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Sample records for vx nerve agent

  1. Extraction of nerve agent VX from soils.

    Science.gov (United States)

    Montauban, Cécile; Bégos, Arlette; Bellier, Bruno

    2004-05-15

    The development and optimization of a method allowing the extraction of intact organophosphorus chemical warfare agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) from several types of soils are presented here. This involved the selection of an appropriate buffer to bring the sample to a pH close to the pK(a) of VX but sufficiently low to avoid its basic hydrolysis. Buffering with Tris (pH 9) and subsequent extraction of the aqueous layer by a 85:15 (v/v) hexane/dichloromethane mixture allows rapid and sensitive flame photometric detection of VX at spiking levels lower than 10 microg x g(-1), even after 3 months of aging. Extraction yields were close to 60% in complex matrixes. This method also allows recovery and identification of a characteristic degradation product of VX, bis(2-diisopropylaminoethyl) disulfide, which appears to be formed during the aging process. The performance of this method is far better than that of OPCW reference operating procedure, which does not allow extraction of detectable amounts of VX (spiked at 10 microg x g(-1)) in one of the soils used for this study.

  2. Fingerprinting malathion vapor: a simulant for VX nerve agent

    Science.gov (United States)

    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.

  3. Identification of VX type nerve agents using cryodeposition GC-FTIR

    Science.gov (United States)

    Söderström, Martin T.

    1998-06-01

    Analysis of VX type nerve agents with a gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR) system using cryodeposition of the eluents is described. An interpretation system based on comparison of characteristic spectral features to the features in reference spectra, is used to characterize side chains in VX type nerve agents.

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

    Science.gov (United States)

    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.

  5. Structure-activity relationship for the reactivators of acetylcholinesterase inhibited by nerve agent VX.

    Science.gov (United States)

    Kuca, Kamil; Musilek, Kamil; Jun, Daniel; Karasova, Jana; Soukup, Ondrej; Pejchal, Jaroslav; Hrabinova, Martina

    2013-08-01

    Nerve agents such as sarin, VX and tabun are organophosphorus compounds able to inhibit an enzyme acetylcholinesterase (AChE). AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. None from the known AChE reactivators is able to reactivate AChE inhibited by all kinds of nerve agents. In this work, reactivation potency of seventeen structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was outlined. VX was chosen as appropriate member of the nerve agent family.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-08-08

    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.

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

    Science.gov (United States)

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

    2011-10-21

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

  9. Acute lung injury following inhalation exposure to nerve agent VX in guinea pigs.

    Science.gov (United States)

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

    2006-05-01

    A microinstillation technique of inhalation exposure was utilized to assess lung injury following chemical warfare nerve agent VX [methylphosphonothioic acid S-(2-[bis(1-methylethyl)amino]ethyl) O-ethyl ester] exposure in guinea pigs. Animals were anesthetized using Telazol-meditomidine, gently intubated, and VX was aerosolized using a microcatheter placed 2 cm above the bifurcation of the trachea. Different doses (50.4 microg/m3, 70.4 micro g/m(m3), 90.4 microg/m(m3)) of VX were administered at 40 pulses/min for 5 min. Dosing of VX was calculated by the volume of aerosol produced per 200 pulses and diluting the agent accordingly. Although the survival rate of animals exposed to different doses of VX was similar to the controls, nearly a 20% weight reduction was observed in exposed animals. After 24 h of recovery, the animals were euthanized and bronchoalveolar lavage (BAL) was performed with oxygen free saline. BAL was centrifuged and separated into BAL fluid (BALF) and BAL cells (BALC) and analyzed for indication of lung injury. The edema by dry/wet weight ratio of the accessory lobe increased 11% in VX-treated animals. BAL cell number was increased in VX-treated animals compared to controls, independent of dosage. Trypan blue viability assay indicated an increase in BAL cell death in 70.4 microg/m(m3) and 90.4 microg/m(m3) VX-exposed animals. Differential cell counting of BALC indicated a decrease in macrophage/monocytes in VX-exposed animals. The total amount of BAL protein increased gradually with the exposed dose of VX and was highest in animals exposed to 90.4 microg/m(m3), indicating that this dose of VX caused lung injury that persisted at 24 h. In addition, histopathology results also suggest that inhalation exposure to VX induces acute lung injury.

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

    Science.gov (United States)

    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.

  11. Favorable pendant-amino metal chelation in VX nerve agent model systems.

    Science.gov (United States)

    Bandyopadhyay, Indrajit; Kim, Min Jeong; Lee, Yoon Sup; Churchill, David G

    2006-03-16

    We have performed DFT computational studies [B3LYP, 6-31+G] to obtain metal ion coordination isomers of VX-Me [MeP(O)(OMe)(SCH2CH2NMe2)], a model of two of the most lethal nerve agents: VX [MeP(O)(OEt)(SCH2CH2N(iPr)2)] and Russian-VX [MeP(O)(OCH2CHMe2)(SCH2CH2N(Et)2)]. Our calculations involved geometry optimizations of the neutral VX-Me model as well as complexes with H+, Li+, Na+, K+, Be2+, Mg2+, and Ca2+ that yielded 2-8 different stable chelation modes for each ion that involved mainly mono- and bidentate binding. Importantly, our studies revealed that the [O(P),N] bidentate binding mode, long thought to be the active mode in differentiating the hydrolytic path of VX from other nerve agents, was the most stable for all ions studied here. Binding energy depended mainly on ionic size as well as charge, with binding energies ranging from 364 kcal mol(-1) for Be2+ to 33 kcal mol(-1) for K+. Furthermore, calculated NMR shifts for VX-Me correlate to experimental values of VX.

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

    Science.gov (United States)

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

    2017-03-05

    Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by (31)P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL

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

    NARCIS (Netherlands)

    Joosen, M.J.A.; Schans, M.J. van der; Helden, H.P.M. van

    2010-01-01

    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 t

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Investigating the affinities and persistence of VX nerve agent in environmental matrices.

    Science.gov (United States)

    Love, Adam H; Vance, Andrew L; Reynolds, John G; Davisson, M Lee

    2004-12-01

    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 specific adsorption was forced. No enhanced degradation occurred with goethite in small amounts of 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.

  17. Computational characterization of how the VX nerve agent binds human serum paraoxonase 1.

    Science.gov (United States)

    Fairchild, Steven Z; Peterson, Matthew W; Hamza, Adel; Zhan, Chang-Guo; Cerasoli, Douglas M; Chang, Wenling E

    2011-01-01

    Human serum paraoxonase 1 (HuPON1) is an enzyme that can hydrolyze various chemical warfare nerve agents including VX. A previous study has suggested that increasing HuPON1's VX hydrolysis activity one to two orders of magnitude would make the enzyme an effective countermeasure for in vivo use against VX. This study helps facilitate further engineering of HuPON1 for enhanced VX-hydrolase activity by computationally characterizing HuPON1's tertiary structure and how HuPON1 binds VX. HuPON1's structure is first predicted through two homology modeling procedures. Docking is then performed using four separate methods, and the stability of each bound conformation is analyzed through molecular dynamics and solvated interaction energy calculations. The results show that VX's lone oxygen atom has a strong preference for forming a direct electrostatic interaction with HuPON1's active site calcium ion. Various HuPON1 residues are also detected that are in close proximity to VX and are therefore potential targets for future mutagenesis studies. These include E53, H115, N168, F222, N224, L240, D269, I291, F292, and V346. Additionally, D183 was found to have a predicted pKa near physiological pH. Given D183's location in HuPON1's active site, this residue could potentially act as a proton donor or accepter during hydrolysis. The results from the binding simulations also indicate that steered molecular dynamics can potentially be used to obtain accurate binding predictions even when starting with a closed conformation of a protein's binding or active site.

  18. Quantitation of metabolites of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Barr, John R; Driskell, W J; Aston, Linda S; Martinez, Rodolfo A

    2004-01-01

    Organophosphorus nerve agents are among the most toxic organic compounds known and continue to be a threat for both military and terrorist use. We have developed an isotope-dilution gas chromatography-tandem mass spectrometric (GC-MS-MS) method for quantitating the urinary metabolites of the organophosphorus nerve agents sarin (GB), soman (GD), VX, Russian VX (RVX), and cyclohexylsarin (GF). Urine samples were acidified, extracted into ether-acetonitrile, derivatized by methylation with diazomethane, and analyzed by GC-MS-MS. The limits of detection were less than 1 micro g/L for all analytes.

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

    Science.gov (United States)

    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.

  20. Phosphoproteomic analysis reveals compensatory effects in the piriform cortex of VX nerve agent exposed rats.

    Science.gov (United States)

    Nirujogi, Raja Sekhar; Wright, James D; Manda, Srikanth S; Zhong, Jun; Na, Chan Hyun; Meyerhoff, James; Benton, Bernard; Jabbour, Rabih; Willis, Kristen; Kim, Min-Sik; Pandey, Akhilesh; Sekowski, Jennifer W

    2015-01-01

    To gain insights into the toxicity induced by the nerve agent VX, an MS-based phosphoproteomic analysis was carried out on the piriform cortex region of brains from VX-treated rats. Using isobaric tag based TMT labeling followed by titanium dioxide enrichment strategy, we identified 9975 unique phosphosites derived from 3287 phosphoproteins. Temporal changes in the phosphorylation status of peptides were observed over a time period of 24 h in rats exposed to a 1× LD50, intravenous (i.v.) dose with the most notable changes occurring at the 1 h postexposure time point. Five major functional classes of proteins exhibited changes in their phosphorylation status: (i) ion channels/transporters, including ATPases, (ii) kinases/phosphatases, (iii) GTPases, (iv) structural proteins, and (v) transcriptional regulatory proteins. This study is the first quantitative phosphoproteomic analysis of VX toxicity in the brain. Understanding the toxicity and compensatory signaling mechanisms will improve the understanding of the complex toxicity of VX in the brain and aid in the elucidation of novel molecular targets that would be important for development of improved countermeasures. All MS data have been deposited in the ProteomeXchange with identifier PXD001184 (http://proteomecentral.proteomexchange.org/dataset/PXD001184).

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

    Science.gov (United States)

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

    2010-10-06

    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.

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

    Science.gov (United States)

    Josse, Denis; Wartelle, Julien; Cruz, Catherine

    2015-05-05

    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.

