ADS)

    Xie, Haifen; Ting, Yu; Sun, Xiaoxiang; Jia, Zhou; Huang, Yiping

    2004-12-01

    The piezoelectric sensor device coated with nanosize ZSM-5 zeolite films has beem fabricated. The Nerve agent simulant Dimethylmethylphosphonate has been tested with this piezoelectric sensor devices. The frequency shifts to time at 1 ppm, 5ppm and 20ppm DMMP are examined respectively. The minimum detection concentration of 1ppm DMMP has been obtained in the N2 at 293K. 1 ppm is lower than the EC50 concentration value (where EC50 is the airborne concentration sufficient to induce severe effects in 50% of those exposed for 30 min). The frequency sensitivity was found to be about 60HZ / ppm. The effect of acetone on the ZSM-5 zeolite film was also investigated for the selectivity test. Using principle component analysis (PCA), we can qualify and quantify these testing gases.

  12. Detoxification of organophosphorus pesticides and nerve agents through RSDL: efficacy evaluation by (31)P NMR spectroscopy.

    PubMed

    Elsinghorst, Paul W; Worek, Franz; Koller, Marianne

    2015-03-01

    Intoxication by organophosphorus compounds, especially by pesticides, poses a considerable risk to the affected individual. Countermeasures involve both medical intervention by means of antidotes as well as external decontamination to reduce the risk of dermal absorption. One of the few decontamination options available is Reactive Skin Decontamination Lotion (RSDL), which was originally developed for military use. Here, we present a (31)P NMR spectroscopy based methodology to evaluate the detoxification efficacy of RSDL with respect to a series of organophosphorus pesticides and nerve agents. Kinetic analysis of the obtained NMR data provided degradation half-lives proving that RSDL is also reasonably effective against organophosphorus pesticides. Unexpected observations of different RSDL degradation patterns are presented in view of its reported oximate-catalyzed mechanism of action. PMID:25597861

  13. CATALYTIC DETOXIFICATION OF NERVE AGENT AND PESTICIDE ORGANOPHOSPHATES BY BUTYRYLCHOLINESTERASE ASSISTED WITH NON-PYRIDINIUM OXIMES

    PubMed Central

    Radić, Zoran; Dale, Trevor; Kovarik, Zrinka; Berend, Suzana; Garcia, Edzna; Zhang, Limin; Amitai, Gabriel; Green, Carol; Radić, Božica; Duggan, Brendan M.; Ajami, Dariush; Rebek, Julius; Taylor, Palmer

    2016-01-01

    SYNOPSIS We present here a comprehensive in vitro, ex vivo and in vivo study on hydrolytic detoxification of nerve agent and pesticide organophosphates (OPs) catalyzed by purified human butyrylcholinesterase (hBChE) in combination with novel non-pyridinium oxime reactivators. We identified 2-trimethylammonio-6-hydroxybenzaldehyde oxime (TAB2OH) as an efficient reactivator of OP-hBChE conjugates formed by the nerve agents, VX and cyclosarin, and the pesticide, paraoxon. It was also functional in reactivation of sarin and tabun inhibited hBChE. A three to five-fold enhancement of in vitro reactivation of VX, cyclosarin and paraoxon inhibited hBChE was observed, when compared to the commonly used N-methylpyridinium aldoxime reactivator, 2PAM. Kinetic analysis showed the enhancement resulted from improved molecular recognition of corresponding OP-hBChE conjugates by TAB2OH. The unique features of TAB2OH stem from an exocyclic quaternary nitrogen and a hydroxyl, both ortho to an oxime group on a benzene ring. pH dependences reveal participation of the hydroxyl (pKa=7.6) forming an additional ionizing nucleophile to potentiate the oxime (pKa=10) at physiological pH. The TAB2OH protective indices in therapy of sarin and paraoxon exposed mice were enhanced by 30% – 60% when they were treated with a combination of TAB2OH and sub-stoichiometric hBChE. These results establish that oxime-assisted catalysis is feasible for OP bioscavenging. PMID:23216060

  14. Nerve Agent Exposure Elicits Site-Specific Changes in Protein Phosphorylation in Mouse Brain

    PubMed Central

    Zhu, Hongwen; O’Brien, Jennifer J.; O’Callaghan, James P.; Miller, Diane B.; Zhang, Qiang; Rana, Minal; Tsui, Tiffany; Peng, Youyi; Tomesch, John; Hendrick, Joseph P.; Wennogle, Lawrence P; Snyder, Gretchen L.

    2010-01-01

    Organophosphorus (OP) compounds cause toxic symptoms, including convulsions, coma, and death, as the result of irreversible inhibition of acetylcholinesterase (AChE). The development of effective treatments to block these effects and attenuate long-term cognitive and motor disabilities that result from OP intoxication is hampered by a limited understanding of the CNS pathways responsible for these actions. We employed a candidate method (called CNSProfile™) to identify changes in the phosphorylation state of key neuronal phosphoproteins evoked by the OP compound, diisopropyl fluorophosphate (DFP). Focused microwave fixation was used to preserve the phosphorylation state of phosphoproteins in brains of DFP-treated mice; hippocampus and striatum were analyzed by immunoblotting with a panel of phospho-specific antibodies. DFP exposure elicited comparable effects on phosphorylation of brain phosphoproteins in both C57BL/6 and FVB mice. DFP treatment significantly altered phosphorylation at regulatory residues on glutamate receptors, including Serine897 (S897) of the NR1 NMDA receptor. NR1 phosphorylation was bi-directionally regulated after DFP in striatum versus hippocampus. NR1 phosphorylation was reduced in striatum, but elevated in hippocampus, compared with controls. DARPP-32 phosphorylation in striatum was selectively increased at the Cdk5 kinase substrate, Threonine75 (T75). Phencynonate hydrochloride, a muscarinic cholinergic antagonist, prevented seizure-like behaviors and the observed changes in phosphorylation induced by DFP. The data reveal region-specific effects of nerve agent exposure on intracellular signaling pathways that correlate with seizure-like behavior and which are reversed by the muscarinic receptor blockade. This approach identifies specific targets for nerve agents, including substrates for Cdk5 kinase, which may be the basis for new anti-convulsant therapies. PMID:20423708

  15. Good manufacturing practice: manufacturing of a nerve agent antidote nanoparticle suspension.

    PubMed

    Clark, Andrew P-Z; Dixon, Hong; Cantu, Norma L; Cabell, Larry A; McDonough, Joe A

    2013-01-01

    We have established a current good manufacturing practice (GMP) manufacturing process to produce a nanoparticle suspension of 1,1'-methylenebis-4-[(hydroxyimino)methyl]pyridinium dimethanesulfonate (MMB4 DMS) in cottonseed oil (CSO) as a nerve agent antidote for a Phase 1 clinical trial. Bis-pyridinium oximes such as MMB4 were previously developed for emergency treatment of organophosphate nerve agent intoxication. Many of these compounds offer efficacy superior to monopyridinium oximes, but they have poor thermal stability due to hydrolytic cleavage in aqueous solution. We previously developed a nonaqueous nanoparticle suspension to improve the hydrothermal stability, termed Enhanced Formulation (EF). An example of this formulation technology is a suspension of MMB4 DMS nanoparticles in CSO. Due to the profound effect of particle size distribution on product quality and performance, particle size must be controlled during the manufacturing process. Therefore, a particle size analysis method for MMB4 DMS in CSO was developed and validated to use in support of good laboratory practice/GMP development and production activities. Manufacturing of EF was accomplished by milling MMB4 DMS with CSO and zirconia beads in an agitator bead mill. The resulting bulk material was filled into 5-mL glass vials at a sterile fill facility and terminally sterilized by gamma irradiation. The clinical lot was tested and released, a Certificate of Analysis was issued, and a 3-year International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) stability study started. The drug product was placed in storage for Phase 1 clinical trial distribution. A dose delivery uniformity study was undertaken to ensure that the correct doses were delivered to the patients in the clinic. PMID:23929446

  16. Detection and classification of organophosphate nerve agent simulants using support vector machines with multiarray sensors.

    PubMed

    Sadik, Omowunmi; Land, Walker H; Wanekaya, Adam K; Uematsu, Michiko; Embrechts, Mark J; Wong, Lut; Leibensperger, Dale; Volykin, Alex

    2004-01-01

    The need for rapid and accurate detection systems is expanding and the utilization of cross-reactive sensor arrays to detect chemical warfare agents in conjunction with novel computational techniques may prove to be a potential solution to this challenge. We have investigated the detection, prediction, and classification of various organophosphate (OP) nerve agent simulants using sensor arrays with a novel learning scheme known as support vector machines (SVMs). The OPs tested include parathion, malathion, dichlorvos, trichlorfon, paraoxon, and diazinon. A new data reduction software program was written in MATLAB V. 6.1 to extract steady-state and kinetic data from the sensor arrays. The program also creates training sets by mixing and randomly sorting any combination of data categories into both positive and negative cases. The resulting signals were fed into SVM software for "pairwise" and "one" vs all classification. Experimental results for this new paradigm show a significant increase in classification accuracy when compared to artificial neural networks (ANNs). Three kernels, the S2000, the polynomial, and the Gaussian radial basis function (RBF), were tested and compared to the ANN. The following measures of performance were considered in the pairwise classification: receiver operating curve (ROC) Az indices, specificities, and positive predictive values (PPVs). The ROC Az) values, specifities, and PPVs increases ranged from 5% to 25%, 108% to 204%, and 13% to 54%, respectively, in all OP pairs studied when compared to the ANN baseline. Dichlorvos, trichlorfon, and paraoxon were perfectly predicted. Positive prediction for malathion was 95%. PMID:15032529

  17. Fragmentation pathways and structural characterization of 14 nerve agent compounds by electrospray ionization tandem mass spectrometry.

    PubMed

    Housman, Kathleen J; Swift, Austin T; Oyler, Jonathan M

    2015-03-01

    Organophosphate nerve agents (OPNAs) are some of the most widely used and proliferated chemical warfare agents. As evidenced by recent events in Syria, these compounds remain a serious military and terrorist threat to human health because of their toxicity and the ease with which they can be used, produced and stored. There are over 2,000 known, scheduled compounds derived from common parent structures with many more possible. To address medical, forensic, attribution, remediation and other requirements, laboratory systems have been established to provide the capability to analyze 'unknown' samples for the presence of these compounds. Liquid chromatography/mass spectrometric methods have been validated and are routinely used in the analysis of samples for a very limited number of these compounds, but limited data exist characterizing the electrospray ionization (ESI) and mass spectrometric fragmentation pathways of the compound families. This report describes results from direct infusion ESI/MS, ESI/MS(2) and ESI/MS(3) analysis of 14 G and V agents, the major OPNA families, using an AB Sciex 4000 QTrap. Using a range of conditions, spectra were acquired and characteristic fragments identified. The results demonstrated that the reproducible and predictable fragmentation of these compounds by ESI/MS, ESI/MS(2) and ESI/MS(3) can be used to describe systematic fragmentation pathways specific to compound structural class. These fragmentation pathways, in turn, may be useful as a predictive tool in the analysis of samples by screening and confirmatory laboratories to identify related compounds for which authentic standards are not readily available. PMID:25519457

  18. Advances in toxicology and medical treatment of chemical warfare nerve agents.

    PubMed

    Moshiri, Mohammd; Darchini-Maragheh, Emadodin; Balali-Mood, Mahdi

    2012-01-01

    Organophosphorous (OP) Nerve agents (NAs) are known as the deadliest chemical warfare agents. They are divided into two classes of G and V agents. Most of them are liquid at room temperature. NAs chemical structures and mechanisms of actions are similar to OP pesticides, but their toxicities are higher than these compounds. The main mechanism of action is irreversible inhibition of Acetyl Choline Esterase (AChE) resulting in accumulation of toxic levels of acetylcholine (ACh) at the synaptic junctions and thus induces muscarinic and nicotinic receptors stimulation. However, other mechanisms have recently been described. Central nervous system (CNS) depression particularly on respiratory and vasomotor centers may induce respiratory failure and cardiac arrest. Intermediate syndrome after NAs exposure is less common than OP pesticides poisoning. There are four approaches to detect exposure to NAs in biological samples: (I) AChE activity measurement, (II) Determination of hydrolysis products in plasma and urine, (III) Fluoride reactivation of phosphylated binding sites and (IV) Mass spectrometric determination of cholinesterase adducts. The clinical manifestations are similar to OP pesticides poisoning, but with more severity and fatalities. The management should be started as soon as possible. The victims should immediately be removed from the field and treatment is commenced with auto-injector antidotes (atropine and oximes) such as MARK I kit. A 0.5% hypochlorite solution as well as novel products like M291 Resin kit, G117H and Phosphotriesterase isolated from soil bacterias, are now available for decontamination of NAs. Atropine and oximes are the well known antidotes that should be infused as clinically indicated. However, some new adjuvant and additional treatment such as magnesium sulfate, sodium bicarbonate, gacyclidine, benactyzine, tezampanel, hemoperfusion, antioxidants and bioscavengers have recently been used for OP NAs poisoning. PMID:23351280

  19. In vivo decontamination of the nerve agent VX using the domestic swine model.

    PubMed

    Misik, Jan; Pavlik, Michal; Novotny, Ladislav; Pavlikova, Ruzena; Chilcott, Robert P; Cabal, Jiri; Kuca, Kamil

    2012-11-01

    The purpose of this in vivo study was to assess a new, putatively optimised method for mass casualty decontamination ("ORCHIDS protocol") for effectiveness in removing the chemical warfare agent VX from the skin of anaesthetised, domestic white pigs. ORCHIDS protocol consists of a 1.5-minute shower with a mild detergent (Argos™) supplemented by physical removal. A standard method of wet decontamination was used for comparison. Experimental animals were divided into four groups (A-D). Two groups were exposed to a supra-lethal percutaneous dose (5 × LD(50); 300 μg kg(-1)) of VX for 1 h prior to decontamination with either the ORCHIDS (C) or standard protocol (D). A third (B, positive control) group was exposed but not subject to decontamination. Blank controls (A) received anaesthesia and the corresponding dose of normal saline instead of VX. Observations of the clinical signs of intoxication were supplemented by measurements of whole blood cholinesterase (ChE) performed on samples of arterial blood acquired at 30-minute intervals for the duration of the study (up to 6 h). Untreated (B) animals displayed typical cholinergic signs consistent with VX intoxication (local fasciculation, mastication, salivation, pilo-erection and motor convulsions) and died 165-240 min post exposure. All animals in both decontamination treatment groups (C, D) survived the duration of the study and exhibited less severe signs of cholinergic poisoning. Thus, both the standard and ORCHIDS protocol were demonstrably effective against exposure to the potent nerve agent VX, even after a delay of 1 h. A critical advantage of the ORCHIDS protocol is the relatively short shower duration (1½ min compared to 3 min). In practice, this could substantially improve the rate at which individuals could be decontaminated by emergency responders following exposure to toxic materials such as chemical warfare agents. PMID:22963275

  20. Advances in toxicology and medical treatment of chemical warfare nerve agents

    PubMed Central

    2012-01-01

    Organophosphorous (OP) Nerve agents (NAs) are known as the deadliest chemical warfare agents. They are divided into two classes of G and V agents. Most of them are liquid at room temperature. NAs chemical structures and mechanisms of actions are similar to OP pesticides, but their toxicities are higher than these compounds. The main mechanism of action is irreversible inhibition of Acetyl Choline Esterase (AChE) resulting in accumulation of toxic levels of acetylcholine (ACh) at the synaptic junctions and thus induces muscarinic and nicotinic receptors stimulation. However, other mechanisms have recently been described. Central nervous system (CNS) depression particularly on respiratory and vasomotor centers may induce respiratory failure and cardiac arrest. Intermediate syndrome after NAs exposure is less common than OP pesticides poisoning. There are four approaches to detect exposure to NAs in biological samples: (I) AChE activity measurement, (II) Determination of hydrolysis products in plasma and urine, (III) Fluoride reactivation of phosphylated binding sites and (IV) Mass spectrometric determination of cholinesterase adducts. The clinical manifestations are similar to OP pesticides poisoning, but with more severity and fatalities. The management should be started as soon as possible. The victims should immediately be removed from the field and treatment is commenced with auto-injector antidotes (atropine and oximes) such as MARK I kit. A 0.5% hypochlorite solution as well as novel products like M291 Resin kit, G117H and Phosphotriesterase isolated from soil bacterias, are now available for decontamination of NAs. Atropine and oximes are the well known antidotes that should be infused as clinically indicated. However, some new adjuvant and additional treatment such as magnesium sulfate, sodium bicarbonate, gacyclidine, benactyzine, tezampanel, hemoperfusion, antioxidants and bioscavengers have recently been used for OP NAs poisoning. PMID:23351280

  1. Comparison of High Resolution and Tandem Mass Spectrometry for the Analysis of Nerve Agent Metabolites in Urine

    PubMed Central

    Hamelin, Elizabeth I.; Bragg, William; Shaner, Rebecca L.; Swaim, Leigh L.; Johnson, Rudolph C.

    2015-01-01

    Rationale Although use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. High-resolution mass spectrometry (HRMS) was compared to tandem mass spectrometry (MS/MS) analysis for the quantitation of five urinary metabolites specific to VX, Russian VX, soman, sarin and cyclosarin nerve agents. The HRMS method was further evaluated for qualitative screening of metabolites not included in the test panel. Methods Nerve agent metabolites were extracted from urine using solid phase extraction, separated using hydrophilic interaction chromatography and analyzed using both tandem and high resolution mass spectrometry. MS/MS results were obtained using selected reaction monitoring with unit resolution; HRMS results were obtained using a mass extraction window of 10 ppm at a mass resolution of 50,000. The benchtop Orbitrap HRMS instrument was operated in full scan mode, to measure the presence of unexpected agents. Results The assessment of two quality control samples demonstrated high accuracy (99.5-104%) and high precision (2-9%) for both HRMS and MS/MS. Sensitivity, as described by the limit of detection, was overlapping for both detectors (0.2-0.7 ng/mL). Additionally, the HRMS method positively confirmed the presence of a nerve agent metabolite, not included in the test panel, using the accurate mass and relative retention time. Conclusions The precision, accuracy, and sensitivity were comparable between the current MS/MS method and this newly developed HRMS analysis for five nerve agent metabolites. HRMS showed additional capabilities beyond the current method by confirming the presence of a metabolite not included in the test panel. PMID:23821563

  2. Improving the promiscuous nerve agent hydrolase activity of a thermostable archaeal lactonase.

    PubMed

    Merone, Luigia; Mandrich, Luigi; Porzio, Elena; Rossi, Mosé; Müller, Susanne; Reiter, Georg; Worek, Franz; Manco, Giuseppe

    2010-12-01

    The thermostable Phosphotriesterase-Like Lactonase from Sulfolobus solfataricus (SsoPox) hydrolyzes lactones and, at a lower rate, neurotoxic organophosphorus compounds. The persistent demand of detoxification tools in the field of agricultural wastes and restoring of conditions after terrorist acts prompted us to exploit SsoPox as a "starter" to evolve its ancillary nerve agents hydrolytic capability. A directed evolution strategy yielded, among several variants, the single mutant W263F with k(cat) and specificity constant against paraoxon 16- and 6-fold enhanced, respectively, compared to the wild type. Furthermore, a phenomenon of enzyme activation by SDS has been observed, which allowed to increase those values 150- and 28-fold, respectively. The activity of SsoPox against the deadly nerve gas Cyclosarin has been reported for the first time and proved to be substantially unaffected for variant W263F. Finally, outperforming efficiency of W263F was demonstrated, under severe stressing conditions, with respect to the best known phosphotriesterase PTE from Brevundimonas diminuta. PMID:20667718

  3. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  4. 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

  5. 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...

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

    PubMed

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

    2014-08-01

    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 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 to 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

  7. Direct derivatization and gas chromatography-tandem mass spectrometry identification of nerve agent biomarkers in urine samples.

    PubMed

    Subramaniam, Raja; Östin, Anders; Nilsson, Calle; Åstot, Crister

    2013-06-01

    Rapid determination of nerve agent biomarkers at low-ppb levels in urine samples was achieved by direct derivatization and sample analysis using gas chromatography-tandem mass spectrometry. The studied biomarkers were alkylphosphonic acids (APAs), as they are specific hydrolysis products of organophosphorus nerve agents that can be used to verify nerve agent exposure. The sample preparation technique employed involves rapid direct derivatization (5min) of acidified urine samples (25μL) using a highly fluorinated phenyldiazomethane reagent [1-(diazomethyl)-3,5-bis(trifluoromethyl)benzene]. The derivatization conditions were optimized using statistical experimental design and multivariate data analysis. The APA derivatives were analyzed by GC-MS and MS/MS using negative ion chemical ionization. The selectivity and sensitivity of analyses performed by low and high resolution single ion monitoring MS-mode were compared with those performed by multiple reaction monitoring MS/MS-mode. The MS/MS technique offered the greatest sensitivity and selectivity of the tested mass spectrometric techniques, with limits of detection ranging from 0.5 to 1ng APAs/mL of urine. The method's robustness was evaluated using urine samples from the OPCW 2nd biomedical confidence building exercise and all APAs present in the samples were conclusively identified. The method thus offers excellent performance and is viable for the simultaneous trace determination of a wide range of nerve agent markers. PMID:23603296

  8. Development of an autonomous detector for sensing of nerve agents based on functionalized silicon nanowire field-effect transistors.

    PubMed

    Clavaguera, Simon; Raoul, Nicolas; Carella, Alexandre; Delalande, Michael; Celle, Caroline; Simonato, Jean-Pierre

    2011-10-15

    The ability to detect minute traces of chemical warfare agents is mandatory both for military forces and homeland security. Various detectors based on different technologies are available but still suffer from serious drawbacks such as false positives. There is still a need for the development of innovative reliable sensors, in particular for organophosphorus nerve agents like Sarin. We report herein on the fabrication of a portable, battery-operated, microprocessor-based prototype sensor system relying on silicon nanowire field-effect transistors for the detection of nerve agents. A fast, supersensitive and highly selective detection of organophosphorus molecules is reported. The results show also high selectivity in complex mixtures and on contaminated materials. PMID:21962681

  9. Intrinsic optical fiber sensor for sensing organophosphate nerve agent using the modified cladding approach

    NASA Astrophysics Data System (ADS)

    Bansal, Lalitkumar; El-Sherif, Mahmoud

    2004-03-01

    The concept of modified cladding based sensors represents the largest class of intrinsic fiber optic chemical sensors. In this design, the passive cladding of the optical fiber is replaced by an active coating, called modified cladding. The analyte in this case diffuses into the coating and induces changes in the absorbance, fluorescence, or some other spectroscopic property of the modified cladding, the coating acts as a chemo-chromic transducer and sensing takes place by intensity modulation. This design i.e. of the coating based sensors, has found enormous applicability in the realm of chemical and biochemical sensing which also includes environmental monitoring and detection of chemical warfare agents. In this paper, the development of an intrinsic fiber optic sensor for detection of organophosphate dimethyl-methyl phoshopnate (DMMP) is presented. DMMP is a chemical precursor to the nerve agent sarin. The chemo-chromic transducer material used as a modified coating on the fiber core is NDSA (Naphthalene disulphonic acid) doped polypyrrole. This coating material shows conductivity and absorbance change when exposed to DMMP. The fabrication of the sensor device is a three step process which involves (a) etching a small section of the optical fiber to expose the core, (b) coating the etched section of the optical fiber with the polymer, (c) integration of sensor components and testing. Thin film characterization is done using the UV-Vis spectrophotometer on in-situ coated films of polypyrrole on a glass substrate to check for absorbance change upon exposure to DMMP. The development procedure is presented next and encouraging results are discussed.

  10. A high-throughput diagnostic method for measuring human exposure to organophosphorus nerve agents.

    PubMed

    Knaack, Jennifer S; Zhou, Yingtao; Abney, Carter W; Jacob, Justin T; Prezioso, Samantha M; Hardy, Katelyn; Lemire, Sharon W; Thomas, Jerry; Johnson, Rudolph C

    2012-11-01

    An automated high-throughput immunomagnetic separation (IMS) method for diagnosing exposure to the organophosphorus nerve agents (OPNAs) sarin (GB), cyclohexylsarin (GF), VX, and Russian VX (RVX) was developed to increase sample processing capacity for emergency response applications. Diagnosis of exposure to OPNAs was based on the formation of OPNA adducts to butyrylcholinesterase (BuChE). Data reported with this method represent a ratio of the agent-specific BuChE adduct concentration, relative to the total BuChE peptide concentration that provides a nonactivity measurement expressed as percent adducted. All magnetic bead transfer steps and washes were performed using instrumentation in a 96-well format allowing for simultaneous extraction of 86 clinical samples plus reference materials. Automating extractions increased sample throughput 50-fold, as compared to a previously reported manual method. The limits of detection, determined using synthetic peptides, were 1 ng/mL for unadducted BuChE and GB-, GF-, VX-, and RVX-adducted BuChE. The automated method was characterized using unexposed serum and serum pools exposed to GB, GF, VX, or RVX. Variation for the measurement of percent adducted was <12% for all characterized quality control serum pools. Twenty-six (26) serum samples from individuals asymptomatic for cholinesterase inhibitor exposure were analyzed using this method, and no background levels of OPNA exposure were observed. Unexposed BuChE serum concentrations measured using this method ranged from 2.8 μg/mL to 10.6 μg/mL, with an average concentration of 6.4 μg/mL. PMID:23083472

  11. Reaction of nerve agents with phosphate buffer at pH 7.

    PubMed

    Creasy, William R; Fry, Roderick A; McGarvey, David J

    2012-07-12

    Chemical weapon nerve agents, including isopropyl methylphosphonofluoridate (GB or Sarin), pinacolyl methylphosphonofluoridate (GD or Soman), and S-(2-diisopropylaminoethyl) O-ethyl methylphosphonothioate (VX), are slow to react in aqueous solutions at midrange pH levels. The nerve agent reactivity increases in phosphate buffer at pH 7, relative to distilled water or acetate buffer. Reactions were studied using (31)P NMR. Phosphate causes faster reaction to the corresponding alkyl methylphosphonic acids, and produces a mixed phosphate/phosphonate compound as an intermediate reaction product. GB has the fastest reaction rate, with a bimolecular rate constant of 4.6 × 10(-3) M(-1)s(-1)[PO(4)(3-)]. The molar product branching ratio of GB acid to the pyro product (isopropyl methylphosphonate phosphate anhydride) is 1:1.4, independent of phosphate concentration, and the pyro product continues to react much slower to form GB acid. The pyro product has two doublets in the (31)P NMR spectrum. The rate of reaction for GD is slower than GB, with a rate constant of 1.26 × 10(-3) M(-1)s(-1) [PO(4)(3-)]. The rate for VX is considerably slower, with a rate constant of 1.39 × 10(-5) M(-1)s(-1) [PO(4)(3-)], about 2 orders of magnitude slower than the rate for GD. The rate constant of the reaction of GD with pyrophosphate at pH 8 is 2.04 × 10(-3) min(-1) at a concentration of 0.0145 M. The rate of reaction for diisopropyl fluorophosphate is 2.84 × 10(-3) min(-1) at a concentration of 0.153 M phosphate, a factor of 4 slower than GD and a factor of 15 slower than GB, and there is no detectable pyro product. The half-lives of secondary reaction of the GB pyro product in 0.153 and 0.046 M solution of phosphate are 23.8 and 28.0 h, respectively, which indicates little or no dependence on phosphate. PMID:22667763

  12. Pediatric nerve agent poisoning: medical and operational considerations for emergency medical services in a large American city.

    PubMed

    Foltin, George; Tunik, Michael; Curran, Jennifer; Marshall, Lewis; Bove, Joseph; van Amerongen, Robert; Cherson, Allen; Langsam, Yedidyah; Kaufman, Bradley; Asaeda, Glenn; Gonzalez, Dario; Cooper, Arthur

    2006-04-01

    Most published recommendations for treatment of pediatric nerve agent poisoning are based on standard resuscitation doses for these agents. However, certain medical and operational concerns suggest that an alternative approach may be warranted for treatment of children by emergency medical personnel after mass chemical events. (1) There is evidence both that suprapharmacological doses may be warranted and that side effects from antidote overdosage can be tolerated. (2) There is concern that many emergency medical personnel will have difficulty determining both the age of the child and the severity of the symptoms. Therefore, the Regional Emergency Medical Advisory Committee of New York City and the Fire Department, City of New York, Bureau of Emergency Medical Services, in collaboration with the Center for Pediatric Emergency Medicine of the New York University School of Medicine and the Bellevue Hospital Center, have developed a pediatric nerve agent antidote dosing schedule that addresses these considerations. These doses are comparable to those being administered to adults with severe symptoms and within limits deemed tolerable after inadvertent nerve agent overdose in children. We conclude that the above approach is likely a safe and effective alternative to weight-based dosing of children, which will be nearly impossible to attain under field conditions. PMID:16651913

  13. Efficacy of an oximate-based skin decontaminant against organophosphate nerve agents determined in vivo and in vitro.

    PubMed

    Sawyer, T W; Parker, D; Thomas, N; Weiss, M T; Bide, R W

    1991-05-01

    Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol methylether 550. Although this formulation has shown good efficacy, concern has been expressed as to the potential toxicity of the reaction products of KBDO and organophosphate (OP) nerve agents. This report details the high efficacy of this lotion in inactivating OPs as measured by the systemic toxicity of the OP/RSD mixtures in rats. In addition, primary cultures of chick embryo neurons were also used to test the efficacy of the RSD. By relating the anticholinesterase activity in these cultures of the OP/RSD mixture to that of pure OP standards, a sensitive measure of the value of the RSD in inactivating tabun, sarin, soman and VX was obtained. Experiments with all four nerve agents in this in vitro system provided a good correlation with the in vivo data, and also indicated that the inactivation process was time- and agent-dependent and also related to the ratio of OP to RSD. PMID:2048130

  14. An Enhanced Butyrylcholinesterase Method to Measure Organophosphorus Nerve Agent Exposure in Humans

    PubMed Central

    Pantazides, Brooke G.; Watson, Caroline M.; Carter, Melissa D.; Crow, Brian S.; Perez, Jonas W.; Blake, Thomas A.; Thomas, Jerry D.; Johnson, Rudolph C.

    2016-01-01

    Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be used to confirm exposure in humans. A highly accurate method to detect G-series and V-series OPNA adducts to BChE in 75 μL of filtered blood, serum, or plasma has been developed using immunomagnetic separation (IMS) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS). The reported IMS method captures > 88% of the BChE in a specimen and corrects for matrix effects on peptide calibrators. The optimized method has been used to quantify baseline BChE levels (unadducted and OPNA-adducted) in a matched set of serum, plasma and whole blood (later processed in-house for plasma content) from 192 unexposed individuals to determine the interchangeability of the tested matrices. The results of these measurements demonstrate the ability to accurately measure BChE regardless of the format of the blood specimen received. Criteria for accepting or denying specimens were established through a series of sample stability and processing experiments. The results of these efforts are an optimized and rugged method that is transferrable to other laboratories and an increased understanding of the BChE biomarker in matrix. PMID:24604326

  15. Electrochemical Sensor for Organophosphate Pesticides and Nerve Agents Using Zirconia Nanoparticles as Selective Sorbents

    SciTech Connect

    Liu, Guodong; Lin, Yuehe

    2005-09-15

    Electrochemical sensor for detection of organophosphate (OP) pesticides and nerve agents using zirconia (ZrO₂) nanoparticles as selective sorbents is presented. Zirconia nanoparticles were electrodynamically deposited onto the polycrystalline gold electrode by cyclic voltammetry. Because of a strong affinity of zirconia to the phosphoric group, nitroaromatic OPs strongly bind to the ZrO₂ nanoparticle surface. The electrochemical characterization and anodic stripping voltammetric performance of bound OPs were evaluated using cyclic voltammetric and square-wave voltammetric (SWV) analysis. SWV was used to monitor the amount of bound OPs and provide simple, fast, and facile quantitative methods for nitroaromatic OP compounds. The sensor surface can be regenerated by successively running SWV scanning. Operational parameters, including the amount of nanoparticles, adsorption time, and the pH of the reaction medium have been optimized. The stripping voltammetric response is highly linear over the 5–200 ng/mL (ppb) methyl parathion range examined (2-min adsorption), with a detection limit of 1 ng/mL (10 min accumulation), and good precision (RSD=5.3 %, n = 10). The promising stripping voltammetric performances open new opportunities for fast, simple, and sensitive analyzing of OPs in environmental and biological samples. These findings can lead to a widespread use of electrochemical sensors to detect OP contaminates.

  16. Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

    PubMed Central

    Hulse, Elspeth J.; Davies, James O. J.; Simpson, A. John; Sciuto, Alfred M.

    2014-01-01

    Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities. PMID:25419614

  17. Huperzine a as a pretreatment candidate drug against nerve agent toxicity. (Reannouncement with new availability information)

    SciTech Connect

    Grunwald, J.; Raveh, L.; Doctor, B.P.; Ashani, Y.

    1994-12-31

    Huperzine A (HUP) is a naturally-occurring, potent, reversible inhibitor of acetylcholinesterase (AChE) that crosses the blood-brain barrier. To examine its ability to protect against nerve agent poisoning, HUP was administered i.p. to mice, and the s.c. LD50 of soman was determined at various time intervals after pretreatment. Results were compared to those obtained for animals treated with physostigmine. A protective ratio of approximately 2 was maintained for at least 6 hr after a single injection of HUP, without the need for any post-challenge drug therapy. By contrast, pretreatment with physostigmine increased the LD50 of soman by 1.4- to 1.5-fold for only up to 90 min. The long-lasting antidotal efficacy displayed by HUP correlated with the time course of the blood-AChE inhibition. The results suggest that the protection of animals by HUP from soman poisoning was achieved by temporarily sequestering the active site region of the physiologically important AChE.