  3. Colorimetric dipstick for assay of organophosphate pesticides and nerve agents represented by paraoxon, sarin and VX.

    Science.gov (United States)

    Pohanka, Miroslav; Karasova, Jana Zdarova; Kuca, Kamil; Pikula, Jiri; Holas, Ondrej; Korabecny, Jan; Cabal, Jiri

    2010-04-15

    A dipstick for fast assay of nerve agents and organophosphate pesticides was developed. Indicator pH papers were used as detectors. The principle of the assay is based on enzymatic hydrolysis of acetylcholine into acetic acid and choline by acetylcholinesterase. Acidification of the reaction medium due to accumulation of acetic acid was visible. The colour changed from dark red to yellow as the pH indicator recognized pH shift. Presence of an organophosphate pesticide or a nerve agent results in irreversible inhibition of acetylcholinesterase intercepted on the dipstick. The inhibition stops the enzymatic reaction. The inhibition appears as no change of the medium pH. Three compounds were assayed: paraoxon-ethyl as representative organophosphate pesticides and nerve agents sarin and VX. The achieved limit of detection was 5 x 10(-8)M for paraoxon-ethyl and 5 x 10(-9)M for sarin and VX. Dipsticks were found stable for at least one month. Suitability of these dipsticks for routine assay is discussed.

  4. Evidence for nonacetylcholinesterase targets of organophosphorus nerve agent: supersensitivity of acetylcholinesterase knockout mouse to VX lethality.

    Science.gov (United States)

    Duysen, E G; Li, B; Xie, W; Schopfer, L M; Anderson, R S; Broomfield, C A; Lockridge, O

    2001-11-01

    The possibility that organophosphate toxicity is due to inhibition of targets other than acetylcholinesterase (AChE, EC 3.1.1.7) was examined in AChE knockout mice. Mice (34-55 days old) were grouped for this study, after it was determined that AChE, butyrylcholinesterase (BChE), and carboxylesterase activities had reached stable values by this age. Mice with 0, 50, or 100% AChE activity were treated subcutaneously with the nerve agent VX. The LD50 for VX was 10 to 12 microg/kg in AChE-/-, 17 microg/kg in AChE+/-, and 24 microg/kg in AChE+/+ mice. The same cholinergic signs of toxicity were present in AChE-/- mice as in wild-type mice, even though AChE-/- mice have no AChE whose inhibition could lead to cholinergic signs. Wild-type mice, but not AChE-/- mice, were protected by pretreatment with atropine. Tissues were extracted from VX-treated and untreated animals and tested for AChE, BChE, and acylpeptide hydrolase activity. VX treatment inhibited 50% of the AChE activity in brain and muscle of AChE+/+ and +/- mice, 50% of the BChE activity in all three AChE genotypes, but did not significantly inhibit acylpeptide hydrolase activity. It was concluded that the toxicity of VX must be attributed to inhibition of nonacetylcholinesterase targets in the AChE-/- mouse. Organophosphorus ester toxicity in wild-type mice is probably due to inhibition or binding to several proteins, only one of which is AChE.

  5. Natural Detoxification Capacity to Inactivate Nerve Agents Sarin and VX in the Rat Blood

    Directory of Open Access Journals (Sweden)

    Jiří Bajgal

    2016-03-01

    Full Text Available Background: The method of continual determination of the rat blood cholinesterase activity was developed to study the changes of the blood cholinesterases following different intervetions. Aims: The aim of this study is registration of cholinesterase activity in the rat blood and its changes to demonstrate detoxification capacity of rats to inactivate sarin or VX in vivo. Methods: The groups of female rats were premedicated (ketamine and xylazine and cannulated to a. femoralis. Continual blood sampling (0.02 ml/min and monitoring of the circulating blood cholinesterase activity were performed. Normal activity was monitored 1–2 min and then the nerve agent was administered i.m. (2× LD50. Using different time intervals of the leg compression and relaxation following the agent injection, cholinesterase activity was monitored and according to the inhibition obtained, detoxification capacity was assessed. Results: Administration of sarin to the leg, then 1 and 5 min compression and 20 min later relaxation showed that further inhibition in the blood was not observed. On the other hand, VX was able to inhibit blood cholinesterases after this intervention. Conclusions: The results demonstrated that sarin can be naturally detoxified on the contrary to VX. Described method can be used as model for other studies dealing with changes of cholinesterases in the blood following different factors.

  6. Liquid chromatography tandem mass spectrometry applied to quantitation of the organophosphorus nerve agent VX in microdialysates from blood probes.

    Science.gov (United States)

    Stubbs, S J; Read, R W

    2010-05-15

    VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methylphosphonothiolate) is a low volatility organophosphorus (OP) nerve agent and therefore the most likely route of exposure is via percutaneous absorption. Microdialysis has been used as a tool to study percutaneous poisoning by VX in the anesthetised guinea pig. A liquid chromatography tandem mass spectrometry (LC-MS-MS) method using positive electrospray ionisation (ESI) was used to quantitate VX in microdialysate samples collected from microdialysis probes, implanted into a blood vessel of anesthetised guinea pigs. The method resulted from modification of a LC-MS-MS method previously developed for the analysis of dermal microdialysates. Modification increased the sensitivity of the method, allowing quantitation of the trace levels of VX in blood microdialysates, over the range 0.002-1 ng/ml, with linear calibration. Quantitative results have been used to determine the time course of VX concentrations in the blood of guinea pigs following percutaneous poisoning.

  7. Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.

    Science.gov (United States)

    Gao, Xiugong; Lin, Hsiuling; Ray, Radharaman; Ray, Prabhati

    2013-05-01

    Organophosphorus (OP) compounds represent an important group of chemical warfare nerve agents that remains a significant and constant military and civilian threat. OP compounds are considered acting primarily via cholinergic pathways by binding irreversibly to acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Many studies over the past years have suggested that other mechanisms of OP toxicity exist, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. Here we performed a microarray study in which cultured human neural cells were exposed to 0.1 or 10 μM of VX for 1 h. Global gene expression changes were analyzed 6, 24, and 72 h post exposure. Functional annotation and pathway analysis of the differentially expressed genes has revealed many genes, networks and canonical pathways that are related to nervous system development and function, or to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In particular, the neuregulin pathway impacted by VX exposure has important implications in many nervous system diseases including schizophrenia. These results provide useful information valuable in developing suitable antidotes for more effective prevention and treatment of, as well as in developing biomarkers for, VX-induced chronic neurotoxicity.

  8. In vitro selection and efficacy of topical skin protectants against the nerve agent VX.

    Science.gov (United States)

    Millerioux, J; Cruz, C; Bazire, A; Lallement, G; Lefeuvre, L; Josse, D

    2009-04-01

    Against highly toxic chemicals that are quickly absorbed in the skin, topical formulations could adequately complement specific protective suits and equipments. In this work, we evaluated in vitro and compared the skin protection efficacy against the nerve agent VX of four different topical formulations: oil-in-water and water-in-oil emulsions, a perfluorinated-based cream and a hydrogel. Semi-permeable silicone membrane, pig-ear and human abdominal split-thickness skin samples mounted in diffusion cells were compared as in vitro permeation tests. The results showed that silicone membrane could be used instead of skin samples to screen for potentially effective formulations. However, the results indicated that due to potentially significant interactions between formulations and skin, relevant ranking of formulations according to their protective efficacy could require tests with skin samples. The main phase of emulsions, water or oil, was not found to be critical for skin protective efficacy against VX. Instead, specific film-forming ingredients such as perfluorinated-based polymers and silicones could significantly affect the skin protective efficacy of formulations. We showed that a hydrogel containing specific hydrophilic polymers was by far the most effective of the formulations evaluated against VX skin permeation in vitro.

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

    Science.gov (United States)

    Nambiar, Madhusoodana P; Gordon, Richard K; Rezk, Peter E; Katos, Alexander M; Wajda, Nikolai A; Moran, Theodore S; Steele, Keith E; Doctor, Bhupendra P; Sciuto, Alfred M

    2007-03-01

    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(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.

  10. Acute toxic effects of nerve agent VX on respiratory dynamics and functions following microinsillation inhalation exposure in guinea pigs.

    Science.gov (United States)

    Rezk, Peter E; Graham, Jacob R; Moran, Theodore S; Gordon, Richard K; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2007-03-01

    Exposure to a chemical warfare nerve agent (CWNA) leads to severe respiratory distress, respiratory failure, or death if not treated. We investigated the toxic effects of nerve agent VX on the respiratory dynamics of guinea pigs following exposure to 90.4 mug/m3 of VX or saline by microinstillation inhalation technology for 10 min. Respiratory parameters were monitored by whole-body barometric plethysmography at 4, 24, and 48 h, 7 d, 18 d, and 4 wk after VX exposure. VX-exposed animals showed a significant decrease in the respiratory frequency (RF) at 24 and 48 h of recovery (p value .0329 and .0142, respectively) compared to the saline control. The tidal volume (TV) slightly increased in VX exposed animals at 24 and significantly at 48 h (p = .02) postexposure. Minute ventilation (MV) increased slightly at 4 h but was reduced at 24 h and remained unchanged at 48 h. Animals exposed to VX also showed an increase in expiratory (Te) and relaxation time (RT) at 24 and 48 h and a small reduction in inspiratory time (Ti) at 24 h. A significant increase in end expiratory pause (EEP) was observed at 48 h after VX exposure (p = .049). The pseudo lung resistance (Penh) was significantly increased at 4 h after VX exposure and remained slightly high even at 48 h. Time-course studies reveal that most of the altered respiratory dynamics returned to normal at 7 d after VX exposure except for EEP, which was high at 7 d and returned to normal at 18 d postexposure. After 1 mo, all the monitored respiratory parameters were within normal ranges. Bronchoalveolar lavage (BAL) 1 mo after exposure showed virtually no difference in protein levels, cholinesterase levels, cell number, and cell death in the exposed and control animals. These results indicate that sublethal concentrations of VX induce changes in respiratory dynamics and functions that over time return to normal levels.

  11. Mutagenesis of organophosphorus hydrolase to enhance hydrolysis of the nerve agent VX.

    Science.gov (United States)

    Gopal, S; Rastogi, V; Ashman, W; Mulbry, W

    2000-12-20

    Organophosphorus hydrolase (OPH) is capable of hydrolyzing a wide variety of organophosphorus pesticides and chemical warfare agents. However, the hydrolytic activity of OPH against the warfare agent VX is less than 0.1% relative to its activity against parathion and paraoxon. Based on the crystal structure of OPH and the similarities it shares with acetylcholinesterase, eight OPH mutants were constructed with the goal of increasing OPH activity toward VX. The activities of crude extracts from these mutants were measured using VX, demeton-S methyl, diisopropylfluoro-phosphate, ethyl parathion, paraoxon, and EPN as substrates. One mutant (L136Y) displayed a 33% increase in the relative VX hydrolysis rate compared to wild type enzyme. The other seven mutations resulted in 55-76% decreases in the relative rates of VX hydrolysis. There was no apparent relationship between the hydrolysis rates of VX and the rates of the other organophosphorus compounds tested.

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

    Science.gov (United States)

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

    2015-04-08

    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.