  18. Percutaneous exposure to the nerve agent VX: Efficacy of combined atropine, obidoxime and diazepam treatment.

    PubMed

    Joosen, Marloes J A; van der Schans, Marcel J; van Helden, Herman P M

    2010-10-01

    The nerve agent VX is most likely to enter the body via liquid contamination of the skin. After percutaneous exposure, the slow uptake into the blood, and its slow elimination result in toxic levels in plasma for a period of several hours. Consequently, this has implications for the development of toxic signs and for treatment onset. In the present study, clinical signs, toxicokinetics and effects on respiration, electroencephalogram and heart rate were investigated in hairless guinea pigs after percutaneous exposure to 500 microg/kg VX. We found that full inhibition of AChE and partial inhibition of BuChE in blood were accompanied by the onset of clinical signs, reflected by a decline in respiratory minute volume, bronchoconstriction and a decrease in heart rate. Furthermore, we investigated the therapeutic efficacy of a single dose of atropine, obidoxime and diazepam, administered at appearance of first clinical signs, versus that of repetitive dosing of these drugs on the reappearance of signs. A single shot treatment extended the period to detrimental physiological decline and death for several hours, whereas repetitive administration remained effective as long as treatment was continued. In conclusion, percutaneous VX poisoning showed to be effectively treatable when diagnosed on time and when continued over the entire period of time during which VX, in case of ineffective decontamination, penetrates the skin. PMID:20599844

  19. Impurity profiling to match a nerve agent to its precursor source for chemical forensics applications.

    PubMed

    Fraga, Carlos G; Acosta, Gabriel A Pérez; Crenshaw, Michael D; Wallace, Krys; Mong, Gary M; Colburn, Heather A

    2011-12-15

    Chemical forensics is a developing field that aims to attribute a chemical (or mixture) of interest to its source by the analysis of the chemical itself or associated material constituents. Herein, for the first time, trace impurities detected by gas chromatography/mass spectrometry and originating from a chemical precursor were used to match a synthesized nerve agent to its precursor source. Specifically, six batches of sarin (GB, isopropyl methylphosphonofluoridate) and its intermediate methylphosphonic difluoride (DF) were synthesized from two commercial stocks of 97% pure methylphosphonic dichloride (DC); the GB and DF were then matched by impurity profiling to their DC stocks from a collection of five possible stocks. Source matching was objectively demonstrated through the grouping by hierarchal cluster analysis of the GB and DF synthetic batches with their respective DC precursor stocks based solely upon the impurities previously detected in five DC stocks. This was possible because each tested DC stock had a unique impurity profile that had 57% to 88% of its impurities persisting through product synthesis, decontamination, and sample preparation. This work forms a basis for the use of impurity profiling to help find and prosecute perpetrators of chemical attacks. PMID:22040126

  20. Selective real-time detection of gaseous nerve agent simulants using multiwavelength photoacoustics.

    PubMed

    Gurton, Kristan P; Felton, Melvin; Tober, Richard

    2012-08-15

    An optical detection method is presented that is designed to detect and identify the presence of macromolecular gas species (e.g., organophosphate-based nerve agent simulants) at trace level concentrations. The technique is based on a modified version of conventional laser photoacoustic (PA) spectroscopy, in which optical absorption is typically measured using a single laser source. We demonstrate the ability to simultaneously measure multiple absorption-related parameters that serve as a concentration-independent identifier. Three continuous wave mid-infrared laser sources, operating at 8.68, 9.29, and 10.35 μm, are combined and propagated axially through a specially designed flow through PA cell. Each laser is modulated at a different frequency and the resultant acoustic signal(s) are detected and deconvolved using a PC-based 24 bit dynamic signal acquisition device. Species detection and identification is achieved by tabulating independent ratios of the acoustic response for each laser source. Quantitative absorption measured is verified using a Fourier transform infrared spectrometer. Results show good detection and species separation/identification at moderately low ppm concentrations. PMID:23381295

  1. Effect of exposure area on nerve agent absorption through skin in vitro.

    PubMed

    Dalton, Christopher; Graham, Stuart; Jenner, John

    2015-12-25

    Diffusion cells are used to determine the penetration of chemicals through skin in vitro. The cells have a limited surface area defined by the edge of the donor chamber. Should the penetrant spread rapidly to this containment limit the penetration rate can be accurately quantified. For the hazard assessment of small droplets of toxic chemicals, such as cholinesterase inhibitors, limiting skin surface spread in vitro could lead to underestimation of percutaneous penetration and hence underestimation of systemic toxicity in vivo. The current study investigated the dependency of the percutaneous penetration of undiluted radiolabelled nerve agents (VX and soman (GD), 10 μl) on skin surface spread (pig and guinea pig) using Franz-type glass diffusion cells with an area available for diffusion of either 2.54 cm(2) or 14.87 cm(2). Both VX and GD spread to the edge of the 2.54 cm(2) cells, but, not the 14.87 cm(2) cells over the study duration. Amounts of VX and GD penetrating pig and guinea pig skin in the 2.54 cm(2) cells were less than in the 14.87 cm(2) cells (except for GD under unoccluded conditions); however, penetration rates expressed per unit area were similar. Artificial limitation of skin surface spread in vitro does not impact percutaneous penetration in vitro as long as penetration is expressed in terms of mass per unit area. PMID:26391143

  2. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    SciTech Connect

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2011-10-02

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

  3. Nerve agents. Approaches to treatment/pretreatment. Annual report no. 2, 1 July-31 December 1983

    SciTech Connect

    Gray, A.P.; Platz, R.D.; Chang, T.C.; Leverone, T.R.; Ferrick, D.A.

    1984-01-31

    The ultimate objective of this work is to develop potential antidotes for the therapeutic and/or prophylactic treatment of nerve agent intoxication. Particular concern is with soman intoxication where aging of the inhibited enzyme acetylcholinesterase (AChE) is a serious complication factor. Primary emphasis continued to be placed on the investigation of compounds able to inhibit the synthesis of acetylcholine (ACh). A secondary area of interest the investigation of the possibility of combining the ability to slow the rate of aging with the ability to reactivate soman-inhibited AChE. With respect to inhibitors of ACh synthesis, we have continued to investigate the effects of hemicholinium-3 (HC-3), an inhibitor of choline transport and naphthylvinylpyridine hydroxyethyl bromide (B-111), an inhibitor of choline acetyltransferase (CAT), after intracerebroventricular injection in the rat. The ability of HC-3 to prevent the rise in brain ACh levels induced by soman has been confirmed. The ability of B-111 to inhibit brain CAT activity both in soman-treated and untreated rats has been confirmed, although results have been somewhat inconsistent.

  4. Investigating the Affinities and Persistence of VX Nerve Agent in Environmental Matrices

    SciTech Connect

    Love, A H; Vance, A L; Reynolds, J G; Davisson, M L

    2004-03-09

    Laboratory experiments were conducted to determine environmental variables that affect the affinities and persistence of the nerve agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) at dilute concentrations in environmental matrices. Quantitative analyses of VX and its degradation products were performed using LC-MS. Batch hydrolysis experiments demonstrated an increasing hydrolysis rate as pH increased, as shown in previous studies, but also indicated that dissolved aqueous constituents can cause significant differences in the absolute hydrolysis rate. Adsorption isotherms from batch aqueous experiments revealed that VX has a high affinity for hydrophobic organics, a moderate affinity for montmorillonite clay, and a very low affinity for an iron-oxyhydroxide soil mineral, goethite. The adsorption on goethite was increased with the presence of dissolved organic matter in solution. VX degraded rapidly when dried onto goethite, when an inner-sphere complex was forced. No enhanced degradation occurred with goethite in small amounts water. These results suggest that aqueous conditions have important controls on VX adsorption and degradation in the environment and a more mechanistic understanding of these controls is needed in order to enable accurate predictions of its long-term fate and persistence.

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

    SciTech Connect

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

    2009-09-02

    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{sub 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.

  6. 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. PMID:19394314

  7. High-separation efficiency micro-fabricated multi-capillary gas chromatographic columns for simulants of the nerve agents and blister agents

    PubMed Central

    2014-01-01

    To achieve both high speed and separation efficiency in the separation of a mixture of nerve and blister agent simulants, a high-aspect-ratio micro-fabricated multi-capillary column (MCC, a 50-cm-long, 450-μm-deep, and 60-μm-wide four-capillary column) was fabricated by the application of the microelectromechanical system (MEMS) techniques. Mixtures of chemical warfare agent (CWA) simulants - dimethyl methylphosphonate (DMMP), triethyl phosphate (TEP), and methyl salicylate - were used as samples. The fabricated MCC allowed for the separation of all the components of the gaseous mixture within 24 s, even when the difference in boiling point was 4°C, as in the case of TEP and methyl salicylate. Furthermore, interfering agents - dichloromethane, ethanol, and toluene - were also included in the subsequent gaseous mixture samples. The boiling point of these six components ranged from 78°C to 219°C. All six components were clearly separated within 70 s. This study is the first to report the clear separation of gas mixtures of components with close boiling points. The column efficiency was experimentally determined to be 12,810 plates/m. PMID:24899869

  8. High-separation efficiency micro-fabricated multi-capillary gas chromatographic columns for simulants of the nerve agents and blister agents

    NASA Astrophysics Data System (ADS)

    Li, Yi; Du, Xiaosong; Wang, Yang; Tai, Huiling; Qiu, Dong; Lin, Qinghao; Jiang, Yadong

    2014-05-01

    To achieve both high speed and separation efficiency in the separation of a mixture of nerve and blister agent simulants, a high-aspect-ratio micro-fabricated multi-capillary column (MCC, a 50-cm-long, 450-μm-deep, and 60-μm-wide four-capillary column) was fabricated by the application of the microelectromechanical system (MEMS) techniques. Mixtures of chemical warfare agent (CWA) simulants - dimethyl methylphosphonate (DMMP), triethyl phosphate (TEP), and methyl salicylate - were used as samples. The fabricated MCC allowed for the separation of all the components of the gaseous mixture within 24 s, even when the difference in boiling point was 4°C, as in the case of TEP and methyl salicylate. Furthermore, interfering agents - dichloromethane, ethanol, and toluene - were also included in the subsequent gaseous mixture samples. The boiling point of these six components ranged from 78°C to 219°C. All six components were clearly separated within 70 s. This study is the first to report the clear separation of gas mixtures of components with close boiling points. The column efficiency was experimentally determined to be 12,810 plates/m.

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

    SciTech Connect

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

    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 the 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.

  10. Selective enrichment of the degradation products of organophosphorus nerve agents by zirconia based solid-phase extraction.

    PubMed

    Kanaujia, Pankaj K; Pardasani, Deepak; Tak, Vijay; Purohit, Ajay K; Dubey, D K

    2011-09-23

    Selective extraction and enrichment of nerve agent degradation products has been achieved using zirconia based commercial solid-phase extraction cartridges. Target analytes were O-alkyl alkylphosphonic acids and alkylphosphonic acids, the environmental markers of nerve agents such as sarin, soman and VX. Critical extraction parameters such as modifier concentration, nature and volume of washing and eluting solvents were investigated. Amongst other anionic compounds, selectivity in extraction was observed for organophosphorus compounds. Recoveries of analytes were determined by GC-MS which ranged from 80% to 115%. Comparison of zirconia based solid-phase extraction method with anion-exchange solid-phase extraction revealed its selectivity towards phosphonic acids. The limits of detection (LOD) and limit of quantification (LOQ) with selected analytes were achieved down to 4.3 and 8.5 ng mL(-1), respectively, in selected ion monitoring mode. PMID:21862029

  11. 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.

  12. Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

    PubMed

    Myers, Todd M; Langston, Jeffrey L

    2011-06-01

    To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity. PMID:21396400

  13. Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6.

    PubMed

    Allgardsson, Anders; Berg, Lotta; Akfur, Christine; Hörnberg, Andreas; Worek, Franz; Linusson, Anna; Ekström, Fredrik J

    2016-05-17

    Organophosphorus nerve agents interfere with cholinergic signaling by covalently binding to the active site of the enzyme acetylcholinesterase (AChE). This inhibition causes an accumulation of the neurotransmitter acetylcholine, potentially leading to overstimulation of the nervous system and death. Current treatments include the use of antidotes that promote the release of functional AChE by an unknown reactivation mechanism. We have used diffusion trap cryocrystallography and density functional theory (DFT) calculations to determine and analyze prereaction conformers of the nerve agent antidote HI-6 in complex with Mus musculus AChE covalently inhibited by the nerve agent sarin. These analyses reveal previously unknown conformations of the system and suggest that the cleavage of the covalent enzyme-sarin bond is preceded by a conformational change in the sarin adduct itself. Together with data from the reactivation kinetics, this alternate conformation suggests a key interaction between Glu202 and the O-isopropyl moiety of sarin. Moreover, solvent kinetic isotope effect experiments using deuterium oxide reveal that the reactivation mechanism features an isotope-sensitive step. These findings provide insights into the reactivation mechanism and provide a starting point for the development of improved antidotes. The work also illustrates how DFT calculations can guide the interpretation, analysis, and validation of crystallographic data for challenging reactive systems with complex conformational dynamics. PMID:27140636

  14. Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6

    PubMed Central

    Allgardsson, Anders; Berg, Lotta; Akfur, Christine; Hörnberg, Andreas; Linusson, Anna; Ekström, Fredrik J.

    2016-01-01

    Organophosphorus nerve agents interfere with cholinergic signaling by covalently binding to the active site of the enzyme acetylcholinesterase (AChE). This inhibition causes an accumulation of the neurotransmitter acetylcholine, potentially leading to overstimulation of the nervous system and death. Current treatments include the use of antidotes that promote the release of functional AChE by an unknown reactivation mechanism. We have used diffusion trap cryocrystallography and density functional theory (DFT) calculations to determine and analyze prereaction conformers of the nerve agent antidote HI-6 in complex with Mus musculus AChE covalently inhibited by the nerve agent sarin. These analyses reveal previously unknown conformations of the system and suggest that the cleavage of the covalent enzyme–sarin bond is preceded by a conformational change in the sarin adduct itself. Together with data from the reactivation kinetics, this alternate conformation suggests a key interaction between Glu202 and the O-isopropyl moiety of sarin. Moreover, solvent kinetic isotope effect experiments using deuterium oxide reveal that the reactivation mechanism features an isotope-sensitive step. These findings provide insights into the reactivation mechanism and provide a starting point for the development of improved antidotes. The work also illustrates how DFT calculations can guide the interpretation, analysis, and validation of crystallographic data for challenging reactive systems with complex conformational dynamics. PMID:27140636

  15. Single-Channel Microchip for Fast Screening and Detailed Identification of Nitroaromatic Explosives and Organophosphate Nerve Agents

    SciTech Connect

    Wang, Joseph; Pumera, Martin; Chatrathi, Madhu P.; Escarpa, Alberto; Musameh, Mustafa; Collins, George E.; Mulchandani, Ashok; Lin, Yuehe )

    2002-02-25

    A single-channel chip-based analytical microsystem which allows rapid flow-injection measurements of the total content of organic-explosive or nerve-agent compounds, as well as detailed micellar chromatographic identification of the individual ones is described. The protocol involves repetitive rapid flow-injection (screening) assays - for providing a timely warning and alarm - and switching to the separation (fingerprint identification) mode only when harmful compounds are detected. While micellar electrokinetic chromatography (MEKC), in the presence of sodium dodecyl sulfate (SDS), is used for separating the neutral nitroaromatic-explosive and nerve-agent compounds, an operation without SDS leads to high-speed measurements of the 'total' explosives or nerve-agent content. Switching between the 'flow-injection' and 'separation' modes is accomplished by rapidly exchanging the SDS-free and SDS-containing buffers in the separation channel. Amperometric detection was used for monitoring the separation. Key factors influencing the sample throughput, resolution, and sensitivity have been assessed and optimized. Assays rates of ca. 360 and 30 per hour can thus be realized for the 'total' screening and 'individual' measurements, respectively. Ultimately, such development will lead to the creation of a field-deployable microanalyzer, and will enable transporting the forensic laboratory to the sample source.

  16. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  17. A cyclization-induced emission enhancement (CIEE)-based ratiometric fluorogenic and chromogenic probe for the facile detection of a nerve agent simulant DCP.

    PubMed

    Mahapatra, Ajit Kumar; Maiti, Kalipada; Manna, Saikat Kumar; Maji, Rajkishor; Mondal, Sanchita; Das Mukhopadhyay, Chitrangada; Sahoo, Prithidipa; Mandal, Debasish

    2015-06-14

    The first ratiometric fluorescent probe for the detection of a nerve agent simulant was developed based on tandem phosphorylation and intramolecular cyclization, by which high sensitivity as well as large emission shift could be achieved. PMID:25980383

  18. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  19. Feature generation and statistical analysis of physiological responses to nerve-agent exposure. Final report, January 1984-January 1985

    SciTech Connect

    Fu; Swain, P.H.; Anuta, P.E.

    1986-04-01

    This report describes research carried out on the problem of automated information extraction from multichannel physiological signals. Analog tapes were obtained of data recorded during an animal study of the ventilatory requirements after nerve-agent exposure. The main objective of the research was to determine if the physiological signals contained information relevant to the state of the subject. It was also of great interest to determine if the feature condition of the subject could be predicted from the data obtained at a point shortly after initial contact with the agent. This study also included development of techniques for compression and processing of large volumes of data. This report covers data digitalization, feature generation, and data analysis. Because of the limited numbers of tapes available with adequate quality signals, only three experiments were analyzed in depth. Feature generation and analysis algorithms were developed and used on data from these experiments. Statistical and physiological feature evaluations of the data revealed that information from several signals, when displayed as biplots, permitted differentiation among the carrying states of the animals. Results of this contract indicate that these techniques may be useful in developing algorithms which predict the consequences for casualties based on data obtained shortly after nerve agent exposure.

  20. 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. PMID:17356819

  1. Improving the catalytic activity of hyperthermophilic Pyrococcus prolidases for detoxification of organophosphorus nerve agents over a broad range of temperatures.

    PubMed

    Theriot, Casey M; Du, Xuelian; Tove, Sherry R; Grunden, Amy M

    2010-08-01

    Prolidase isolated from the hyperthermophilic archaeon Pyrococcus furiosus has potential for application for decontamination of organophosphorus compounds in certain pesticides and chemical warfare agents under harsh conditions. However, current applications that use an enzyme-based cocktail are limited by poor long-term enzyme stability and low reactivity over a broad range of temperatures. To obtain a better enzyme for OP nerve agent decontamination and to investigate structural factors that influence protein thermostability and thermoactivity, randomly mutated P. furiosus prolidases were prepared by using XL1-red-based mutagenesis and error-prone PCR. An Escherichia coli strain JD1 (lambdaDE3) (auxotrophic for proline [DeltaproA] and having deletions in pepQ and pepP dipeptidases with specificity for proline-containing dipeptides) was constructed for screening mutant P. furiosus prolidase expression plasmids. JD1 (lambdaDE3) cells were transformed with mutated prolidase expression plasmids and plated on minimal media supplemented with 50 muM Leu-Pro as the only source of proline. By using this positive selection, Pyrococcus prolidase mutants with improved activity over a broader range of temperatures were isolated. The activities of the mutants over a broad temperature range were measured for both Xaa-Pro dipeptides and OP nerve agents, and the thermoactivity and thermostability of the mutants were determined. PMID:20422176

  2. A 'chemically-gated' photoresponsive compound as a visible detector for organophosphorus nerve agents.

    PubMed

    Nourmohammadian, Farahnaz; Wu, Tuoqi; Branda, Neil R

    2011-10-21

    We describe a versatile and convenient visible detection method for organophosphorus compounds based on a colorless 'pro-photoresponsive' organic molecule that undergoes photochemical ring-closing to produce a colored isomer only after it reacts with vapors of the phosphorylating agent. PMID:21901219

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

    SciTech Connect

    von Bredow, J.; Corcoran, K.; Maitland, G.; Kaminskis, A.; Adams, N.

    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 from incapacitation. Physostigmine, nerve agent pretreatment, cynomolgus monkeys soman (GD).

  4. Chromo-fluorogenic detection of nerve-agent mimics using triggered cyclization reactions in push-pull dyes.

    PubMed

    Costero, Ana M; Parra, Margarita; Gil, Salvador; Gotor, Raúl; Mancini, Pedro M E; Martínez-Máñez, Ramón; Sancenón, Félix; Royo, Santiago

    2010-07-01

    A family of azo and stilbene derivatives (1-9) are synthesized, and their chromo-fluorogenic behavior in the presence of nerve-agent simulants, diethylchlorophosphate (DCP), diisopropylfluorophosphate (DFP), and diethylcyanophosphate (DCNP) in acetonitrile and mixed solution of water/acetonitrile (3:1 v/v) buffered at pH 5.6 with MES, is investigated. The prepared compounds contain 2-(2-N,N-dimethylaminophenyl)ethanol or 2-[(2-N,N-dimethylamino)phenoxy]ethanol reactive groups, which are part of the conjugated pi-system of the dyes and are able to give acylation reactions with phosphonate substrates followed by a rapid intramolecular N-alkylation. The nerve-agent mimic-triggered cyclization reaction transforms a dimethylamino group into a quaternary ammonium, inducing a change of the electronic properties of the delocalized systems that results in a hypsochromic shift of the absorption band of the dyes. Similar reactivity studies are also carried out with other "non-toxic" organophosphorus compounds, but no changes in the UV/Vis spectra were observed. The emission behaviour of the reagents in acetonitrile and water-acetonitrile 3:1 v/v mixtures is also studied in the presence of nerve-agent simulants and other organophosphorous derivatives. The reactivity between 1-9 and DCP, DCNP, or DFP in buffered water-acetonitrile 3:1 v/v solutions under pseudo first-order kinetic conditions, using an excess of the corresponding simulant, are studied in order to determine the rate constants (k) and the half-life times (t(1/2)=ln2/k) for the reaction. The detection limits in water/acetonitrile 3:1 v/v are also determined for 1-9 and DCP, DCNP, and DFP. Finally, the chromogenic detection of nerve agent simulants both in solution and in gas phase are tested using silica gel containing adsorbed compounds 1, 2, 3, 4, or 5 with fine results. PMID:20512798

  5. Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo

    PubMed Central

    Ilyushin, Denis G.; Smirnov, Ivan V.; Belogurov, Alexey A.; Dyachenko, Igor A.; Zharmukhamedova, Tatiana Iu.; Novozhilova, Tatjana I.; Bychikhin, Eugene A.; Serebryakova, Marina V.; Kharybin, Oleg N.; Murashev, Arkadii N.; Anikienko, Konstantin A.; Nikolaev, Eugene N.; Ponomarenko, Natalia A.; Genkin, Dmitry D.; Blackburn, G. Michael; Masson, Patrick; Gabibov, Alexander G.

    2013-01-01

    The creation of effective bioscavengers as a pretreatment for exposure to nerve agents is a challenging medical objective. We report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. Development of a CHO-based expression system using genes encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics which protect mice against 4.2 LD50 of S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate without perturbation of long-term behavior. PMID:23297221

  6. Toxicity and medical countermeasure studies on the organophosphorus nerve agents VM and VX

    PubMed Central

    Rice, Helen; Dalton, Christopher H.; Price, Matthew E.; Graham, Stuart J.; Green, A. Christopher; Jenner, John; Groombridge, Helen J.; Timperley, Christopher M.

    2015-01-01

    To support the effort to eliminate the Syrian Arab Republic chemical weapons stockpile safely, there was a requirement to provide scientific advice based on experimentally derived information on both toxicity and medical countermeasures (MedCM) in the event of exposure to VM, VX or VM–VX mixtures. Complementary in vitro and in vivo studies were undertaken to inform that advice. The penetration rate of neat VM was not significantly different from that of neat VX, through either guinea pig or pig skin in vitro. The presence of VX did not affect the penetration rate of VM in mixtures of various proportions. A lethal dose of VM was approximately twice that of VX in guinea pigs poisoned via the percutaneous route. There was no interaction in mixed agent solutions which altered the in vivo toxicity of the agents. Percutaneous poisoning by VM responded to treatment with standard MedCM, although complete protection was not achieved.

  7. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1999-11-01

    Several important developments have occurred in recent years in the chemotherapy for and prophylaxis of parasitic infections. Although mefloquine is clearly the most effective agent for prevention of chloroquine-resistant falciparum malaria, its use has been compromised by side effects, both real and imagined. Well-designed studies have shown that side effects occur no more frequently with low-dose mefloquine than with chloroquine. Use of mefloquine in pregnant women has not been associated with birth defects, but the incidence of stillbirths may be increased. Malarone is a new agent that combines atovaquone and proguanil, and it may be as effective as mefloquine; however, it is not yet available in the United States. Several newer agents have appeared in response to the development of multidrug resistant Plasmodium falciparum, especially in Southeast Asia. Halofantrine is available for the treatment of mild to moderate malaria due to P. falciparum and for P. vivax infections. Because of severe toxic effects, use of halofantrine should be restricted to only those unusual and rare situations in which other agents cannot be used. Artemisinin (an extract of the Chinese herbal remedy qinghaosu) and two derivatives, artesunate and artemether, are active against multidrug resistant P. falciparum and are widely used in Asia in oral, parenteral, and rectal forms. The antibacterial azithromycin in combination with atovaquone or quinine has now been reported to treat babesiosis effectively in experimental animals and in a few patients. Azithromycin in combination with paromomycin has also shown promise in the treatment of cryptosporidiosis (and toxoplasmosis when combined with pyrimethamine) in patients with the acquired immunodeficiency syndrome (AIDS). Albendazole is currently the only systemic agent available for treatment of microsporidiosis, an infection primarily of patients with AIDS. In addition, albendazole and ivermectin have emerged as effective broad

  8. Comprehensive gas chromatography with Time of Flight MS and large volume introduction for the detection of fluoride-induced regenerated nerve agent in biological samples.

    PubMed

    van der Meer, J A; Trap, H C; Noort, D; van der Schans, M J

    2010-05-15

    Recently, several methods have been developed to verify exposure to nerve agents. Most of these methods, such as the fluoride reactivation technique and the analysis of inhibited phosphonylated butyrylcholinesterase (BuChE), are based on mass spectrometry. The high specificity of the mass spectrometer might also imply a disadvantage, because the acquisition mass, i.e. the identity of the analyte must be known beforehand in order to direct the MS analysis in the most sensitive mode. In real cases, the identity of the nerve agent is not always known beforehand and the mass spectrometer should be operated in a scanning mode, with the consequence that sensitivity of the method will be lower. Comprehensive GC, or GC x GC, is a technique which offers enhanced separation. The implied larger selectivity of the GC separation allows mass spectrometry to be conducted in a less specific, scanning, mode. By the use of this configuration, the identity of the nerve agent does not have to be known beforehand but can be traced. In order to be able to detect lower concentrations and assess lower exposure levels, a large volume injection technique was developed allowing sample sizes up to 100 microL. The technique was tested with plasma samples that had been inhibited with various nerve agents. Subsequently, the cholinesterase-bound nerve agent was regenerated by the fluoride reactivation technique. Using the newly developed comprehensive GC-MS method it was possible to detect nerve agent at an exposure level of 1% BuChE inhibition, which is approximately 70 pg nerve agent/mL. These low exposure levels cannot be verified with a cholinesterase (ChE) activity assay. Moreover, the identity of the regenerated nerve agent was verified by the mass spectrum that was generated by the TOF mass spectrometer. This paper presents a technique able to deliver full-scan data on the analysis of nerve agents in biomedical samples at relevant exposure levels (1% BuChE inhibition). This full-scan data

  9. Antifungal agents.

    PubMed

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  10. 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

    2015-01-01

    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

  11. Ionization mechanism of the ambient pressure pyroelectric ion source (APPIS) and its applications to chemical nerve agent detection.

    PubMed

    Neidholdt, Evan L; Beauchamp, J L

    2009-11-01

    We present studies of the ionization mechanism operative in the ambient pressure pyroelectric ionization source (APPIS), along with applications that include detection of simulants for chemical nerve agents. It is found that ionization by APPIS occurs in the gas-phase. As the crystal is thermally cycled over a narrow temperature range, electrical discharges near the surface of the crystal produce energetic species which, through reactions with atmospheric molecules, result in reactant ions such as protonated water clusters or clusters of hydroxide and water. Reactant ions can be observed directly in the mass spectrometer. These go on to react with trace neutrals via proton transfer reactions to produce the ions observed in mass spectra, which are usually singly protonated or deprotonated species. Further implicating gas-phase ionization, observed product distributions are highly dependent on the composition of ambient gases, especially the concentration of water vapor and oxygen surrounding the source. For example, basic species such as triethylamine are observed as singly protonated cations at a water partial pressure of 10 torr. At a water pressure of 4 torr, reactive oxygen species are formed and lead to observation of protonated amine oxides. The ability of the APPIS source to detect basic molecules with high proton affinities makes it highly suited for the detection of chemical nerve agents. We demonstrate this application using simulants corresponding to VX and GA (Tabun). With the present source configuration pyridine is detected readily at a concentration of 4 ppm, indicating ultimate sensitivity in the high ppb range. PMID:19682922

  12. Immobilization of organophosphate hydrolase on biocompatible gelatin pads and its use in removal of organophosphate compounds and nerve agents.

    PubMed

    Kanugula, Anantha KoteswaraRao; Repalle, Elisha Raju; Pandey, Jay Prakash; Sripad, Gunwar; Mitra, Chanchal Kumar; Dubey, Devender Kumar; Siddavattam, Dayananda

    2011-02-01

    Bacterial organophosphate hydrolases (OPH) have been shown to hydrolyze structurally diverse group of organophosphate (OP) compounds and nerve agents. Due to broad substrate range and unusual catalytic properties, the OPH has successfully been used to develop eco-friendly strategies for detection and decontamination of OP compounds. However, their usage has failed to gain necessary acceptance, due to short half-life of the enzyme and loss of activity during process development. In the present study, we report a simple procedure for immobilization of OPH on biocompatible gelatin pads. The covalent coupling of OPH using glutaraldehyde spacer has been found to dramatically improve the enzyme stability. There is no apparent loss of OPH activity in OPH-gelatin pads stored at room temperature for more than six months. As revealed by a number of kinetic parameters, the catalytic properties of immobilized enzyme are found to be comparable to the free enzyme. Further, the OPH-gelatin pads effectively eliminate OP insecticide methyl parathion and nerve agent sarin. PMID:21469599

  13. Conjugated poly(fluorene-quinoxaline) for fluorescence imaging and chemical detection of nerve agents with its paper-based strip.

    PubMed

    Jo, Seonyoung; Kim, Daigeun; Son, Sang-Ho; Kim, Yongkyun; Lee, Taek Seung

    2014-01-22

    Conjugated polymer of poly(fluorene-co-quinoxaline) was synthesized via Suzuki coupling polymerization. The emission color of the polymer can be tuned depending on the concentration of the polymer in solution. A low-energy bandgap is observed both in the concentrated solution and in the solid state, caused by aggregation of the polymer chains, resulting in long wavelength emission from the quinoxaline moiety, while short wavelength emission can be seen in diluted, well-dissolved solution. The presence of quinoxaline units enables us to demonstrate fluorescence switching and imaging. Paper-based strips containing the polymer are prepared via simple immersion of filter paper in the polymer solution for practical use in the detection of nerve agents. The emission of the paper-based strip is quenched upon exposure to diethyl chlorophosphate (DCP), a nerve agent simulant, and the initial emission intensity can be almost restored by treatment with aqueous sodium hydroxide solution, making a possible reversible paper-based sensor. PMID:24372409

  14. Quantification of nerve agent adducts with albumin in rat plasma using liquid chromatography-isotope dilution tandem mass spectrometry.

    PubMed

    Bao, Yi; Liu, Qin; Chen, Jia; Lin, Ying; Wu, Bidong; Xie, Jianwei

    2012-03-16

    A sensitive method for the determination of the organophosphorus nerve agents sarin, soman and VX adducts with tyrosine residue of albumin in rat plasma has been developed and validated using liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS). O-(O-Alkyl methylphosphonyl) tyrosine adducts and their deuterated products that were used as the internal standards were synthesised to establish the quantitative isotope-dilution method. Protein purification and solid-phase extraction (SPE) were applied to improve the recovery efficiency, reduce interference and achieve high sensitivity. The method provided a detection limit of 0.01 ng/mL for sarin and soman adducts and 0.05 ng/mL for the VX adduct. The value of the intra-day relative standard deviation over the calibration range was less than 6.16% (n=6), and that of the inter-day was less than 12.7% (n=6). The recovery varied from 86% to 111%. This sensitive method was successfully applied to the analysis of adducts in rat plasma after nerve agent exposure, and the results demonstrated the dose-effect relationships. PMID:22305360

  15. 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

  16. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  17. 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

    2013-11-01

    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. PMID:24093669

  18. Comparison of status epilepticus models induced by pilocarpine and nerve agents - a systematic review of the underlying aetiology and adopted therapeutic approaches.

    PubMed

    Tang, F R; Loke, W K; Ling, E A

    2011-01-01

    Among potential radiological, nuclear, biological and chemical weapons, cholinergic nerve agents from chemical weapons remain a realistic terrorist threat due to its combination of high lethality, demonstrated use and relative abundance of un-destroyed stockpiles in various militaries around the world. While current fielded antidotes are able to mitigate acute poisoning, effective neuroprotection in the field remains a challenge amongst subjects with established status epilepticus following nerve agent intoxication. Due to ethical, safety and surety issues, extensive preclinical and clinical research on cholinergic nerve agents is not possible. This may have been a contributory factor for the slow progress in uncovering new neuroprotectants for nerve agent casualties with established status epilepticus. To overcome this challenge, comparative research with surrogate chemicals that produce similar hypercholinergic toxicity but with less security concerns would be a useful approach forward. In this paper, we will systemically compare the mechanism of seizure generation, propagation and the subsequent clinical, hematologic, and metabolic, biochemical, neuroinflammatory changes and current therapeutic approaches reported in pilocarpine, soman, and sarin models of seizures. This review will be an important first step in closing this knowledge gap among different closely related models of seizures and neurotoxicity. Hopefully, it will spur further efforts in using surrogate cholinergic models by the wider scientific community to expedite the development of a new generation of antidotes that are better able to protect against delayed neurological effects inflicted by nerve agents. PMID:21182477

  19. A 10-minute point-of-care assay for detection of blood protein adducts resulting from low level exposure to organophosphate nerve agents.

    PubMed

    VanDine, Robert; Babu, Uma Mahesh; Condon, Peter; Mendez, Arlene; Sambursky, Robert

    2013-03-25

    The OrganoTox test is a rapid, point-of-care assay capable of detecting clinically relevant organophosphate (OP) poisoning after low-level exposure to sarin, soman, tabun, or VX chemical nerve agents. The test utilizes either a finger stick peripheral blood sample or plasma specimen. While high-level nerve agent exposure can quickly lead to death, low-level exposure produces vague, nondescript signs and symptoms that are not easily clinically differentiated from other conditions. In initial testing, the OrganoTox test was used to detect the presence of blood protein-nerve agent adducts in exposed blood samples. In order to mimic the in vivo exposure as closely as possible, nerve agents stored in organic solvents were spiked in minute quantities into whole blood samples. For performance testing, 40 plasma samples were spiked with sarin, soman, tabun, or VX and 10 normal plasma samples were used as the negative control. The 40 nerve agent-spiked plasma samples included 10 replicates of each agent. At the clinically relevant low-level exposure of 10 ng/ml, the OrganoTox test demonstrated 100% sensitivity for soman, tabun, and VX and 80% sensitivity for sarin. The OrganoTox test demonstrated greater than 97% specificity with 150 blood samples obtained from healthy adults. No cross-reactivity or interference from pesticide precursor compounds was found. A rapid test for nerve agent exposure will help identify affected patients earlier in the clinical course and trigger more appropriate medical management in a more timely manner. PMID:23200942

  20. Efficient heterogeneous and environmentally friendly degradation of nerve agents on a tungsten-based POM.

    PubMed

    Mizrahi, Dana M; Saphier, Sigal; Columbus, Ishay

    2010-07-15

    Common (chemical warfare agent) CWA decontaminants exhibit harsh and corrosive characteristics, and are harmful to the environment. In the course of our quest for active sorbents as efficient decontaminants, Keggin-type polyoxometalate (POM) (NH(4))(3)PW(12)O(40) was tested for oxidative degradation of CWAs. Although oxidation did not take place, sarin (GB) and VX were smoothly decontaminated to non-toxic products within 1 and 10 days, respectively. Degradation was carried out directly on the powder, eliminating the need for solvents. Mustard gas (HD), whose degradation is highly dependent on oxidation, was not decontaminated by this POM. Solid state MAS NMR ((31)P and (13)C) was utilized both for POM characterization and for decontamination studies monitoring. PMID:20363072

  1. 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

  2. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology.

    PubMed

    Piermartiri, Tetsade; Pan, Hongna; Figueiredo, Taiza H; Marini, Ann M

    2015-01-01

    α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders. PMID:26569216

  3. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  4. Development of a high-throughput screening for nerve agent detoxifying materials using a fully-automated robot-assisted biological assay.

    PubMed

    Wille, T; Thiermann, H; Worek, F

    2010-04-01

    Developing improved medical countermeasures against chemical warfare agents (nerve agents) is urgently needed but time-consuming and costly. Here we introduce a robot-assisted liquid handling system with warming, cooling and incubating facilities to screen the detoxifying properties of biological and chemical materials against nerve agents. Two biological tests were established and plasma from various species, DFPase and three cyclodextrins were used as test materials. In test 1, plasma was mixed with sarin or VX and the inhibitory potency of the incubate was determined with human acetylcholinesterase (AChE) at 0, 30 and 60 min. In test 2, test materials and nerve agents were mixed and incubated. Between 0 and 40 min samples were taken and incubated for 3 min with AChE and the residual AChE inhibition was determined to enable the semi-quantitative evaluation of the detoxification kinetics. The automated assays proved to be highly reproducible. It was possible to pre-select detoxifying reagents with test 1 and to determine more detailed detoxifying kinetics with test 2. In conclusion, the automated assay may be considered as a versatile tool for the high-throughput screening of potential detoxifying materials against different nerve agents. With this two-step assay it is possible to screen effectively for detoxifying materials in a high-throughput system. PMID:19961920

  5. Agent Building Software

    NASA Technical Reports Server (NTRS)

    2000-01-01

    AgentBuilder is a software component developed under an SBIR contract between Reticular Systems, Inc., and Goddard Space Flight Center. AgentBuilder allows software developers without experience in intelligent agent technologies to easily build software applications using intelligent agents. Agents are components of software that will perform tasks automatically, with no intervention or command from a user. AgentBuilder reduces the time and cost of developing agent systems and provides a simple mechanism for implementing high-performance agent systems.

  6. Reserve osmosis removal of organic compounds. 2. Opportunity poisons and nerve agent hydrolysates. Technical report, June 1990-December 1994

    SciTech Connect

    Burrows, W.D.; Sincero, A.P.; Schmidt, M.O.

    1995-03-01

    Reverse osmosis (RO) rejection of acetic acid, fluoro-, chloro- and bromoacetic acids and hydrazine was investigated in a pilot scale (3 gpm) test unit; RO rejection of methylphosphonic acid and ethyl,-isopropyl and pinacolyl methylphosphonic acids (nerve agent hydrolysates) was investigated in a bench scale (6 L/hr) test unit. Rejection of acetic acid derivatives was found to be pH and pKa dependent; molecular weight was not a factor for total acids, but rejection was inversely related to molecular weight for free (undissociated) acids. Rejection of all methylphosphonates exceeded 99 percent at pH 3 to 10 and was not pH dependent. Rejection of hydrazine sulfate (a surrogate for UDMH) was no better than 90 percent at pH 7.

  7. Reverse osmosis removal of organic compounds II. Opportunity poisons and nerve agent hydrolysates. Technical report, June 1990-December 1994

    SciTech Connect

    Burrows, W.D.; Sincero, A.P.; Schmidt, M.O.

    1995-03-01

    Reverse osmosis (RO) rejection of acetic acid, fluoro-, chloro- and bromoacetic acids and hydrazine was investigated in a pilot scale (3 gpm) test unit; RO rejection of methylphosphonic acid and ethyl, isopropyl and pinacolyl methylphosphonic acids (nerve agent hydrolysates) was investigated in a bench scale (6 L/hr) test unit. Rejection of acetic acid derivatives was found to be pH and pKa dependent; molecular weight was not a factor for total acids, but rejection was inversely related to molecular weight for free (undissociated) acids. Rejection of all methylphosphonates exceeded 99 percent at pH 3 to 10 and was not pH dependent. Rejection of hydrazine sulfate (a surrogate for UDMH) was no better than 90 percent at pH 7.

  8. Detection of DNT, TNT, HF, and nerve agents using photoluminescence and interferometry from a porous silicon chip

    NASA Astrophysics Data System (ADS)

    Sailor, Michael J.; Trogler, William C.; Content, Stephane; Letant, Sonia; Sohn, Honglae; Fainman, Yeshaiahu; Shames, Paul E.

    2000-07-01

    Porous silicon chips have been used to detect vapors of explosives and a simulant for the nerve agents Sarin, Soman, and GF using two different transduction modes: reflectivity and photoluminescence. Detection of nitroaromatic compounds is achieved by monitoring the photoluminescence of a nanocrystalline porous Si film on exposure to the analyte of interest in a flowing air stream. Photoluminescence is quenched on exposure to the nitroaromatic. Detection limits of 2 ppb and 1 ppb were observed for 2,4-dinitrotoluene, and 2,4,6-trinitrotoluene, respectively (exposure times of 5 min for each, in air). Specificity for detection is achieved in a two-channel system using catalytic oxidation of the nitroaromatic.

  9. V-type nerve agents phosphonylate ubiquitin at biologically relevant lysine residues and induce intramolecular cyclization by an isopeptide bond.

    PubMed

    Schmidt, Christian; Breyer, Felicitas; Blum, Marc-Michael; Thiermann, Horst; Worek, Franz; John, Harald

    2014-08-01

    Toxic organophosphorus compounds (e.g., pesticides and nerve agents) are known to react with nucleophilic side chains of different amino acids (phosphylation), thus forming adducts with endogenous proteins. Most often binding to serine, tyrosine, or threonine residues is described as being of relevance for toxicological effects (e.g., acetylcholinesterase and neuropathy target esterase) or as biomarkers for post-exposure analysis (verification, e.g., albumin and butyrylcholinesterase). Accordingly, identification of novel protein targets might be beneficial for a better understanding of the toxicology of these compounds, revealing new bioanalytical verification tools, and improving knowledge on chemical reactivity. In the present study, we investigated the reaction of ubiquitin (Ub) with the V-type nerve agents Chinese VX, Russian VX, and VX in vitro. Ub is a ubiquitous protein with a mass of 8564.8 Da present in the extra- and intracellular space that plays an important physiological role in several essential processes (e.g., proteasomal degradation, DNA repair, protein turnover, and endocytosis). Reaction products were analyzed by matrix-assisted laser desorption/ionization-time-of-flight- mass spectrometry (MALDI-TOF MS) and μ-high-performance liquid chromatography online coupled to UV-detection and electrospray ionization MS (μHPLC-UV/ESI MS). Our results originally document that a complex mixture of at least mono-, di, and triphosphonylated Ub adducts was produced. Surprisingly, peptide mass fingerprint analysis in combination with MALDI and ESI MS/MS revealed that phosphonylation occurred with high selectivity in at least 6 of 7 surface-exposed lysine residues that are essential for the biological function of Ub. These reaction products were found not to age. In addition, we herein report for the first time that phosphonylation induced intramolecular cyclization by formation of an isopeptide bond between the ε-amino group of a formerly phosphonylated

  10. Enhanced Stability of Blood Matrices Using a Dried Sample Spot Assay to Measure Human Butyrylcholinesterase Activity and Nerve Agent Adducts

    PubMed Central

    Perez, Jonas W.; Pantazides, Brooke G.; Watson, Caroline M.; Thomas, Jerry D.; Blake, Thomas A.; Johnson, Rudolph C.

    2015-01-01

    Dried matrix spots are safer to handle and easier to store than wet blood products, but factors such as intra-spot variability and unknown sample volumes have limited their appeal as a sampling format for quantitative analyses. In this work, we introduce a dried spot activity assay for quantifying butyrylcholinesterase (BChE) specific activity which is BChE activity normalized to the total protein content in a sample spot. The method was demonstrated with blood, serum, and plasma spotted on specimen collection devices (cards) which were extracted to measure total protein and BChE activity using a modified Ellman assay. Activity recovered from dried spots was ∼80% of the initial spotted activity for blood and >90% for plasma and serum. Measuring total protein in the sample and calculating specific activity substantially improved quantification and reduced intra-spot variability. Analyte stability of nerve agent adducts was also evaluated, and the results obtained via BChE-specific activity measurements were confirmed by quantification of BChE adducts using a previously established LC-MS/MS method. The spotted samples were up to 10-times more resistant to degradation compared to unspotted control samples when measuring BChE inhibition by the nerve agents sarin and VX. Using this method, both BChE activity and adducts can be accurately measured from a dried sample spot. This use of a dried sample spot with normalization to total protein is robust, demonstrates decreased intra-spot variability without the need to control for initial sample volume, and enhances analyte stability. PMID:25955132

  11. Medical countermeasure against respiratory toxicity and acute lung injury following inhalation exposure to chemical warfare nerve agent VX

    SciTech Connect

    Nambiar, Madhusoodana P.; Doctor, Bhupendra P.

    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 did 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.

  12. Detection of munitions grade g-series nerve agents using Raman excitation at 1064 nm

    NASA Astrophysics Data System (ADS)

    Roy, Eric; Wilcox, Phillip G.; Hoffland, Soren; Pardoe, Ian

    2015-05-01

    Raman spectroscopy is a powerful tool for obtaining molecular structure information of a sample. While Raman spectroscopy is a common laboratory based analytical tool, miniaturization of opto-electronic components has allowed handheld Raman analyzers to become commercially available. These handheld systems are utilized by Military and First Responder operators tasked with rapidly identifying potentially hazardous chemicals in the field. However, one limitation of many handheld Raman detection systems is strong interference caused by fluorescence of the sample or underlying surface which obscures the characteristic Raman signature of the target analyte. Munitions grade chemical warfare agents (CWAs) are produced and stored in large batches and typically have more impurities from the storage container, degradation, or unreacted precursors. In this work, Raman spectra of munitions grade CWAs were collected using a handheld Raman spectrometer with a 1064 nm excitation laser. While Raman scattering generated by a 1064 nm laser is inherently less efficient than excitation at shorter wavelengths, high quality spectra were easily obtained due to significantly reduced fluorescence of the munitions grade CWAs. The spectra of these less pure, but more operationally relevant, munitions grade CWAs were then compared to spectra of CASARM grade CWAs, as well as Raman spectra collected using the more common 785 nm excitation laser.

  13. Crystal structures of brain group-VIII phospholipase A2 in nonaged complexes with the organophosphorus nerve agents soman and sarin.

    PubMed

    Epstein, Todd M; Samanta, Uttamkumar; Kirby, Stephen D; Cerasoli, Douglas M; Bahnson, Brian J

    2009-04-21

    Insecticide and nerve agent organophosphorus (OP) compounds are potent inhibitors of the serine hydrolase superfamily of enzymes. Nerve agents, such as sarin, soman, tabun, and VX exert their toxicity by inhibiting human acetycholinesterase at nerve synapses. Following the initial phosphonylation of the active site serine, the enzyme may reactivate spontaneously or through reaction with an appropriate nucleophilic oxime. Alternatively, the enzyme-nerve agent complex can undergo a secondary process, called "aging", which dealkylates the nerve agent adduct and results in a product that is highly resistant to reactivation by any known means. Here we report the structures of paraoxon, soman, and sarin complexes of group-VIII phospholipase A2 from bovine brain. In each case, the crystal structures indicate a nonaged adduct; a stereoselective preference for binding of the P(S)C(S) isomer of soman and the P(S) isomer of sarin was also noted. The stability of the nonaged complexes was corroborated by trypsin digest and electrospray ionization mass spectrometry, which indicates nonaged complexes are formed with diisopropylfluorophosphate, soman, and sarin. The P(S) stereoselectivity for reaction with sarin was confirmed by reaction of racemic sarin, followed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate each stereoisomer. The P(S) stereoisomers of soman and sarin are known to be the more toxic stereoisomers, as they react preferentially to inhibit human acetylcholinesterase. The results obtained for nonaged complexes of group-VIII phospholipase A2 are compared to those obtained for other serine hydrolases and discussed to partly explain determinants of OP aging. Furthermore, structural insights can now be exploited to engineer variant versions of this enzyme with enhanced nerve agent binding and hydrolysis functions. PMID:19271773

  14. Assessing protection against OP pesticides and nerve agents provided by wild-type HuPON1 purified from Trichoplusia ni larvae or induced via adenoviral infection.

    PubMed

    Hodgins, Sean M; Kasten, Shane A; Harrison, Joshua; Otto, Tamara C; Oliver, Zeke P; Rezk, Peter; Reeves, Tony E; Chilukuri, Nageswararao; Cerasoli, Douglas M

    2013-03-25

    Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of organophosphorus (OP) pesticides and nerve agents. We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms. First, recombinant HuPON1 purified from cabbage loopers (iPON1; Trichoplusia ni) was administered to guinea pigs, followed by exposure to at least 2 times the median lethal dose (LD(50)) 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 exposed to sequential doses of GD, VX, or (as reported previously) diazoxon, the toxic metabolite of the OP pesticide diazinon. In both animal models, the exogenously added HuPON1 protected animals against otherwise lethal doses of the OP pesticides but not against the nerve agents. Together, the results support prior modeling and in vitro activity data which suggest that wild-type HuPON1 does not have sufficient catalytic activity to provide in vivo protection against nerve agents. PMID:23123254

  15. Comparison of inhibition kinetics of several organophosphates, including some nerve agent surrogates, using human erythrocyte and rat and mouse brain acetylcholinesterase.

    PubMed

    Coban, Alper; Carr, Russell L; Chambers, Howard W; Willeford, Kenneth O; Chambers, Janice E

    2016-04-25

    Because testing of nerve agents is limited to only authorized facilities, our laboratory developed several surrogates that resemble nerve agents because they phosphylate the acetylcholinesterase (AChE) with the same moiety as the actual nerve agents. The inhibition kinetic parameters were determined for AChE by surrogates of cyclosarin (NCMP), sarin (NIMP, PIMP and TIMP) and VX (NEMP and TEMP) and other organophosphorus compounds derived from insecticides. All compounds were tested with rat brain and a subset was tested with mouse brain and purified human erythrocyte AChE. Within the compounds tested on all AChE sources, chlorpyrifos-oxon had the highest molecular rate constant followed by NCMP and NEMP. This was followed by NIMP then paraoxon and DFP with rat and mouse brain AChE but DFP was a more potent inhibitor than NIMP and paraoxon with human AChE. With the additional compounds tested only in rat brain, TEMP was slightly less potent than NEMP but more potent than PIMP which was more potent than NIMP. Methyl paraoxon was slightly less potent than paraoxon but more potent than TIMP which was more potent than DFP. Overall, this study validates that the pattern of inhibitory potencies of our surrogates is comparable to the pattern of inhibitory potencies of actual nerve agents (i.e., cyclosarin>VX>sarin), and that these are more potent than insecticidal organophosphates. PMID:26965078

  16. RSD931, a novel anti-tussive agent acting on airway sensory nerves

    PubMed Central

    Adcock, J J; Douglas, G J; Garabette, M; Gascoigne, M; Beatch, G; Walker, M; Page, C P

    2003-01-01

    .05) inhibited spontaneous and capsaicin-induced discharges in both pulmonary and bronchial C-fibres respectively. Lidocaine also significantly (P<0.05) reduced capsaicin-evoked bronchoconstriction. These studies suggest that the anti-tussive actions of RSD931 are mediated via inhibition of discharges in Aδ-fibres originating from airway RARs. The mechanism of action of RSD931 is distinct from that of the local anaesthetic lidocaine and RSD931 may represent a novel class of anti-tussive agent. PMID:12569065

  17. Three-phase hollow fiber liquid-phase microextraction of organophosphorous nerve agent degradation products from complex samples.

    PubMed

    Desoubries, Charlotte; Chapuis-Hugon, Florence; Bossée, Anne; Pichon, Valérie

    2012-07-01

    Degradation products of chemical warfare agents are considered as important environmental and biological markers of chemical attacks. Alkyl methylphosphonic acids (AMPAs), resulting from the fast hydrolysis of nerve agents, such as sarin and soman, and the methylphosphonic acid (MPA), final degradation product of AMPAs, were determined from complex matrices by using an emergent and miniaturized extraction technique, the hollow fiber liquid-phase microextraction (HF-LPME), before their analysis by liquid chromatography coupled to mass spectrometry (LC-MS). After studying different conditions of separation in the reversed phase LC-MS analysis, the sample treatment method was set up. The three-phase HF-LPME was carried out by using a porous polypropylene (PP) hollow fiber impregnated with 1-octanol that separates the donor and acceptor aqueous media. Various extraction parameters were evaluated such as the volume of the sample, the effect of the pH and the salt addition to the sample, the pH of the acceptor phase, the extraction temperature, the stirring speed of the sample, the immersion time in the organic solvent and the time of extraction. The optimum conditions were applied to the determination of MPA and five AMPAs in real samples, such as surface waters and urine. Compounds were extracted from a 3 mL acidified sample into only 6 μL of alkaline water without any other pretreatment of the complex matrices. Enrichment factors (EFs) higher than 170 were obtained for three less polar AMPAs. Limits of quantification (LOQs) in the 0.013-5.3 ng mL(-1) range were obtained after microextraction of AMPAs from river water and in the range of 0.056-4.8 ng mL(-1) from urine samples with RSD values between 1 and 9%. PMID:22705170

  18. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  19. Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Fan, Lixue; Wang, Feijian; Luo, Yuan; Sui, Xin; Li, Wanhua; Zhang, Xiaohong; Wang, Yongan

    2016-05-01

    The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration.The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and

  20. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  1. Development of a new method for the identification of degradation products of V-type nerve agents by liquid chromatography-tandem mass spectrometry.

    PubMed

    Lee, Jin Young; Lee, Yong Han

    2014-01-01

    Degradation products of V-type nerve agents are important markers of these toxic chemical warfare agents; hence their detection and identification are of high importance from verification point of view of Chemical Weapons Convention. The new analytical technique using quantitation-enhanced data-dependent (QED) method has been developed for the analysis of the degradation products, 2-(N,N-dialkylamino)ethanesulfonic acids of V-type nerve agents, by using liquid chromatography-tandem mass spectrometry (Thermo-Scientific Vantage triple stage quadrupole mass spectrometer, Thermo Finnigan Surveyor, San Jose, CA, USA) via an atmospheric pressure ionization source/interface operated in eletrospray ionization mode. With a single analytical run, we could perform the quantitative analysis of the 2-(N,N-dialkylamino)ethanesulfonic acids by the selected reaction monitoring scan mode with limit of detection at 0.1 ng/mL and identify their isomeric compounds by product ion scan mode, simultaneously. The QED method will be applicable to the trace analysis of degradation products of V-type nerve agents in the environmental matrices in the Organisation for the Prohibition of Chemical Weapons proficiency test. PMID:24470166

  2. Recognition and Treatment of Nerve Agent Casualties: Evidence of Reduced Learner Engagement During Video-based Training.

    PubMed

    Bukoski, Alex; Uhlich, Rindi; Tucker, Johnny; Cooper, Chris; Barnes, Steve

    2016-05-01

    Changes in electrodermal activity (EDA) correlate with arousal and stress during stimulating experiences. We hypothesized that associations exist between short-term performance gains and changes in EDA. A total of 187 combat medics were randomly assigned to simulation (S), live tissue (L), or video (V) based training in the recognition and treatment of nerve agent casualties. Change in EDA from baseline to training was quantified for tonic and phasic responses and was categorized as positive (>+10%), no change (±10%), or negative (<-10%). Cognitive and psychomotor skills assessments were applied before and after the baseline/training period to quantify short-term performance changes. Statistically significant differences in both EDA arousal measures between training modalities (p < 0.001 with L > S ∼ V) were observed. Notably, larger proportions of trainees experienced negative changes in tonic (67%) and phasic (21%) EDA measures in the V group when compared to the L and S groups. Regardless of training modality, negative tonic and phasic EDA responses were associated with lower psychomotor performance gains and this finding approached statistical significance (tonic: p = 0.056, phasic: p = 0.08). No significant differences were noted in pre- to post-training cognitive performance between EDA response categories. As quantified by EDA response to training, reduced arousal was associated with lower short-term psychomotor, but not cognitive, performance gains. PMID:27168569

  3. In situ infrared aerosol spectroscopy for a variety of nerve agent simulants using flow-through photoacoustics.

    PubMed

    Gurton, Kristan P; Felton, Melvin; Dahmani, Rachid; Ligon, David

    2007-09-01

    We present newly measured results of an ongoing experimental program established to measure optical cross sections in the mid- and long-wave infrared for a variety of chemically and biologically based aerosols. For this study we consider only chemically derived aerosols, and in particular, a group of chemical compounds often used as simulants for the detection of extremely toxic organophosphorus nerve agents. These materials include: diethyl methylphosphonate (DEMP), dimethyl methylphosphonate (DMMP), diisopropyl methylphosphonate (DIMP), and diethyl phthalate (DEP). As reported in a prior study [Appl. Opt. 44, 4001 (2005)], we combine two optical techniques well suited for aerosol spectroscopy [i.e., flow-through photoacoustics and Fourier transform infrared (FTIR) emission spectroscopy], to measure in situ the absolute extinction and absorption cross sections over a variety of wavelengths spanning the IR spectral region from 3 to 13 mum. Aerosol size distribution(s), particle number density, and dosimetric measurements are recorded simultaneously in order to present optical cross sections that are aerosol mass normalized, i.e., m(2)/gram. Photoacoustic results, conducted at a series of CO(2) laser lines, compare well with measured broadband FTIR spectral extinction. Both FTIR and photoacoustic data also compare well with Mie theory calculations based on measured size distributions and previously published complex indices of refraction. PMID:17805369

  4. Structural elucidation of direct analysis in real time ionized nerve agent simulants with infrared multiple photon dissociation spectroscopy.

    PubMed

    Rummel, Julia L; Steill, Jeffrey D; Oomens, Jos; Contreras, Cesar S; Pearson, Wright L; Szczepanski, Jan; Powell, David H; Eyler, John R

    2011-06-01

    Infrared multiple photon dissociation (IRMPD) was used to generate vibrational spectra of ions produced with a direct analysis in real time (DART) ionization source coupled to a 4.7 T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The location of protonation on the nerve agent simulants diisopropyl methylphosphonate (DIMP) and dimethyl methylphosphonate (DMMP) was studied while solutions of the compounds were introduced for extended periods of time with a syringe pump. Theoretical vibrational spectra were generated with density functional theory calculations. Visual comparison of experimental mid-IR IRMPD spectra and theoretical spectra could not establish definitively if a single structure or a mixture of conformations was present for the protonated parent of each compound. However, theoretical calculations, near-ir IRMPD spectra, and frequency-to-frequency and statistical comparisons indicated that the protonation site for both DIMP and DMMP was predominantly, if not exclusively, the phosphonyl oxygen instead of one of the oxygen atoms with only single bonds. PMID:21491962

  5. In situ infrared aerosol spectroscopy for a variety of nerve agent simulants using flow-through photoacoustics

    NASA Astrophysics Data System (ADS)

    Gurton, Kristan P.; Felton, Melvin; Dahmani, Rachid; Ligon, David

    2007-09-01

    We present newly measured results of an ongoing experimental program established to measure optical cross sections in the mid- and long-wave infrared for a variety of chemically and biologically based aerosols. For this study we consider only chemically derived aerosols, and in particular, a group of chemical compounds often used as simulants for the detection of extremely toxic organophosphorus nerve agents. These materials include: diethyl methylphosphonate (DEMP), dimethyl methylphosphonate (DMMP), diisopropyl methylphosphonate (DIMP), and diethyl phthalate (DEP). As reported in a prior study [Appl. Opt. 44, 4001 (2005)], we combine two optical techniques well suited for aerosol spectroscopy [i.e., flow-through photoacoustics and Fourier transform infrared (FTIR) emission spectroscopy], to measure in situ the absolute extinction and absorption cross sections over a variety of wavelengths spanning the IR spectral region from 3 to 13 μm. Aerosol size distribution(s), particle number density, and dosimetric measurements are recorded simultaneously in order to present optical cross sections that are aerosol mass normalized, i.e., m2/gram. Photoacoustic results, conducted at a series of CO2 laser lines, compare well with measured broadband FTIR spectral extinction. Both FTIR and photoacoustic data also compare well with Mie theory calculations based on measured size distributions and previously published complex indices of refraction.

  6. Peripheral site ligand conjugation to a non-quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase.

    PubMed

    de Koning, Martijn C; van Grol, Marco; Noort, Daan

    2011-09-25

    Commonly employed pyridinium-oxime (charged) reactivators of nerve agent inhibited acetylcholinesterase (AChE) do not readily pass the blood brain barrier (BBB) because of the presence of charge(s). Conversely, non-ionic oxime reactivators often suffer from a lack of reactivating potency due to a low affinity for the active site of AChE. It was therefore hypothesized that an extra contribution in affinity may be achieved by covalently connecting a peripheral site ligand (PSL) to a non-ionic reactivator, which may result in a higher reactivation potency of the total construct. This validity of this approach, which proved successful for charged pyridinium oximes in earlier work, is now further exemplified with the covalent linkage of a neutral PSL via a spacer to a non-ionic and otherwise almost non-reactivating α-ketoaldoxime. It is demonstrated that the linkage of the PSL resulted in a remarkable increase in reactivation potency of the hybrid compounds. Although the molecules reported here are still inefficient reactivators compared to the current pyridinium oximes, the presented approach holds promise for the future design and synthesis of non-ionic oxime reactivators with improved BBB penetration and may be suited as well for non-oxime reactivators thus further widening the scope in the ongoing search for broad-spectrum reactivators. PMID:21504785

  7. A rationally designed mutant of plasma platelet-activating factor acetylhydrolase hydrolyzes the organophosphorus nerve agent soman.

    PubMed

    Kirby, Stephen D; Norris, Joseph; Sweeney, Richard; Bahnson, Brian J; Cerasoli, Douglas M

    2015-12-01

    Organophosphorus compounds (OPs) such as sarin and soman are some of the most toxic chemicals synthesized by man. They exert toxic effects by inactivating acetylcholinesterase (AChE) and bind secondary target protein. Organophosphorus compounds are hemi-substrates for enzymes of the serine hydrolase superfamily. Enzymes can be engineered by amino acid substitution into OP-hydrolyzing variants (bioscavengers) and used as therapeutics. Some enzymes associated with lipoproteins, such as human plasma platelet-activating factor acetylhydrolase (pPAF-AH), are also inhibited by OPs; these proteins have largely been ignored for engineering purposes because of complex interfacial kinetics and a lack of structural data. We have expressed active human pPAF-AH in bacteria and previously solved the crystal structure of this enzyme with OP adducts. Using these structures as a guide, we created histidine mutations near the active site of pPAF-AH (F322H, W298H, L153H) in an attempt to generate novel OP-hydrolase activity. Wild-type pPAF-AH, L153H, and F322H have essentially no hydrolytic activity against the nerve agents tested. In contrast, the W298H mutant displayed novel somanase activity with a kcat of 5min(-1) and a KM of 590μM at pH7.5. There was no selective preference for hydrolysis of any of the four soman stereoisomers. PMID:26343853

  8. High-throughput immunomagnetic scavenging technique for quantitative analysis of live VX nerve agent in water, hamburger, and soil matrixes.

    PubMed

    Knaack, Jennifer S; Zhou, Yingtao; Abney, Carter W; Prezioso, Samantha M; Magnuson, Matthew; Evans, Ronald; Jakubowski, Edward M; Hardy, Katelyn; Johnson, Rudolph C

    2012-11-20

    We have developed a novel immunomagnetic scavenging technique for extracting cholinesterase inhibitors from aqueous matrixes using biological targeting and antibody-based extraction. The technique was characterized using the organophosphorus nerve agent VX. The limit of detection for VX in high-performance liquid chromatography (HPLC)-grade water, defined as the lowest calibrator concentration, was 25 pg/mL in a small, 500 μL sample. The method was characterized over the course of 22 sample sets containing calibrators, blanks, and quality control samples. Method precision, expressed as the mean relative standard deviation, was less than 9.2% for all calibrators. Quality control sample accuracy was 102% and 100% of the mean for VX spiked into HPLC-grade water at concentrations of 2.0 and 0.25 ng/mL, respectively. This method successfully was applied to aqueous extracts from soil, hamburger, and finished tap water spiked with VX. Recovery was 65%, 81%, and 100% from these matrixes, respectively. Biologically based extractions of organophosphorus compounds represent a new technique for sample extraction that provides an increase in extraction specificity and sensitivity. PMID:23126363

  9. Liquid-liquid-solid microextraction and detection of nerve agent simulants by on-membrane Fourier transform infrared spectroscopy.

    PubMed

    Garg, Prabhat; Purohit, Ajay; Tak, Vijay K; Kumar, Ajeet; Dubey, D K

    2012-11-01

    A coupling of novel liquid-liquid-solid microextraction (LLSME) technique based on porous hydrophobic membrane and Fourier-transform infrared spectroscopy has been presented for the detection, identification and quantification of markers and simulants of nerve agents. Two isomers O,O'-dihexyl methylphosphonate (DHMP) and O,O'-dipentyl isopropylphosphonate (DPIPP) were chosen as model analytes for the study. In the present technique, organic phase was immobilised within the pores of membrane after fixing it in an assembly, which was then immersed into aqueous sample of target analytes for extraction. The analytes were directly determined on the surface of membrane by FTIR spectroscopy without elution. On comparison with solid phase microextraction (SPME), LLSME was found to be much more efficient. The method was optimised and quantitative analyses were performed using calibration curves obtained via Beer's law and employing processing of spectra obtained, via a multivariate calibration technique partial least square (PLS). Relative standard deviations (RSDs) for intraday repeatability and interday reproducibility were found to be in the range of 0.20-0.50% and 0.20-0.60%, respectively. Limit of detection (LOD) was achieved up to 15 ng mL(-1). Applicability of the method was tested with an unknown real sample obtained in an international official proficiency test (OPT). PMID:23084054

  10. First-principles molecular dynamics simulations of condensed-phase V-type nerve agent reaction pathways and energy barriers.

    PubMed

    Gee, Richard H; Kuo, I-Feng W; Chinn, Sarah C; Raber, Ellen

    2012-03-14

    Computational studies of condensed-phase chemical reactions are challenging in part because of complexities in understanding the effects of the solvent environment on the reacting chemical species. Such studies are further complicated due to the demanding computational resources required to implement high-level ab initio quantum chemical methods when considering the solvent explicitly. Here, we use first-principles molecular dynamics simulations to examine condensed-phase decontamination reactions of V-type nerve agents in an explicit aqueous solvent. Our results include a detailed study of hydrolysis, base-hydrolysis, and nucleophilic oxidation of both VX and R-VX, as well as their protonated counterparts (i.e., VXH(+) and R-VXH(+)). The decontamination mechanisms and chemical reaction energy barriers, as determined from our simulations, are found to be in good agreement with experiment. The results demonstrate the applicability of using such simulations to assist in understanding new decontamination technologies or other applications that require computational screening of condensed-phase chemical reaction mechanisms. PMID:22298156

  11. Preparation and performance of a colorimetric biosensor using acetylcholinesterase and indoxylacetate for assay of nerve agents and drugs

    PubMed Central

    Vlcek, Vitezslav

    2014-01-01

    Different toxic compounds can target the cholinergic nervous system. Acetylcholinesterase (AChE; EC 3.1.1.7) is one of the most crucial components of the cholinergic nervous system and thus many of the toxins interact with this enzyme. As to inhibitors, nerve agents used as chemical warfare, some insecticides, and drugs influencing the cholinergic system are common examples of AChE inhibitors. Once inhibited by a neurotoxic compound, a serious cholinergic crisis can occur. On the other hand, sensitivity of AChE to the inhibition can be used for analytical purposes. In this study, a simple disposable biosensor with AChE as a recognition element was devised. AChE was immobilized onto a cellulose matrix and indoxylacetate was used as a chromogenic substrate. The enzyme reaction was assessed by the naked eye using arbitrary units and pyridostigmine, tacrine, paraoxon, carbofuran, soman and VX were assayed as selected inhibitors. A good stability of the biosensors was found, with no aging over a quarter of a year and minimal sensitivity to the interference of organic solvents. The limit of detection ranged from 10 to 100 nmol/L for the compounds tested with a sample volume of 40 µL. PMID:26109903

  12. Preparation and performance of a colorimetric biosensor using acetylcholinesterase and indoxylacetate for assay of nerve agents and drugs.

    PubMed

    Pohanka, Miroslav; Vlcek, Vitezslav

    2014-12-01

    Different toxic compounds can target the cholinergic nervous system. Acetylcholinesterase (AChE; EC 3.1.1.7) is one of the most crucial components of the cholinergic nervous system and thus many of the toxins interact with this enzyme. As to inhibitors, nerve agents used as chemical warfare, some insecticides, and drugs influencing the cholinergic system are common examples of AChE inhibitors. Once inhibited by a neurotoxic compound, a serious cholinergic crisis can occur. On the other hand, sensitivity of AChE to the inhibition can be used for analytical purposes. In this study, a simple disposable biosensor with AChE as a recognition element was devised. AChE was immobilized onto a cellulose matrix and indoxylacetate was used as a chromogenic substrate. The enzyme reaction was assessed by the naked eye using arbitrary units and pyridostigmine, tacrine, paraoxon, carbofuran, soman and VX were assayed as selected inhibitors. A good stability of the biosensors was found, with no aging over a quarter of a year and minimal sensitivity to the interference of organic solvents. The limit of detection ranged from 10 to 100 nmol/L for the compounds tested with a sample volume of 40 µL. PMID:26109903

  13. Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification.

    PubMed

    Yang, Jun; Fan, Lixue; Wang, Feijian; Luo, Yuan; Sui, Xin; Li, Wanhua; Zhang, Xiaohong; Wang, Yongan

    2016-05-01

    The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration. PMID:26730700

  14. Magnetic multi-walled carbon nanotubes assisted dispersive solid phase extraction of nerve agents and their markers from muddy water.