  13. Toxicokinetics of the nerve agent (+/-)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration.

    Science.gov (United States)

    van der Schans, Marcel J; Lander, Brenda J; van der Wiel, Herma; Langenberg, Jan P; Benschop, Hendrik P

    2003-08-15

    In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(+/-)P(+/-)-soman and (+/-)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (+/-)-VX. A validated method was developed to determine blood levels of (+/-)-VX by means of achiral gas chromatography at blood levels > or =10 pg/ml. The ratio of the two enantiomers of VX in blood could be measured at levels > or =1 ng/ml by using chiral HPLC in combination with off-line gas chromatographic analysis. In order to obtain basic information on the toxicokinetics of (+/-)-VX, i.e., under conditions of 100% bioavailability, the blood levels of this agent were measured in hairless guinea pigs at iv doses corresponding with 1 and 2 LD50. The derived AUCs indicate a reasonable linearity of the toxicokinetics with dose. Also, the toxicokinetics in marmoset primates was studied at an absolute iv dose corresponding with 1 LD50 in the hairless guinea pig which led to approximately the same levels of (+/-)-VX in blood as observed at 2 LD50 in the hairless guinea pig. Finally, the toxicokinetics of (+/-)-VX were measured in hairless guinea pigs via the most relevant porte d' entrée for this agent, which is the percutaneous route at a dose corresponding with 1 LD50 (pc). Large variations were observed between individual animals in the rate of penetration of (+/-)-VX and in concomitant progression of AChE inhibition in blood of these animals. Blood levels of (+/-)-VX increased gradually over a 6-h period of time. After a 7-h penetration period, the total AUC corresponded with 2.5% bioavailability relative to iv administration. In contrast with the G-agents C(+/-)P(+/-)-soman and (+/-)-sarin, stereospecificity in the sequestration of the two enantiomers of (+/-)-VX is not a prominent phenomenon. It appears that (+/-)-VX is substantially more persistent in vivo than the two G-agents. This persistence may undermine the efficacy of pretreatment with carbamates of percutaneous

  14. Toxicokinetics of the nerve agent (±)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration

    NARCIS (Netherlands)

    Schans, M.J. van der; Lander, B.J.; Wiel, H. van der; Langenberg, J.P.; Benschop, H.P.

    2003-01-01

    In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(±)P(±)-soman and (±)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (±)-VX. A validated method was developed to determine blood levels of (±)-VX by means of achiral gas chromatograp

  15. Characterization of a phosphodiesterase capable of hydrolyzing EA 2192, the most toxic degradation product of the nerve agent VX.

    Science.gov (United States)

    Ghanem, Eman; Li, Yingchun; Xu, Chengfu; Raushel, Frank M

    2007-08-07

    Glycerophosphodiesterase (GpdQ) from Enterobacter aerogenes is a nonspecific diesterase that enables Escherichia coli to utilize alkyl phosphodiesters, such as diethyl phosphate, as the sole phosphorus source. The catalytic properties of GpdQ were determined, and the best substrate found was bis(p-nitrophenyl) phosphate with a kcat/Km value of 6.7 x 10(3) M-1 s-1. In addition, the E. aerogenes diesterase was tested as a catalyst for the hydrolysis of a series of phosphonate monoesters which are the hydrolysis products of the highly toxic organophosphonate nerve agents sarin, soman, GF, VX, and rVX. Among the phosphonate monoesters tested, the hydrolysis product of rVX, isobutyl methyl phosphonate, was the best substrate with a kcat/Km value of 33 M-1 s-1. The ability of GpdQ to hydrolyze the phosphonate monoesters provides an alternative selection strategy in the search of enhanced variants of the bacterial phosphotriesterase (PTE) for the hydrolysis of organophosphonate nerve agents. This investigation demonstrated that the previously reported activity of GpdQ toward the hydrolysis of methyl demeton-S is due to the presence of a diester contaminant in the commercial material. Furthermore, it was shown that GpdQ is capable of hydrolyzing a close analogue of EA 2192, the most toxic and persistent degradation product of the nerve agent VX.

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

    Science.gov (United States)

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

    2017-03-01

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

  17. An unexpected plasma cholinesterase activity rebound after challenge with a high dose of the nerve agent VX.

    Science.gov (United States)

    Dorandeu, F; Foquin, A; Briot, R; Delacour, C; Denis, J; Alonso, A; Froment, M T; Renault, F; Lallement, G; Masson, P

    2008-06-27

    Organophosphorus chemical warfare agents (nerve agents) are to be feared in military operations as well as in terrorist attacks. Among them, VX (O-ethyl-S-[2-(diisopropylamino)ethyl] methylphosphonothioate) is a low volatility liquid that represents a percutaneous as well as an inhalation hazard if aerosolized. It is a potent irreversible cholinesterase (ChE) inhibitor that causes severe signs and symptoms, including respiratory dysfunction that stems from different mechanisms. VX-induced pulmonary oedema was previously reported in dogs but mechanisms involved are not well understood, and its clinical significance remains to be assessed. An experimental model was thus developed to study VX-induced cardiovascular changes and pulmonary oedema in isoflurane-anaesthetized swine. In the course of this study, we observed a fast and unexpected rebound of plasma ChE activity following inhibition provoked by the intravenous injection of 6 and 12 microg kg(-1) of VX. In whole blood ChE activity, the rebound could stay unnoticed. Further investigations showed that the rebound of plasma esterase activity was neither related to spontaneous reactivation of ChE nor to VX-induced increase in paraoxonase/carboxylesterase activities. A bias in Ellman assay, haemoconcentration or severe liver cytolysis were also ruled out. All in all, these results suggest that the rebound was likely due to the release of butyrylcholinesterase into the blood stream from ChE producing organs. Nature of the organ(s) and mechanisms involved in enzyme release will need further investigations as it may represent a mechanism of defence, i.e. VX scavenging, that could advantageously be exploited.

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

    Science.gov (United States)

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

    2011-12-01

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

  19. An animal model to study health effects during continuous low-dose exposure to the nerve agent VX.

    Science.gov (United States)

    Rocksén, David; Elfsmark, Daniel; Heldestad, Victoria; Wallgren, Karin; Cassel, Gudrun; Göransson Nyberg, Ann

    2008-08-19

    In the present study, we have developed an animal model to study long-term health effects of continuous exposure of toxic chemical agents, in awake, freely moving rats. The aim was to evaluate the effect of low-dose exposure of the nerve agent VX, and to find specific biomarkers for intoxication. To exclude the influence of stress, we used an implanted radio-telemetric device for online registration of physiological parameters, and an osmotic pump, implanted subcutaneously, for continuous exposure of the toxic agent. Our results showed that the lowest observable effect dose of VX in Wistar rats was 5 microg/kg/24 h, after continuous exposure by the osmotic pump. Although we observed significant inhibition of acetylcholinesterase (AChE) in blood and a significant decrease in body weight gain at this dose, no change in blood pressure, heart rate or respiratory rate was registered. However, a significant decrease in the thyroid hormone, free T4, was measured in blood after 8 weeks, indicating that low doses of VX might affect the thyroid function. Rats given repeated daily injections were more sensitive to VX and needed only 1/10 of the concentration to reach a similar level of AChE inhibition, compared to animals exposed by the osmotic pump. Moreover, the results showed that exposure of VX in our experimental design, does not induce an increase in corticosterone blood levels. Thus, the model used in this investigation renders minimal stress and will not cause unnecessary pain to the animals, indicating that this model could be a useful tool to study long-term effects of various toxic substances in freely moving rats.

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

    Science.gov (United States)

    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.

  1. Abdominal bloating and irritable bowel syndrome like symptoms following microinstillation inhalation exposure to chemical warfare nerve agent VX in guinea pigs.

    Science.gov (United States)

    Katos, Alexandre M; Conti, Michele L; Moran, Theodore S; Gordon, Richard K; Doctor, Bhupendra P; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2007-05-01

    While assessing the methylphosphonothioic acid S-(2-(bis(1-methylethyl)amino)ethyl)O-ethyl ester (VX) induced respiratory toxicity and evaluating therapeutics against lung injury, we observed that the animals were experiencing abnormal swelling in the abdominal area. Nerve agent has been known to increase salivary, nasal and gastrointestinal secretion and cause diarrhea. This study was initiated to investigate the effect of VX on the gastrointestinal tract (GI) since abdominal pathology may affect breathing and contribute to the on going respiratory toxicity. The mid-abdominal diameter and the size of the lower left abdomen was measured before and after 27.3 mg/m3 VX exposure by microinstillation and at 30 min intervals up to 2 h post-VX exposure. Both VX and saline exposed animals exhibited a decrease in circumference of the upper abdomen, although the decrease was slightly higher in VX-exposed animals up to 1 h. The waist diameter increased slightly in VX-exposed animals from 60 to 90 min post-VX exposure but was similar to saline controls. The lower left abdomen near to the cecum, 6 cm below and 2cm to the right of the end of the sternum, showed an increase in size at 30-60 min that was significantly increased at 90-120 min post-VX exposure. In addition, VX-exposed animals showed loose fecal matter compared to controls. Necropsy at 24h showed an increased small intestine twisting motility in VX-exposed animals. Body tissue AChE assay showed high inhibition in the esophagus and intestine in VX-exposed animals indicating that a significant amount of the agent is localized to the GI following microinstillation exposure. These results suggest that microinstillatipn inhalation VX exposure induces gastrointestinal disturbances similar to that of irritable bowel syndrome and bloating.

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

    OpenAIRE

    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 a...

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

    OpenAIRE

    Rice, Helen; Dalton, Christopher H.; Price, Matthew E.; Stuart J Graham; 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 p...

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

    Science.gov (United States)

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

    2006-06-01

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

  5. Evaluation of Veriox as a Skin Decontamination Product after Dermal Exposure to the Nerve Agent VX

    Science.gov (United States)

    2016-09-01

    proprietary peracids. A 1:6 dilution in deionized water was prepared according to the manufacturer’s formula each test day. VX Exposure: Neat VX was...were analyzed by probit analysis using SAS NLIN and special purpose probit programs developed by Battelle (Columbus, Ohio) to generate an interim LD50

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

    Science.gov (United States)

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

    2006-12-01

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

  7. Identification of metabolites of nerve agent VX in serum collected from a victim.

    Science.gov (United States)

    Tsuchihashi, H; Katagi, M; Nishikawa, M; Tatsuno, M

    1998-09-01

    A human serum sample collected from a victim of the Osaka VX incident was analyzed according to our developed technique for metabolites of VX. Gas chromatography-mass spectrometry (GC-MS) in full-scan electron impact and chemical ionization modes were used, and, for more reliable confirmation, GC-MS-MS was also employed. In the serum sample, both ethyl methylphosphonic acid and 2-(diisopropylamino-ethyl)methyl sulfide were detected. These results indicated that the techniques using GC-MS and GC-MS-MS were applicable to biological samples such as serum. These results also provide the first documented, unequivocal identification of the specific metabolites of VX in victim's serum and, furthermore, clarify a part of the metabolic pathway of VX in the human body.

  8. Evaluation of potency of known oximes (pralidoxime, trimedoxime, HI-6, methoxime, obidoxime) to in vitro reactivate acetylcholinesterase inhibited by pesticides (chlorpyrifos and methylchlorpyrifos) and nerve agent (Russian VX).

    Science.gov (United States)

    Musílek, Kamil; Kuca, Kamil; Jun, Daniel

    2007-01-01

    Nerve agents and pesticides belong to the group of organophosphates. They are able to inhibit irreversibly the enzyme acetylcholinesterase (AChE). Acetylcholinesterase reactivators were designed for the treatment of nerve agent intoxications. Their potency to reactivate pesticide-inhibited AChE was many times evaluated. In this study, five commonly used AChE reactivators (pralidoxime, methoxime, HI-6, obidoxime, trimedoxime) for the reactivation of AChE inhibited by two pesticides (chlorpyrifos and methylchlorpyrifos) were used. Russian VX (nerve agent) as a member of nerve agents' family was taken for comparison. Obtained results show that oximes developed against nerve agent intoxication are less effective for intoxication with organophosphorus pesticides. Especially, methylchlorpyrifos-inhibited AChE was found to be poorly reactivated by the compounds used.

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

    Science.gov (United States)

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

    2016-03-04

    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.

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

    Science.gov (United States)

    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.

  11. The oxime pro-2-PAM provides minimal protection against the CNS effects of the nerve agents sarin, cyclosarin, and VX in guinea pigs.

    Science.gov (United States)

    Shih, Tsung-Ming; Guarisco, John A; Myers, Todd M; Kan, Robert K; McDonough, John H

    2011-01-01

    This study examined whether pro-2-PAM, a pro-drug dihydropyridine derivative of the oxime 2-pralidoxime (2-PAM) that can penetrate the brain, could prevent or reverse the central toxic effects of three nerve agents; sarin, cyclosarin, and VX. The first experiment tested whether pro-2-PAM could reactivate guinea pig cholinesterase (ChE) in vivo in central and peripheral tissues inhibited by these nerve agents. Pro-2-PAM produced a dose-dependent reactivation of sarin- or VX-inhibited ChE in both peripheral and brain tissues, but with substantially greater reactivation in peripheral tissues compared to brain. Pro-2-PAM produced 9-25% reactivation of cyclosarin-inhibited ChE in blood, heart, and spinal cord, but no reactivation in brain or muscle tissues. In a second experiment, the ability of pro-2-PAM to block or terminate nerve agent-induced electroencephalographic seizure activity was evaluated. Pro-2-PAM was able to block sarin- or VX-induced seizures (16-33%) over a dose range of 24-32 mg/kg, but was ineffective against cyclosarin-induced seizures. Animals that were protected from seizures showed significantly less weight loss and greater behavioral function 24 h after exposure than those animals that were not protected. Additionally, brains were free from neuropathology when pro-2-PAM prevented seizures. In summary, pro-2-PAM provided modest reactivation of sarin- and VX-inhibited ChE in the brain and periphery, which was reflected by a limited ability to block or terminate seizures elicited by these agents. Pro-2-PAM was able to reactivate blood, heart, and spinal cord ChE inhibited by cyclosarin, but was not effective against cyclosarin-induced seizures.

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

    Science.gov (United States)

    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.

  13. Identification of novel disulfide adducts between the thiol containing leaving group of the nerve agent VX and cysteine containing tripeptides derived from human serum albumin.

    Science.gov (United States)

    Kranawetvogl, Andreas; Küppers, Jim; Gütschow, Michael; Worek, Franz; Thiermann, Horst; Elsinghorst, Paul W; John, Harald

    2016-12-09

    Chemical warfare agents represent a continuous and considerable threat to military personnel and the civilian population. Such compounds are prohibited by the Chemical Weapons Convention, to which adherence by the member states is strictly controlled. Therefore, reliable analytical methods for verification of an alleged use of banned substances are required. Accordingly, current research focuses on long-term biomarkers derived from covalent adducts with biomolecules such as proteins. Recently, we have introduced a microbore liquid chromatography/electrospray ionization high-resolution tandem mass spectrometry method allowing for the investigation of two different classes of adducts of the nerve agent VX with human serum albumin (HSA). Phosphonylated tyrosine residues and novel disulfide adducts at cysteine residues of HSA were produced by enzymatic cleavage with pronase and detected simultaneously. Notably, the thiol containing leaving group of VX (2-(diisopropylamino)ethanethiol, DPAET) formed disulfide adducts that were released as cysteine and proline containing dipeptides originating from at least two different sites of HSA. Aim of this study was to identify assumed and novel adducts of DPAET with HSA using synthetic peptide reference compounds. Two novel tripeptides were identified representing disulfide adducts with DPAET (Met-Pro-Cys-DPAET, MPC-DPAET and Asp-Ile-Cys-DPAET, DIC-DPAET). MPC-DPAET was shown to undergo partial in-source decay during electrospray ionization for MS detection thereby losing the N-terminal Met residue. This results in the more stable Pro-Cys-DPAET (PC-DPAET) dipeptide detectable as protonated ion. The limit of detection for MPC-DPAET was evaluated, revealing toxicologically relevant VX plasma concentrations. The results provide novel insights into the reactivity of VX and its endogenous targets. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Application of capillary gas chromatography to the study of hydrolysis of the nerve agent VX in rat plasma.

    Science.gov (United States)

    Bonierbale, E; Debordes, L; Coppet, L

    1997-01-24

    We present here a gas chromatography technique allowing the detection and quantification of VX [O-ethyl S-(2-diisopropylaminoethyl)methylphosphonothiolate] as well as its P-S bond hydrolysis product diisopropylaminoethanethiol directly from spiked rat plasma. This technique was applied to study VX hydrolysis in rat plasma. We observed that 53 +/- 4% of 374 microM VX disappeared from spiked plasma after 2 h. VX disappearance was mainly related to enzymatic cleavage of the P-S bond (Km = 2.5 mM and Vmax = 13.3 nmol min-1 ml-1 of rat plasma). The activity was totally inhibited by 1 mM Hg2+ and was also inhibited by metal chelators.

  15. Characterization of isomeric VX nerve agent adducts on albumin in human plasma using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Saeidian, Hamid; Mirkhani, Valioallah; Mousavi Faraz, Sajjad; Taghi Naseri, Mohammad; Babri, Mehran

    2015-01-01

    This study includes the characterization of isomeric VX organophosphorus adducts on albumin in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). VX or its structural isomers were spiked into a vial containing plasma in order to obtain phosphorylated albumin. After pronase and trypsin digestion, the resulting solutions were analyzed to confirm adduct formation with the amino acid tyrosine on the albumin in human plasma. The LC-MS/MS experiments show that VX and its isomers can be attached to tyrosine on the albumin in human blood. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as ethylene, formic acid and ammonia elimination and an intermolecular electrophilic aromatic substitution reaction. The proposed mechanisms for the formation of the fragments were confirmed through the analysis of fragments of deuterated adducts.

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

    OpenAIRE

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

    2013-01-01

    The V-type nerve agents (VX and VR) are among the most toxic substances known. The high toxicity and environmental persistence of VX makes the development of novel decontamination methods particularly important. The enzyme phosphotriesterase (PTE) is capable of hydrolyzing VX but with an enzymatic efficiency more than 5-orders of magnitude lower than with its best substrate, paraoxon. PTE has previously proven amenable to directed evolution for the improvement of catalytic activity against se...

  17. Analysis of VX nerve agent hydrolysis products in wastewater effluents by ion chromatography with amperometric and conductivity detection.

    Science.gov (United States)

    Piao, Haishan; Marx, Randall B; Schneider, Steven; Irvine, David A; Staton, John

    2005-09-30

    An analytical method, based on the use of ion chromatography, was developed to monitor the levels of three regulated VX hydrolysis products in the effluent from a biological wastewater treatment process--ethylmethylphosphonic acid, methylphosphonic acid and 2-(diisopropyl)aminoethanethiol. Previous methods have not been applied to wastewater matrices or 2-(diisopropyl)aminoethanethiol. Despite the specificity and sensitivity constraints of this method, it was possible to measure the compounds in bioreactor effluents down to a level substantially below the US Army discharge limit of 0.1% (w/v). Analytical data was confirmed by liquid chromatography-mass spectrometry (LC-MS) at an independent laboratory.

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

    Science.gov (United States)

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

    2013-07-17

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

  19. Detoxification of VX and Other V‐Type Nerve Agents in Water at 37 °C and pH 7.4 by Substituted Sulfonatocalix[4]arenes

    Science.gov (United States)

    Schneider, Christian; Bierwisch, Anne; Koller, Marianne; Worek, Franz

    2016-01-01

    Abstract Sulfonatocalix[4]arenes with an appended hydroxamic acid residue can detoxify VX and related V‐type neurotoxic organophosphonates with half‐lives down to 3 min in aqueous buffer at 37 °C and pH 7.4. The detoxification activity is attributed to the millimolar affinity of the calixarene moiety for the positively charged organophosphonates in combination with the correct arrangement of the hydroxamic acid group. The reaction involves phosphonylation of the hydroxamic acid followed by a Lossen rearrangement, thus rendering the mode of action stoichiometric rather than catalytic. Nevertheless, these calixarenes are currently the most efficient low‐molecular‐weight compounds for detoxifying persistent V‐type nerve agents under mild conditions. They thus represent lead structures for novel antidotes that allow treatment of poisonings by these highly toxic chemicals. PMID:27627873

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

    OpenAIRE

    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 pre...

  1. The Oxime Pro-2-PAM Provides Minimal Protection Against the CNS Effects of the Nerve Agents Sarin, Cyclosarin, and VX in Guinea Pigs

    Science.gov (United States)

    2011-01-01

    Figure 2. Representative micrographs of neuronal damage in CA1 hippocampus (A–D), basolateral (BL) amygdalae (E–H), piriform cortex (I–L) and striatum (M...E) BL amygdala, (I) piriform cortex, and (M) striatum. Although animals that received pro-2-PAM at 1 min after VX or sarin and that had their... piriform cortex (K, sarin; L, VX) and striatum (O, sarin; P, VX). Magnification 200×. A B C D E F G H I J K L M N O P

  2. Organophosphate Nerve Agent Detection with Europium Complexes

    OpenAIRE

    Schwierking, Jake R.; Laird W. Menzel; E. Roland Menzel

    2004-01-01

    We explore the detection of paraoxon, a model compound for nonvolatile organophosphate nerve agents such as VX. The detection utilizes europium complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing ligands. Both europium luminescence quenching and luminescence enhancement modalities are involved in the detection, which is simple, rapid, and sensitive. It is adaptable as well to the more volatile fluorophosphate nerve agents. It involves nothing more than visual lumines...