    PubMed

    Pardasani, Deepak; Kanaujia, Pankaj K; Purohit, Ajay K; Shrivastava, Anchal Roy; Dubey, D K

    2011-10-30

    The multi-walled carbon nano-tubes (MWCNT) were magnetized with iron oxide nanoparticles and were characterized by SEM and EDX analyses. These magnetized MWCNT (Mag-CNT) were used as sorbent in dispersive solid phase extraction (DSPE) mode to extract nerve agents and their markers. Mag-CNT were dispersed in water and collected with the help of an external magnet. From Mag-CNT, the adsorbed analytes were eluted and analyzed by GC-FPD in phosphorus mode. DSPE was found to be advantageous over conventional solid phase extraction (SPE) in terms of operational simplicity, speed, handling of large sample volume and recoveries. Extraction parameters such as eluting solvent, sorbent amount, pH and salinity of aqueous samples were optimized. Optimized extraction conditions included 40 mg of Mag-CNT as sorbent, chloroform as eluent, pH 3-11 and salinity 20%. Under the optimized conditions, recoveries from distilled water ranged from 60 to 96% and were comparable in tap and muddy water. Limits of quantification and limits of detection of 0.15 ng/ml and 0.05 ng/ml, respectively, were achieved. Superiority of Mag-CNT over conventional C(18) SPE was also established. PMID:22063538

  15. Transcriptional responses of the nerve agent-sensitive brain regions amygdala, hippocampus, piriform cortex, septum, and thalamus following exposure to the organophosphonate anticholinesterase sarin

    PubMed Central

    2011-01-01

    Background Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used microarray analysis to identify gene expression changes in the rat piriform cortex, a region of the rat brain sensitive to nerve agent exposure, over a 24-h time period following sarin-induced seizure. We found significant differences in gene expression profiles and identified secondary responses that potentially lead to brain injury and cell death. To advance our understanding of the molecular mechanisms involved in sarin-induced toxicity, we analyzed gene expression changes in four other areas of the rat brain known to be affected by nerve agent-induced seizure (amygdala, hippocampus, septum, and thalamus). Methods We compared the transcriptional response of these four brain regions to sarin-induced seizure with the response previously characterized in the piriform cortex. In this study, rats were challenged with 1.0 × LD50 sarin and subsequently treated with atropine sulfate, 2-pyridine aldoxime methylchloride, and diazepam. The four brain regions were collected at 0.25, 1, 3, 6, and 24 h after seizure onset, and total RNA was processed for microarray analysis. Results Principal component analysis identified brain region and time following seizure onset as major sources of variability within the dataset. Analysis of variance identified genes significantly changed following sarin-induced seizure, and gene ontology analysis identified biological pathways, functions, and networks of genes significantly affected by sarin-induced seizure over the 24-h time course. Many of the molecular functions and pathways identified as being most significant across all of the brain regions were indicative of an inflammatory response. There were also a number of

  16. 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. PMID:25495198

  17. Encapsulation of a Nerve Agent Detoxifying Enzyme by a Mesoporous Zirconium Metal-Organic Framework Engenders Thermal and Long-Term Stability.

    PubMed

    Li, Peng; Moon, Su-Young; Guelta, Mark A; Harvey, Steven P; Hupp, Joseph T; Farha, Omar K

    2016-07-01

    Immobilized enzymes typically have greater thermal and operational stability than their soluble form. Here we report that for the first time, a nerve agent detoxifying enzyme, organophosphorus acid anhydrolase (OPAA), has been successfully encapsulated into a water-stable zirconium metal-organic framework (MOF). This MOF features a hierarchical mesoporous channel structure and exhibits a 12 wt % loading capacity of OPAA. The thermal and long-term stabilities of OPAA are both significantly enhanced after immobilization. PMID:27341436

  18. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  19. Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

    PubMed

    Aracava, Yasco; Pereira, Edna F R; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X

    2009-12-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. PMID:19741148

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

    PubMed Central

    Theriot, Casey M.; Semcer, Rebecca L.; Shah, Saumil S.; Grunden, Amy M.

    2011-01-01

    Prolidases hydrolyze Xaa-Pro dipeptides and can also cleave the P-F and P-O bonds found in organophosphorus (OP) compounds, including the nerve agents soman and sarin. Ph1prol (PH0974) has previously been isolated and characterized from Pyrococcus horikoshii and was shown to have higher catalytic activity over a broader pH range, higher affinity for metal, and increased thermostability compared to P. furiosus prolidase, Pfprol (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 were prepared. Four Ph1prol mutants (A195T/G306S-, Y301C/K342N-, E127G/E252D-, and E36V-Ph1prol) were isolated which had greater thermostability and improved activity over a broader range of temperatures against Xaa-Pro dipeptides and OP nerve agents compared to wild type Pyrococcus prolidases. PMID:22162664

  1. 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.

  2. Improving the catalytic activity of hyperthermophilic Pyrococcus horikoshii prolidase for detoxification of organophosphorus nerve agents over a broad range of temperatures.

    PubMed

    Theriot, Casey M; Semcer, Rebecca L; Shah, Saumil S; Grunden, Amy M

    2011-01-01

    Prolidases hydrolyze Xaa-Pro dipeptides and can also cleave the P-F and P-O bonds found in organophosphorus (OP) compounds, including the nerve agents soman and sarin. Ph1prol (PH0974) has previously been isolated and characterized from Pyrococcus horikoshii and was shown to have higher catalytic activity over a broader pH range, higher affinity for metal, and increased thermostability compared to P. furiosus prolidase, Pfprol (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 were prepared. Four Ph1prol mutants (A195T/G306S-, Y301C/K342N-, E127G/E252D-, and E36V-Ph1prol) were isolated which had greater thermostability and improved activity over a broader range of temperatures against Xaa-Pro dipeptides and OP nerve agents compared to wild type Pyrococcus prolidases. PMID:22162664

  3. Polyelectrolyte functionalized multi-walled carbon nanotubes as strong anion-exchange material for the extraction of acidic degradation products of nerve agents.

    PubMed

    Kanaujia, Pankaj K; Pardasani, Deepak; Purohit, Ajay K; Tak, Vijay; Dubey, D K

    2011-12-30

    Extraction, enrichment and gas chromatography mass spectrometric analysis of degradation products of nerve agents from water is of significant importance for verification of Chemical Weapons Convention (CWC) and gathering forensic evidence of use of nerve agents. Multi-walled carbon nanotubes (MWCNTs) were non-covalently functionalized with poly(diallyldimethylammonium chloride) (PDDA) to afford the cationic functionalized nano-tubes, which were used as solid-phase anionic-exchanger sorbents to extract the acidic degradation products of nerve agents from water. Extraction efficiencies of MWCNTs-PDDA were compared with those of mixed mode anion-exchange (HLB) and silica based strong anion-exchange (Si-SAX) cartridges. Optimized extraction parameters included MWCNTs-PDDA 12 mg, washing solvent 5 mL water and eluting solvent 3 mL of 0.1M aqueous HCl followed by 3 mL methanol. At 1 ng mL(-1) spiking concentration of mono- and di-basic phosphonic acids, MWCNTs-PDDA exhibited higher extraction efficiencies in comparison to Si-SAX and HLB. The limits of detection were achieved down to 0.05 and 0.11 ng mL(-1) in selected ion and full scan monitoring mode respectively; and limits of quantification in selected ion monitoring mode were achieved down to 0.21 ng mL(-1). PMID:22119612

  4. 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

  5. Direct gas-phase detection of nerve and blister warfare agents utilizing active capillary plasma ionization mass spectrometry.

    PubMed

    Wolf, J-C; Schaer, M; P Siegenthaler, P; Zenobi, R

    2015-01-01

    Ultrasensitive direct gas-phase detection of chemical warfare agents (CWAs) is demonstrated utilizing active capillary plasma ionization and triple quadrupole mass spectrometry (MS) instrumentation. Four G- agents, two V-agents and various blistering agents [including sulfur mustard (HD)] were detected directly in the gas phase with limits of detection in the low parts per trillion (ng m(-3)) range. The direct detection of HD was shown for dry carrier gas conditions, but signals vanished when humidity was present, indicating a possible direct detection of HD after sufficient gas phase pretreatment. The method provided sufficient sensitivity to monitor directly the investigated volatile CWAs way below their corresponding minimal effect dose, and in most cases even below the eight hours worker exposure concentration. In general, the ionization is very soft, with little to no in-source fragmentation. Especially for the G-agents, some dimer formation occurred at higher concentrations. This adds complexity, but also further selectivity, to the corresponding mass spectra. Our results show that the active capillary plasma ionization is a robust, sensitive, "plug and play" ambient ionization source suited (but not exclusively) to the very sensitive detection of CWAs. It has the potential to be used with portable MS instrumentation. PMID:26307710

  6. Task 89-07: Evaluation of the in vitro efficacy of candidate pretreatment and treatment (pt) compounds against vesicants and nerve agents. Final report, January 1990-January 1993

    SciTech Connect

    Hobson, D.W.; Blank, J.A.; Starner, R.A.

    1993-10-01

    MREF Task 89-07 encompassed four vesicant assays and four nerve agent assays. The four vesicant assays evaluated the candidate P and T compound solubility limitations, direct cytotoxic effects, efficacy against HD-induced cellular nicotinamide adenine dinucleotide (NAD+) depletion, and efficacy against HD-induced cytotoxicity. Normal human epidermal cells (NHEKs) were used to evaluate candidate PT compound efficacy against HD-induced NAD+ depletion, and peripheral blood mononuclear leukocytes (PBMC) were used in direct cytotoxicity and HD-induced cytotoxicity assays. The four nerve agent assays assessed candidate PT compound direct inhibitory effects on acetylcholinesterase (AChE) activity, candidate PT compound efficacy in reactivating Tabun (GA) - and O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-inhibited A ThE, and candidate PT compound efficacy in slowing the aging rate of Soman (GD) inhibited AChE. All nerve agent and vesicant assays with the exception of the direct cytotoxicity and HD-induced cytotoxicity assays were initially established under MREF Task 88-36. The direct cytotoxicity and HD-induced cytotoxicity assays were transitioned to the MREF from USAMRICD and validated for use in routine screening procedures, including the generation of control database values, under Task 89-07. Solubility data were obtained for 37 compounds submitted for evaluation in the vesicant assays. Thirty-five of these compounds were evaluated for direct cytotoxicity, and their effect against HD-induced cytotoxicity, while 13 compound is were evaluated for efficacy against HD-induced NAD+ depletion. AChE reactivation, ACHE aging, ACHE inhibition, In vitro, Cytotoxicity , Vesicant assays, Nerve ag.

  7. Aminolysis of a model nerve agent: a computational reaction mechanism study of O,S-dimethyl methylphosphonothiolate.

    PubMed

    Mandal, Debasish; Sen, Kaushik; Das, Abhijit K

    2012-08-16

    The mechanism for the aminolysis of a model nerve agent, O,S-dimethyl methylphosphonothiolate, is investigated both at density functional level using M062X method with 6-311++G(d,p) basis set and at ab initio level using the second-order Møller-Plesset perturbation theory (MP2) with the 6-311+G(d,p) basis set. The catalytic role of an additional NH(3) and H(2)O molecule is also examined. The solvent effects of acetonitrile, ethanol, and water are taken into account employing the conductor-like screening model (COSMO) at the single-point M062X/6-311++G(d,p) level of theory. Two possible dissociation pathways, methanethiol and methyl alcohol dissociations, along with two different neutral mechanisms, a concerted one and a stepwise route through two neutral intermediates, for each pathway are investigated. Hyperconjugation stabilization that has an effect on the stability of generated transition states are investigated by natural bond order (NBO) approach. Additionally, quantum theory of atoms in molecules analysis is performed to evaluate the bond critical (BCP) properties and to quantify strength of different types of interactions. The calculated results predict that the reaction of O,S-dimethyl methylphosphonothiolate with NH(3) gives rise to parallel P-S and P-O bond cleavages, and in each cleavage the neutral stepwise route is always favorable than the concerted one. The mechanism of NH(3) and H(2)O as catalyst is nearly similar, and they facilitate the shuttle of proton to accelerate the reaction. The steps involving the H(2)O-mediated proton transfer are the most suitable ones. The first steps for the stepwise process, the formation of neutral intermediate, are the rate-determining step. It is observed that in the presence of catalyst the reaction in the stepwise path possesses almost half the activation energy of the uncatalyzed one. A bond-order analysis using Wiberg bond indexes obtained by NBO calculation predicts that usually all individual steps of the

  8. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  9. Mobile Agents Applications.

    ERIC Educational Resources Information Center

    Martins, Rosane Maria; Chaves, Magali Ribeiro; Pirmez, Luci; Rust da Costa Carmo, Luiz Fernando

    2001-01-01

    Discussion of the need to filter and retrieval relevant information from the Internet focuses on the use of mobile agents, specific software components which are based on distributed artificial intelligence and integrated systems. Surveys agent technology and discusses the agent building package used to develop two applications using IBM's Aglet…

  10. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

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

    SciTech Connect

    Liu, Guodong; Lin, Yuehe

    2006-02-01

    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 greatly 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.

  12. Fe3O4 magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent.

    PubMed

    Liang, Minmin; Fan, Kelong; Pan, Yong; Jiang, Hui; Wang, Fei; Yang, Dongling; Lu, Di; Feng, Jing; Zhao, Jianjun; Yang, Liu; Yan, Xiyun

    2013-01-01

    Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 μM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds. PMID:23153113

  13. Solvent Effects on the Reactions of the Nerve Agent VX with KF/Al2O3: Heterogeneous or Homogeneous Decontamination?

    PubMed

    Fridkin, Gil; Yehezkel, Lea; Columbus, Ishay; Zafrani, Yossi

    2016-03-01

    Solvent effects on the reactions of the extremely toxic nerve agent VX with KF/Al2O3 powder were explored. Small quantities of water or methanol (5-10 wt %), which effectively mobilized all components while maintaining the heterogeneous nature of the reaction, promoted much faster rates than those obtained with larger quantities. Any amount of acetonitrile resulted in extremely slow transformations. Surprisingly, 5-50 wt % of heptane led to fast reactions due to the combination of its ability to mediate fast diffusion of VX and a MAS centrifugation effect. PMID:26838963

  14. Unique emission from norbornene derived terpyridine--a selective chemodosimeter for G-type nerve agent surrogates.

    PubMed

    Sarkar, Santu; Mondal, Arobendo; Tiwari, Ashwani Kumar; Shunmugam, Raja

    2012-05-01

    A new chemodosimeter for a G-type agent that exploits norbornene derived terpyridine (NDT)-lanthanide unique emission is reported. The unusual emission between terpyridine and norbornene motifs of NDT is attributed to the significant difference in the position of the HOMO and LUMO wave functions that prevents the non-radiative relaxation pathway. An interesting magenta emission from NDT along with Eu(III) is utilized as a new fluorometric chemodosimeter that selectively detects (by changing the observed magenta emission to blue) G-type agent surrogates. A detection limit of 40 ppb is obtained and the selectivity for reactive surrogates over a variety of other close chemical analogs is demonstrated. PMID:22407316

  15. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  16. Kromoscopy for detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Ewing, Kenneth J.; Sanghera, Jas; Aggarwal, Ishwar D.; Block, Myron J.

    2004-12-01

    The ability of a Kromoscope to discriminate between chemical warfare agent simulants and toxic industrial chemicals is evaluated. The Kromoscope response to the simulants DMMP and DIMP is compared to a pesticide (diazanon) and cyclopentanol. The response of a mid-infrared Kromoscope to the nerve agents VX and GB and the stimulant DF are calculated.

  17. Chemical crowd control agents.

    PubMed

    Menezes, Ritesh G; Hussain, Syed Ather; Rameez, Mansoor Ali Merchant; Kharoshah, Magdy A; Madadin, Mohammed; Anwar, Naureen; Senthilkumaran, Subramanian

    2016-03-01

    Chemical crowd control agents are also referred to as riot control agents and are mainly used by civil authorities and government agencies to curtail civil disobedience gatherings or processions by large crowds. Common riot control agents used to disperse large numbers of individuals into smaller, less destructive, and more easily controllable numbers include chloroacetophenone, chlorobenzylidenemalononitrile, dibenzoxazepine, diphenylaminearsine, and oleoresin capsicum. In this paper, we discuss the emergency medical care needed by sufferers of acute chemical agent contamination and raise important issues concerning toxicology, safety and health. PMID:26658556

  18. Hydrolysis of DFP and the Nerve Agent (S)-Sarin by DFPase Proceeds Along Two Different Reaction Pathways: Implica-tions for Engineering Bioscavengers

    SciTech Connect

    Wymore, Troy W; Langan, Paul; Smith, Jeremy C; Field, Martin J.; Parks, Jerry M

    2014-01-01

    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 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 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 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.

  19. Detection and classification characteristics of arrays of carbon black/organic polymer composite chemiresistive vapor detectors for the nerve agent simulants dimethylmethylphosphonate and diisopropylmethylphosponate.

    PubMed

    Hopkins, A R; Lewis, N S

    2001-03-01

    Arrays of conducting polymer composite vapor detectors have been evaluated for performance in the presence of the nerve agent simulants dimethylmethylphosphonate (DMMP) and diisopropylmethylphosponate (DIMP). Limits of detection for DMMP on unoptimized carbon black/ organic polymer composite vapor detectors in laboratory air were estimated to be 0.047-0.24 mg m(-3). These values are lower than the EC50 value (where EC50 is the airborne concentration sufficient to induce severe effects in 50% of those exposed for 30 min) for the nerve agents sarin (methylphosphonofluoridic acid, 1-methylethyl ester) and soman (methylphosphonofluoridic acid, 1,2,2-trimethylpropyl ester), which has been established as approximately 0.8 mg m(-3). Arrays of these vapor detectors were easily able to resolve signatures due to exposures to DMMP from those due to DIMP or due to a variety of other test analytes (including water, methanol, benzene, toluene, diesel fuel, lighter fluid, vinegar, and tetrahydrofuran) in a laboratory air background. In addition, DMMP at 27 mg m(-3) could be detected and differentiated from the signatures of the other test analytes in the presence of backgrounds of potential interferences, including water, methanol, benzene, toluene, diesel fuel, lighter fluid, vinegar, and tetrahydrofuran, even when these interferents were present in much higher concentrations than that of the DMMP or DIMP being detected. PMID:11289432

  20. Detection and classification characteristics of arrays of carbon black/organic polymer composite chemiresistive vapor detectors for the nerve agent simulants Dimethylmethylphosphonate and Diisopropy

    NASA Astrophysics Data System (ADS)

    Hopkins, Alan R.; Lewis, Nathan S.

    2002-06-01

    Arrays of conducting polymer composite vapor detectors have been evaluated for performance in the presence of the nerve agent simulants dimethylmethylphosphonate (DMMP) and diisopropylmethylphosponate (DIMP). Limits of detection for DMMP on unoptimized carbon black-organic polymer composite vapor detectors in laboratory air were estimated to be 0.047-0.24 mg m-3. These values are lower than the EC50 value for the nerve agents sarin (methylphosphonofluoridic acid, (1-methylethyl) ester) and soman, which have been established as equals 0.8 mg m-3. Arrays of these vapor detectors were easily able to resolve signatures due to exposures to DMMP from those due to DIMP or due to a variety of other test analytes in a laboratory air background. In addition, DMMP at 27 mg m-3 could be detected and differentiated from the signatures of the other test analytes in the presence of backgrounds of potential interferents in the background ambient, including water, methanol, benzene, toluene, diesel fuel, lighter fluid, vinegar and tetrahydrofuran, even when these interferents were present in much higher concentrations than that of the DMMP or DIMP being detected.

  1. Hydrolysis of DFP and the nerve agent (S)-sarin by DFPase proceeds along two different reaction pathways: implications for engineering bioscavengers.

    PubMed

    Wymore, Troy; Field, Martin J; Langan, Paul; Smith, Jeremy C; Parks, Jerry M

    2014-05-01

    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 Ca(2+), 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

  2. Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization.

    PubMed

    Lin, Ying; Chen, Jia; Yan, Long; Guo, Lei; Wu, Bidong; Li, Chunzheng; Feng, Jianlin; Liu, Qin; Xie, Jianwei

    2014-08-01

    A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples. PMID:24633564

  3. 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

  4. Role of percutaneous posterior tibial nerve stimulation either alone or combined with an anticholinergic agent in treating patients with overactive bladder

    PubMed Central

    Kızılyel, Sadık; Karakeçi, Ahmet; Ozan, Tunç; Ünüş, İhsan; Barut, Osman; Onur, Rahmi

    2015-01-01

    Objective To evaluate the efficacy of percutaneous tibial nerve stimulation (PTNS), either alone or combined with an anticholinergic agent, in treating patients with an overactive bladder (OAB) in whom previous conservative treatment failed. Material and methods In this study, we included a total of 30 female patients with OAB in whom all conventional therapies failed between January 2010 and April 2011. Patients were randomly divided into three groups: Group 1, PTNS group; Group 2, patients receiving an anticholinergic agent; and Group 3, patients receiving both PTNS and anticholinergic agent. PTNS treatment continued for 12 weeks with each session lasting 30 min. Results All parameters of the bladder diary significantly improved in all groups (p<0.05). Similarly, all scores measured by questionnaires (UDI-6, IIQ-7, and OABSS) revealed significant improvements in all groups. When the improvements in symptoms were compared among the groups, there was a statistically significantly higher improvement in groups 1 and 3 than in Group 2. Conclusion PTNS is a safe, simple, and minimally invasive treatment modality in patients with OAB, and it may be suggested either alone or in combination with anticholinergics when conventional treatments fail. PMID:26623150

  5. Determination of hydrolytic degradation products of nerve agents by injection port fluorination in gas chromatography/mass spectrometry for the verification of the Chemical Weapons Convention.

    PubMed

    Pardasani, Deepak; Mazumder, Avik; Gupta, Arvinda K; Kanaujia, Pankaj K; Tak, Vijay; Dubey, Devendra K

    2007-01-01

    Retrospective detection and identification of markers of chemical warfare agents are important aspects of verification of the Chemical Weapons Convention. Alkyl alkylphosphonic acids (AAPAs) and alkylphosphonic acids (APAs) are important markers of nerve agents. We describe the development and optimization of a new gas chromatography/mass spectrometry (GC/MS) injection port fluorination method for the derivatization of AAPAs and APAs. The process involved the injection of acids with trifluoroacetic anhydride in GC/MS, where acids are converted into their corresponding volatile fluorides. Various reaction conditions such as fluorinating agent, injection port temperature and splitless time were optimized. The maximum reaction efficiency of the acids with trifluoroacetic anhydride was observed at 230 degrees C injection port temperature with a splitless time of 2 min. APAs showed best analytical efficiencies at 400 degrees C injection port temperature, while the other conditions were similar to those of AAPAs. The linearities of response for APAs and AAPAs were in the range of 1-25 and 5-100 microg mL(-1), respectively, with limits of detection ranging from 500 pg to 800 ng mL(-1). PMID:17703510

  6. 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. PMID:24517492

  7. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  8. Travel Agent Course Outline.

    ERIC Educational Resources Information Center

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  9. Development and application of acute exposure guideline levels (AEGLs) for chemical warfare nerve and sulfur mustard agents.

    PubMed

    Watson, Annetta; Opresko, Dennis; Young, Robert; Hauschild, Veronique

    2006-01-01

    Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios. PMID:16621779

  10. Development and Application of Acute Exposure Guideline Levels (AEGLs) for Chemical Warfare Nerve and Sulfur Mustard Agents.

    SciTech Connect

    Watson, Annetta Paule; Opresko, Dennis M; Young, Robert A; Hauschild, Veronique

    2006-01-01

    Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios.

  11. Pediatric Antifungal Agents

    PubMed Central

    Cohen-Wolkowiez, Michael; Moran, Cassandra; Benjamin, Daniel K.; Smith, P Brian

    2009-01-01

    Purpose of review In immunocompromised hosts, invasive fungal infections are common and fatal. In the past decade, the antifungal armamentarium against invasive mycoses has expanded greatly. The purpose of this report is to review the most recent literature addressing the use of antifungal agents in children. Recent findings Most studies evaluating the safety and efficacy of antifungal agents are limited to adults. However, important progress has been made in describing the pharmacokinetics and safety of newer antifungal agents in children, including the echinocandins. Summary Dosage guidelines for newer antifungal agents are currently based on adult and limited pediatric data. Because important developmental pharmacology changes occur throughout childhood impacting the pharmacokinetics of these agents, antifungal studies specifically designed for children are necessary. PMID:19741525

  12. How do agents represent?

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  13. Standard Agent Framework 1

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4)more » Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.« less

  14. Biological warfare agents

    PubMed Central

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-01-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies. PMID:21829313

  15. Dioxin, agent orange

    SciTech Connect

    Gough, M.

    1986-01-01

    This book presents information on the following topics: dioxin, a prevalent problem; nobody wanted dioxin; agent organe and Vietnam; what we know about and may learn about agent orange and Veterans' health; agent organe and birth defects; dioxin in Missouri; 2, 4, 5-T: the U.S.' disappearing herbicide; Seveso: high-level environmental exposure; the nitro explosion; industrial exposures to dioxin; company behavior in the face of dioxin exposures; dioxin and specific cancers; animal tests of dioxin toxicity; dioxin decions; the present and the future.

  16. Chromatographic separation of simulants of nerve and blister agents by combining one- and two-channel columns with different stationary phases.

    PubMed

    Yuan, Huan; Du, Xiaosong; Li, Yi; Zhao, Xulan; Xu, Ming

    2016-04-01

    A two-channel gas chromatography column and a single-channel column were made by deep reactive-ion etching technology. The two short columns were coated with different stationary phases, and then linked without a modulator. This is to aim at increasing the sample capacity and achieving a higher separation efficiency in complex environments. The results show that the capacity of the connected column is approximately 4 and 1.5 times larger than that of the single- and two-channel columns, respectively. The linked column was utilized to separate a six-component mixture, composed of three simulants of nerve and blister agents and three interfering vapors. The results demonstrate that the combined column has a remarkably higher separation efficiency than the individual columns, and an acceptable resolution is achieved although the total length of the linked column is only 1.5 m. PMID:26843525

  17. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  18. Riot Control Agents

    MedlinePlus

    ... your clothing, rapidly wash your entire body with soap and water, and get medical care as quickly ... agent from your skin with large amounts of soap and water. Washing with soap and water will ...

  19. Catalytic-site conformational equilibrium in nerve-agent adducts of acetylcholinesterase: possible implications for the HI-6 antidote substrate specificity.

    PubMed

    Artursson, Elisabet; Andersson, Per Ola; Akfur, Christine; Linusson, Anna; Börjegren, Susanne; Ekström, Fredrik

    2013-05-01

    Nerve agents such as tabun, cyclosarin and Russian VX inhibit the essential enzyme acetylcholinesterase (AChE) by organophosphorylating the catalytic serine residue. Nucleophiles, such as oximes, are used as antidotes as they can reactivate and restore the function of the inhibited enzyme. The oxime HI-6 shows a notably low activity on tabun adducts but can effectively reactivate adducts of cyclosarin and Russian VX. To examine the structural basis for the pronounced substrate specificity of HI-6, we determined the binary crystal structures of Mus musculus AChE (mAChE) conjugated by cyclosarin and Russian VX and found a conformational mobility of the side chains of Phe338 and His447. The interaction between HI-6 and tabun-adducts of AChE were subsequently investigated using a combination of time resolved fluorescence spectroscopy and X-ray crystallography. Our findings show that HI-6 binds to tabun inhibited Homo sapiens AChE (hAChE) with an IC50 value of 300μM and suggest that the reactive nucleophilic moiety of HI-6 is excluded from the phosphorus atom of tabun. We propose that a conformational mobility of the side-chains of Phe338 and His447 is a common feature in nerve-agent adducts of AChE. We also suggest that the conformational mobility allow HI-6 to reactivate conjugates of cyclosarin and Russian VX while a reduced mobility in tabun conjugated AChE results in steric hindrance that prevents efficient reactivation. PMID:23376121

  20. Effect of cation-exchange pretreatment of aqueous soil extracts on the gas chromatographic-mass spectrometric determination of nerve agent hydrolysis products after tert.-butyldimethylsilylation.

    PubMed

    Kataoka, M; Tsunoda, N; Ohta, H; Tsuge, K; Takesako, H; Seto, Y

    1998-10-23

    The efficiency of pretreatment of aqueous soil extracts using a cation-exchange resin has been investigated by gas chromatographic-mass spectrometric (GC-MS) determination of nerve agent hydrolysis products after tert.-butyldimethylsilyl (TBDMS) derivatization. An aqueous solution containing methylphosphonic acid (MPA) and its monoalkyl esters, ethyl methylphosphonic acid, isopropyl methylphosphonic acid and pinacolyl methylphosphonic acid, was dried, and these phosphonic acids were derivatized with N-methyl-N-(tert.-butyldimethylsilyl)trifluoro-acetamide and analyzed by GC-MS. The yields of TBDMS derivatives were significantly decreased by the addition of calcium and magnesium ions to an aqueous solution (approximately 0.5 mM) before derivatization. The extent of lowered yields was related to the hydrophilicity of phosphonic acids. MPA and its monoalkyl esters were spiked into soil samples (sand, alluvial soil and volcanic ash soil), extracted with distilled water, dried, silylated and applied to GC-MS. The yields of TBDMS derivatives of monoalkyl esters from soil samples were low (3-42%) and MPA derivative was scarcely detected (yield: < 0.7%). By desalting the aqueous soil extract by passage through a strong cation-exchange resin, the yields of TBDMS derivatives of monoalkyl esters were significantly improved (12-69%) and MPA derivative was detected (yield: 2-36%). The extent of improved yields was related to the concentrations of divalent metal cations in aqueous soil extracts. In combination with desalting by the cation-exchange resin, GC-MS after TBDMS derivatization enables detection of nerve agent hydrolysis products in soils at sub-ppm (0.2 microgram/g) concentrations. PMID:9818434

  1. Novel substituted phenoxyalkyl pyridinium oximes enhance survival and attenuate seizure-like behavior of rats receiving lethal levels of nerve agent surrogates.

    PubMed

    Chambers, Janice E; Meek, Edward C; Bennett, Joshua P; Bennett, W Shane; Chambers, Howard W; Leach, C Andrew; Pringle, Ronald B; Wills, Robert W

    2016-01-01

    Novel substituted phenoxyalkyl pyridinium oximes, previously shown to reactivate brain cholinesterase in rats treated with high sublethal dosages of surrogates of sarin and VX, were tested for their ability to prevent mortality from lethal doses of these two surrogates. Rats were treated subcutaneously with 0.6mg/kg nitrophenyl isopropyl methylphosphonate (NIMP; sarin surrogate) or 0.65mg/kg nitrophenyl ethyl methylphosphonate (NEMP; VX surrogate), dosages that were lethal within 24h to all tested rats when they received only 0.65mg/kg atropine at the time of initiation of seizure-like behavior (about 30min). If 146mmol/kg 2-PAM (human equivalent dosage) was also administered, 40% and 33% survival was obtained with NIMP and NEMP, respectively, while the novel Oximes 1 and 20 provided 65% and 55% survival for NIMP and 75 and 65% for NEMP, respectively. In addition, both novel oximes resulted in a highly significant decrease in time to cessation of seizure-like behavior compared to 2-PAM during the first 8h of observation. Brain cholinesterase inhibition was slightly less in novel oxime treated rats compared to 2-PAM in the 24h survivors. The lethality data indicate that 24h survival is improved by two of the novel oximes compared to 2-PAM. The cessation of seizure-like behavior data strongly suggest that these novel oximes are able to penetrate the blood-brain barrier and can combat the hypercholinergic activity that results in seizures. Therefore this oxime platform has exceptional promise as therapy that could both prevent nerve agent-induced lethality and attenuate nerve agent-induced seizures. PMID:26705700

  2. A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

    PubMed Central

    Miller, Steven L.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Prager, Eric M.; Almeida-Suhett, Camila P.; Apland, James P.; Braga, Maria F.M.

    2015-01-01

    Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2XLD50), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. PMID:25689173

  3. Agent amplified communication

    SciTech Connect

    Kautz, H.; Selman, B.; Milewski, A.

    1996-12-31

    We propose an agent-based framework for assisting and simplifying person-to-person communication for information gathering tasks. As an example, we focus on locating experts for any specified topic. In our approach, the informal person-to-person networks that exist within an organization are used to {open_quotes}referral chain{close_quotes} requests for expertise. User-agents help automate this process. The agents generate referrals by analyzing records of e-mail communication patterns. Simulation results show that the higher responsiveness of an agent-based system can be effectively traded for the higher accuracy of a completely manual approach. Furthermore, preliminary experience with a group of users on a prototype system has shown that useful automatic referrals can be found in practice. Our experience with actual users has also shown that privacy concerns are central to the successful deployment of personal agents: an advanced agent-based system will therefore need to reason about issues involving trust and authority.

  4. LARGE SCALE PURIFICATION OF BUTYRYLCHOLINESTERASE FROM HUMAN PLASMA SUITABLE FOR INJECTION INTO MONKEYS; A POTENTIAL NEW THERAPEUTIC FOR PROTECTION AGAINST COCAINE AND NERVE AGENT TOXICITY

    PubMed Central

    Lockridge, Oksana; Schopfer, Lawrence M.; Winger, Gail; Woods, James H.

    2005-01-01

    Pretreatment of animals with butyrylcholinesterase (EC 3.1.1.8 BChE) provides complete protection from the acute effects of organophosphorus nerve agents. Butyrylcholinesterase has also been shown to protect from cocaine toxicity. Large amounts of highly purified butyrylcholinesterase are needed to test the effectiveness of this new therapeutic agent in monkeys. Only a minimum amount of endotoxin can be present in a therapeutic intended for injection into monkeys. Our goal was to develop a large scale purification method for human BChE from human plasma with precautions to minimize endotoxin content. A protocol was developed that processed up to 100 L of human plasma at a time. Dialysis in pH 4.0 buffer, ion exchange chromatography at pH 4, affinity chromatography on procainamide-Sepharose, and HPLC ion exchange at pH 7.4 yielded highly purified human BChE containing a low endotoxin level of about 800 EU/ml. The purified BChE produced by this method had a mean residence time of 56 h in mice and 93 h in monkeys, and caused no toxic effects. The absence of a toxic effect in monkeys demonstrates that the endotoxin level of 800 EU/ml was well tolerated by monkeys. PMID:16788731

  5. 'Dilute-and-shoot' RSLC-MS-MS method for fast detection of nerve and vesicant chemical warfare agent metabolites in urine.

    PubMed

    Rodin, Igor; Braun, Arcady; Stavrianidi, Andrey; Baygildiev, Timur; Shpigun, Oleg; Oreshkin, Dmitry; Rybalchenko, Igor

    2015-01-01

    A sensitive screening method based on fast liquid chromatography tandem mass-spectrometry (RSLC-MS-MS) has shown the feasibility of separation and detection of low concentration β-lyase metabolites of sulfur mustard and of nerve agent phosphonic acids in urine. The analysis of these compounds is of interest because they are specific metabolites of the chemical warfare agents (CWAs), sulfur mustard (HD), sarin (GB), soman (GD), VX and Russian VX (RVX). The 'dilute-and-shoot' RSLC-MS-MS method provides a sensitive and direct approach for determining CWA exposure in non-extracted non-derivatized samples from urine. Chromatographic separation of the metabolites was achieved using a reverse phase column with gradient mobile phases consisting of 0.5% formic acid in water and acetonitrile. Identification and quantification of species were achieved using electrospray ionization-tandem mass-spectrometry monitoring two precursor-to-product ion transitions for each compound. The method demonstrates linearity over at least two orders of magnitude and had detection limits of 0.5 ng/mL in urine. PMID:25326204

  6. Subchronic exposure to low-doses of the nerve agent VX: physiological, behavioral, histopathological and neurochemical studies.

    PubMed

    Bloch-Shilderman, Eugenia; Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

    2008-08-15

    The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 microg/kg/day, 0.05 LD(50)) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition (approximately 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction (approximately 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures. PMID:18485435

  7. Subchronic exposure to low-doses of the nerve agent VX: Physiological, behavioral, histopathological and neurochemical studies

    SciTech Connect

    Bloch-Shilderman, Eugenia Rabinovitz, Ishai; Egoz, Inbal; Raveh, Lily; Allon, Nahum; Grauer, Ettie; Gilat, Eran; Weissman, Ben Avi

    2008-08-15

    The highly toxic organophosphorous compound VX [O-ethyl-S-(isoporopylaminoethyl) methyl phosphonothiolate] undergoes an incomplete decontamination by conventional chemicals and thus evaporates from urban surfaces, e.g., pavement, long after the initial insult. As a consequence to these characteristics of VX, even the expected low levels should be examined for their potential to induce functional impairments including those associated with neuronal changes. In the present study, we developed an animal model for subchronic, low-dose VX exposure and evaluated its effects in rats. Animals were exposed to VX (2.25 {mu}g/kg/day, 0.05 LD{sub 50}) for three months via implanted mini osmotic pumps. The rapidly attained continuous and marked whole-blood cholinesterase inhibition ({approx} 60%), fully recovered 96 h post pump removal. Under these conditions, body weight, blood count and chemistry, water maze acquisition task, sensitivity to the muscarinic agonist oxotremorine, peripheral benzodiazepine receptors density and brain morphology as demonstrated by routine histopathology, remained unchanged. However, animals treated with VX showed abnormal initial response in an Open Field test and a reduction ({approx} 30%) in the expression of the exocytotic synaptobrevin/vesicle associate membrane protein (VAMP) in hippocampal neurons. These changes could not be detected one month following termination of exposure. Our findings indicate that following a subchronic, low-level exposure to the chemical warfare agent VX some important processes might be considerably impaired. Further research should be addressed towards better understanding of its potential health ramifications and in search of optimal countermeasures.

  8. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  9. MpcAgent

    SciTech Connect

    Nutaro, James

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of the building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.

  10. MpcAgent

    2013-11-29

    MpcAgent software is a module for the VolltronLite platform from PNNL that regulates the operation of rooftop air conditioning units in small to medium commercial buildings for the purpose of reducing peak power consumption. The MpcAgent accomplishes this by restricting the number of units that may operate simultaneously and using a model predictive control strategy to select which units to operate in each control period. The outcome of this control is effective control of themore » building air temperature at the user specified set point while avoiding expensive peak demand charges that result from running all HVAC units simultaneously.« less

  11. Gadofullerene MRI contrast agents.

    PubMed

    Bolskar, Robert D

    2008-04-01

    A promising new class of MRI contrast-enhancing agents with high relaxivities is based on gadolinium-containing metallofullerenes, which are also termed gadofullerenes. Detailed study of the water-proton relaxivity properties and intermolecular nanoclustering behavior of gadofullerene derivatives has revealed valuable information about their relaxivity mechanisms and given a deeper understanding of this new class of paramagnetic contrast agent. Here, the latest findings on water-solubilized gadofullerene materials and how these findings relate to their future applications in MRI are reviewed and discussed. PMID:18373426

  12. Agent Persuasion Mechanism of Acquaintance

    NASA Astrophysics Data System (ADS)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  13. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 107.1620 Section 107.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance...

  14. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 108.1620 Section 108.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA...

  15. Can Subscription Agents Survive?

    ERIC Educational Resources Information Center

    Tuttle, Marcia

    1985-01-01

    With the saturation of traditional markets for their services, subscription agents have evolved from orders and invoices to serving customers by communicating with librarians and publishers and making automated and paper products available. Magazine fulfillment centers, publisher discounts, and electronic publishing will influence the subscription…

  16. Remote Agent Experiment

    NASA Technical Reports Server (NTRS)

    Benard, Doug; Dorais, Gregory A.; Gamble, Ed; Kanefsky, Bob; Kurien, James; Millar, William; Muscettola, Nicola; Nayak, Pandu; Rouquette, Nicolas; Rajan, Kanna; Norvig, Peter (Technical Monitor)

    2000-01-01

    Remote Agent (RA) is a model-based, reusable artificial intelligence (At) software system that enables goal-based spacecraft commanding and robust fault recovery. RA was flight validated during an experiment on board of DS1 between May 17th and May 21th, 1999.

  17. E-Learning Agents

    ERIC Educational Resources Information Center

    Gregg, Dawn G.

    2007-01-01

    Purpose: The purpose of this paper is to illustrate the advantages of using intelligent agents to facilitate the location and customization of appropriate e-learning resources and to foster collaboration in e-learning environments. Design/methodology/approach: This paper proposes an e-learning environment that can be used to provide customized…

  18. Battlefield agent collaboration

    NASA Astrophysics Data System (ADS)

    Budulas, Peter P.; Young, Stuart H.; Emmerman, Philip J.

    2001-09-01

    Small air and ground physical agents (robots) will be ubiquitous on the battlefield of the 21st century, principally to lower the exposure to harm of our ground forces in urban and open terrain scenarios. Teams of small collaborating physical agents conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA), intelligence, chemical and biological agent detection, logistics, decoy, sentry; and communications relay will have advanced sensors, communications, and mobility characteristics. It is anticipated that there will be many levels of individual and team collaboration between the soldier and robot, robot to robot, and robot to mother ship. This paper presents applications and infrastructure components that illustrate each of these levels. As an example, consider the application where a team of twenty small robots must rapidly explore and define a building complex. Local interactions and decisions require peer to peer collaboration. Global direction and information fusion warrant a central team control provided by a mother ship. The mother ship must effectively deliver/retrieve, service, and control these robots as well as fuse the information gathered by these highly mobile robot teams. Any level of collaboration requires robust communications, specifically a mobile ad hoc network. The application of fixed ground sensors and mobile robots is also included in this paper. This paper discusses on going research at the U.S. Army Research Laboratory that supports the development of multi-robot collaboration. This research includes battlefield visualization, intelligent software agents, adaptive communications, sensor and information fusion, and multi-modal human computer interaction.

  19. Mobility control agent

    SciTech Connect

    Argabright, P.A.; Phillips, B.L.; Rhudy, J.S.

    1983-05-17

    Polymer mobility control agents useful in supplemental oil recovery processes, which give improved reciprocal relative mobilities, are prepared by initiating the polymerization of a monomer containing a vinyl group with a catalyst comprising a persulfate and ferrous ammonium sulfate. The vinyl monomer is an acrylyl, a vinyl cyanide, a styryl and water soluble salts thereof.

  20. A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists

    SciTech Connect

    Miller, Steven L.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Prager, Eric M.; Almeida-Suhett, Camila P.; Apland, James P.; and others

    2015-04-15

    Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD{sub 50} of 62 μg/kg. The onset of behaviorally-observed SE was accompanied by a dramatic decrease in brain AChE activity; rats who did not develop SE had significantly less reduction of AChE activity in the basolateral amygdala than rats who developed SE. Atropine sulfate (ATS) at 2 mg/kg, administered 20 min after soman exposure (1.2 × LD{sub 50}), terminated seizures. ATS at 0.5 mg/kg, given along with an oxime within 1 min after exposure, allowed testing of anticonvulsants at delayed time-points. The AMPA/GluK1 receptor antagonist LY293558, or the specific GluK1 antagonist UBP302, administered 1 h post-exposure, terminated SE. There were no degenerating neurons in soman-exposed P21 rats, but both the amygdala and the hippocampus were smaller than in control rats at 30 and 90 days post-exposure; this pathology was not present in rats treated with LY293558. Behavioral deficits present at 30 days post-exposure, were also prevented by LY293558 treatment. Thus, in immature animals, a single injection of atropine is sufficient to halt nerve agent-induced seizures, if administered timely. Testing anticonvulsants at delayed time-points requires early administration of ATS at a low dose, sufficient to counteract only peripheral toxicity. LY293558 administered 1 h post-exposure, prevents brain pathology and behavioral deficits. - Highlights: • The LD{sub 50} of soman was determined in postnatal-day-21 rats. • Rats with no seizures after 1.2XLD{sub 50} soman had less reduction of AChE in the amygdala. • Atropine sulfate (ATS) at 2 mg/kg, given at 20 min after

  1. Magnetic Electrochemical Sensing Platform for Biomonitoring of Exposure to Organophosphorus Pesticides and Nerve Agents Based on Simultaneous Measurement of Total Enzyme Amount and Enzyme Activity

    SciTech Connect

    Du, Dan; Wang, Jun; Wang, Limin; Lu, Donglai; Smith, Jordan N.; Timchalk, Charles; Lin, Yuehe

    2011-05-15

    We report a new approach for electrochemical quantification of enzymatic inhibition and phosphorylation for biomonitoring of exposure to organophosphorus (OP) pesticides and nerve agents based on a magnetic beads (MBs) immunosensing platform. The principle of this approach is based on the combination of MBs immuno-capture based enzyme activity assay and competitive immunoassay of total amount of enzyme for simultaneous detection of enzyme inhibition and phosphorylation in biological fluids. Butyrylcholinesterase (BChE) was chosen as a model enzyme. In competitive immunoassay, the target total BChE in a sample (mixture of OP-inhibited BChE and active BChE) competes with the BChE modified on the MBs to bind to the limited anti-BChE antibody labeled with quantum dots (QDs-anti-BChE), and followed by electrochemical stripping analysis of the bound QDs conjugate on the MBs. This assay shows a linear response over the total BChE concentration range of 0.1~20 nM. Simultaneously, real time BChE activity was measured on an electrochemical carbon nanotube-based sensor coupled with microflow injection system after immuno-capture by MBs-anti-BChE conjugate. Therefore, the formed phosphorylated adduct (OP-BChE) can be estimated by the difference values of the total amount BChE (including active and OP-inhibited) and active BChE from established calibration curves. This approach not only eliminates the difficulty in screening of low-dose OP exposure (less than 20% inhibition of BChE) because of individual variation of BChE values, but also avoids the drawback of the scarce availability of OP-BChE antibody. It is sensitive enough to detect 0.5 nM OP-BChE, which is less than 2% BChE inhibition. This method offers a new method for rapid, accurate, selective and inexpensive quantification of phosphorylated adducts and enzyme inhibition for biomonitoring of OP and nerve agent exposures.

  2. Characterization of chemical agent transport in paints.

    PubMed

    Willis, Matthew P; Gordon, Wesley; Lalain, Teri; Mantooth, Brent

    2013-09-15

    A combination of vacuum-based vapor emission measurements with a mass transport model was employed to determine the interaction of chemical warfare agents with various materials, including transport parameters of agents in paints. Accurate determination of mass transport parameters enables the simulation of the chemical agent distribution in a material for decontaminant performance modeling. The evaluation was performed with the chemical warfare agents bis(2-chloroethyl) sulfide (distilled mustard, known as the chemical warfare blister agent HD) and O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), an organophosphate nerve agent, deposited on to two different types of polyurethane paint coatings. The results demonstrated alignment between the experimentally measured vapor emission flux and the predicted vapor flux. Mass transport modeling demonstrated rapid transport of VX into the coatings; VX penetrated through the aliphatic polyurethane-based coating (100 μm) within approximately 107 min. By comparison, while HD was more soluble in the coatings, the penetration depth in the coatings was approximately 2× lower than VX. Applications of mass transport parameters include the ability to predict agent uptake, and subsequent long-term vapor emission or contact transfer where the agent could present exposure risks. Additionally, these parameters and model enable the ability to perform decontamination modeling to predict how decontaminants remove agent from these materials. PMID:23872337

  3. Biosensor for direct determination of organophosphate nerve agents using recombinant Escherichia coli with surface-expressed organophosphorus hydrolase. 1. Potentiometric microbial electrode.

    PubMed

    Mulchandani, A; Mulchandani, P; Kaneva, I; Chen, W

    1998-10-01

    A potentiometric microbial biosensor for the direct measurement of organophosphate (OP) nerve agents was developed by modifying a pH electrode with an immobilized layer of Escherichia coli cells expressing organophosphorus hydrolase (OPH) on the cell surface. OPH catalyzes the hydrolysis of organophosporus pesticides to release protons, the concentration of which is proportional to the amount of hydrolyzed substrate. The sensor signal and response time were optimized with respect to the buffer pH, ionic concentration of buffer, temperature, and weight of cells immobilized using paraoxon as substrate. The best sensitivity and response time were obtained using a sensor constructed with 2.5 mg of cells and operating in pH 8.5, 1 mM HEPES buffer. Using these conditions, the biosensor was used to measure as low as 2 microM of paraoxon, methyl parathion, and diazinon. The biosensor had very good storage and multiple use stability. The use of cells with the metabolic enzyme expressed on cell surface as a biological transducer provides advantages of no resistances to mass transport of the analyte and product across the cell membrane and low cost due to elimination of enzyme purification, over the conventional microbial biosensors based on cells expressing enzyme intracellularly and enzyme-based sensors, respectively. PMID:9784751

  4. Single vial sample preparation of markers of nerve agents by dispersive solid-phase extraction using magnetic strong anion exchange resins.

    PubMed

    Singh, Varoon; Chinthakindi, Sridhar; Purohit, Ajay Kumar; Pardasani, Deepak; Tak, Vijay; Dubey, Devendra Kumar

    2015-05-22

    A sample preparation method involving extraction, enrichment and derivatization of acidic degradation products of nerve agents was developed using magnetic strong anion exchange resins (MSAX). The method was performed in a single vial involving magnetic dispersive solid phase extraction (MDSPE). Analytes were derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) in the presence of resins. MSAX were custom synthesized using Fe3O4 nanoparticles as core, 4-vinylpyridine-co-divinylbenzene as polymer shell and quaternary pyridinium function as anion-exchanger. Hydroxide ions were the counter-anions of MSAX to effectively capture the acidic alkyl alkylphosphonic acids (AAPAs) and alkylphosphonic acids (APAs). Quantitative measurements of analytes were performed in the selected ion monitoring mode of GC-MS. Full scan mode of analysis was followed for identifications. Under the optimized conditions analytes were recovered in the range of 39.7-98.8% (n=3, relative standard deviations (RSD) from 0.3 to 6.5%). Limits of detection (LODs) were in the range of 0.1-1.1ngmL(-1); and the linear dynamic range was 5-1000ngmL(-1) with r(2) of 0.9977-0.9769. Applicability of the method was tested with rain-, tap-, muddy-water and Organization for Prohibition of Chemical Weapons (OPCW) Proficiency Test samples. PMID:25863924

  5. On-line solid phase extraction-liquid chromatography-mass spectrometry for trace determination of nerve agent degradation products in water samples.

    PubMed

    Røen, Bent T; Sellevåg, Stig R; Lundanes, Elsa

    2013-01-25

    Three primary nerve agent degradation products (ethyl-, isopropyl- and pinacolyl methylphosphonic acid) have been determined in water samples using on-line solid phase extraction-liquid chromatography and mass spectrometry (SPE-LC-MS) with electrospray ionisation. Porous graphitic carbon was employed for analyte enrichment followed by hydrophilic interaction chromatography. Diethylphosphate was applied as internal standard for quantitative determination of the alkyl methylphosphonic acids (AMPAs). By treating the samples with strong cation-exhange columns on Ba, Ag and H form, the major inorganic anions in water were removed by precipitation prior to the SPE-LC-MS determination. The AMPAs could be determined in tap water with limits of detection of 0.01-0.07 μg L(-1) with the [M-H](-) ions extracted at an accuracy of ±5 mDa. The within and between assay precisions at analyte concentrations of 5 μg L(-1) were 2-3%, and 5-9% relative standard deviation, respectively. The developed method was employed for determination of the AMPAs in three natural waters and a simulated waste water sample, spiked at 5 μg L(-1). Recoveries of ethyl-, isopropyl- and pinacolyl methylphosphonic acid were 80-91%, 92-103% and 99-106%, respectively, proving the applicability of the technique for natural waters of various origins. PMID:23312321

  6. Signature-Discovery Approach for Sample Matching of a Nerve-Agent Precursor using Liquid Chromatography–Mass Spectrometry, XCMS, and Chemometrics

    SciTech Connect

    Fraga, Carlos G.; Clowers, Brian H.; Moore, Ronald J.; Zink, Erika M.

    2010-05-15

    This report demonstrates the use of bioinformatic and chemometric tools on liquid chromatography mass spectrometry (LC-MS) data for the discovery of ultra-trace forensic signatures for sample matching of various stocks of the nerve-agent precursor known as methylphosphonic dichloride (dichlor). The use of the bioinformatic tool known as XCMS was used to comprehensively search and find candidate LC-MS peaks in a known set of dichlor samples. These candidate peaks were down selected to a group of 34 impurity peaks. Hierarchal cluster analysis and factor analysis demonstrated the potential of these 34 impurities peaks for matching samples based on their stock source. Only one pair of dichlor stocks was not differentiated from one another. An acceptable chemometric approach for sample matching was determined to be variance scaling and signal averaging of normalized duplicate impurity profiles prior to classification by k-nearest neighbors. Using this approach, a test set of dichlor samples were all correctly matched to their source stock. The sample preparation and LC-MS method permitted the detection of dichlor impurities presumably in the parts-per-trillion (w/w). The detection of a common impurity in all dichlor stocks that were synthesized over a 14-year period and by different manufacturers was an unexpected discovery. Our described signature-discovery approach should be useful in the development of a forensic capability to help in criminal investigations following chemical attacks.

  7. Distributed Agents for Autonomy

    NASA Astrophysics Data System (ADS)

    Blake, Rick; Amigoni, Francesco; Brambilla, Andrea; de la Rosa Steinz, Sonia; Lavagna, Michele; le Duc, Ian; Page, Jonathan; Page, Oliver; Steel, Robin; Wijnands, Quirien

    2010-08-01

    The Distributed Agents for Autonomy (DAFA) Study has been performed for ESA by SciSys UK Ltd, Vega GmbH and Politecnico di Milano. An analysis of past, present and future space missions has been conducted, structured around a set of three pre-defined mission scenarios: Formation Flying, Earth Observation and Planetary Exploration. This analysis led to the definition of a framework of use cases where the application of distributed autonomy seems necessary or appropriate, and a set of metrics that may be used to assess such deployments. Agent technology and architectures were extensively surveyed and the results used to elaborate each of the mission scenarios to the point where a software prototype could be constructed. Such a prototype was developed for a scenario based on the ExoMars mission and this has been used to highlight the advantages of a DAFA approach to the mission architecture.

  8. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  9. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  10. Surface polymerization agents

    SciTech Connect

    Taylor, C.; Wilkerson, C.

    1996-12-01

    This is the final report of a 1-year, Laboratory-Directed R&D project at LANL. A joint technical demonstration was proposed between US Army Missile Command (Redstone Arsenal) and LANL. Objective was to demonstrate that an unmanned vehicle or missile could be used as a platform to deliver a surface polymerization agent in such a manner as to obstruct the filters of an air-breathing mechanism, resulting in operational failure.

  11. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  12. Perioperative allergy: uncommon agents.

    PubMed

    Caimmi, S; Caimmi, D; Cardinale, F; Indinnimeo, L; Crisafulli, G; Peroni, D G; Marseglia, G L

    2011-01-01

    Anesthesia may often be considered as a high-risk procedure and anaphylaxis remains a major cause of concern for anesthetists who routinely administer many potentially allergenic agents. Neuromuscular blocking agents, latex and antibiotics are the substances involved in most of the reported reactions. Besides these three agents, a wide variety of substances may cause an anaphylactic reaction during anesthesia. Basically all the administered drugs or substances may be potential causes of anaphylaxis. Among them, those reported the most in literature include hypnotics, opioids, local anesthetics, colloids, dye, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Iodinated Contrast Media (ICM), antiseptics, aprotinin, ethylene oxyde and formaldehyde, and protamine and heparins. No premedication can effectively prevent an allergic reaction and a systematic preoperative screening is not justified for all patients; nevertheless, an allergy specialist should evaluate those patients with a history of anesthesia-related allergy. Patients must be fully informed of investigation results, and advised to provide a detailed report prior to future anesthesia. PMID:22014927

  13. 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. PMID:12704086

  14. Liposome encapsulation of chelating agents

    DOEpatents

    Rahman, Yueh Erh

    1976-01-13

    A method for transferring a chelating agent across a cellular membrane by encapsulating the charged chelating agent within liposomes and carrying the liposome-encapsulated chelating agent to the cellular membrane where the liposomes containing the chelating agent will be taken up by the cells, thereby transferring the chelating agent across the cellular membrane. A chelating agent can be introduced into the interior of a cell of a living organism wherein the liposomes will be decomposed, releasing the chelating agent to the interior of the cell. The released chelating agent will complex intracellularly deposited toxic heavy metals, permitting the more soluble metal complex to transfer across the cellular membrane from the cell and subsequently be removed from the living organism.

  15. Hydroxypyridonate and hydroxypyrimidinone chelating agents

    SciTech Connect

    Raymond, Kenneth N.; Doble, Daniel M.; Sunderland, Christopher J.; Thompson, Marlon

    2005-01-25

    The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

  16. Collaborating with Autonomous Agents

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Cross, Charles D.; Fan, Henry; Hempley, Lucas E.; Motter, Mark A.; Neilan, James H.; Qualls, Garry D.; Rothhaar, Paul M.; Tran, Loc D.; Allen, B. Danette

    2015-01-01

    With the anticipated increase of small unmanned aircraft systems (sUAS) entering into the National Airspace System, it is highly likely that vehicle operators will be teaming with fleets of small autonomous vehicles. The small vehicles may consist of sUAS, which are 55 pounds or less that typically will y at altitudes 400 feet and below, and small ground vehicles typically operating in buildings or defined small campuses. Typically, the vehicle operators are not concerned with manual control of the vehicle; instead they are concerned with the overall mission. In order for this vision of high-level mission operators working with fleets of vehicles to come to fruition, many human factors related challenges must be investigated and solved. First, the interface between the human operator and the autonomous agent must be at a level that the operator needs and the agents can understand. This paper details the natural language human factors e orts that NASA Langley's Autonomy Incubator is focusing on. In particular these e orts focus on allowing the operator to interact with the system using speech and gestures rather than a mouse and keyboard. With this ability of the system to understand both speech and gestures, operators not familiar with the vehicle dynamics will be able to easily plan, initiate, and change missions using a language familiar to them rather than having to learn and converse in the vehicle's language. This will foster better teaming between the operator and the autonomous agent which will help lower workload, increase situation awareness, and improve performance of the system as a whole.

  17. Chemical warfare agents.

    PubMed

    Ganesan, K; Raza, S K; Vijayaraghavan, R

    2010-07-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  18. Pharmacologic agents targeting autophagy

    PubMed Central

    Vakifahmetoglu-Norberg, Helin; Xia, Hong-guang; Yuan, Junying

    2015-01-01

    Autophagy is an important intracellular catabolic mechanism critically involved in regulating tissue homeostasis. The implication of autophagy in human diseases and the need to understand its regulatory mechanisms in mammalian cells have stimulated research efforts that led to the development of high-throughput screening protocols and small-molecule modulators that can activate or inhibit autophagy. Herein we review the current landscape in the development of screening technology as well as the molecules and pharmacologic agents targeting the regulatory mechanisms of autophagy. We also evaluate the potential therapeutic application of these compounds in different human pathologies. PMID:25654545

  19. Chemical warfare agents

    PubMed Central

    Ganesan, K.; Raza, S. K.; Vijayaraghavan, R.

    2010-01-01

    Among the Weapons of Mass Destruction, chemical warfare (CW) is probably one of the most brutal created by mankind in comparison with biological and nuclear warfare. Chemical weapons are inexpensive and are relatively easy to produce, even by small terrorist groups, to create mass casualties with small quantities. The characteristics of various CW agents, general information relevant to current physical as well as medical protection methods, detection equipment available and decontamination techniques are discussed in this review article. A brief note on Chemical Weapons Convention is also provided. PMID:21829312

  20. Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

    PubMed

    Pittman, Sherry K; Gracias, Neilia G; Fehrenbacher, Jill C

    2016-05-01

    Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. PMID:26883566

  1. A liquid chromatography tandem mass spectrometric method on in vitro nerve agents poisoning characterization and reactivator efficacy evaluation by determination of specific peptide adducts in acetylcholinesterase.

    PubMed

    Yan, Long; Chen, Jia; Xu, Bin; Guo, Lei; Xie, Yan; Tang, Jijun; Xie, Jianwei

    2016-06-10

    The terroristic availability of highly toxic nerve agents (NAs) highlights the necessity for a deep understanding of their toxicities and effective medical treatments. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for a characterization of the NAs poisoning and an evaluation on the efficacy of reactivators in in vitro was developed for the first time. After exposure to sarin or VX and pepsin digestion, the specific peptides of acetylcholinesterase (AChE) in a purified status, i.e. undecapeptide "GESAGAASVGM" in free, unaged, or aged status was identified and quantified. A key termination procedure is focused to make the reaction system "frozen" and precisely "capture" the poisoning, aging and spontaneous reactivation status of AChE, and the abundance of such specific peptides can thus be simultaneously measured. In our established method, as low as 0.72% and 0.84% inhibition level of AChE induced by 0.5nM sarin and VX can be detected from the measurement of peptide adducts, which benefits a confirmation of NAs exposure, especially at extremely low levels. Comparing with conventional colorimetric Ellman assays, our method provides not only enzyme activity and inhibition rate, but also the precise poisoning status of NAs exposed AChE. Based on the full information provided by this method, the efficacy of reactivators, such as HI-6, obidoxime and pralidoxime, in the typical treatment of NAs poisoned AChE in in vitro was further evaluated. Our results showed that this method is a promising tool for the characterization of NAs poisoning and the evaluation of reactivator efficacy. PMID:27179675

  2. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    SciTech Connect

    Chen, Aiqiong; Du, Dan; Lin, Yuehe

    2012-02-09

    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  3. Effectiveness and reaction networks of H2O2 vapor with NH3 gas for decontamination of the toxic warfare nerve agent, VX on a solid surface.

    PubMed

    Gon Ryu, Sam; Wan Lee, Hae

    2015-01-01

    The nerve agent, O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) must be promptly eliminated following its release into the environment because it is extremely toxic, can cause death within a few minutes after exposure, acts through direct skin contact as well as inhalation, and persists in the environment for several weeks after release. A mixture of hydrogen peroxide vapor and ammonia gas was examined as a decontaminant for the removal of VX on solid surfaces at ambient temperature, and the reaction products were analyzed by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectrometry (NMR). All the VX on glass wool filter disks was found to be eliminated after 2 h of exposure to the decontaminant mixtures, and the primary decomposition product was determined to be non-toxic ethyl methylphosphonic acid (EMPA); no toxic S-[2-(diisopropylamino)ethyl] methylphosphonothioic acid (EA-2192), which is usually produced in traditional basic hydrolysis systems, was found to be formed. However, other by-products, such as toxic O-ethyl S-vinyl methylphosphonothioate and (2-diisopropylaminoethyl) vinyl disulfide, were detected up to 150 min of exposure to the decontaminant mixture; these by-products disappeared after 3 h. The two detected vinyl byproducts were identified first in this study with the decontamination system of liquid VX on solid surfaces using a mixture of hydrogen peroxide vapor and ammonia gas. The detailed decontamination reaction networks of VX on solid surfaces produced by the mixture of hydrogen peroxide vapor and ammonia gas were suggested based on the reaction products. These findings suggest that the mixture of hydrogen peroxide vapor and ammonia gas investigated in this study is an efficient decontaminant mixture for the removal of VX on solid surfaces at ambient temperature despite the formation of a toxic by-product in the reaction process. PMID:26327407

  4. Evaluation of acetylcholine, seizure activity and neuropathology following high-dose nerve agent exposure and delayed neuroprotective treatment drugs in freely moving rats.

    PubMed

    Acon-Chen, Cindy; Koenig, Jeffrey A; Smith, Garrett R; Truitt, Amber R; Thomas, Thaddeus P; Shih, Tsung-Ming

    2016-06-01

    Organophosphorus nerve agents such as soman (GD) inhibit acetylcholinesterase, producing an excess of acetylcholine (ACh), which results in respiratory distress, convulsions and status epilepticus that leads to neuropathology. Several drugs (topiramate, clobazam, pregnanolone, allopregnanolone, UBP 302, cyclopentyladenosine [CPA], ketamine, midazolam and scopolamine) have been identified as potential neuroprotectants that may terminate seizures and reduce brain damage. To systematically evaluate their efficacy, this study employed in vivo striatal microdialysis and liquid chromatography to respectively collect and analyze extracellular ACh in freely moving rats treated with these drugs 20 min after seizure onset induced by a high dose of GD. Along with microdialysis, EEG activity was recorded and neuropathology assessed at 24 h. GD induced a marked increase of ACh, which peaked at 30 min post-exposure to 800% of control levels and then steadily decreased toward baseline levels. Approximately 40 min after treatment, only midazolam (10 mg/kg) and CPA (60 mg/kg) caused a significant reduction of ACh levels, with CPA reducing ACh levels more rapidly than midazolam. Both drugs facilitated a return to baseline levels at least 55 min after treatment. At 24 h, only animals treated with CPA (67%), midazolam (18%) and scopolamine (27%) exhibited seizure termination. While all treatments except for topiramate reduced neuropathology, CPA, midazolam and scopolamine showed the greatest reduction in pathology. Our results suggest that delayed treatment with CPA, midazolam, or scopolamine is effective at reducing GD-induced seizure activity and neuropathology, with CPA and midazolam capable of facilitating a reduction in GD-induced ACh elevation. PMID:27329284

  5. Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig.

    PubMed

    Snider, Thomas H; Babin, Michael C; Jett, David A; Platoff, Gennady E; Yeung, David T

    2016-01-01

    Anticholinesterases, such as organophosphorus pesticides and warfare nerve agents, present a significant health threat. Onset of symptoms after exposure can be rapid, requiring quick-acting, efficacious therapy to mitigate the effects. The goal of the current study was to identify the safest antidote with the highest therapeutic index (TI = oxime 24-hr LD50/oxime ED50) from a panel of four oximes deemed most efficacious in a previous study. The oximes tested were pralidoxime chloride (2-PAM Cl), MMB4 DMS, HLö-7 DMS, and obidoxime Cl2. The 24-hr median lethal dose (LD50) for the four by intramuscular (IM) injection and the median effective dose (ED50) were determined. In the ED50 study, male guinea pigs clipped of hair received 2x LD50 topical challenges of undiluted Russian VX (VR), VX, or phorate oxon (PHO) and, at the onset of cholinergic signs, IM therapy of atropine (0.4 mg/kg) and varying levels of oxime. Survival was assessed at 3 hr after onset clinical signs. The 3-hr 90th percentile dose (ED90) for each oxime was compared to the guinea pig pre-hospital human-equivalent dose of 2-PAM Cl, 149 µmol/kg. The TI was calculated for each OP/oxime combination. Against VR, MMB4 DMS had a higher TI than HLö-7 DMS, whereas 2-PAM Cl and obidoxime Cl2 were ineffective. Against VX, MMB4 DMS > HLö-7 DMS > 2-PAM Cl > obidoxime Cl2. Against PHO, all performed better than 2-PAM Cl. MMB4 DMS was the most effective oxime as it was the only oxime with ED90 < 149 µmol/kg against all three topical OPs tested. PMID:27432237

  6. Effectiveness of Donepezil, Rivastigmine, and (±)Huperzine A in Counteracting the Acute Toxicity of Organophosphorus Nerve Agents: Comparison with Galantamine

    PubMed Central

    Aracava, Yasco; Pereira, Edna F. R.; Akkerman, Miriam; Adler, Michael

    2009-01-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (±)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 × LD50 soman (42 μg/kg s.c.). All animals that were pretreated with galantamine (6–8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (±)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 × LD50 soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 × LD50 soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 × LD50 soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman. PMID:19741148

  7. Comparison of 2-PAM and pro-2-PAM containing treatment regimens as antagonists of nerve agent-induced lethality and incapacitation. Final report, June 1981-December 1985

    SciTech Connect

    Talbot, B.G.; Harris, L.W.; Lennox, W.J.; Anderson, D.A.; Green, M.D.

    1986-09-01

    In vivo, (2-Puridine Aldoxine Methioidide) reactivates phosphonylated acetylcholinesterase AChE peripherally, but is effective in restoring AChE centrally because the quaternary nitrogen atom of 2-PAM prevents penetration of the brain. The problem was solved by the synthesis of the 1,6-dihyropyridine derivative of 2-PAM, pro-2-PAM (PP). Functional brain AChE is related to return to control performance on an accelerating rotarod (ARR) in animals intoxicated with soman. There should be a difference in the time to recovery of control ARR performance between PP- and 2-PAM-treated, sarin-intoxicated animals. In the present work, an ARR decrement free dosage (DFD) of each of these oximes (30 mg/kg, im) in combination with DFD of atropine (A) and mecamylamine (M) (0.79 mg/kg each, im) was used as pretreatment against sarin-induced deficit. The same antidotes were given pre-and post- intoxication (as pretreatment and therapy) to anatagonize sarin-induced lethality; the PP containing antidote provided significantly greater protection than that by the 2-PAM antidote which in turn provided significant protection over control. Neither antidote when given as pretreatment and therapy provided protection above control against soman-induced physical incapacitation, but they were equally effective in antagonizing VX-induced physical incapacitation. The reversal of sarin-induced physical debilitation reflects the central actions of PP and supports the notion that functional brain AChE activity is essential for rapid recovery from the debilitating effeclts on nerve agents.

  8. Application of gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry to the analysis of chemical warfare samples, found to contain residues of the nerve agent sarin, sulphur mustard and their degradation products.

    PubMed

    Black, R M; Clarke, R J; Read, R W; Reid, M T

    1994-02-25

    Samples of clothing, grave debris, soil and munition fragments, collected from the Kurdish village of Birjinni, were analysed by GC-MS with selected ion monitoring (SIM) for traces of chemical warfare agents and their degradation products. Positive analyses were confirmed, where possible, by full scan mass spectra, or at low concentrations by additional GC-MS-SIM analysis using chemical ionisation, by higher resolution GC-MS-SIM, and by GC-tandem mass spectrometry using multiple reaction monitoring. Sulphur mustard and/or thiodiglycol were detected in six soil samples; isopropyl methylphosphonic acid and methylphosphonic acid, the hydrolysis products of the nerve agent sarin, were detected in six different soil samples. Trace amounts of intact sarin were detected on a painted metal fragment associated with one of these soil samples. The results demonstrate the application of different GC-MS and GC-MS-MS techniques to the unequivocal identification of chemical warfare agent residues in the environment at concentrations ranging from low ppb to ppm (w/w). They also provide the first documented unequivocal identification of nerve agent residues in environmental samples collected after a chemical attack. PMID:8143028

  9. Cleaning agents and asthma.

    PubMed

    Quirce, S; Barranco, P

    2010-01-01

    Although cleaners represent a significant part of the working population worldwide, they remain a relatively understudied occupational group. Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. Cleaning workers are exposed to a large variety of cleaning products containing both irritants and sensitizers, as well as to common indoor allergens and pollutants. Thus, the onset or aggravation of asthma in this group could be related to an irritant-induced mechanism or to specific sensitization. The main sensitizers contained in cleaning products are disinfectants, quaternary ammonium compounds (such as benzalkonium chloride), amine compounds, and fragrances.The strongest airway irritants in cleaning products are bleach (sodium hypochlorite), hydrochloric acid, and alkaline agents (ammonia and sodium hydroxide), which are commonly mixed together. Exposure to the ingredients of cleaning products may give rise to both new-onset asthma, with or without a latency period, and work-exacerbated asthma. High-level exposure to irritants may induce reactive airways dysfunction syndrome. Cleaning workers may also have a greater relative risk of developing asthma due to prolonged low-to-moderate exposure to respiratory irritants. In addition, asthma-like symptoms without confirmed asthma are also common after exposure to cleaning agents. In many cleaners, airway symptoms induced by chemicals and odors cannot be explained by allergic or asthmatic reactions. These patients may have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity, and this condition is termed airway sensory hyperreactivity. PMID:21313993

  10. [New agents for hypercholesterolemia].