  3. In vivo skin absorption and distribution of the nerve agent VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic white pig.

    Science.gov (United States)

    Chilcott, R P; Dalton, C H; Hill, I; Davison, C M; Blohm, K L; Clarkson, E D; Hamilton, M G

    2005-07-01

    The purpose of this study was to characterize the skin absorption and distribution of VX (O-ethyl-S-[2 (diisopropylamino)ethyl] methylphosphonothioate) in the domestic pig in order to evaluate the animal as a potential model for assessing pretreatments against toxic anti-cholinesterase compounds. A liquid droplet (equivalent to a 2 x LD50 dose) of radiolabelled VX was applied to the inner ear-skin of each anaesthetized animal. Blood and tissue samples (liver, lung, kidney, heart and skin exposure sites) were obtained post-mortem. The amount of radioactivity in each sample was measured by liquid scintillation counting, from which the skin absorption rate and dose distribution of VX were calculated. A substantial proportion (22 +/- 3%) of the applied dose remained within the skin at the site of application. It is conceivable that strategies to minimize or remove this reservoir may be of benefit in the early treatment of VX-exposed casualties. Image analysis of autoradiographs of exposed skin sites indicated that each milligram of radioactive VX covered an area of 1.2 +/- 0.5 cm2. The average skin absorption rate of 14C-VX was 661 +/- 126 microg/cm2 per hour. Comparison of these data with previous studies suggests that human skin is less permeable to VX than pig skin, but VX spreads over a greater surface area when applied to human skin. Thus, paradoxically, while pig-ear skin is more permeable than human skin, the difference in skin surface spreading may lead to the absorption of an equivalent systemic dose.

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

    Science.gov (United States)

    2011-01-01

    normalization period was applied. After the normalization period, EEG record- ing was initiated along with the continuous collection of dialysate samples at 15...was continued for 255 min (17 samples) after nerve agent exposure. After collection, the dialysate samples were frozen and kept at -20C until...included. Electroencephalogram Seizure occurrence was recorded via cortical EEG. EEG recordings and dialysate sampling were started simulta- neously

  5. Effects of repeated low-dose exposure of the nerve agent VX on monoamine levels in different brain structures in mice.

    Science.gov (United States)

    Graziani, S; Christin, D; Daulon, S; Breton, P; Perrier, N; Taysse, L

    2014-05-01

    In a previous report, alterations of the serotonin metabolism were previously reported in mice intoxicated with repeated low doses of soman. In order to better understand the effects induced by repeated low-dose exposure to organophosphorus compounds on physiological and behavioural functions, the levels of endogenous monoamines (serotonin and dopamine) in different brain areas in mice intoxicated with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl phosphonothioate) (VX) were analysed by HPLC method with electrochemical detection. Animals were injected once a day for three consecutive days with 0.10 LD50 of VX (5 μg/kg, i.p). Neither severe signs of cholinergic toxicity nor pathological changes in brain tissue of exposed animals were observed. Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30% inhibition 24 h after the last injection of VX), but remained unchanged in the brain. Serotonin and dopamine (DA) metabolism appeared significantly modified. During the entire period of investigation, at least one of the three parameters investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During the toxic challenge, an increase of the serotonin metabolism was noted in hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This increase was maintained 4 weeks after exposure in HPC, pons medulla and CER whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The lack of correlation between brain ChE activity and neurochemical outcomes points out to independent mechanisms. The involvement in possibly long-lasting behavioural disorders is discussed.

  6. Human scalp permeability to the chemical warfare agent VX.

    Science.gov (United States)

    Rolland, P; Bolzinger, M-A; Cruz, C; Briançon, S; Josse, D

    2011-12-01

    The use of chemical warfare agents such as VX in terrorism act might lead to contamination of the civilian population. Human scalp decontamination may require appropriate products and procedures. Due to ethical reasons, skin decontamination studies usually involve in vitro skin models, but human scalp skin samples are uncommon and expensive. The purpose of this study was to characterize the in vitro permeability to VX of human scalp, and to compare it with (a) human abdominal skin, and (b) pig skin from two different anatomic sites: ear and skull roof, in order to design a relevant model. Based on the VX skin permeation kinetics and distribution, we demonstrated that (a) human scalp was significantly more permeable to VX than abdominal skin and (b) pig-ear skin was the most relevant model to predict the in vitro human scalp permeability. Our results indicated that the follicular pathway significantly contributed to the skin absorption of VX through human scalp. In addition, the hair follicles and the stratum corneum significantly contributed to the formation of a skin reservoir for VX.

  7. Annual Report 2013-2014: Theoretical Studies of Nerve Agents Adsorbed on Surfaces

    Science.gov (United States)

    2014-07-08

    agents: sarin, a nerve gas , (see Fig. 1) and VX type nerve agents . Although both nerve agents are organophosphates, they differ in the ester linkage...Environmental Effects in the Adsorption of DMMP, Sarin, and VX on gamma-Al2O3: Photolysis and Surface Hydroxylation. Journal of Physical Chemistry C...L Whitten Professor of Chemistry North Carolina State University Raleigh, NC 27695 Telephone Number: 919-515-7960 Email: whitten@ncsu.edu

  8. Organophosphate Nerve Agent Detection with Europium Complexes

    Directory of Open Access Journals (Sweden)

    Jake R. Schwierking

    2004-01-01

    Full Text Available We explore the detection of paraoxon, a model compound for nonvolatile organophosphate nerve agents such as VX. The detection utilizes europium complexes with 1,10 phenanthroline and thenoyltrifluoroacetone as sensitizing ligands. Both europium luminescence quenching and luminescence enhancement modalities are involved in the detection, which is simple, rapid, and sensitive. It is adaptable as well to the more volatile fluorophosphate nerve agents. It involves nothing more than visual luminescence observation under sample illumination by an ordinary hand-held ultraviolet lamp.

  9. The impact of skin decontamination on the time for effective treatment of low volatile nerve agent

    NARCIS (Netherlands)

    Joosen, M.J.A.; Schans, M.J. van der; Noort, D.

    2013-01-01

    Low volatile organophosphorous (OP) nerve agents such as VX, will most likely enter the body via the skin. In previous investigations conducted in hairless guinea pigs, it was shown that skin exposure to VX resulted in a slow and variable onset of observable signs of toxicity. Repeated treatments

  10. The impact of skin decontamination on the time for effective treatment of low volatile nerve agent

    NARCIS (Netherlands)

    Joosen, M.J.A.; Schans, M.J. van der; Noort, D.

    2013-01-01

    Low volatile organophosphorous (OP) nerve agents such as VX, will most likely enter the body via the skin. In previous investigations conducted in hairless guinea pigs, it was shown that skin exposure to VX resulted in a slow and variable onset of observable signs of toxicity. Repeated treatments ad

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

    OpenAIRE

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

    2014-01-01

    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 charac...

  12. Effective, Facile, and Selective Hydrolysis of the Chemical Warfare Agent VX Using Zr6-Based Metal-Organic Frameworks.

    Science.gov (United States)

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

    2015-11-16

    The nerve agent VX is among the most toxic chemicals known to mankind, and robust solutions are needed to rapidly and selectively deactivate it. Herein, we demonstrate that three Zr6-based metal-organic frameworks (MOFs), namely, UiO-67, UiO-67-NH2, and UiO-67-N(Me)2, are selective and highly active catalysts for the hydrolysis of VX. Utilizing UiO-67, UiO-67-NH2, and UiO-67-N(Me)2 in a pH 10 buffered solution of N-ethylmorpholine, selective hydrolysis of the P-S bond in VX was observed. In addition, UiO-67-N(Me)2 was found to catalyze VX hydrolysis with an initial half-life of 1.8 min. This half-life is nearly 3 orders of magnitude shorter than that of the only other MOF tested to date for hydrolysis of VX and rivals the activity of the best nonenzymatic materials. Hydrolysis utilizing Zr-based MOFs is also selective and facile in the absence of pH 10 buffer (just water) and for the destruction of the toxic byproduct EA-2192.

  13. REM sleep pathways and anticholinesterase intoxication: A mechanism for nerve agent-induced, central respiratory failure.

    NARCIS (Netherlands)

    Kok, A.

    1993-01-01

    The mechanism of death following exposure to anticholinesterases, such as the highly toxic nerve agents soman and VX, and other organophosphate anticholinesterases such as the insecticide parathion, remains unclear, although evidence from nerve agent research suggests that death occurs by an atropin

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

    Science.gov (United States)

    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 ...

  15. Analogues with fluorescent leaving groups for screening and selection of enzymes that efficiently hydrolyze organophosphorus nerve agents.

    Science.gov (United States)

    Briseño-Roa, Luis; Hill, Jim; Notman, Stuart; Sellers, David; Smith, Andy P; Timperley, Christopher M; Wetherell, Janet; Williams, Nichola H; Williams, Gareth R; Fersht, Alan R; Griffiths, Andrew D

    2006-01-12

    Enzymes that efficiently hydrolyze highly toxic organophosphorus nerve agents could potentially be used as medical countermeasures. As sufficiently active enzymes are currently unknown, we synthesized twelve fluorogenic analogues of organophosphorus nerve agents with the 3-chloro-7-oxy-4-methylcoumarin leaving group as probes for high-throughput enzyme screening. This set included analogues of the pesticides paraoxon, parathion, and dimefox, and the nerve agents DFP, tabun, sarin, cyclosarin, soman, VX, and Russian-VX. Data from inhibition of acetylcholinesterase, in vivo toxicity tests of a representative analogue (cyclosarin), and kinetic studies with phosphotriesterase (PTE) from Pseudomonas diminuta, and a mammalian serum paraoxonase (PON1), confirmed that the analogues mimic the parent nerve agents effectively. They are suitable tools for high-throughput screens for the directed evolution of efficient nerve agent organophosphatases.

  16. 用气相色谱-原子发射光谱法检测VX、Bz及其降解产物%Determination of Nerve Agents VX, Bz and Their Degradation Products by GC-AED

    Institute of Scientific and Technical Information of China (English)

    周永新; 李前远; 靳志云; 娄艳红

    2000-01-01

    应用气相色谱-原子发射光谱(GC-AED)同时检测S-2-二异丙基氨乙基)甲基硫赶膦酸乙酯(VX)、二苯羟乙酸-3-喹咛环酯(Bz)战剂及其降解产物等5种化合物, 得到了C、 H、 S、 N、 O、 P 6种元素色谱图, 通过选择合适的检测元素, 其检出限VX为15.6 mg/L, Bz为16.79 mg/L, 二异丙基氨基乙硫醇为3.02 mg/L,3-羟基喹咛为28.40 mg/L,二苯羟乙酸甲酯为31.78 mg/L, 定量测定结果令人满意.