    PubMed

    Pintó, Xavier; García Gómez, María Carmen

    2016-02-19

    An elevated proportion of high cardiovascular risk patients do not achieve the therapeutic c-LDL goals. This owes to physicians' inappropriate or insufficient use of cholesterol lowering medications or to patients' bad tolerance or therapeutic compliance. Another cause is an insufficient efficacy of current cholesterol lowering drugs including statins and ezetimibe. In addition, proprotein convertase subtilisin kexin type 9 inhibitors are a new cholesterol lowering medications showing safety and high efficacy to reduce c-LDL in numerous already performed or underway clinical trials, potentially allowing an optimal control of hypercholesterolemia in most patients. Agents inhibiting apolipoprotein B synthesis and microsomal transfer protein are also providing a new potential to decrease cholesterol in patients with severe hypercholesterolemia and in particular in homozygote familial hypercholesterolemia. Last, cholesteryl ester transfer protein inhibitors have shown powerful effects on c-HDL and c-LDL, although their efficacy in cardiovascular prevention and safety has not been demonstrated yet. We provide in this article an overview of the main characteristics of therapeutic agents for hypercholesterolemia, which have been recently approved or in an advanced research stage. PMID:25817449

  11. Holograms as Teaching Agents

    NASA Astrophysics Data System (ADS)

    Walker, Robin A.

    2013-02-01

    Hungarian physicist Dennis Gabor won the Pulitzer Prize for his 1947 introduction of basic holographic principles, but it was not until the invention of the laser in 1960 that research scientists, physicians, technologists and the general public began to seriously consider the interdisciplinary potentiality of holography. Questions around whether and when Three-Dimensional (3-D) images and systems would impact American entertainment and the arts would be answered before educators, instructional designers and students would discover how much Three-Dimensional Hologram Technology (3DHT) would affect teaching practices and learning environments. In the following International Symposium on Display Holograms (ISDH) poster presentation, the author features a traditional board game as well as a reflection hologram to illustrate conventional and evolving Three-Dimensional representations and technology for education. Using elements from the American children's toy Operation® (Hasbro, 2005) as well as a reflection hologram of a human brain (Ko, 1998), this poster design highlights the pedagogical effects of 3-D images, games and systems on learning science. As teaching agents, holograms can be considered substitutes for real objects, (human beings, organs, and animated characters) as well as agents (pedagogical, avatars, reflective) in various learning environments using many systems (direct, emergent, augmented reality) and electronic tools (cellphones, computers, tablets, television). In order to understand the particular importance of utilizing holography in school, clinical and public settings, the author identifies advantages and benefits of using 3-D images and technology as instructional tools.

  12. Learning models of intelligent agents

    SciTech Connect

    Carmel, D.; Markovitch, S.

    1996-12-31

    Agents that operate in a multi-agent system need an efficient strategy to handle their encounters with other agents involved. Searching for an optimal interactive strategy is a hard problem because it depends mostly on the behavior of the others. In this work, interaction among agents is represented as a repeated two-player game, where the agents` objective is to look for a strategy that maximizes their expected sum of rewards in the game. We assume that agents` strategies can be modeled as finite automata. A model-based approach is presented as a possible method for learning an effective interactive strategy. First, we describe how an agent should find an optimal strategy against a given model. Second, we present an unsupervised algorithm that infers a model of the opponent`s automaton from its input/output behavior. A set of experiments that show the potential merit of the algorithm is reported as well.

  13. Flexible, secure agent development framework

    DOEpatents

    Goldsmith; Steven Y.

    2009-04-07

    While an agent generator is generating an intelligent agent, it can also evaluate the data processing platform on which it is executing, in order to assess a risk factor associated with operation of the agent generator on the data processing platform. The agent generator can retrieve from a location external to the data processing platform an open site that is configurable by the user, and load the open site into an agent substrate, thereby creating a development agent with code development capabilities. While an intelligent agent is executing a functional program on a data processing platform, it can also evaluate the data processing platform to assess a risk factor associated with performing the data processing function on the data processing platform.

  14. New antifungal agents.

    PubMed

    Gupta, Aditya K; Tomas, Elizabeth

    2003-07-01

    Currently, use of standard antifungal therapies can be limited because of toxicity, low efficacy rates, and drug resistance. New formulations are being prepared to improve absorption and efficacy of some of these standard therapies. Various new antifungals have demonstrated therapeutic potential. These new agents may provide additional options for the treatment of superficial fungal infections and they may help to overcome the limitations of current treatments. Liposomal formulations of AmB have a broad spectrum of activity against invasive fungi, such as Candida spp., C. neoformans, and Aspergillus spp., but not dermatophyte fungi. The liposomal AmB is associated with significantly less toxicity and good rates of efficacy, which compare or exceed that of standard AmB. These factors may provide enough of an advantage to patients to overcome the increased costs of these formulations. Three new azole drugs have been developed, and may be of use in both systemic and superficial fungal infections. Voriconazole, ravuconazole, and posaconazole are triazoles, with broad-spectrum activity. Voriconazole has a high bioavailability, and has been used with success in immunocompromised patients with invasive fungal infections. Ravuconazole has shown efficacy in candidiasis in immunocompromised patients, and onychomycosis in healthy patients. Preliminary in vivo studies with posaconazole indicated potential use in a variety of invasive fungal infections including oropharyngeal candidiasis. Echinocandins and pneumocandins are a new class of antifungals, which act as fungal cell wall beta-(1,3)-D-glucan synthase enzyme complex inhibitors. Caspofungin (MK-0991) is the first of the echinocandins to receive Food and Drug Administration approval for patients with invasive aspergillosis not responding or intolerant to other antifungal therapies, and has been effective in patients with oropharyngeal and esophageal candidiasis. Standardization of MIC value determination has improved the

  15. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  16. Hepatocytes as Immunological Agents.

    PubMed

    Crispe, Ian N

    2016-01-01

    Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314

  17. Agent Assignment for Process Management: Pattern Based Agent Performance Evaluation

    NASA Astrophysics Data System (ADS)

    Jablonski, Stefan; Talib, Ramzan

    In almost all workflow management system the role concept is determined once at the introduction of workflow application and is not reevaluated to observe how successfully certain processes are performed by the authorized agents. This paper describes an approach which evaluates how agents are working successfully and feed this information back for future agent assignment to achieve maximum business benefit for the enterprise. The approach is called Pattern based Agent Performance Evaluation (PAPE) and is based on machine learning technique combined with post processing technique. We report on the result of our experiments and discuss issues and improvement of our approach.

  18. Agent-based enterprise integration

    SciTech Connect

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  19. Collaborating Fuzzy Reinforcement Learning Agents

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.

    1997-01-01

    Earlier, we introduced GARIC-Q, a new method for doing incremental Dynamic Programming using a society of intelligent agents which are controlled at the top level by Fuzzy Relearning and at the local level, each agent learns and operates based on ANTARCTIC, a technique for fuzzy reinforcement learning. In this paper, we show that it is possible for these agents to compete in order to affect the selected control policy but at the same time, they can collaborate while investigating the state space. In this model, the evaluator or the critic learns by observing all the agents behaviors but the control policy changes only based on the behavior of the winning agent also known as the super agent.

  20. Biosensor for direct determination of organophosphate nerve agents using recombinant Escherichia coli with surface-expressed organophosphorus hydrolase. 2. Fiber-optic microbial biosensor.

    PubMed

    Mulchandani, A; Kaneva, I; Chen, W

    1998-12-01

    A fiber-optic microbial biosensor suitable for direct measurement of organophosphate nerve agents was developed. The unique features of this novel microbial biosensor were the recombinant Escherichia coli cells expressing the enzyme organophosphorus hydrolase on the cell surface and the optical detection of the products of enzyme-catalyzed organophosphate hydrolysis. The use of cells with the metabolic enzyme expressed on the cell surface as a biological sensing element provides advantages of no resistance to mass transport of the analyte and product across the cell membrane and low cost due to elimination of enzyme purification, over the conventional microbial biosensors based on cells expressing enzyme intracellularly and enzyme-based sensors, respectively. The use of an optical transducer allows the detection of different organophosphates in a mixture, presently not feasible with acetylcholinesterase-based biosensors. E. coli cells expressing organophosphorus hydrolase (OPH) on the cell surface were immobilized in low melting temperature agarose on a nylon membrane and attached to the common end of a bifurcated fiber-optic bundle. OPH-expressing E. coli cells catalyzed the hydrolysis of organophosphorus pesticides to form stoichiometric amounts of chromophoric products that absorb light at specific wavelengths. The backscattered radiation of the specific wavelength incident light was measured using a photomultiplier detector and correlated to the organophosphate concentration. The best sensitivity and response time were obtained using a sensor constructed with 1.5 mg of cells operating in pH 9, 50 mM HEPES buffer with 100 mM NaCl and 0.05 mM CoCl2 at 30 degrees C. At optimized conditions, the biosensor measured paraoxon, parathion, and coumaphos pesticides with high selectivity against triazine and carbamate pesticides in approximately 10 min. The lower detection limits were 3 microM for paraoxon and parathion and 5 microM for coumaphos. When stored in the

  1. New agents for prostate cancer.

    PubMed

    Agarwal, N; Di Lorenzo, G; Sonpavde, G; Bellmunt, J

    2014-09-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid

  2. Broad-spectrum antiviral agents

    PubMed Central

    Zhu, Jun-Da; Meng, Wen; Wang, Xiao-Jia; Wang, Hwa-Chain R.

    2015-01-01

    Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents. PMID:26052325

  3. The Agent of Change: The Agent of Conflict.

    ERIC Educational Resources Information Center

    Hatfield, C. R., Jr.

    This speech examines the role of change agents in third world societies and indicates that the change agent must, to some extent, manipulate the social situation, even if his view of society is a more optimistic one than he finds in reality. If he considers strains and stresses to be the lubricants of change, then his focus on conflict as a…

  4. Incorporating BDI Agents into Human-Agent Decision Making Research

    NASA Astrophysics Data System (ADS)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  5. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  6. TACtic- A Multi Behavioral Agent for Trading Agent Competition

    NASA Astrophysics Data System (ADS)

    Khosravi, Hassan; Shiri, Mohammad E.; Khosravi, Hamid; Iranmanesh, Ehsan; Davoodi, Alireza

    Software agents are increasingly being used to represent humans in online auctions. Such agents have the advantages of being able to systematically monitor a wide variety of auctions and then make rapid decisions about what bids to place in what auctions. They can do this continuously and repetitively without losing concentration. To provide a means of evaluating and comparing (benchmarking) research methods in this area the trading agent competition (TAC) was established. This paper describes the design, of TACtic. Our agent uses multi behavioral techniques at the heart of its decision making to make bidding decisions in the face of uncertainty, to make predictions about the likely outcomes of auctions, and to alter the agent's bidding strategy in response to the prevailing market conditions.

  7. Gelled Anti-icing Agents

    NASA Technical Reports Server (NTRS)

    Markles, O. F.; Sperber, H. H.

    1983-01-01

    Pectin added to antifreeze/water mixture. Formulations include water with dimethyl sulfoxide (DMSO) as deicer and pectin as gel former. Without gelling agent, deicer runs off vertical surfaces. Without pectin solution will completely evaporate in far less time. Agents developed have wide potential for ice prevention on runways, highways, bridges and sidewalks.

  8. Agent-Based Literacy Theory

    ERIC Educational Resources Information Center

    McEneaney, John E.

    2006-01-01

    The purpose of this theoretical essay is to explore the limits of traditional conceptualizations of reader and text and to propose a more general theory based on the concept of a literacy agent. The proposed theoretical perspective subsumes concepts from traditional theory and aims to account for literacy online. The agent-based literacy theory…

  9. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs. PMID:18991707

  10. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  11. Markov Tracking for Agent Coordination

    NASA Technical Reports Server (NTRS)

    Washington, Richard; Lau, Sonie (Technical Monitor)

    1998-01-01

    Partially observable Markov decision processes (POMDPs) axe an attractive representation for representing agent behavior, since they capture uncertainty in both the agent's state and its actions. However, finding an optimal policy for POMDPs in general is computationally difficult. In this paper we present Markov Tracking, a restricted problem of coordinating actions with an agent or process represented as a POMDP Because the actions coordinate with the agent rather than influence its behavior, the optimal solution to this problem can be computed locally and quickly. We also demonstrate the use of the technique on sequential POMDPs, which can be used to model a behavior that follows a linear, acyclic trajectory through a series of states. By imposing a "windowing" restriction that restricts the number of possible alternatives considered at any moment to a fixed size, a coordinating action can be calculated in constant time, making this amenable to coordination with complex agents.

  12. Probing the role of P dbnd O stretching mode enhancement in nerve-agent sensors: Simulation of the adsorption of diisopropylfluorophosphate on the model MgO and CaO surfaces

    NASA Astrophysics Data System (ADS)

    Kolodziejczyk, Wojciech; Majumdar, D.; Roszak, Szczepan; Leszczynski, Jerzy

    2007-12-01

    The interactions of diisopropylfluorophosphate (DFP) with model MgO and CaO surfaces have been investigated using density functional (DFT) and Møller-Plesset second order perturbation techniques. The geometries were fully optimized at the DFT level. The calculated interaction energies and the corresponding thermodynamic properties show that DFP is physisorbed on these two model oxide surfaces and adsorption on the MgO surface is stronger. Analyses of the calculated IR and Raman spectra point to the enhancement of the P dbnd O stretching mode with respect to the isolated DFP and this property could be used to detect nerve-agents using surface-enhanced Raman spectroscopy.

  13. [Decontamination of chemical and biological warfare agents].

    PubMed

    Seto, Yasuo

    2009-01-01

    Chemical and biological warfare agents (CBWA's) are diverse in nature; volatile acute low-molecular-weight toxic compounds, chemical warfare agents (CWA's, gaseous choking and blood agents, volatile nerve gases and blister agents, nonvolatile vomit agents and lacrymators), biological toxins (nonvolatile low-molecular-weight toxins, proteinous toxins) and microbes (bacteria, viruses, rickettsiae). In the consequence management against chemical and biological terrorism, speedy decontamination of victims, facilities and equipment is required for the minimization of the damage. In the present situation, washing victims and contaminated materials with large volumes of water is the basic way, and additionally hypochlorite salt solution is used for decomposition of CWA's. However, it still remains unsolved how to dispose large volumes of waste water, and the decontamination reagents have serious limitation of high toxicity, despoiling nature against the environments, long finishing time and non-durability in effective decontamination. Namely, the existing decontamination system is not effective, nonspecifically affecting the surrounding non-target materials. Therefore, it is the urgent matter to build up the usable decontamination system surpassing the present technologies. The symposiast presents the on-going joint project of research and development of the novel decontamination system against CBWA's, in the purpose of realizing nontoxic, fast, specific, effective and economical terrorism on-site decontamination. The projects consists of (1) establishment of the decontamination evaluation methods and verification of the existing technologies and adaptation of bacterial organophosphorus hydrolase, (2) development of adsorptive elimination technologies using molecular recognition tools, and (4) development of deactivation technologies using photocatalysis. PMID:19122437

  14. Knowledge focus via software agents

    NASA Astrophysics Data System (ADS)

    Henager, Donald E.

    2001-09-01

    The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be

  15. 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. PMID:17705326

  16. Agent Communications using Distributed Metaobjects

    SciTech Connect

    Goldsmith, Steven Y.; Spires, Shannon V.

    1999-06-10

    There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementation up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.

  17. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, Paul H.; Brainard, James R.; Jarvinen, Gordon D.; Ryan, Robert R.

    1997-01-01

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC.sub.16 H.sub.14 N.sub.6. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques.

  18. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, P.H.; Brainard, J.R.; Jarvinen, G.D.; Ryan, R.R.

    1997-12-30

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC{sub 16}H{sub 14}N{sub 6}. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques. 10 figs.

  19. Specific Adhesion to Cellulose and Hydrolysis of Organophosphate Nerve Agents by a Genetically Engineered Escherichia coli Strain with a Surface-Expressed Cellulose-Binding Domain and Organophosphorus Hydrolase

    PubMed Central

    Wang, Aijun A.; Mulchandani, Ashok; Chen, Wilfred

    2002-01-01

    A genetically engineered Escherichia coli cell expressing both organophosphorus hydrolase (OPH) and a cellulose-binding domain (CBD) on the cell surface was constructed, enabling the simultaneous hydrolysis of organophosphate nerve agents and immobilization via specific adsorption to cellulose. OPH was displayed on the cell surface by use of the truncated ice nucleation protein (INPNC) fusion system, while the CBD was surface anchored by the Lpp-OmpA fusion system. Production of both INPNC-OPH and Lpp-OmpA-CBD fusion proteins was verified by immunoblotting, and the surface localization of OPH and the CBD was confirmed by immunofluorescence microscopy. Whole-cell immobilization with the surface-anchored CBD was very specific, forming essentially a monolayer of cells on different supports, as shown by electron micrographs. Optimal levels of OPH activity and binding affinity to cellulose supports were achieved by investigating expression under different induction levels. Immobilized cells degraded paraoxon rapidly at an initial rate of 0.65 mM/min/g of cells (dry weight) and retained almost 100% efficiency over a period of 45 days. Owing to its superior degradation capacity and affinity to cellulose, this immobilized-cell system should be an attractive alternative for large-scale detoxification of organophosphate nerve agents. PMID:11916685

  20. Introducing Infectious Agents and Cancer

    PubMed Central

    Buonaguro, Franco M; Lewis, George K; Pelicci, PierGiuseppe

    2006-01-01

    Infectious Agents and Cancer is a new open access, peer-reviewed, online journal, which encompasses all aspects of basic, clinical and translational research that provide an insight into the association between chronic infections and cancer. PMID:23509916

  1. Diamine curing agents for polyurethanes

    NASA Technical Reports Server (NTRS)

    Bell, V. L.; St. Clair, T. L.

    1975-01-01

    Three aromatic diamines have properties that make them promising candidates as curing agents for converting isocyanates to polyurethanes with higher adhesive strengths, higher softening temperatures, better toughness, and improved abrasion resistance.

  2. Triggered pore-forming agents

    DOEpatents

    Bayley, Hagan; Walker, Barbara J.; Chang, Chung-yu; Niblack, Brett; Panchal, Rekha

    1998-01-01

    An inactive pore-forming agent which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell.

  3. Tissue Penetration of Antifungal Agents

    PubMed Central

    Felton, Timothy; Troke, Peter F.

    2014-01-01

    SUMMARY Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. PMID:24396137

  4. AL Amyloidosis and Agent Orange

    MedlinePlus

    ... for survivors' benefits . Research on AL amyloidosis and herbicides The Health and Medicine Division (formally known as ... to the compounds of interest found in the herbicide Agent Orange and AL amyloidosis." VA made a ...

  5. Agent-based forward analysis

    SciTech Connect

    Kerekes, Ryan A.; Jiao, Yu; Shankar, Mallikarjun; Potok, Thomas E.; Lusk, Rick M.

    2008-01-01

    We propose software agent-based "forward analysis" for efficient information retrieval in a network of sensing devices. In our approach, processing is pushed to the data at the edge of the network via intelligent software agents rather than pulling data to a central facility for processing. The agents are deployed with a specific query and perform varying levels of analysis of the data, communicating with each other and sending only relevant information back across the network. We demonstrate our concept in the context of face recognition using a wireless test bed comprised of PDA cell phones and laptops. We show that agent-based forward analysis can provide a significant increase in retrieval speed while decreasing bandwidth usage and information overload at the central facility. n

  6. Launch Commit Criteria Monitoring Agent

    NASA Technical Reports Server (NTRS)

    Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Dan A.; Kelly, Andrew O.; Boeloeni, Ladislau

    2005-01-01

    The Spaceport Processing Systems Branch at NASA Kennedy Space Center has developed and deployed a software agent to monitor the Space Shuttle's ground processing telemetry stream. The application, the Launch Commit Criteria Monitoring Agent, increases situational awareness for system and hardware engineers during Shuttle launch countdown. The agent provides autonomous monitoring of the telemetry stream, automatically alerts system engineers when predefined criteria have been met, identifies limit warnings and violations of launch commit criteria, aids Shuttle engineers through troubleshooting procedures, and provides additional insight to verify appropriate troubleshooting of problems by contractors. The agent has successfully detected launch commit criteria warnings and violations on a simulated playback data stream. Efficiency and safety are improved through increased automation.

  7. What makes virtual agents believable?

    NASA Astrophysics Data System (ADS)

    Bogdanovych, Anton; Trescak, Tomas; Simoff, Simeon

    2016-01-01

    In this paper we investigate the concept of believability and make an attempt to isolate individual characteristics (features) that contribute to making virtual characters believable. As the result of this investigation we have produced a formalisation of believability and based on this formalisation built a computational framework focused on simulation of believable virtual agents that possess the identified features. In order to test whether the identified features are, in fact, responsible for agents being perceived as more believable, we have conducted a user study. In this study we tested user reactions towards the virtual characters that were created for a simulation of aboriginal inhabitants of a particular area of Sydney, Australia in 1770 A.D. The participants of our user study were exposed to short simulated scenes, in which virtual agents performed some behaviour in two different ways (while possessing a certain aspect of believability vs. not possessing it). The results of the study indicate that virtual agents that appear resource bounded, are aware of their environment, own interaction capabilities and their state in the world, agents that can adapt to changes in the environment and exist in correct social context are those that are being perceived as more believable. Further in the paper we discuss these and other believability features and provide a quantitative analysis of the level of contribution for each such feature to the overall perceived believability of a virtual agent.

  8. A Rapid and Sensitive Strip-Based Quick Test for Nerve Agents Tabun, Sarin, and Soman Using BODIPY-Modified Silica Materials.

    PubMed

    Climent, Estela; Biyikal, Mustafa; Gawlitza, Kornelia; Dropa, Tomáš; Urban, Martin; Costero, Ana M; Martínez-Máñez, Ramón; Rurack, Knut

    2016-08-01

    Test strips that in combination with a portable fluorescence reader or digital camera can rapidly and selectively detect chemical warfare agents (CWAs) such as Tabun (GA), Sarin (GB), and Soman (GD) and their simulants in the gas phase have been developed. The strips contain spots of a hybrid indicator material consisting of a fluorescent BODIPY indicator covalently anchored into the channels of mesoporous SBA silica microparticles. The fluorescence quenching response allows the sensitive detection of CWAs in the μg m(-3) range in a few seconds. PMID:27124609

  9. 46 CFR Sec. 2 - General Agents' authority.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... RESPONSIBILITY OF GENERAL AGENTS TO UNDERTAKE EMERGENCY REPAIRS IN FOREIGN PORTS Sec. 2 General Agents' authority. The General Agents are hereby delegated authority to undertake for the account of the...

  10. Chemical Warfare Agent Degradation and Decontamination

    SciTech Connect

    Talmage, Sylvia Smith; Watson, Annetta Paule; Hauschild, Veronique; Munro, Nancy B; King, J.

    2007-02-01

    The decontamination of chemical warfare agents (CWA) from structures, environmental media, and even personnel has become an area of particular interest in recent years due to increased homeland security concerns. In addition to terrorist attacks, scenarios such as accidental releases of CWA from U.S. stockpile sites or from historic, buried munitions are also subjects for response planning. To facilitate rapid identification of practical and effective decontamination approaches, this paper reviews pathways of CWA degradation by natural means as well as those resulting from deliberately applied solutions and technologies; these pathways and technologies are compared and contrasted. We then review various technologies, both traditional and recent, with some emphasis on decontamination materials used for surfaces that are difficult to clean. Discussion is limited to the major threat CWA, namely sulfur mustard (HD, bis(2-chloroethyl)sulfide), VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate), and the G-series nerve agents. The principal G-agents are GA (tabun, ethyl N,N-dimethylphosphoramidocyanidate), GB (sarin, isopropyl methylphosphonofluoridate), and GD (soman, pinacolyl methylphosphonofluoridate). The chemical decontamination pathways of each agent are outlined, with some discussion of intermediate and final degradation product toxicity. In all cases, and regardless of the CWA degradation pathway chosen for decontamination, it will be necessary to collect and analyze pertinent environmental samples during the treatment phase to confirm attainment of clearance levels.

  11. A amphoteric copolymer profile modification agent

    SciTech Connect

    Wang HongGuan; Yu LianCheng; Tian HongKun

    1995-11-01

    This report provides a new gel profile modification agent prepared by an amphoteric copolymer (FT-213) and a novel crosslinking agent (BY), and introduces the preparations of the amphoteric polymer, the crosslinking agent and the profile modification agent, the action mechanism, the test conditions and the evaluations of the performance of the agent. The 45 well treatments in oilfields demonstrate that the agent can be prepared conveniently, the agent has better compatibility and application performances, and the treatment life is longer with the use of the agent. 80,000 tons incremental oil and 60,000 m{sup 3} decreasing water production have been achieved.

  12. A multi-agent architecture for geosimulation of moving agents

    NASA Astrophysics Data System (ADS)

    Vahidnia, Mohammad H.; Alesheikh, Ali A.; Alavipanah, Seyed Kazem

    2015-10-01

    In this paper, a novel architecture is proposed in which an axiomatic derivation system in the form of first-order logic facilitates declarative explanation and spatial reasoning. Simulation of environmental perception and interaction between autonomous agents is designed with a geographic belief-desire-intention and a request-inform-query model. The architecture has a complementary quantitative component that supports collaborative planning based on the concept of equilibrium and game theory. This new architecture presents a departure from current best practices geographic agent-based modelling. Implementation tasks are discussed in some detail, as well as scenarios for fleet management and disaster management.

  13. Next Generation Remote Agent Planner

    NASA Technical Reports Server (NTRS)

    Jonsson, Ari K.; Muscettola, Nicola; Morris, Paul H.; Rajan, Kanna

    1999-01-01

    In May 1999, as part of a unique technology validation experiment onboard the Deep Space One spacecraft, the Remote Agent became the first complete autonomous spacecraft control architecture to run as flight software onboard an active spacecraft. As one of the three components of the architecture, the Remote Agent Planner had the task of laying out the course of action to be taken, which included activities such as turning, thrusting, data gathering, and communicating. Building on the successful approach developed for the Remote Agent Planner, the Next Generation Remote Agent Planner is a completely redesigned and reimplemented version of the planner. The new system provides all the key capabilities of the original planner, while adding functionality, improving performance and providing a modular and extendible implementation. The goal of this ongoing project is to develop a system that provides both a basis for future applications and a framework for further research in the area of autonomous planning for spacecraft. In this article, we present an introductory overview of the Next Generation Remote Agent Planner. We present a new and simplified definition of the planning problem, describe the basics of the planning process, lay out the new system design and examine the functionality of the core reasoning module.

  14. Optical recognition of biological agents

    NASA Astrophysics Data System (ADS)

    Baumgart, Chris W.; Linder, Kim Dalton; Trujillo, Josh J.

    2008-04-01

    Differentiation between particulate biological agents and non-biological agents is typically performed via a time-consuming "wet chemistry" process or through the use of fluorescent and spectroscopic analysis. However, while these methods can provide definitive recognition of biological agents, many of them have to be performed in a laboratory environment, or are difficult to implement in the field. Optical recognition techniques offer an additional recognition approach that can provide rapid analysis of a material in-situ to identify those materials that may be biological in nature. One possible application is to use these techniques to "screen" suspicious materials and to identify those that are potentially biological in nature. Suspicious materials identified by this screening process can then be analyzed in greater detail using the other, more definitive (but time consuming) analysis techniques. This presentation will describe the results of a feasibility study to determine whether optical pattern recognition techniques can be used to differentiate biological related materials from non-biological materials. As part of this study, feature extraction algorithms were developed utilizing multiple contrast and texture based features to characterize the macroscopic properties of different materials. In addition, several pattern recognition approaches using these features were tested including cluster analysis and neural networks. Test materials included biological agent simulants, biological agent related materials, and non-biological materials (suspicious white powders). Results of a series of feasibility tests will be presented along with a discussion of the potential field applications for these techniques.

  15. Investigational antimicrobial agents of 2013.

    PubMed

    Pucci, Michael J; Bush, Karen

    2013-10-01

    New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  16. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  17. Environmentally responsive MRI contrast agents

    PubMed Central

    Davies, Gemma-Louise; Kramberger, Iris; Davis, Jason J.

    2015-01-01

    Biomedical imaging techniques can provide a vast amount of anatomical information, enabling diagnosis and the monitoring of disease and treatment profile. MRI uniquely offers convenient, non-invasive, high resolution tomographic imaging. A considerable amount of effort has been invested, across several decades, in the design of non toxic paramagnetic contrast agents capable of enhancing positive MRI signal contrast. Recently, focus has shifted towards the development of agents capable of specifically reporting on their local biochemical environment, where a switch in image contrast is triggered by a specific stimulus/biochemical variable. Such an ability would not only strengthen diagnosis but also provide unique disease-specific biochemical insight. This feature article focuses on recent progress in the development of MRI contrast switching with molecular, macromolecular and nanoparticle-based agents. PMID:24040650

  18. Polycatechol Nanoparticle MRI Contrast Agents.

    PubMed

    Li, Yiwen; Huang, Yuran; Wang, Zhao; Carniato, Fabio; Xie, Yijun; Patterson, Joseph P; Thompson, Matthew P; Andolina, Christopher M; Ditri, Treffly B; Millstone, Jill E; Figueroa, Joshua S; Rinehart, Jeffrey D; Scadeng, Miriam; Botta, Mauro; Gianneschi, Nathan C

    2016-02-01

    Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID:26681255

  19. Agent review phase one report.

    SciTech Connect

    Zubelewicz, Alex Tadeusz; Davis, Christopher Edward; Bauer, Travis LaDell

    2009-12-01

    This report summarizes the findings for phase one of the agent review and discusses the review methods and results. The phase one review identified a short list of agent systems that would prove most useful in the service architecture of an information management, analysis, and retrieval system. Reviewers evaluated open-source and commercial multi-agent systems and scored them based upon viability, uniqueness, ease of development, ease of deployment, and ease of integration with other products. Based on these criteria, reviewers identified the ten most appropriate systems. The report also mentions several systems that reviewers deemed noteworthy for the ideas they implement, even if those systems are not the best choices for information management purposes.

  20. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  1. Thyroid dysfunction from antineoplastic agents.

    PubMed

    Hamnvik, Ole-Petter Riksfjord; Larsen, P Reed; Marqusee, Ellen

    2011-11-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  2. Erythropoietic agents and the elderly.

    PubMed

    Agarwal, Neeraj; Prchal, Josef T

    2008-10-01

    Erythropoietin (Epo) is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development that either act as ligands for the cell surface receptors of Epo or promote Epo production, which stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents under active investigation include continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase hypoxia-inducible factor-1 (HIF-1), thereby stimulating Epo production and iron availability and supply. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of Epo levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as "neocytolysis." The relative decrease in the serum Epo level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  3. Erythropoietic Agents and the Elderly

    PubMed Central

    Agarwal, Neeraj; Prchal, Josef T.

    2008-01-01

    Erythropoietin is a peptide hormone that stimulates erythropoiesis. There are several agents in clinical use and in development, which either act as ligands for the cell surface receptors of erythropoietin or promote erythropoietin production that stimulates erythropoiesis. These are known as erythropoietic agents. The agents already in use include epoetin alfa, epoetin beta, and darbepoetin alfa. Newer agents stimulating erythropoiesis (such as continuous erythropoietin receptor activator (CERA) or proline hydroxylase inhibitors that increase HIF-1 thereby stimulating erythropoietin production and iron availability and supply) are under active investigation. Erythropoietic agents have been shown to promote neuronal regeneration and to decrease post-stroke infarct size in mouse models. They have also been reported to shorten survival when used to treat anemia in many cancer patients and to increase thromboembolism. In contrast, rapid decrease of erythropoietin levels as observed in astronauts and high-altitude dwellers upon rapid descent to sea level leads to the decrease of erythroid mass, a phenomenon known as neocytolysis. The relative decrease in the serum erythropoietin level is known to occur in some subjects with otherwise unexplained anemia of aging. Anemia by itself is a predictor of poor physical function in the elderly and is a significant economic burden on society. One out of every five persons in the United States will be elderly by 2050. Erythropoietic agents, by preventing and treating otherwise unexplained anemias of the elderly and anemia associated with other disease conditions of the elderly, have the potential to improve the functional capacity and to decrease the morbidity and mortality in the elderly, thereby alleviating the overall burden of medical care in society. PMID:18809098

  4. Analysis of decontamination solutions of G agents to detect reformation of agent. Final report, December 1991-March 1992

    SciTech Connect

    Beaudry, W.T.; Buchanan, J.H.; Rohrbaugh, D.K.; Samuel, J.B.; Szafraniec, L.L.

    1993-01-01

    Agents from a full scale binary munition test were decontaminated with caustic in a 300 gal holding tank. Analysis of the contents by standard methods revealed a trace amount of G agent present despite the highly caustic solution. A technical review of the analytical methods was carried out to determine if the G agent was actually present or an artifact of the analysis. A literature search revealed similar concerns when brine solutions from nerve agent decontamination were analyzed using similar analytical methods. This study concluded that nerve agents reformed at reduced PH or in chloroform extracts of the neutralized or slightly acidic brines. Experiments using nuclear magnetic resonance (NMR), gas chromatography (GC), and GC/mass spectrometry (GC/MS) were used to see where, if any, G agent was present during the analysis. Results obtained confirmed G agent reforming in either the neutral aqueous solution or in the chloroform extract but not in chloroform extracts of the caustic solution. No agent was detected using methylene chloride as the extraction solvent as recommended by the earlier study.

  5. Autonomous sensor manager agents (ASMA)

    NASA Astrophysics Data System (ADS)

    Osadciw, Lisa A.

    2004-04-01

    Autonomous sensor manager agents are presented as an algorithm to perform sensor management within a multisensor fusion network. The design of the hybrid ant system/particle swarm agents is described in detail with some insight into their performance. Although the algorithm is designed for the general sensor management problem, a simulation example involving 2 radar systems is presented. Algorithmic parameters are determined by the size of the region covered by the sensor network, the number of sensors, and the number of parameters to be selected. With straight forward modifications, this algorithm can be adapted for most sensor management problems.

  6. An overview of inotropic agents.

    PubMed

    Vroom, Margreeth B

    2006-09-01

    The use of inotropic agents has been surrounded by many controversies. Recent guidelines for the treatment of patients with chronic and acute heart failure have elucidated some of the issues, but many remain. As a result, a substantial variability in the use of agents between institutions and caregivers remains, which mainly results from the lack of uniform data in the literature. Prospective randomized trials with a long-term follow-up and sufficient power are clearly needed, and a number of trials are currently in progress. PMID:16959760

  7. 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). PMID:27270393

  8. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2013-01-01 2013-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  9. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2012-01-01 2012-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  10. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome and... 7 Agriculture 3 2014-01-01 2014-01-01 false Flavoring agents. 58.629 Section 58.629 Agriculture.... Flavoring agents shall be one or more of those approved in § 58.605....

  11. Why Do Extension Agents Resign?

    ERIC Educational Resources Information Center

    Manton, Linda Nunes; van Es, J. C.

    1985-01-01

    Past and current Illinois extension agents were surveyed via mail questionnaires as to reasons for staying or leaving extension programs. Reasons for leaving included family changes, family moves, opportunity to advance, better salary/benefits, dissatisfaction with administration, and too much time away from family. (CT)

  12. Foodborne illness and microbial agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foodborne illnesses result from the consumption of food containing microbial agents such as bacteria, viruses, parasites or food contaminated by poisonous chemicals or bio-toxins. Pathogen proliferation is due to nutrient composition of foods, which are capable of supporting the growth of microorgan...

  13. Superintendents: The Key Influence Agents.

    ERIC Educational Resources Information Center

    Powell, Randy

    1990-01-01

    By the nature of their positions in schools, administrators are either influence agents or targets. Based on personal interviews with 140 Oregon administrators and a survey of 319 administrators around the state, this article highlights administrators' comments about their administrative influence and about constraints on their influence.…

  14. Triggered pore-forming agents

    DOEpatents

    Bayley, H.; Walker, B.J.; Chang, C.Y.; Niblack, B.; Panchal, R.

    1998-07-07

    An inactive pore-forming agent is revealed which is activated to lytic function by a condition such as pH, light, heat, reducing potential, or metal ion concentration, or substance such as a protease, at the surface of a cell. 30 figs.

  15. Nucleotide cleaving agents and method

    DOEpatents

    Que, Jr., Lawrence; Hanson, Richard S.; Schnaith, Leah M. T.

    2000-01-01

    The present invention provides a unique series of nucleotide cleaving agents and a method for cleaving a nucleotide sequence, whether single-stranded or double-stranded DNA or RNA, using and a cationic metal complex having at least one polydentate ligand to cleave the nucleotide sequence phosphate backbone to yield a hydroxyl end and a phosphate end.

  16. SEM: A Cultural Change Agent

    ERIC Educational Resources Information Center

    Barnes, Bradley; Bourke, Brian

    2015-01-01

    The authors advance the concept that institutional culture is a purposeful framework by which to view SEM's utility, particularly as a cultural change agent. Through the connection of seemingly independent functions of performance and behavior, implications emerge that deepen the understanding of the influence of culture on performance outcomes…

  17. Direct Vasodilators and Sympatholytic Agents.

    PubMed

    McComb, Meghan N; Chao, James Y; Ng, Tien M H

    2016-01-01

    Direct vasodilators and sympatholytic agents were some of the first antihypertensive medications discovered and utilized in the past century. However, side effect profiles and the advent of newer antihypertensive drug classes have reduced the use of these agents in recent decades. Outcome data and large randomized trials supporting the efficacy of these medications are limited; however, in general the blood pressure-lowering effect of these agents has repeatedly been shown to be comparable to other more contemporary drug classes. Nevertheless, a landmark hypertension trial found a negative outcome with a doxazosin-based regimen compared to a chlorthalidone-based regimen, leading to the removal of α-1 adrenergic receptor blockers as first-line monotherapy from the hypertension guidelines. In contemporary practice, direct vasodilators and sympatholytic agents, particularly hydralazine and clonidine, are often utilized in refractory hypertension. Hydralazine and minoxidil may also be useful alternatives for patients with renal dysfunction, and both hydralazine and methyldopa are considered first line for the treatment of hypertension in pregnancy. Hydralazine has also found widespread use for the treatment of systolic heart failure in combination with isosorbide dinitrate (ISDN). The data to support use of this combination in African Americans with heart failure are particularly robust. Hydralazine with ISDN may also serve as an alternative for patients with an intolerance to angiotensin antagonists. Given these niche indications, vasodilators and sympatholytics are still useful in clinical practice; therefore, it is prudent to understand the existing data regarding efficacy and the safe use of these medications. PMID:26033778

  18. Improving agents using reliable communication

    NASA Astrophysics Data System (ADS)

    Zheng, Jinbin

    2013-10-01

    Recent advances in introspective modalities and linear time symmetries do not necessarily obviate the need for web browsers [1]. In our research, we disprove the exploration of agents, which embodies the appropriate principles of electrical engineering. Here we demonstrate that even though semaphores and XML [1] are mostly incompatible, randomized algorithms and write-back caches are mostly incompatible.

  19. Echographic studies of osmotic agents.

    PubMed

    Vucicevic, Z M; Tark, E; Ahmad, S

    1979-09-01

    The effectiveness of osmotic agents, acetazolamide (Diamox), urea, glycerol, and mannitol, and massages (5 and 10 minutes) for inducing hypotony in rabbit eyes was evaluated by ultrasonography. Mannitol was found to have the greatest hypotonic effect followed closely by urea and glycerol, then acetazolamide. The difference between the 5 and 10 minute massages was negligible. PMID:122221

  20. An Autonomous Spacecraft Agent Prototype

    NASA Technical Reports Server (NTRS)

    Pell, Barney; Bernard, Douglas E.; Chien, Steve A.; Gat, Erann; Muscettola, Nicola; Nayak, P. Pandurang; Wagner, Michael D.; Williams, Brian C.

    1997-01-01

    This paper describes the New Millennium Remote Agent (NMRA) architecture for autonomous spacecraft control systems. This architecture integrates traditional real-time monitoring and control with constraint-based planning and scheduling, robust multi-threaded execution, and model-based diagnosis and reconfiguration.

  1. 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.

  2. 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. PMID:24597942

  3. Limonene and tetrahydrofurfurly alcohol cleaning agent

    SciTech Connect

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  4. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, George W.; Carter, Richard D.; Hand, Thomas E.; Powers, Michael T.

    1996-05-07

    The present invention is a tetrahydrofurfuryl alcohol and limonene or terpineol cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  5. Limonene and tetrahydrofurfuryl alcohol cleaning agent

    DOEpatents

    Bohnert, G.W.; Carter, R.D.; Hand, T.E.; Powers, M.T.

    1997-10-21

    The present invention is a tetrahydrofurfuryl alcohol and limonene cleaning agent and method for formulating and/or using the cleaning agent. This cleaning agent effectively removes both polar and nonpolar contaminants from various electrical and mechanical parts and is readily used without surfactants, thereby reducing the need for additional cleaning operations. The cleaning agent is warm water rinsable without the use of surfactants. The cleaning agent can be azeotropic, enhancing ease of use in cleaning operations and ease of recycling.

  6. Laser-based instrumentation for the detection of chemical agents

    SciTech Connect

    Hartford, A. Jr.; Sander, R.K.; Quigley, G.P.; Radziemski, L.J.; Cremers, D.A.

    1982-01-01

    Several laser-based techniques are being evaluated for the remote, point, and surface detection of chemical agents. Among the methods under investigation are optoacoustic spectroscopy, laser-induced breakdown spectroscopy (LIBS), and synchronous detection of laser-induced fluorescence (SDLIF). Optoacoustic detection has already been shown to be capable of extremely sensitive point detection. Its application to remote sensing of chemical agents is currently being evaluated. Atomic emission from the region of a laser-generated plasma has been used to identify the characteristic elements contained in nerve (P and F) and blister (S and Cl) agents. Employing this LIBS approach, detection of chemical agent simulants dispersed in air and adsorbed on a variety of surfaces has been achieved. Synchronous detection of laser-induced fluorescence provides an attractive alternative to conventional LIF, in that an artificial narrowing of the fluorescence emission is obtained. The application of this technique to chemical agent simulants has been successfully demonstrated. 19 figures.

  7. Molecular modeling of organophosphorous agents and their aqueous solutions.

    PubMed

    Vishnyakov, Aleksey; Gor, Gennady Yu; Lee, Ming-Tsung; Neimark, Alexander V

    2011-05-26

    Using molecular dynamics simulations, we modeled solvation and diffusion in aqueous solutions of organophosphorous compounds, including nerve G-agents sarin and soman (methylphosphonofluoridates) and their common simulants DMMP (dimethyl methylphosphonate) and DIFP (diisopropyl fluorophosphate). The aqueous solutions of the organophosphorous compounds were found to display complex molecular scale structures and dynamic properties due to competing interactions between strongly hydrophobic and hydrophilic groups. The mixing of agents with water was proved to be exothermic with negative excess mixing volume, indicating a strongly hydrophilic solvation. This effect was confirmed in a specially performed experiment. We discuss to what extent DMMP and DIFP are suitable simulants for G-agents in experimental studies, as far as their interactions with water are concerned. We also focus on the relevance of the structural features and mobilities of agents in water to their interactions with permselective polyelectrolyte membranes that may be employed as protective barriers against chemical warfare agents. PMID:21542641

  8. Halide test agent replacement study

    SciTech Connect

    Banks, E.M.; Freeman, W.P.; Kovach, B.J.

    1995-02-01

    The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

  9. Biologic agents in juvenile spondyloarthropathies.

    PubMed

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  10. The prospect of selective recognition of nerve agents with modular basket-like hosts. A structure-activity study of the entrapment of a series of organophosphonates in aqueous media.

    PubMed

    Ruan, Yian; Taha, Hashem A; Yoder, Ryan J; Maslak, Veselin; Hadad, Christopher M; Badjić, Jovica D

    2013-03-21

    We designed, prepared, and characterized three cup-shaped cavitands 1-3 for trapping organophosphonates (O═PR(OR')2, 118-197 Å(3)) whose shape and size correspond to G-type chemical warfare agents (132-186 Å(3)). With the assistance of computational (molecular dynamics) and experimental ((1)H NMR spectroscopy) methods, we found that host [1-H3](3+) orients its protonated histamine residues at the rim outside the cavity, in bulk water. In this unfolded form, the cavitand traps a series of organophosphonates 5-13 (K(app) = 87 ± 1 to 321 ± 6 M(-1) at 298.0 K), thereby placing the P-CH3 functional group in the inner space of the host. A comparison of experimental and computed (1)H NMR chemical shifts of both hosts and guests allowed us to derive structure-activity relationships and deduce that, upon the complexation, the more sizable P-OR functional groups in guests drive organophosphonates to the northern portion of the basket [1-H3](3+). This, in turn, causes a displacement of the guest's P-CH3 group and a contraction of the cup-shaped scaffold. The proposed induced-fit model of the recognition is important for turning these modular hosts into useful receptors capable of a selective detection/degradation of organophosphorus nerve agents. PMID:23445375

  11. Nerve conduction, visual evoked responses and electroretinography in tunnel workers previously exposed to acrylamide and N-methylolacrylamide containing grouting agents.

    PubMed

    Goffeng, Lars Ole; Heier, Mona Skard; Kjuus, Helge; Sjöholm, Hans; Sørensen, Kjell Aage; Skaug, Vidar

    2008-01-01

    The study examines possible persisting effects on the peripheral nervous system and visual system in tunnel workers previously exposed to acrylamide and N-methylolacrylamide during grouting work. We compared neurophysiological function in 44 tunnel workers previously exposed during grouting operations (2-10 years post exposure), with 49 tunnel workers with no history of exposure to acrylamide. Nerve conduction velocities (NCV), distal delay, F-response and amplitude in median and ulnar nerves of the right arm, peroneal, sural and tibial nerves of the right leg, visual evoked response (VER) and electroretinography (ERG) were measured. VER and ERG were also performed in 24 subjects more recently exposed to acrylamide grout (16 months post exposure). Exposure to acrylamide containing grouts was assessed by questionnaires. A statistically significant reduction in the mean sensory NCV of the sural nerve (p=0.005), as well as a non-significant reduction of sural amplitude was found in the previously exposed group compared to the control group. VER latencies to the onset of the occipital potential (N75) were prolonged in both exposed groups compared to the control group (p<0.05). ERG 30 Hz flicker amplitude was reduced in the recently exposed group compared to the referents (p<0.05). The results indicate slight subclinical, but persistent toxic effects in the sural nerve and the visual system in tunnel workers exposed to N-methylolacrylamide and acrylamide during grouting operations. PMID:18353610

  12. Laser interrogation of surface agents (LISA) for chemical agent reconnaissance

    NASA Astrophysics Data System (ADS)

    Higdon, N. S.; Chyba, Thomas H.; Richter, Dale A.; Ponsardin, Patrick L.; Armstrong, Wayne T.; Lobb, C. T.; Kelly, Brian T.; Babnick, Robert D.; Sedlacek, Arthur J., III

    2002-06-01

    Laser Interrogation of Surface Agents (LISA) is a new technique which exploits Raman scattering to provide standoff detection and identification of surface-deposited chemical agents. ITT Industries, Advanced Engineering and Sciences Division is developing the LISA technology under a cost-sharing arrangement with the US Army Soldier and Biological Chemical Command for incorporation on the Army's future reconnaissance vehicles. A field-engineered prototype LISA-Recon system is being designed to demonstrate on-the- move measurements of chemical contaminants. In this article, we will describe the LISA technique, data form proof-of- concept measurements, the LISA-Recon design, and some of the future realizations envisioned for military sensing applications.

  13. The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

    ERIC Educational Resources Information Center

    Baker, Lauri M.; Hadley, Gregg

    2014-01-01

    The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and…

  14. Determination of S-2-(N,N-diisopropylaminoethyl)- and S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, nerve agent markers, in water samples using strong anion-exchange disk extraction, in vial trimethylsilylation, and gas chromatography-mass spectrometry analysis.

    PubMed

    Subramaniam, Raja; Åstot, Crister; Juhlin, Lars; Nilsson, Calle; Östin, Anders

    2012-03-16

    Since the establishment of the Chemical Weapons Convention in 1997, the development of analytical methods for unambiguous identification of large numbers of chemicals related to chemical warfare agents has attracted increased interest. The analytically challenging, zwitterionic S-2-(N,N-diisopropylaminoethyl) methylphosphonothiolate (EA-2192), a highly toxic degradation marker of the nerve agent VX, has been reported to resist trimethylsilylation or to result in an unacceptably high limit of detection in GC-MS analysis. In the present study, the problem is demonstrated to be associated with the presence of salt, which hinders trimethysilylation. EA-2192 was extracted from aqueous samples by use of a strong anion-exchange disk, derivatized as a trimethylsilyl derivative via in vial solid-phase trimethylsilylation and identified by GC-MS. The limits of detection were 10 ng/mL and 100 ng/mL (in a water sample) for SIM and SCAN mode respectively. The analytical method was found to be repeatable with relative standard deviation <10%. The performance of the method was evaluated using a proficiency test sample and environmental samples (spiked river water and Baltic Bay water) and compared with the commonly used evaporation-silylation method. The disk method displayed good tolerance to the presence of salt and the spiked EA-2192 was conclusively identified in all matrices. In addition, the applicability of the method was further demonstrated for other selected hydrolysis products of VX and Russian VX, namely S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, ethyl methylphosphonic acid, methylphosphonic acid, and isobutyl methylphosphonic acid. For the synthesis of reference compounds, EA-2192 and its analog from degradation of the Russian VX isomer, the present methods were improved by using a polymer-bound base, resulting in >90% purity based on (1)H NMR. Based on the current results and earlier work on alkylphosphonic acids using the same method, we conclude that the

  15. Neuroprotective "agents" in surgery. Secret "agent" man, or common "agent" machine?

    NASA Technical Reports Server (NTRS)

    Andrews, R. J.

    1999-01-01

    The search for clinically-effective neuroprotective agents has received enormous support in recent years--an estimated $200 million by pharmaceutical companies on clinical trials for traumatic brain injury alone. At the same time, the pathophysiology of brain injury has proved increasingly complex, rendering the likelihood of a single agent "magic bullet" even more remote. On the other hand, great progress continues with technology that makes surgery less invasive and less risky. One example is the application of endovascular techniques to treat coronary artery stenosis, where both the invasiveness of sternotomy and the significant neurological complication rate (due to microemboli showering the cerebral vasculature) can be eliminated. In this paper we review aspects of intraoperative neuroprotection both present and future. Explanations for the slow progress on pharmacologic neuroprotection during surgery are presented. Examples of technical advances that have had great impact on neuroprotection during surgery are given both from coronary artery stenosis surgery and from surgery for Parkinson's disease. To date, the progress in neuroprotection resulting from such technical advances is an order of magnitude greater than that resulting from pharmacologic agents used during surgery. The progress over the last 20 years in guidance during surgery (CT and MRI image-guidance) and in surgical access (endoscopic and endovascular techniques) will soon be complemented by advances in our ability to evaluate biological tissue intraoperatively in real-time. As an example of such technology, the NASA Smart Probe project is considered. In the long run (i.e., in 10 years or more), pharmacologic "agents" aimed at the complex pathophysiology of nervous system injury in man will be the key to true intraoperative neuroprotection. In the near term, however, it is more likely that mundane "agents" based on computers, microsensors, and microeffectors will be the major impetus to improved

  16. CATS-based Agents That Err

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  17. Preliminary effects of real-world factors on the recovery and exploitation of forensic impurity profiles of a nerve-agent simulant from office media.

    PubMed

    Fraga, Carlos G; Sego, Landon H; Hoggard, Jamin C; Acosta, Gabriel A Pérez; Viglino, Emilie A; Wahl, Jon H; Synovec, Robert E

    2012-12-28

    Dimethyl methylphosphonate (DMMP) was used as a chemical threat agent (CTA) simulant for a first look at the effects of real-world factors on the recovery and exploitation of a CTA's impurity profile for source matching. Four stocks of DMMP having different impurity profiles were disseminated as aerosols onto cotton, painted wall board, and nylon coupons according to a thorough experimental design. The DMMP-exposed coupons were then solvent extracted and analyzed for DMMP impurities by comprehensive 2D gas chromatography/mass spectrometry (GC×GC/MS). The similarities between the coupon DMMP impurity profiles and the known (reference) DMMP profiles were measured by dot products of the coupon profiles and known profiles and by score values obtained from principal component analysis. One stock, with a high impurity-profile selectivity value of 0.9 out of 1, had 100% of its respective coupons correctly classified and no false positives from other coupons. Coupons from the other three stocks with low selectivity values (0.0073, 0.012, and 0.018) could not be sufficiently distinguished from one another for reliable matching to their respective stocks. The results from this work support that: (1) extraction solvents, if not appropriately selected, can have some of the same impurities present in a CTA reducing a CTA's useable impurity profile, (2) low selectivity among a CTA's known impurity profiles will likely make definitive source matching impossible in some real-world conditions, (3) no detrimental chemical-matrix interference was encountered during the analysis of actual office media, (4) a short elapsed time between release and sample storage is advantageous for the recovery of the impurity profile because it minimizes volatilization of forensic impurities, and (5) forensic impurity profiles weighted toward higher volatility impurities are more likely to be altered by volatilization following CTA exposure. PMID:23177156

  18. Preliminary Effects of Real-World Factors on the Recovery and Exploitation of Forensic Impurity Profiles of a Nerve-Agent Simulant from Office Media

    SciTech Connect

    Fraga, Carlos G.; Sego, Landon H.; Hoggard, Jamin C.; Perez Acosta, Gabriel A.; Viglino, Emilie A.; Wahl, Jon H.; Synovec, Robert E.

    2012-12-28

    Dimethyl methylphosphonate (DMMP) was used as a chemical threat agent (CTA) simulant for a first look at the effects of real-world factors on the recovery and exploitation of a CTA’s impurity profile for source matching. Four stocks of DMMP having different impurity profiles were disseminated as aerosols onto cotton, painted wall board, and nylon coupons according to a thorough experimental design. The DMMP-exposed coupons were then solvent extracted and analyzed for DMMP impurities by comprehensive 2-D gas chromatography/mass spectrometry (GC×GC/MS). The similarities between the coupon DMMP impurity profiles and the known (reference) DMMP profiles were measured by dot products of the coupon profiles and known profiles and by score values obtained from principal component analysis. One stock, with a high impurity-profile selectivity value of 0.9 out of 1, had 100% of its respective coupons correctly classified and no false positives from other coupons. Coupons from the other three stocks with low selectivity values (0.0073, 0.012, and 0.018) could not be sufficiently distinguished from one another for reliable matching to their respective stocks. The results from this work support that: (1) extraction solvents, if not appropriately selected, can have some of the same impurities present in a CTA reducing a CTA’s useable impurity profile, (2) low selectivity among a CTA’s known impurity profiles will likely make definitive source matching impossible in some real-world conditions, (3) no detrimental chemical-matrix interference was encountered during the analysis of actual office media, (4) a short elapsed time between release and sample storage is advantageous for the recovery of the impurity profile because it minimizes volatilization of forensic impurities, and (5) forensic impurity profiles weighted towards higher volatility impurities are more likely to be altered by volatilization following CTA exposure.

  19. Software agents in molecular computational biology.

    PubMed

    Keele, John W; Wray, James E

    2005-12-01

    Progress made in applying agent systems to molecular computational biology is reviewed and strategies by which to exploit agent technology to greater advantage are investigated. Communities of software agents could play an important role in helping genome scientists design reagents for future research. The advent of genome sequencing in cattle and swine increases the complexity of data analysis required to conduct research in livestock genomics. Databases are always expanding and semantic differences among data are common. Agent platforms have been developed to deal with generic issues such as agent communication, life cycle management and advertisement of services (white and yellow pages). This frees computational biologists from the drudgery of having to re-invent the wheel on these common chores, giving them more time to focus on biology and bioinformatics. Agent platforms that comply with the Foundation for Intelligent Physical Agents (FIPA) standards are able to interoperate. In other words, agents developed on different platforms can communicate and cooperate with one another if domain-specific higher-level communication protocol details are agreed upon between different agent developers. Many software agent platforms are peer-to-peer, which means that even if some of the agents and data repositories are temporarily unavailable, a subset of the goals of the system can still be met. Past use of software agents in bioinformatics indicates that an agent approach should prove fruitful. Examination of current problems in bioinformatics indicates that existing agent platforms should be adaptable to novel situations. PMID:16420735

  20. [Alternative agents used in ADHD].

    PubMed

    Hässler, Frank; Dück, Alexander; Reis, Olaf; Buchmann, Johannes

    2009-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is, with a prevalence of 2% to 6%, one of the most common neurobehavioral disorder affecting children and adolescents, persisting into adulthood. Comorbidity and psychosocial circumstances enter into the choice of intervention strategies. Several agents have been demonstrated effective in treating individuals with ADHD. Direct or indirect attenuation of dopamine and norepinephrine neurotransmission appears closely related to both the stimulant and nonstimulant medications efficacious in ADHD. However, important differences concerning efficacy and side effects exist both between and with the specific classes of agents like neuroleptics, antidepressants, antiepileptics, alpha-agonists, beta-blockers, buspiron, l-dopa, melatonin, pycnogenol, zinc, magnesium, polyunsaturated fatty acids, and homeopathy. Elucidating the various mechanisms of action of ADHD medications may lead to better choices in matching potential responses to the characteristics of individuals. We review the purported mechanism of action and available evidence for selected complementary and alternative medicine therapies for ADHD in childhood and adolescence. PMID:19105161

  1. [Infectious agents and autoimmune diseases].

    PubMed

    Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R

    1992-01-01

    In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352

  2. Oral agents in multiple sclerosis.

    PubMed

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  3. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  4. Injectable agents affecting subcutaneous fats.

    PubMed

    Chen, David Lk; Cohen, Joel L; Green, Jeremy B

    2015-09-01

    Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. PMID:26566569

  5. Agent planning in AgScala

    NASA Astrophysics Data System (ADS)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  6. New therapeutic agents for acromegaly.

    PubMed

    Melmed, Shlomo

    2016-02-01

    The currently available somatostatin receptor ligands (SRLs) and growth hormone (GH) antagonists are used to control levels of GH and insulin-like growth factor 1 (IGF-1) in patients with acromegaly. However, these therapies are limited by wide variations in efficacy, associated adverse effects and the need for frequent injections. A phase III trial of oral octreotide capsules demonstrated that this treatment can safely sustain suppressed levels of GH and IGF-1 and reduce the severity of symptoms in patients with acromegaly previously controlled by injectable SRL therapy, with the added benefit of no injection-site reactions. Phase I and phase II trials of the pan-selective SRL DG3173, the liquid crystal octreotide depot CAM2029 and an antisense oligonucleotide directed against the GH receptor have shown that these agents can be used to achieve biochemical suppression in acromegaly and have favourable safety profiles. This Review outlines the need for new therapeutic agents for patients with acromegaly, reviews clinical trial data of investigational agents and considers how these therapies might best be integrated into clinical practice. PMID:26610414

  7. Chemotherapy and Dietary Phytochemical Agents

    PubMed Central

    Sak, Katrin

    2012-01-01

    Chemotherapy has been used for cancer treatment already for almost 70 years by targeting the proliferation potential and metastasising ability of tumour cells. Despite the progress made in the development of potent chemotherapy drugs, their toxicity to normal tissues and adverse side effects in multiple organ systems as well as drug resistance have remained the major obstacles for the successful clinical use. Cytotoxic agents decrease considerably the quality of life of cancer patients manifesting as acute complaints and impacting the life of survivors also for years after the treatment. Toxicity often limits the usefulness of anticancer agents being also the reason why many patients discontinue the treatment. The nutritional approach may be the means of helping to raise cancer therapy to a new level of success as supplementing or supporting the body with natural phytochemicals cannot only reduce adverse side effects but improve also the effectiveness of chemotherapeutics. Various plant-derived compounds improve the efficiency of cytotoxic agents, decrease their resistance, lower and alleviate toxic side effects, reduce the risk of tumour lysis syndrome, and detoxify the body of chemotherapeutics. The personalised approach using various phytochemicals provides thus a new dimension to the standard cancer therapy for improving its outcome in a complex and complementary way. PMID:23320169

  8. Pharmacologic Agents for Chronic Diarrhea

    PubMed Central

    2015-01-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  9. Multi-agent autonomous system

    NASA Technical Reports Server (NTRS)

    Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

    2010-01-01

    A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

  10. Pharmacologic Agents for Chronic Diarrhea.

    PubMed

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  11. Chelating agents and cadmium intoxication

    SciTech Connect

    Shinobu, L.A.

    1985-01-01

    A wide range of conventional chelating agents have been screened for (a) antidotal activity in acute cadmium poisoning and (b) ability to reduce aged liver and kidney deposits of cadmium. Chelating agents belonging to the dithiocarbamate class have been synthesized and tested in both the acute and chronic modes of cadmium intoxication. Several dithiocarbamates, not only provide antidotal rescue, but also substantially decrease the intracellular deposits of cadmium associated with chronic cadmium intoxication. Fractionating the cytosol from the livers and kidneys of control and treated animals by Sephadex G-25 gel filtration clearly demonstrates that the dithiocarbamates are reducing the level of metallothionein-bound cadmium. However, the results of cell culture (Ehrlich ascites) studies designed to investigate the removal of cadmium from metallothionein and subsequent transport of the resultant cadmium complex across the cell membrane were inconclusive. In other in vitro investigations, the interaction between isolated native Cd, Zn-metallothionein and several chelating agents was explored. Ultracentrifugation, equilibrium dialysis, and Sephadex G-25 gel filtration studies have been carried out in an attempt to determine the rate of removal of cadmium from metallothionein by these small molecules. Chemical shifts for the relevant cadmium-dithiocarbamate complexes have been determined using natural abundance Cd-NMR.

  12. The Fate of Chemical Warfare Agents in the Environment

    SciTech Connect

    Talmage, Sylvia Smith; Munro, Nancy B; Watson, Annetta Paule; King, J.; Hauschild, Veronique

    2007-05-01

    Chemical Warfare Agents, Second Edition has been totally revised since the successful first edition and expanded to about three times the length, with many new chapters and much more in-depth consideration of all the topics. The chapters have been written by distinguished international experts in various aspects of chemical warfare agents and edited by an experienced team to produce a clear review of the field. The book now contains a wealth of material on the mechanisms of action of the major chemical warfare agents, including the nerve agent cyclosarin, formally considered to be of secondary importance, as well as ricin and abrin. Chemical Warfare Agents, Second Edition discusses the physico-chemical properties of chemical warfare agents, their dispersion and fate in the environment, their toxicology and management of their effects on humans, decontamination and protective equipment. New chapters cover the experience gained after the use of sarin to attack travelers on the Tokyo subway and how to deal with the outcome of the deployment of riot control agents such as CS gas. This book provides a comprehensive review of chemical warfare agents, assessing all available evidence regarding the medical, technical and legal aspects of their use. It is an invaluable reference work for physicians, public health planners, regulators and any other professionals involved in this field.

  13. Chemopreventive Agent Development | Division of Cancer Prevention

    Cancer.gov

    This group promotes and supports research on early chemopreventive agent development, from preclinical studies to phas | Research on early chemopreventive agent development, from preclinical studies to phase I clinical trials.

  14. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  15. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  16. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  17. 7 CFR 58.629 - Flavoring agents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.629 Flavoring agents. Flavoring agents either natural or artificial shall be wholesome...

  18. 7 CFR 58.628 - Sweetening agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.628 Sweetening agents. Sweetening agents shall be clean and wholesome and consist of one...

  19. 7 CFR 58.720 - Acidifying agents.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Quality Specifications for Raw Material § 58.720 Acidifying agents. Acidifying agents if used shall be those permitted by the Food...

  20. Intelligent Agent Architectures: Reactive Planning Testbed

    NASA Technical Reports Server (NTRS)

    Rosenschein, Stanley J.; Kahn, Philip

    1993-01-01

    An Integrated Agent Architecture (IAA) is a framework or paradigm for constructing intelligent agents. Intelligent agents are collections of sensors, computers, and effectors that interact with their environments in real time in goal-directed ways. Because of the complexity involved in designing intelligent agents, it has been found useful to approach the construction of agents with some organizing principle, theory, or paradigm that gives shape to the agent's components and structures their relationships. Given the wide variety of approaches being taken in the field, the question naturally arises: Is there a way to compare and evaluate these approaches? The purpose of the present work is to develop common benchmark tasks and evaluation metrics to which intelligent agents, including complex robotic agents, constructed using various architectural approaches can be subjected.

  1. Security Measures to Protect Mobile Agents

    NASA Astrophysics Data System (ADS)

    Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

    2010-11-01

    The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

  2. Intelligent Agents as Cognitive Tools for Education.

    ERIC Educational Resources Information Center

    Baylor, Amy

    1999-01-01

    Examines the educational potential for intelligent agents as cognitive tools. Discusses the role of intelligent agents: managing large amounts of information (information overload), serving as a pedagogical expert, and creating programming environments for the learner. (AEF)

  3. Learning other agents` preferences in multiagent negotiation

    SciTech Connect

    Bui, H.H.; Kieronska, D.; Venkatesh, S.

    1996-12-31

    In multiagent systems, an agent does not usually have complete information about the preferences and decision making processes of other agents. This might prevent the agents from making coordinated choices, purely due to their ignorance of what others want. This paper describes the integration of a learning module into a communication-intensive negotiating agent architecture. The learning module gives the agents the ability to learn about other agents` preferences via past interactions. Over time, the agents can incrementally update their models of other agents` preferences and use them to make better coordinated decisions. Combining both communication and learning, as two complement knowledge acquisition methods, helps to reduce the amount of communication needed on average, and is justified in situations where communication is computationally costly or simply not desirable (e.g. to preserve the individual privacy).

  4. Extinguishing agent for combustible metal fires

    DOEpatents

    Riley, John F.; Stauffer, Edgar Eugene

    1976-10-12

    A low chloride extinguishing agent for combustible metal fires comprising from substantially 75 to substantially 94 weight percent of sodium carbonate as the basic fire extinguishing material, from substantially 1 to substantially 5 weight percent of a water-repellent agent such as a metal stearate, from substantially 2 to substantially 10 weight percent of a flow promoting agent such as attapulgus clay, and from substantially 3 to substantially 15 weight percent of a polyamide resin as a crusting agent.

  5. 14 CFR 221.11 - Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Agent. 221.11 Section 221.11 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Who is Authorized To Issue and File Tariffs § 221.11 Agent. An agent may issue and...

  6. STUDIES OF WATERBORNE AGENTS OF VIRAL GASTROENTERITIS

    EPA Science Inventory

    The etiologic agent of a large outbreak of waterborne viral gastroenteritis was detected employing immune electron microscopy (IEM) and a newly developed solid phase radioimmunoassay (RIA). This agent, referred to as the Snow Mountain Agent (SMA), is 27-32 nm. in diameter, has cu...

  7. Agent-based modeling of complex infrastructures

    SciTech Connect

    North, M. J.

    2001-06-01

    Complex Adaptive Systems (CAS) can be applied to investigate complex infrastructures and infrastructure interdependencies. The CAS model agents within the Spot Market Agent Research Tool (SMART) and Flexible Agent Simulation Toolkit (FAST) allow investigation of the electric power infrastructure, the natural gas infrastructure and their interdependencies.

  8. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 2 2013-04-01 2013-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  9. 24 CFR 232.1011 - Management agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Management agents. 232.1011 Section... Management agents. (a) An operator or borrower may, with the prior written approval of HUD, execute a management agent agreement setting forth the duties and procedures for matters related to the management...

  10. 46 CFR 153.1106 - Cleaning agents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cleaning agents. 153.1106 Section 153.1106 Shipping... Handling of Categories A, B, C, and D Cargo and Nls Residue § 153.1106 Cleaning agents. No tank cleaning agent other than water or steam may be used to clean an NLS residue from a cargo tank except...

  11. Online Deception Detection Using BDI Agents

    ERIC Educational Resources Information Center

    Merritts, Richard A.

    2013-01-01

    This research has two facets within separate research areas. The research area of Belief, Desire and Intention (BDI) agent capability development was extended. Deception detection research has been advanced with the development of automation using BDI agents. BDI agents performed tasks automatically and autonomously. This study used these…

  12. The Ontogenesis of Agent: Linguistic Expression.

    ERIC Educational Resources Information Center

    Olswang, Lesley Barrett; Carpenter, Robert L.

    1982-01-01

    Some of the findings of a longitudinal study of three infants between their 11th and 22nd months to document development of linguistic expression of the agent concept indicated that first vocalizations were inconsistently associated with nonverbal agentive behaviors and later mature utterances coded agent-action-recipient events. (MC)

  13. Infants Attribute to Agents Goals and Dispositions

    ERIC Educational Resources Information Center

    Luo, Yuyan; Choi, You-jung

    2012-01-01

    This commentary article is to be published alongside: Hernik, M., & Southgate, V. (2012). What do infants know about agents' goals? The authors see this issue consisting of two closely related questions. First, what is an agent to infants? Second, how do infants attribute goals to agents? Hernik and Southgage (H&S) focused on the second question.…

  14. Construction and Evaluation of Animated Teachable Agents

    ERIC Educational Resources Information Center

    Bodenheimer, Bobby; Williams, Betsy; Kramer, Mattie Ruth; Viswanath, Karun; Balachandran, Ramya; Belynne, Kadira; Biswas, Gautam

    2009-01-01

    This article describes the design decisions, technical approach, and evaluation of the animation and interface components for an agent-based system that allows learners to learn by teaching. Students learn by teaching an animated agent using a visual representation. The agent can answer questions about what she has been taught and take quizzes.…

  15. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  16. Honey - A Novel Antidiabetic Agent

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

    2012-01-01

    Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

  17. Copper complexes as anticancer agents.

    PubMed

    Marzano, Cristina; Pellei, Maura; Tisato, Francesco; Santini, Carlo

    2009-02-01

    Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field. PMID:19199864

  18. Pathogenic agents in freshwater resources

    NASA Astrophysics Data System (ADS)

    Geldreich, Edwin E.