  17. Facile hydrolysis-based chemical destruction of the warfare agents VX, GB, and HD by alumina-supported fluoride reagents.

    Science.gov (United States)

    Gershonov, E; Columbus, I; Zafrani, Y

    2009-01-02

    A facile solvent-free hydrolysis (chemical destruction) of the warfare agents VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate), GB (O-isopropyl methylphosphonofluoridate or sarin), and HD (2,2'-dichloroethyl sulfide or sulfur mustard) upon reaction with various solid-supported fluoride reagents is described. These solid reagents include different alumina-based powders such as KF/Al(2)O(3), AgF/KF/Al(2)O(3), and KF/Al(2)O(3) enriched by so-called coordinatively unsaturated fluoride ions (termed by us as ECUF-KF/Al(2)O(3)). When adsorbed on these sorbents, the nerve agent VX quickly hydrolyzed (t(1/2) range between 0.1-6.3 h) to the corresponding nontoxic phosphonic acid EMPA as a major product (>90%) and to the relatively toxic desethyl-VX (<10%). The latter byproduct was further hydrolyzed to the nontoxic MPA product (t(1/2) range between 2.2-161 h). The reaction rates and the product distribution were found to be strongly dependent on the nature of the fluoride ions in the KF/Al(2)O(3) matrix and on its water content. All variations of the alumina-supported fluoride reagents studied caused an immediate hydrolysis of the highly toxic GB (t(1/2) < 10 min) to form the corresponding nontoxic phosphonic acid IMPA. A preliminary study of the detoxification of HD on these catalyst supports showed the formation of the nontoxic 1,4-thioxane as a major product together with minor amounts of TDG and vinylic compounds within a few days. The mechanisms and the efficiency of these processes were successfully studied by solid-state (31)P, (13)C, and (19)F MAS NMR.

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

    Science.gov (United States)

    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.

  19. Fate of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX) on soil following accelerant-based fire and liquid decontamination.

    Science.gov (United States)

    Gravett, M R; Hopkins, F B; Self, A J; Webb, A J; Timperley, C M; Riches, J R

    2014-08-01

    In the event of alleged use of organophosphorus nerve agents, all kinds of environmental samples can be received for analysis. These might include decontaminated and charred matter collected from the site of a suspected chemical attack. In other scenarios, such matter might be sampled to confirm the site of a chemical weapon test or clandestine laboratory decontaminated and burned to prevent discovery. To provide an analytical capability for these contingencies, we present a preliminary investigation of the effect of accelerant-based fire and liquid decontamination on soil contaminated with the nerve agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX). The objectives were (a) to determine if VX or its degradation products were detectable in soil after an accelerant-based fire promoted by aviation fuel, including following decontamination with Decontamination Solution 2 (DS2) or aqueous sodium hypochlorite, (b) to develop analytical methods to support forensic analysis of accelerant-soaked, decontaminated and charred soil and (c) to inform the design of future experiments of this type to improve analytical fidelity. Our results show for the first time that modern analytical techniques can be used to identify residual VX and its degradation products in contaminated soil after an accelerant-based fire and after chemical decontamination and then fire. Comparison of the gas chromatography-mass spectrometry (GC-MS) profiles of VX and its impurities/degradation products from contaminated burnt soil, and burnt soil spiked with VX, indicated that the fire resulted in the production of diethyl methylphosphonate and O,S-diethyl methylphosphonothiolate (by an unknown mechanism). Other products identified were indicative of chemical decontamination, and some of these provided evidence of the decontaminant used, for example, ethyl 2-methoxyethyl methylphosphonate and bis(2-methoxyethyl) methylphosphonate following decontamination with DS2. Sample preparation

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

    Science.gov (United States)

    2010-01-01

    Biological Interactions 187 (2010) 318–324 Table 1 ChE reactivation by oxime treatments in brain regions, peripheral tissues and blood components following...the significant ChE reactivation by oxime treatments in brain regions, peripheral tissues and blood components following exposure to GB, GF, and VX.a...regions, peripheral tis- ues, or blood components , when an oxime treatment significantly eactivated nerve agent-inhibited ChE. For example, if an

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. Being prepared: emergency treatment following a nerve agent release.

    Science.gov (United States)

    Bailey, Abby M; Baker, Stephanie N; Baum, Regan A; Chandler, Hannah E; Weant, Kyle A

    2014-01-01

    Nerve agents are extremely toxic and are some of the most lethal substances on earth. This group of chemicals consists of sarin, cyclosarin, soman, tabun, VX, and VR. It is currently unknown how many countries possess these chemicals and in what quantities. These agents work through altering the transmission and breakdown of acetylcholine by binding to, and inactivating, acetylcholinesterase. This results in an uncontrolled and overwhelming stimulation of both muscarinic and nicotinic receptors. Receptor activation at these sites can lead to a wide variety of clinical symptoms, with death frequently resulting from pulmonary edema. Antidotal therapy in this setting largely consists of atropine, pralidoxime, and benzodiazepines, all of which must be administered emergently to limit the progression of symptoms and prevent the enzyme inactivation from becoming permanent. This article reviews the mechanism of action of the nerve agents and their effects on the human body, the currently available therapies to mitigate their impact, and important therapeutic considerations for health care practitioners in the emergency department.

  4. Rational design of organophosphorus hydrolase with high catalytic efficiency for detoxifying a V-type nerve agent.

    Science.gov (United States)

    Jeong, Young-Su; Choi, Jung Min; Kyeong, Hyun-Ho; Choi, Jae-Youl; Kim, Eui-Joong; Kim, Hak-Sung

    2014-07-01

    V-type nerve agents, known as VX, are organophosphate (OP) compounds, and show extremely toxic effects on human and animals by causing cholinergic overstimulation of synapses. The bacterial organophosphorus hydrolase (OPH) has attracted much attention for detoxifying V-type agents through hydrolysis of the P-S bond. However, low catalytic efficiency of OPH has limited the practical use of the enzyme. Here we present rational design of OPH with high catalytic efficiency for a V-type nerve agent. Based on the model structure of the enzyme and substrate docking simulation, we predicted the key residues that appear to enhance the access of the substrate to the active site of the enzyme, and constructed numerous OPH mutants. Of them, double mutant, L271/Y309A, was shown to exhibit a 150-fold higher catalytic efficiency for VX than the wild-type.

  5. Different inhibition of acetylcholinesterase in selected parts of the rat brain following intoxication with VX and Russian VX.

    Science.gov (United States)

    Hajek, Petr; Bajgar, Jiri; Slizova, Dasa; Krs, Otakar; Kuca, Kamil; Capek, Lukas; Fusek, Josef

    2009-01-01

    Differences between acetylcholinesterase (AChE) inhibition in the brain structures following VX and RVX exposure are not known as well as information on the possible correlation of biochemical and histochemical methods detecting AChE activity. Therefore, inhibition of AChE in different brain parts detected by histochemical and biochemical techniques was compared in rats intoxicated with VX and RVX. AChE activities in defined brain regions 30 min after treating rats with VX and Russian VX intramuscularly (1.0 x LD(50)) were determined by using biochemical and histochemical methods. AChE inhibition was less expressed for RVX, in comparison with VX. Frontal cortex and pontomedullar areas containing ncl. reticularis has been found as the most sensitive areas for the action of VX. For RVX, these structures were determined to be frontal cortex, dorsal septum, and hippocampus, respectively. Histochemical and biochemical results were in good correlation (R(xy) = 0.8337). Determination of AChE activity in defined brain structures was a more sensitive parameter for VX or RVX exposure than the determination of AChE activity in the whole-brain homogenate. This activity represents a "mean" of the activities in different structures. Thus, AChE activity is the main parameter investigated in studies searching for target sites following nerve-agent poisoning contributing to better understanding of toxicodynamics of nerve agents.

  6. Female rats are less susceptible during puberty to the lethal effects of percutaneous exposure to VX

    Directory of Open Access Journals (Sweden)

    Linnzi K.M. Wright

    2016-01-01

    Full Text Available Nerve agents with low volatility such as VX are primarily absorbed through the skin when released during combat or a terrorist attack. The barrier function of the stratum corneum may be compromised during certain stages of development, allowing VX to more easily penetrate through the skin. However, age-related differences in the lethal potency of VX have yet to be evaluated using the percutaneous (pc route of exposure. Thus, we estimated the 24 and 48 h median lethal dose for pc exposure to VX in male and female rats during puberty and early adulthood. Pubescent, female rats were less susceptible than both their male and adult counterparts to the lethal effects associated with pc exposure to VX possibly because of hormonal changes during that stage of development. This study emphasizes the need to control for both age and sex when evaluating the toxicological effects associated with nerve agent exposure in the rat model.

  7. Photoassisted reaction of chemical warfare agent VX droplets under UV light irradiation.

    Science.gov (United States)

    Zuo, Guo-Min; Cheng, Zhen-Xing; Li, Guo-Wen; Wang, Lian-Yuan; Chen, Hong

    2005-08-11

    A photoassisted reaction of O-ethyl S-[2-(diisopropylamino) ethyl] methylphosphonothioate (VX) droplets in air was carried out. The experimental results indicated that VX droplets could be easily and chemically transformed into other compounds under irradiation of a germicidal lamp over sufficient time. Quantum chemical calculation results demonstrated that UV light less than 278 nm wavelength could possibly initiate photoreaction of VX and that both P-S and P=O bonds in the VX molecule were lengthened. The identification of reaction products by gas and liquid chromatography mass spectroscopy and NMR revealed that the VX molecule in air under UV light irradiation could undergo isomerization of S-esters to O-esters, cleavage of P-S, S-C, and C-N bonds, and ozonation of tertiary amines.

  8. Biocatalytic nerve agent detoxification in fire fighting foams.

    Science.gov (United States)

    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.

  9. An evaluation of the spectral properties of nerve agents for laser ionization mass spectrometry.

    Science.gov (United States)

    Imasaka, Tomoko; Imasaka, Totaro

    2014-01-01

    Excitation energies, oscillator strengths, and vacuum-ultraviolet/deep-ultraviolet absorption spectra were calculated for nerve agents, such as sarin, soman, VX, tabun, mustard gas, and analogs. We used time-dependent density functional theory (TD-DFT) methods that included B3LYP combined with basis sets of cc-pVDZ and cc-pVTZ, and ωB97XD with cc-pVTZ. The vertical ionization energies were also calculated for these compounds, in order to collect additional information relative to the optimal pathways for multiphoton ionization in mass spectrometry.