    1996-02-01

    Numerous pathogenic agents have been found in freshwaters used as sources for water supplies, recreational bathing and irrigation. These agents include bacterial pathogens, enteric viruses, several protozoans and parasitic worms more common to tropical waters. Although infected humans are a major source of pathogens, farm animals (cattle, sheep, pigs), animal pets (dogs, cats) and wildlife serve as significant reservoirs and should not be ignored. The range of infected individuals within a given warm-blooded animal group (humans included) may range from 1 to 25%. Survival times for pathogens in the water environment may range from a few days to as much as a year (Ascaris, Taenia eggs), with infective dose levels varying from one viable cell for several primary pathogenic agents to many thousands of cells for a given opportunistic pathogen.As pathogen detection in water is complex and not readily incorporated into routine monitoring, a surrogate is necessary. In general, indicators of faecal contamination provide a positive correlation with intestinal pathogen occurrences only when appropriate sample volumes are examined by sensitive methodology.Pathways by which pathogens reach susceptible water users include ingestion of contaminated water, body contact with polluted recreational waters and consumption of salad crops irrigated by polluted freshwaters. Major contributors to the spread of various water-borne pathogens are sewage, polluted surface waters and stormwater runoff. All of these contributions are intensified during periods of major floods. Several water-borne case histories are cited as examples of breakdowns in public health protection related to water supply, recreational waters and the consumption of contaminated salad crops. In the long term, water resource management must focus on pollution prevention from point sources of waste discharges and the spread of pathogens in watershed stormwater runoff.

  19. Trace determination of primary nerve agent degradation products in aqueous soil extracts by on-line solid phase extraction-liquid chromatography-mass spectrometry using ZrO2 for enrichment.

    PubMed

    Røen, Bent Tore; Sellevåg, Stig Rune; Dybendal, Kjersti E; Lundanes, Elsa

    2014-02-14

    A method for determination of the primary nerve agent degradation products ethyl-, isopropyl-, isobutyl-, cyclohexyl- and pinacolyl methylphosphonic acid in aqueous soil extracts has been developed utilizing on-line solid phase extraction-liquid chromatography and mass spectrometry (SPE-LC-MS). Four different stationary phases (ZrO2, TiO2, polymeric mixed mode anion exchange and porous graphitic carbon) were investigated for their suitability as SPE materials in the on-line SPE-LC-MS setup. Zirconium dioxide was chosen due to its high affinity for the alkyl methylphosphonic acids (AMPAs), and its compatibility with LC-MS. Aqueous soil extracts were acidified with 0.1% acetic acid and aliquots of 300μL were injected on a 2mm×10mm ZrO2 column. Separation of the analytes was performed on a reversed phase column with acetonitrile/water gradient and 15mM ammonium acetate. Method validation was performed with the analytes added to an aqueous extract of a loam soil, and the AMPAs could be determined at concentrations as low as 0.05-0.5μgL(-1). The method was linear (R(2)>0.995) from the limit of quantification (LOQ) to 100×LOQ, and the within assay repeatability was below 10% and 5% relative standard deviation at LOQ and 50×LOQ, respectively. The developed method was employed for determination of the AMPAs which had been added to the aqueous extracts of five different soil types from cultivated and uncultivated areas. The obtained recoveries showed that the analytes could be determined at the sensitivities achieved in the method validation in four of the extracts. For the first time, we have demonstrated a method capable of detecting primary nerve agent degradation products at sub ppb levels in the aqueous extracts of various soils. The method requires no sample preparation after soil extraction other than pH adjustment of the aqueous extract. PMID:24461638

  20. Anticancer agents from marine sponges.

    PubMed

    Ye, Jianjun; Zhou, Feng; Al-Kareef, Ammar M Q; Wang, Hong

    2015-01-01

    Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics. PMID:25402340

  1. Fluorescent whitening agents in detergents.

    PubMed

    Eckhardt, C; von Rütte, R

    1975-01-01

    Washing is a form of textile care which is characterized by its repetitive nature. Washing methods vary enormously in different parts of the world. The main types of detergents and fluorescent whitening agents (FWAs) are described. Washing slows down the deterioration in use of white goods, and yellowing is counteracted by FWAs. FWAs also enhance the freshness and brightness of most pale shades. Cost calculations show clearly the economic advantages of using FWAs in washing: the useful life of textiles can be prolonged considerably for a very small additional cost. PMID:1064549

  2. Method For Detecting Biological Agents

    DOEpatents

    Chen, Liaohai; McBranch, Duncan W.; Wang, Hsing-Lin; Whitten, David G.

    2005-12-27

    A sensor is provided including a polymer capable of having an alterable measurable property from the group of luminescence and electrical conductivity, the polymer having an intermediate combination of a recognition element, a tethering element and a property-altering element bound thereto and capable of altering the measurable property, the intermediate combination adapted for subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the intermediate combination from the polymer results in a detectable change in the alterable measurable property, and, detecting said detectable change in the alterable measurable property.

  3. Concomitant changes in formaldehyde-induced fluorescence of dopamine interneurones and in slow inhibitory post-synaptic potentials of the rabbit superior cervical ganglion, induced by stimulation of the preganglionic nerve or by a muscarinic agent

    PubMed Central

    Libet, B.; Owman, Ch.

    1974-01-01

    1. Dopamine was identified by formaldehyde histochemistry and cytospectrofluorometry in the rabbit's superior cervical ganglion. Dopamine was localized to the intraganglionic `small intensely fluorescent' cells, and also to the characteristically beaded fibres forming a network in close contact with virtually all ganglion cell bodies. The extensive beaded fibres are therefore presumed to be processes of the small intensely fluorescent cells. 2. Changes in the dopamine content of these interneurones were studied by recording alterations in their relative fluorescence intensity in conjunction with changes in the slow inhibitory post-synaptic potential (s.-i.p.s.p.) response of the ganglion to orthodromic nerve input. 3. Dopamine content was lower after several hours in vitro even without special stimulation; this was in accord with a regularly observed spontaneous reduction of the s.-i.p.s.p. response. 4. After a period of conditioning stimulation of the preganglionic nerve, in the presence of an anticholinesterase agent (eserine) and an inhibitor of catecholamine synthesis (α-methyl-p-tyrosine), the s.-i.p.s.p. was selectively and markedly reduced. The dopamine fluorescence in the small intensely fluorescent cell interneurones was also significantly reduced, to a mean value of about 55 or 60% of the fluorescence in the dopamine interneurones of the paired but unstimulated control ganglion. A significant reduction in dopamine fluorescence was always accompanied by a marked loss of s.-i.p.s.p. response; the reverse was not always true. 5. Treatment with the muscarinic agent bethanechol for 30 min, with no α-methyl-p-tyrosine or eserine present, similarly resulted in reductions in the s.-i.p.s.p. response of the ganglia and in the formaldehyde-induced fluorescence of the dopamine interneurones. 6. A functional uptake of extrinsic dopamine by the dopamine interneurones was also demonstrated: temporary exposure to dopamine restored a large fraction of both the s

  4. Mobile agent location in distributed environments

    NASA Astrophysics Data System (ADS)

    Fountoukis, S. G.; Argyropoulos, I. P.

    2012-12-01

    An agent is a small program acting on behalf of a user or an application which plays the role of a user. Artificial intelligence can be encapsulated in agents so that they can be capable of both behaving autonomously and showing an elementary decision ability regarding movement and some specific actions. Therefore they are often called autonomous mobile agents. In a distributed system, they can move themselves from one processing node to another through the interconnecting network infrastructure. Their purpose is to collect useful information and to carry it back to their user. Also, agents are used to start, monitor and stop processes running on the individual interconnected processing nodes of computer cluster systems. An agent has a unique id to discriminate itself from other agents and a current position. The position can be expressed as the address of the processing node which currently hosts the agent. Very often, it is necessary for a user, a processing node or another agent to know the current position of an agent in a distributed system. Several procedures and algorithms have been proposed for the purpose of position location of mobile agents. The most basic of all employs a fixed computing node, which acts as agent position repository, receiving messages from all the moving agents and keeping records of their current positions. The fixed node, responds to position queries and informs users, other nodes and other agents about the position of an agent. Herein, a model is proposed that considers pairs and triples of agents instead of single ones. A location method, which is investigated in this paper, attempts to exploit this model.

  5. Triazole: A Promising Antitubercular Agent.

    PubMed

    Keri, Rangappa S; Patil, Siddappa A; Budagumpi, Srinivasa; Nagaraja, Bhari Mallanna

    2015-10-01

    Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs. PMID:25643871

  6. Chemopreventive agents targeting tumor microenvironment.

    PubMed

    Sharma, Sharada H; Thulasingam, Senthilkumar; Nagarajan, Sangeetha

    2016-01-15

    Recent studies have shown that tumor development and progression depend not only on the perturbed genes that govern cell proliferation, but is also highly determined by the non-tumor cells of the stromal compartment surrounding the tumor called tumor microenvironment (TME). These findings highlight the importance of targeting the microenvironment in combination with therapies aimed at tumor cells as a valuable approach. The innate and adaptive immune cells in the TME interact among themselves and also with the endothelial cells, pericytes and mast cells of the stromal compartment through various autocrine and paracrine manner to regulate abnormal cell proliferation. Direct cytotoxic killing of cancer cells and/or reversion of the immunosuppressive TME are to be considered as better strategies for chemoprevention and chemotherapy. With a growing emphasis on a "hallmark targeting" strategy for cancer therapy, the TME now appears as a promising target for cancer prevention using natural products. Clarification on the nontumor stromal cells, the mediators involved, interactions with immune response cells, and immune-evasive mechanisms are needed in order to manipulate the characteristics of the TME by natural pharmacological agents to design effective therapies. This review will provide a glimpse on the roles played by various non-tumor cells in tumor progression and their intervention by pharmacological agents. PMID:26679106

  7. A Review of Luting Agents

    PubMed Central

    Pameijer, Cornelis H.

    2012-01-01

    Due to the availability of a large number of luting agents (dental cements) proper selection can be a daunting task and is usually based on a practitioner's reliance on experience and preference and less on in depth knowledge of materials that are used for the restoration and luting agent properties. This review aims at presenting an overview of current cements and discusses physical properties, biocompatibility and other properties that make a particular cement the preferred choice depending on the clinical indication. Tables are provided that outline the different properties of the generic classification of cements. It should be noted that no recommendations are made to use a particular commercial cement for a hypothetical clinical situation. The choice is solely the responsibility of the practitioner. The appendix is intended as a guide for the practitioner towards a recommended choice under commonly encountered clinical scenarios. Again, no commercial brands are recommended although the author recognizes that some have better properties than others. Please note that this flowchart strictly presents the author's opinion and is based on research, clinical experience and the literature. PMID:22505909

  8. Nanoparticle-based theranostic agents

    PubMed Central

    Xie, Jin; Lee, Seulki; Chen, Xiaoyuan

    2010-01-01

    Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology. PMID:20691229

  9. Innovative Agents in Multiple Myeloma

    PubMed Central

    Faiman, Beth; Richards, Tiffany

    2014-01-01

    Multiple myeloma (MM) remains an incurable cancer of the bone marrow plasma cells. However, the overall survival of patients with MM has increased dramatically within the past decade. This is due, in part, to newer agents such as immunomodulatory drugs (lenalidomide, thalidomide, and pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib, MLN9708). These and several other new classes of drugs have arisen from an improved understanding of the complex environment in which genetic changes occur. Improved understanding of genetic events will enable clinicians to better stratify risk before and during therapy, tailor treatment, and test the value of personalized interventions. The ultimate goal in this incurable disease setting is to reduce the impact of cancer- or chemotherapy-related side effects. Nurses and advanced practitioners are integral to the treatment team. Thus, each should be aware of changes to the current drug landscape. Targeted drugs with sophisticated mechanisms of action are currently under investigation. Patients gain access to newer drugs within the context of clinical trials. Awareness of such trials will help accrual and determine if therapeutic benefit exists. In this article, we will describe new agents with unique and targeted mechanisms of action that have activity in patients with relapsed and/or refractory multiple myeloma. PMID:25089218

  10. Surfactants as blackbird stressing agents

    USGS Publications Warehouse

    Lefebvre, P.W.; Seubert, J.L.

    1970-01-01

    Applications of wetting-agent solutions produce mortality in birds. The exact cause of death is undetermined but it is believed that destruction of the insulating qualities of the plumage permits ambient cold temperatures and evaporation to lower the body temperature to a lethal level. The original concept of using these materials as bird-control tools was developed in 1958 at the Patuxent Wildlife Research Center, Bureau of Sport Fisheries and Wildlife Laurel, Maryland. Early field trials by personnel of the Division of Wildlife Services and the Denver Wildlife Research Center indicated that ground-application techniques had promise but limitations of the equipment precluded successful large-scale roost treatments. In 1966, Patuxent Center personnel began using tanker-type aircraft to evaluate high-volume aerial applications of wetting agents. The success of these tests led to the use of small aircraft to make low-volume, high-concentration aerial applications just prior to expected rainfall. Recent trials of the low-volume method show that, with some limitations, it is effective, inexpensive, and safe to the environment. Current research emphasizes the screening of new candidate materials for efficacy, biodegradability, and toxicity to plants and non-target animals, as well as basic investigations of the avian physiological mechanisms involved. Field trials to develop more effective application techniques will continue.

  11. Electric power market agent design

    NASA Astrophysics Data System (ADS)

    Oh, Hyungseon

    The electric power industry in many countries has been restructured in the hope of a more economically efficient system. In the restructured system, traditional operating and planning tools based on true marginal cost do not perform well since information required is strictly confidential. For developing a new tool, it is necessary to understand offer behavior. The main objective of this study is to create a new tool for power system planning. For the purpose, this dissertation develops models for a market and market participants. A new model is developed in this work for explaining a supply-side offer curve, and several variables are introduced to characterize the curve. Demand is estimated using a neural network, and a numerical optimization process is used to determine the values of the variables that maximize the profit of the agent. The amount of data required for the optimization is chosen with the aid of nonlinear dynamics. To suggest an optimal demand-side bidding function, two optimization problems are constructed and solved for maximizing consumer satisfaction based on the properties of two different types of demands: price-based demand and must-be-served demand. Several different simulations are performed to test how an agent reacts in various situations. The offer behavior depends on locational benefit as well as the offer strategies of competitors.

  12. Camouflaging Agents for Vitiligo Patients.

    PubMed

    Hossain, Claudia; Porto, Dennis A; Hamzavi, Iltefat; Lim, Henry W

    2016-04-01

    Vitiligo is an acquired condition resulting in patches of depigmented skin that is cosmetically disfiguring and can subsequently be psychologically disturbing. For patients seeking to mask their vitiligo, camouflage options have historically been limited and been designated as a cosmetic, rather than a medical, concern. As research has indicated that proper concealment of vitiligo lesions can vastly improve quality of life, we believe it is essential that dermatologists become aware of all the options available to their patients and that discussions of camouflage options be broached from the first visit. Methods for concealment include cosmetic tattoos, dihydroxyacetone, general cosmetics, and various topical camouflage agents, including the newest product, Microskin™. We conducted a literature review of all of the available options for vitiligo concealment and evaluated their advantages and disadvantages. Ultimately, temporary methods of concealment are recommended; but the particular agent used can come from discussion with the patient based on the location of the lesions, degree of concealment desired, cost, and availability. PMID:27050692

  13. Anchor Toolkit - a secure mobile agent system

    SciTech Connect

    Mudumbai, Srilekha S.; Johnston, William; Essiari, Abdelilah

    1999-05-19

    Mobile agent technology facilitates intelligent operation insoftware systems with less human interaction. Major challenge todeployment of mobile agents include secure transmission of agents andpreventing unauthorized access to resources between interacting systems,as either hosts, or agents, or both can act maliciously. The Anchortoolkit, designed by LBNL, handles the transmission and secure managementof mobile agents in a heterogeneous distributed computing environment. Itprovides users with the option of incorporating their security managers.This paper concentrates on the architecture, features, access control anddeployment of Anchor toolkit. Application of this toolkit in a securedistributed CVS environment is discussed as a case study.

  14. SAF1. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, S.Y

    1997-06-01

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  15. Reversal agents in anaesthesia and critical care

    PubMed Central

    Pani, Nibedita; Dongare, Pradeep A; Mishra, Rajeeb Kumar

    2015-01-01

    Despite the advent of short and ultra-short acting drugs, an in-depth knowledge of the reversal agents used is a necessity for any anaesthesiologist. Reversal agents are defined as any drug used to reverse the effects of anaesthetics, narcotics or potentially toxic agents. The controversy on the routine reversal of neuromuscular blockade still exists. The advent of newer reversal agents like sugammadex have made the use of steroidal neuromuscular blockers like rocuronium feasible in rapid sequence induction situations. We made a review of the older reversal agents and those still under investigation for drugs that are regularly used in our anaesthesia practice. PMID:26644615

  16. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the Department authorized to serve as passport...

  17. 30 CFR 250.145 - How do I designate an agent or a local agent?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false How do I designate an agent or a local agent? 250.145 Section 250.145 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND... SHELF General Special Types of Approvals § 250.145 How do I designate an agent or a local agent? (a)...

  18. Mother ship and physical agents collaboration

    NASA Astrophysics Data System (ADS)

    Young, Stuart H.; Budulas, Peter P.; Emmerman, Philip J.

    1999-07-01

    This paper discusses ongoing research at the U.S. Army Research Laboratory that investigates the feasibility of developing a collaboration architecture between small physical agents and a mother ship. This incudes the distribution of planning, perception, mobility, processing and communications requirements between the mother ship and the agents. Small physical agents of the future will be virtually everywhere on the battlefield of the 21st century. A mother ship that is coupled to a team of small collaborating physical agents (conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA); logistics; sentry; and communications relay) will be used to build a completely effective and mission capable intelligent system. The mother ship must have long-range mobility to deploy the small, highly maneuverable agents that will operate in urban environments and more localized areas, and act as a logistics base for the smaller agents. The mother ship also establishes a robust communications network between the agents and is the primary information disseminating and receiving point to the external world. Because of its global knowledge and processing power, the mother ship does the high-level control and planning for the collaborative physical agents. This high level control and interaction between the mother ship and its agents (including inter agent collaboration) will be software agent architecture based. The mother ship incorporates multi-resolution battlefield visualization and analysis technology, which aids in mission planning and sensor fusion.

  19. Intelligent agent support for automated radiology exam

    NASA Astrophysics Data System (ADS)

    Shang, Yi; Popescu, Mihail

    2000-10-01

    A difficult problem in automatic medical image understanding is that for every image type such as x-ray and every body organ such as heart, there exist specific solutions that do not allow for generalization. Just collecting all the specific solutions will not achieve the vision of a computerized physician. To address this problem, we propose an intelligent agent approach that is based on agent-oriented programming is that it combines the benefits of object-oriented programming and expert system. For radiology image understanding, we present a multi- agent system that is composed of two major types of intelligent agents: radiologist agents and patient agents. A patient agent asks for multiple opinions from radiologists agents in interpreting a given set of images and then integrates the opinions. A radiologist agent decomposes the image recognition task into smaller problems that are solved collectively by multiple intelligent sub-agents. Finally, we present a preliminary implementation and running examples of the multi-agent system.

  20. Knowledge Management in Role Based Agents

    NASA Astrophysics Data System (ADS)

    Kır, Hüseyin; Ekinci, Erdem Eser; Dikenelli, Oguz

    In multi-agent system literature, the role concept is getting increasingly researched to provide an abstraction to scope beliefs, norms, goals of agents and to shape relationships of the agents in the organization. In this research, we propose a knowledgebase architecture to increase applicability of roles in MAS domain by drawing inspiration from the self concept in the role theory of sociology. The proposed knowledgebase architecture has granulated structure that is dynamically organized according to the agent's identification in a social environment. Thanks to this dynamic structure, agents are enabled to work on consistent knowledge in spite of inevitable conflicts between roles and the agent. The knowledgebase architecture is also implemented and incorporated into the SEAGENT multi-agent system development framework.

  1. Other potentially useful new injectable anesthetic agents.

    PubMed

    Ilkiw, J E

    1992-03-01

    Ultrashort barbiturates are not ideal injectable anesthetic agents, and new agents continue to be released as investigators pursue the goal of finding a more ideal agent. Of the new injectable agents discussed, propofol seems to be the most promising drug. Propofol should find a place in veterinary practice as an outpatient anesthetic agent because it has a rapid, smooth, and complete recovery even after repeated or continuous administration. Midazolam does not induce anesthesia in healthy, small animals and, as such, can only be used in combination with other injectable agents, such as ketamine or the thiobarbiturates. In our practice, Telazol has found a place in the anesthetic management of feral cats and aggressive dogs, where it is used for heavy sedation or to induce anesthesia. The role of flumazenil, as a reversal agent, in veterinary practice remains to be determined; however, the role in small domestic animals is unlikely to be significant. PMID:1585555

  2. 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

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

    PubMed

    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 genotoxicity, 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 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. PMID:9719666

  4. Drug therapy reviews: antirheumatic agents.

    PubMed

    Evens, R P

    1979-05-01

    The pathophysiology, symptoms and drug treatment of rheumatic disease are reviewed. Antirheumatic drugs reviewed are salicylates (including aspirin, sodium salicylate, choline salicylate, choline magnesium salicylate, salsalate), phenylpropionic acid derivatives (fenoprofen, ibuprofen, naproxen), indole derivatives (sulindac, tolmetin and indomethacin), pyrazolone derivatives (phenylbutazone, oxyphenbutazone), gold compounds, penicillamine, antimalarials mefenamic acid, corticosteroids and immunosuppressives. Simple analgesic therapy (acetaminophen, aspirin, propoxyphene) is used in the early stage of the disease. As the disease progresses, aspirin remains the drug of choice for antiinflammatory activity but the phenylpropionic acid or indole derivatives may be preferred in patients unable to tolerate salicylates. If such nonsteroidal antiinflammatory agents are not effective, parenteral therapy with gold compounds or oral penicillamine usually is indicated. Indomethacin or phenylbutazone, then antimalarials, are resorted to next. Corticosteroids or immunosuppressives are reserved for patients who are unsuccessfully controlled or who have major side effects with the other drugs. Mefenamic acid occupies a very secondary place in rheumatoid arthritis treatment. PMID:377958

  5. [Anticonvulsant agents in neuralgic pain.].

    PubMed

    Jurna, I; Zenz, M

    1992-06-01

    The anticonvulsants, carbamazepine, clonazepam, phenytoin, and valproic acid are capable of depressing attacks of shooting pain in neuralgia. Shooting pain is perceived in trigeminal, intercostal, and other neuralgias, as a consequence of infectious diseases such as herpes zoster, and in the course of polyneuropathies of various causes. It is due to injury of nociceptive afferents, which generate bursts of activity in response to appropriate environmental changes. The anticonvulsant agents have no analgesic property per se, so that background pain remains unchanged. The depression of shooting pain results from the anticonvulsant action of the compounds. Both carbamazepine and phenytoin block synaptic transmission of neuronal hyperactivity by a direct depressant action that includes reduction of sodium conductance and by activation of inhibitory control. Clonazepam and valproic acid act by enhancing GABA-mediated inhibition of synaptic transmission. Carbamazepine is by far the most widely used compound; phenytoin, clonazepam, and valproic acid are not so popular because of their side effects. PMID:18415623

  6. Biotherapeutic agents and vaginal health.

    PubMed

    Al-Ghazzewi, F H; Tester, R F

    2016-07-01

    Treatment of vaginal infection requires different drugs although the recurrence rate post treatment remains high due to adverse effects on the beneficial microbiota. Thus, there are clear clinical advantages for the use of biotherapeutic agents (prebiotics and/or probiotics) for treating these infections. Pre- and probiotic beneficial effects can be delivered topically or systemically. In general, both approaches have the potential to optimize, maintain and restore the ecology of the vaginal ecosystem. Specific carbohydrates provide a therapeutic approach for controlling infections by stimulating the growth of the indigenous lactobacilli but inhibiting the growth and adhesion of pathogens to the vaginal epithelial cells. Overall, little evidence exists to promote the prevention or treatment of vaginal disease with prebiotic carbohydrates in formulations such as pessaries, creams or douches. However, recent reports have promoted prebiotic applications in ecosystems other than the gut and include the mouth, skin and vagina. This review focuses on the utilization of pre- and probiotics for vaginal health. PMID:26757173

  7. Hydrogen bond-mediated recognition of the chemical warfare agent soman (GD).

    PubMed

    Sambrook, Mark R; Hiscock, Jennifer R; Cook, Alexandra; Green, A Christopher; Holden, Ian; Vincent, Jack C; Gale, Philip A

    2012-06-01

    NMR titration studies in acetonitrile-d(3)/DMSO-d(6) mixtures demonstrate that diindolylurea-based receptors can form complexes with the organophosphorus nerve agent soman in organic solution. PMID:22546851

  8. Agent Reward Shaping for Alleviating Traffic Congestion

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan; Agogino, Adrian

    2006-01-01

    Traffic congestion problems provide a unique environment to study how multi-agent systems promote desired system level behavior. What is particularly interesting in this class of problems is that no individual action is intrinsically "bad" for the system but that combinations of actions among agents lead to undesirable outcomes, As a consequence, agents need to learn how to coordinate their actions with those of other agents, rather than learn a particular set of "good" actions. This problem is ubiquitous in various traffic problems, including selecting departure times for commuters, routes for airlines, and paths for data routers. In this paper we present a multi-agent approach to two traffic problems, where far each driver, an agent selects the most suitable action using reinforcement learning. The agent rewards are based on concepts from collectives and aim to provide the agents with rewards that are both easy to learn and that if learned, lead to good system level behavior. In the first problem, we study how agents learn the best departure times of drivers in a daily commuting environment and how following those departure times alleviates congestion. In the second problem, we study how agents learn to select desirable routes to improve traffic flow and minimize delays for. all drivers.. In both sets of experiments,. agents using collective-based rewards produced near optimal performance (93-96% of optimal) whereas agents using system rewards (63-68%) barely outperformed random action selection (62-64%) and agents using local rewards (48-72%) performed worse than random in some instances.

  9. Antagonistic formation motion of cooperative agents

    NASA Astrophysics Data System (ADS)

    Lu, Wan-Ting; Dai, Ming-Xiang; Xue, Fang-Zheng

    2015-02-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonistic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all of the agents make an antagonistic formation motion in a distributed manner. It is shown that all of the agents can be spontaneously divided into several groups and that agents in the same group collaborate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61203080 and 61473051) and the Natural Science Foundation of Chongqing City (Grant No. CSTC 2011BB0081).

  10. Persuasive Conversational Agent with Persuasion Tactics

    NASA Astrophysics Data System (ADS)

    Narita, Tatsuya; Kitamura, Yasuhiko

    Persuasive conversational agents persuade people to change their attitudes or behaviors through conversation, and are expected to be applied as virtual sales clerks in e-shopping sites. As an approach to create such an agent, we have developed a learning agent with the Wizard of Oz method in which a person called Wizard talks to the user pretending to be the agent. The agent observes the conversations between the Wizard and the user, and learns how to persuade people. In this method, the Wizard has to reply to most of the user's inputs at the beginning, but the burden gradually falls because the agent learns how to reply as the conversation model grows.

  11. Pinning synchronization of a mobile agent network

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Sun, You-xian

    2009-11-01

    We investigate the problem of controlling a group of mobile agents in a plane in order to move them towards a desired orbit via pinning control, in which each agent is associated with a chaotic oscillator coupled with those of neighboring agents, and the pinning strategy is to have the common linear feedback acting on a small fraction of agents by random selection. We explore the effects of the pinning probability, feedback gains and agent density in the pinning synchronization of a mobile agent network under a fast-switching constraint, and perform numerical simulations for validation. In particular, we show that there exists a critical pinning density for network synchronization with an unbounded region: above the threshold, the dynamical network can be controlled by pinning; below it, anarchy prevails. And for the network with a single bounded synchronization region, pinning control has little effect as regards enhancing network synchronizability.

  12. Evolutionary algorithms and multi-agent systems

    NASA Astrophysics Data System (ADS)

    Oh, Jae C.

    2006-05-01

    This paper discusses how evolutionary algorithms are related to multi-agent systems and the possibility of military applications using the two disciplines. In particular, we present a game theoretic model for multi-agent resource distribution and allocation where agents in the environment must help each other to survive. Each agent maintains a set of variables representing actual friendship and perceived friendship. The model directly addresses problems in reputation management schemes in multi-agent systems and Peer-to-Peer distributed systems. We present algorithms based on evolutionary game process for maintaining the friendship values as well as a utility equation used in each agent's decision making. For an application problem, we adapted our formal model to the military coalition support problem in peace-keeping missions. Simulation results show that efficient resource allocation and sharing with minimum communication cost is achieved without centralized control.

  13. A New Understanding of Chemical Agent Release

    SciTech Connect

    Nakafuji, G; Greenman, R; Theofanous, T

    2002-07-24

    The evolution of thickened chemical agent released at supersonic velocities, due to a missile defense intercept or a properly functioning warhead, has been misunderstood. Current and historical experimental and modeling efforts have attributed agent breakup to a variety of droplet breakup mechanisms. According to this model, drops of agent fragment into subsequent generations of smaller drops until a stable drop size is reached. Recent experimental data conducted in a supersonic wind tunnel show that agent breakup is not driven by any droplet breakup mechanism. The breakup of agent is instead governed by viscoelastic behavior and aerodynamic history effects. This viscoelastic breakup mechanism results in the formation of threads and sheets of liquid, instead of drops. The evolution and final state of agent released has broad implications not only for aerobreakup models, but also for all atmospheric dispersion models.

  14. Multi-Agent Information Classification Using Dynamic Acquaintance Lists.

    ERIC Educational Resources Information Center

    Mukhopadhyay, Snehasis; Peng, Shengquan; Raje, Rajeev; Palakal, Mathew; Mostafa, Javed

    2003-01-01

    Discussion of automated information services focuses on information classification and collaborative agents, i.e. intelligent computer programs. Highlights include multi-agent systems; distributed artificial intelligence; thesauri; document representation and classification; agent modeling; acquaintances, or remote agents discovered through…

  15. Infrared spectroscopy for chemical agent detection using tailored hypersorbent materials

    NASA Astrophysics Data System (ADS)

    Kozak, Dmitry A.; McGill, R. Andrew; Stievater, Todd H.; Furstenberg, Robert; Pruessner, Marcel W.; Nguyen, Viet

    2015-06-01

    We report long-wave infrared (LWIR, 5-15 μm) and mid-wave infrared (MWIR, 2.5 - 5 μm) differential absorption spectra of different nerve agent simulants and common solutes sorbed to poly(methyldi(1,1,1-trifluoro-2-trifluoromethyl- 2-hydroxypent-4-enyl)silane, HCSFA2, an NRL developed hypersorbent polymer. HCSFA2 is a strong hydrogen-bond acidic polymer which exhibits large gas-polymer partitions for a variety of hazardous chemicals with hydrogen-bond basic properties such as the phosphonate ester G-nerve agents or their simulants. The measured ATR-FTIR differential absorption spectra show complex fingerprint signal changes in the resonances for the sorbent material itself, as well as new resonances arising from chemical bonding between the solute or analyte and the sorbent or the solute itself being present in the sorbent.

  16. Anaphylactoid and adverse reactions to radiocontrast agents.

    PubMed

    Hagan, John B

    2004-08-01

    Over the past 75 years, radiocontrast agents have provided numerous diagnostic and therapeutic advances. The benefits of these agents must be weighed against the potential risks for each individual undergoing radiologic tests. This summary is intended to be a guide for the allergy and immunology specialist to direct him or her to the current literature regarding adverse reactions to traditional and less commonly used radiologic contrast agents. PMID:15242724

  17. Massive Multi-Agent Systems Control

    NASA Technical Reports Server (NTRS)

    Campagne, Jean-Charles; Gardon, Alain; Collomb, Etienne; Nishida, Toyoaki

    2004-01-01

    In order to build massive multi-agent systems, considered as complex and dynamic systems, one needs a method to analyze and control the system. We suggest an approach using morphology to represent and control the state of large organizations composed of a great number of light software agents. Morphology is understood as representing the state of the multi-agent system as shapes in an abstract geometrical space, this notion is close to the notion of phase space in physics.

  18. The EO-1 Autonomous Science Agent Architecture

    NASA Technical Reports Server (NTRS)

    Chien, Steve; Sherwood, Rob; Tran, Daniel; Cichy, Benjamin; Rabideau, Gregg; Castano, Rebecca; Davies, Ashley; Lee, Rachel; Mandl, Dan; Frye, Stuart; Trout, Bruce; Hengemihle, Jerry; D'Agostino, Jeff; Shulman, Seth; Ungar, Stephen; Brakke, Thomas; Boyer, Darrell; Van Gaasbeck, Jim; Greeley, Ronald; Doggett, Thomas; Baker, Victor; Dohm, James; Ip, Felipe

    2004-01-01

    An Autonomous Science Agent is currently flying onboard the Earth Observing One Spacecraft. This software enables the spacecraft to autonomously detect and respond to science events occurring on the Earth. The package includes software systems that perform science data analysis, deliberative planning, and run-time robust execution. Because of the deployment to a remote spacecraft, this Autonomous Science Agent has stringent constraints of autonomy, reliability, and limited computing resources. We describe these constraints and how they are reflected in our agent architecture.

  19. Departments as Agents of Change

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1996-07-01

    Higher education is changing because it has no choice. And, for the most part, outside influences are dictating the processes of change. The more fortunate institutions have had a flat budget during this period, but most have been forced to deal with a declining revenue stream as well. Legislators seem bent on micromanaging state-supported institutions, even as they cut their support. Regulators demand greater institutional accountability. Students and their parents expect more service at lower prices and increased flexibility. Technological advances have dramatically affected the availability and accessibility of extant knowledge. It is no longer a question of whether institutions will change, but rather, who will control the change. Most institutions possess long-standing academic traditions, but these are placed at risk in an increasingly competitive market that holds little sympathy for such traditions and may even see them as obstacles or barriers. As a result, the change agents will undoubtedly have a profound effect on the very nature of academic institutions. From the academic point of view, it would seem prudent to attempt to manage the changes that will inevitably occur. A number of concerned observers, notably the Pew Higher Education Roundtable and the American Association for Higher Education, argue persuasively that the academic department is the logical focus for responding to the current winds of change. Using a marketing metaphor, the academic department has been likened to a "producers' cooperative" of services that consumers seek. Thus, the department should be held accountable for the quality of teaching delivered by its members, for the coherence of its major, for its contributions to the general education curriculum, and for supervising and rewarding its individual faculty members. If departments are to be held accountable, it is surely in their best interest to act in such a way that they are accountable. Expecting academic departments to be

  20. Radioiodine: the classic theranostic agent.

    PubMed

    Silberstein, Edward B

    2012-05-01

    Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and