  10. Cyclosarin-An Organophosphate Nerve Agent

    Directory of Open Access Journals (Sweden)

    G. Krejcova

    2005-04-01

    Full Text Available Organophosphorus compounds ascribed to as nerve agents (sarin, soman, tabun, cyclosarin are highly toxic, and are considered to be the most dangerous chemical compounds. All apparently share a common mechanism of cholinesterase inhibition and can cause similar sv.m .ot oms. The standard therapy, in the case of organophosphorus poisoning, has the prophylactic use of reversibly acting AChE inhibitors and antidotal administration of AChE reactivators-oximes. Unfortunately, none of these oximes can be regarded as a broad spectrum antidote, ie, effective against all nerve agents. While the presently available oximes (pralidoxime, ohidoxime are not considered to be sufficiently effective against nerve agents, especially in the case of soman poisoning, the H oximes (HI-6, HLo7 appear to,be very promising antidotes against nerve agents because these are able to protect the experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses. A lot of research has been pursued on the treatment of sarin, soman, and tabun, but cyclosarin was not considered for such a study for a long time. Recently, attention of researchers has also turned to cyclosarin because of its potential use as a chemical warfare agent. Cyclosarin is highly toxic organophosphorus compound which is resistant to conventional oxime therapy. This paper reviews the latest positionof cyclosarin in standpoint of medical treatment by various reactivators considering the ability of various oximes, HI-6, HS-6, BI-6, and KO33 of their reactivation potency.

  11. Capillary gas chromatographic analysis of nerve agents using large volume injections. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Deinum, T.; Nieuwenhuy, C.

    1994-11-01

    The procedure developed at TNO-Prins Maurits Laboratory (TNO-PML) for the verification of intact organophosphorus chemical warfare agents in water samples was improved. The last step in this procedure, the laborious and non-reproducible transfer of an ethyl acetate extract onto a Tenax-adsorption tube followed by thermal desorption of the Tenax-tube, was replaced by large volume injection of the extract onto a capillary gas chromatographic system. The parameters controlling the injection of a large volume of an extract (200 ul) were investigated and optimized. As ethyl acetate caused severe problems, potential new solvents were evaluated. With the improved procedure, the nerve agents sarin, tabun, soman, diisopropyl fluorophosphate (DFP) and VX could be determined in freshly prepared water samples at pg/ml (ppt) levels. The fate of the nerve agents under study in water at two pH`s (4.8 and 6) was investigated. For VX, the pH should be adjusted before extraction. Moreover, it is worthwhile to acidify water samples to diminish hydrolysis.

  12. Differentiated NSC-34 cells as an in vitro Cell Model for VX

    Science.gov (United States)

    2014-09-11

    June 2014 Published online 11 September 2014 Introduction The organophosphate (OP) nerve agents (NA), including soman, sarin, tabun and VX, act...derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning . Chem Biol Interact 203:160–6. Sundstrom L, Morrison B III, Bradley...for the sensitive detection of organophosphate pesticides, carbamates and nerve agents. Biosens Bioelectron 25:832–8. Zhang Y, Bhavnani BR. (2006

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Rene Kizek

    2013-08-01

    Full Text Available 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.

  15. Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning.

    Science.gov (United States)

    Mumford, Helen; Docx, Cerys J; Price, Matthew E; Green, A Christopher; Tattersall, John E H; Armstrong, Stuart J

    2013-03-25

    Potent organophosphorous (OP) agents, such as VX, are hazardous by absorption through the skin and are resistant to conventional pharmacological antidotal treatments. The residence time of a stoichiometric bioscavenger, human butyrylcholinesterase (huBuChE), in the plasma more closely matches that of VX than do the residence times of conventional therapy drugs (oxime, anti-muscarinic, anticonvulsant). Intramuscular (i.m.) huBuChE afforded almost complete protection when administered prior to the onset of observable cholinergic signs of VX poisoning, but once signs of poisoning became evident the efficacy of i.m. huBuChE decreased. A combination of nerve agent therapy drugs (oxime, anti-muscarinic, anticonvulsant) with huBuChE (i.m.) protected 100% (8/8) of guinea-pigs from a lethal dose of VX (0.74 mg/kg) to 48 h, even when administered on signs of poisoning. Survival was presumed to be due to immediate alleviation of the cholinergic crisis by the conventional pharmacological treatment drugs, in conjunction with bioscavenger that prevented further absorbed agent reaching the AChE targets. Evidence to support this proposed mechanism of action was obtained from PKPD experiments in which multiple blood samples and microdialysate samples were collected from individual conscious ambulatory animals. Plasma concentrations of intramuscularly-administered atropine, diazepam and HI-6 reached a peak within 15 min and were eliminated rapidly within 4h. Plasma concentrations of huBuChE administered by the i.m. route took approximately 24h to reach a peak, but were well-maintained over the subsequent 7days. Thus, the pharmacological therapy rapidly treated the initial signs of poisoning, whilst the bioscavenger provided prolonged protection by neutralising further nerve agent entering the bloodstream and preventing it from reaching the target organs.

  16. Protective effects of N-methyl-D-aspartate receptor antagonism on VX-induced neuronal cell death in cultured rat cortical neurons.

    Science.gov (United States)

    Wang, Yushan; Weiss, M Tracy; Yin, Junfei; Tenn, Catherine C; Nelson, Peggy D; Mikler, John R

    2008-01-01

    Exposure of the central nervous system to organophosphorus (OP) nerve agents induces seizures and neuronal cell death. Here we report that the OP nerve agent, VX, induces apoptotic-like cell death in cultured rat cortical neurons. The VX effects on neurons were concentration-dependent, with an IC(50) of approximately 30 microM. Blockade of N-methyl-D-aspartate receptors (NMDAR) with 50 microM. D-2-amino-5-phosphonovalerate (APV) diminished 30 microM VX-induced total cell death, as assessed by alamarBlue assay and Hoechst staining. In contrast, neither antagonists of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) nor metabotropic glutamate receptors (mGluRs) had any effect on VX-induced neurotoxicity. VX-induced neuronal cell death could not be solely attributed to acetylcholinesterase (AChE) inhibition, since neither the reversible pharmacological cholinesterase inhibitor, physostigmine, nor the muscarinic receptor antagonist, atropine, affected VX-induced cell death. Importantly, APV was found to be therapeutically effective against VX-induced cell death up to 2 h post VX exposure. These results suggest that NMDARs, but not AMPARs or mGluRs, play important roles in VX-induced cell death in cultured rat cortical neurons. Based on their therapeutic effects, NMDAR antagonists may be beneficial in the treatment of VX-induced neurotoxicities.

  17. Chromatographic resolution, characterisation and quantification of VX enantiomers in hemolysed swine blood samples.

    Science.gov (United States)

    Reiter, Georg; Mikler, John; Hill, Ira; Weatherby, Kendal; Thiermann, Horst; Worek, Franz

    2008-09-15

    The present study was initiated to develop a sensitive and highly selective method for the analysis of the enantiomers of the nerve agent VX (O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate) in blood samples for toxicokinetic and therapeutic research. To achieve this goal, analytical and semi-preparative enantioseparation of VX were carried out with gas and liquid chromatography. The GC chiral stationary phase was HYDRODEX-beta-TBDAc (beta cyclodextrin), on which VX was baseline-resolved. On the chiral HPLC phase CHIRALCEL OD-H the enantiomers of VX were isolated with enantiomeric excess >99.99%. They were characterised by specific optical rotation (+/-25.8 deg ml dm(-1)g(-1) at 20 degrees C and 589 nm) and by determination of cholinesterase inhibition rate constants. For the quantitative chiral detection of VX the enantioresolution was realized on the HPLC chiral phase CHIRAL AGP. A specific procedure was developed to isolate VX from swine blood samples thereby stabilising its enantiomers. The limit of detection was 200 fg per enantiomer on column. The absolute recovery of the overall sample preparation procedure was 75%. After an intravenous and percutaneous administration of a supralethal dose of VX in anesthetised swine (+)-VX and (-)-VX could be quantified up to 720 min.

  18. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    Science.gov (United States)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  19. A novel approach to assessing percutaneous VX poisoning in the conscious guinea-pig.

    Science.gov (United States)

    Mumford, Helen; Price, Matthew E; Wetherell, Janet R

    2008-07-01

    Nerve agents like VX (S-2-diisopropylaminoethyl-O-ethyl-methylphosphonothiolate) are potent irreversible acetylcholinesterase (AChE) inhibitors. Following percutaneous nerve agent exposure there is a slower rate of absorption, later onset and longer duration of signs of poisoning. Relatively little is known about the physiological effects of percutaneously applied nerve agent in unanaesthetised laboratory animals. Heart rate (ECG), brain electrical activity (EEG), body temperature, locomotor activity and clinical signs were monitored following percutaneous application of VX to conscious guinea-pigs.A fall in heart rate (bradycardia) preceded incapacitation following the highest VX dose, and occurred in the absence of incapacitation at the lower doses. Following the highest dose of VX (0.592 mg kg(-1)) three out of four animals died within 24 h. The lower two doses of VX (0.296 and 0.148 mg kg(-1)), produced extended periods of bradycardia in the absence of observable signs of poisoning. Bradycardia preceded, or occurred in the absence of, a temperature decrease; seizure-like EEG changes were not observed at any of the VX doses tested. Acetylcholinesterase activity was significantly inhibited in the blood and most brain areas at 48 h. There were significant dose-related decreases in body weight at 24 and 48 h following VX. This preliminary study suggests that decreased heart rate may be an early sign of the toxic effects of VX, whereas temperature and observable clinical signs are not good early indicators of percutaneous VX poisoning in this animal model. Future studies will use this model to assess the benefit of administering medical countermeasures in response to a defined decrease in heart rate.

  20. VX fate on common matrices: evaporation versus degradation.

    Science.gov (United States)

    Columbus, Ishay; Waysbort, Daniel; Marcovitch, Itzhak; Yehezkel, Lea; Mizrahi, Dana M

    2012-04-03

    A study of the volatilization rate of the nerve agent VX (O-ethyl S-2-(N,N-diisopropylamino)ethyl methylphosphonothiolate) from various urban matrices in a specially designed climatic chamber (model system) is described. The performance of the model system combined with the analytical procedure produced profiles of vapor concentration obtained from samples of VX dispersed as small droplets on the surfaces of the matrices. The results indicated that the bitumen-containing surfaces such as asphalt blocks and bitumen sheets conserve VX and slow-release part of it over a long period of time. No complete mass balance could be obtained for these surfaces. Influence of environmental and experimental parameters as well as the efficacy of decontamination procedure were also measured. From smooth surface tiles a fast release of VX was measured and almost a complete mass balance was obtained, which characterizes the behavior of inert surfaces. Experiments carried out on concrete blocks showed fast decay of the concentration profile along with a very poor reconstruction of the initial quantity of VX, implying that this matrix degraded VX actively due to its multiple basic catalytic sites. To complement this study, solid-state NMR measurements were compared to add data concerning agent-fate within the matrices.

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

    Science.gov (United States)

    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.

  2. Female rats are less susceptible during puberty to the lethal effects of percutaneous exposure to VX

    OpenAIRE

    Wright, Linnzi K.M.; Lee, Robyn B.; Clarkson, Edward D.; Lumley, Lucille A

    2016-01-01

    Nerve agents with low volatility such as VX are primarily absorbed through the skin when released during combat or a terrorist attack. The barrier function of the stratum corneum may be compromised during certain stages of development, allowing VX to more easily penetrate through the skin. However, age-related differences in the lethal potency of VX have yet to be evaluated using the percutaneous (pc) route of exposure. Thus, we estimated the 24 and 48 h median lethal dose for pc exposure to ...

  3. VX Hydrolysis by Human Serum Paraoxonase 1: A Comparison of Experimental and Computational Results

    OpenAIRE

    Matthew W Peterson; Steven Z Fairchild; Otto, Tamara C.; Mojdeh Mohtashemi; Cerasoli, Douglas M.; Wenling E Chang

    2011-01-01

    Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mech...

  4. Timing of decontamination and treatment in case of percutaneous VX poisoning: A mini review

    NARCIS (Netherlands)

    Joosen, M.J.A.; Schans, M.J. van der; Kuijpers, W.C.; Helden, H.P.M. van; Noort, D.

    2013-01-01

    Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to

  5. Timing of decontamination and treatment in case of percutaneous VX poisoning: A mini review

    NARCIS (Netherlands)

    Joosen, M.J.A.; Schans, M.J. van der; Kuijpers, W.C.; Helden, H.P.M. van; Noort, D.

    2013-01-01

    Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to im

  6. VX Penetration Following Percutaneous Poisoning: A Dermal Microdialysis Study in the Guinea Pig.

    Science.gov (United States)

    Wetherell, Janet R; Armstrong, Stuart J; Read, Robert W; Clough, Geraldine F

    2008-01-01

    ABSTRACT VX, a potent organophosphorus compound, acts primarily by irreversibly inhibiting acetylcholinesterase resulting in an accumulation of acetylcholine, which produces the characteristic signs of nerve agent poisoning. VX is a low-volatility agent, and therefore the most likely route of absorption into the body is via the skin. This study demonstrates for the first time that it is possible to follow the time course of percutaneous VX penetration using the technique of dermal microdialysis and that VX is absorbed through the skin of the anesthetized guinea pig in a concentration-dependent manner. A linear microdialysis probe (5-kDa cut-off) was implanted in the dermis of the back of the guinea pig and perfused (5 muL/min) with physiological Ringer's solution. VX (296 or 592 mug/kg) was applied (33 muL/kg) over the site of the microdialysis probe and dialysate samples collected for up to 6 h. The VX dialysate concentration was measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Quantitation was performed over the range 0.1 to 100 ng/mL and the calibration was linear. VX was detected within 15 min, reaching a peak at 30 min following both VX doses. After this time the VX concentration decreased. There was a clear dose-dependent recovery of VX in the dialysate and the total amount recovered was statistically significant between the two doses. This study has clearly shown that microdialysis can be used to follow the time course of the percutaneous absorption of VX in the anesthetized guinea pig and will be used in future studies to develop improved medical countermeasures. Crown Copyright (c) 2007 Dstl.

  7. Quantitation of organophosphorus nerve agent metabolites in human urine using isotope dilution gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Driskell, W Jack; Shih, Ming; Needham, Larry L; Barr, Dana B

    2002-01-01

    An isotope dilution gas chromatography-tandem mass spectrometric (GC-MS-MS) method was developed for quantitating the urinary metabolites of the organophosphorus nerve agents sarin, soman, tabun (GA), VX, and GF. Urine samples were concentrated by codistillation with acetonitrile, derivatized by methylation with diazomethane, and analyzed by GC-MS-MS. The limits of detection were less than 4 microg/L for all the analytes except for the GA metabolite, which had a limit of detection of less than 20 microg/L.

  8. VX hydrolysis by human serum paraoxonase 1: a comparison of experimental and computational results.

    Directory of Open Access Journals (Sweden)

    Matthew W Peterson

    Full Text Available Human Serum paraoxonase 1 (HuPON1 is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VX(ts in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VX(ts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VX(ts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.

  9. VX hydrolysis by human serum paraoxonase 1: a comparison of experimental and computational results.

    Science.gov (United States)

    Peterson, Matthew W; Fairchild, Steven Z; Otto, Tamara C; Mohtashemi, Mojdeh; Cerasoli, Douglas M; Chang, Wenling E

    2011-01-01

    Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VX(ts)) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VX(ts) complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VX(ts) coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.

  10. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    Science.gov (United States)

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  11. Decomposition of adsorbed VX on activated carbons studied by 31P MAS NMR.

    Science.gov (United States)

    Columbus, Ishay; Waysbort, Daniel; Shmueli, Liora; Nir, Ido; Kaplan, Doron

    2006-06-15

    The fate of the persistent OP nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) on granular activated carbons that are used for gas filtration was studied by means of 31P magic angle spinning (MAS) NMR spectroscopy. VX as vapor or liquid was adsorbed on carbon granules, and MAS NMR spectra were recorded periodically. The results show that at least 90% of the adsorbed VX decomposes within 20 days or less to the nontoxic ethyl methylphosphonic acid (EMPA) and bis(S-2-diisopropylaminoethane) {(DES)2}. Decomposition occurred irrespective of the phase from which VX was loaded, the presence of metal impregnation on the carbon surface, and the water content of the carbon. Theoretical and practical aspects of the degradation are discussed.

  12. Decomposition of adsorbed VX on activated carbons studied by {sup 31}P MAS NMR

    Energy Technology Data Exchange (ETDEWEB)

    Ishay Columbus; Daniel Waysbort; Liora Shmueli; Ido Nir; Doron Kaplan [Israel Institute for Biological Research, Ness Ziona (Israel). Departments of Organic Chemistry and Physical Chemistry

    2006-06-15

    The fate of the persistent OP nerve agent O-ethyl S-(2-(diisopropylamino)ethyl) methylphosphonothioate (VX) on granular activated carbons that are used for gas filtration was studied by means of 31P magic angle spinning (MAS) NMR spectroscopy. Four types of activated carbon were used, including coal-based BPL. VX as vapor or liquid was adsorbed on carbon granules, and MAS NMR spectra were recorded periodically. The results show that at least 90% of the adsorbed VX decomposes within 20 days or less to the nontoxic ethyl methylphosphonic acid (EMPA) and bis(S-2-diisopropylaminoethane) ((DES){sub 2}). Decomposition occurred irrespective of the phase from which VX was loaded, the presence of metal impregnation on the carbon surface, and the water content of the carbon. Theoretical and practical aspects of the degradation are discussed. 17 refs., 6 figs., 3 tabs.

  13. VX toxicity in the Göttingen minipig.

    Science.gov (United States)

    Langston, Jeffrey L; Myers, Todd M

    2016-12-15

    The present experiments determined the intramuscular LD50 of VX in male Göttingen minipigs at two stages of development. In pubertal animals (115 days old), the LD50 of VX was indeterminate, but approximated 33.3μg/kg. However, in sexually mature animals (152 days old), the LD50 was estimated to be only 17.4μg/kg. Signs of nerve agent toxicity in the Göttingen minipig were similar to those described for other species, with some notable exceptions (such as urticaria and ejaculation). Latencies to the onset of sustained convulsions were inversely related to the administered dose of VX in both ages of minipigs. Additionally, actigraphy was used to quantify the presence of tremor and convulsions and, in some cases, was useful for precisely estimating time of death. The main finding indicates that in minipigs, as in other species, even relatively small differences in age can substantially alter the toxicity of nerve agents. Additionally, actigraphy can serve as a non-invasive method of characterizing the tremors and convulsions that often accompany nerve agent intoxication.

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

    Science.gov (United States)

    2016-05-09

    XXXX American Chemical Society A DOI: 10.1021/acs.analchem.6b01274 Anal. Chem. XXXX, XXX , XXX − XXX This is an open access article published under an...used to simulate nerve agent adducts. Analytical Chemistry Article DOI: 10.1021/acs.analchem.6b01274 Anal. Chem. XXXX, XXX , XXX − XXX B biological matrixes...equilibrated for the next sample (approximately 2 Analytical Chemistry Article DOI: 10.1021/acs.analchem.6b01274 Anal. Chem. XXXX, XXX , XXX − XXX C min

  15. The therapeutic use of localized cooling in the treatment of VX poisoning.

    Science.gov (United States)

    Sawyer, T W; Mikler, J; Worek, F; Reiter, G; Thiermann, H; Tenn, C; Weatherby, K; Bohnert, S

    2011-07-04

    The organophosphate (OP) nerve agent VX is a weaponized chemical warfare agent that has also been used by terrorists against civilians. This contact poison produces characteristic signs of OP poisoning, including miosis, salivation, mastication, dysrhythmias and respiratory distress prior to death. Although successful treatment of OP poisoning can be obtained through decontamination and/or oxime reactivation of agent-inhibited cholinesterase, medical countermeasures that increase the therapeutic window for these measures would be of benefit. An anaesthetized swine model was utilized to examine the effects of lethal VX exposure to the skin, followed by cooling the exposure site prior to decontamination or treatment. The cooling was simply accomplished by using crushed ice in grip-seal plastic bags applied to the exposure sites. Cooling of skin exposed to lethal doses of VX significantly increased the window of opportunity for successful decontamination using the Reactive Skin Decontaminant Lotion(®) (RSDL(®)) or treatment with the oxime antidotes HI-6 and 2PAM. Analyses of blood VX levels showed that cooling acted to slow or prevent the entry of VX into the bloodstream from the skin. If the exposure site is known, the simple and non-invasive application of cooling provides a safe means with which to dramatically increase the therapeutic window in which decontamination and/or antidote treatment against VX are life-saving.

  16. Development of Novel Decontamination Techniques for Chemical Agents (GB, VX, HD) Contaminated Facilities. Phase I. Identification and Evaluation of Novel Decontamination Concepts. Volume 1

    Science.gov (United States)

    1983-02-01

    evaluation were the use of hot gases, :: "vapor circulation and chemical methods, using either monoethanol amine , ¶’ n-octyl-pyridinium aldoxime bromide...ntambor) Chemical Agents Decontamination Concepts Thermal Oximes GB Installation Restoration Facilities Amines VX Structures Concrete Abrasive Ammonia...steam, ammonia, oximes and amines either alone or in series. ** V- nil- -- m- 4’- t. -U °.% INSp 119CURIlY CLASSIFICATION OF THIS PAGElfW~on Date

  17. Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

    Science.gov (United States)

    2010-04-01

    those produced by reaction with true nerve agents. This information will determine the choice of model compounds that will yield suitable nerve agent...and mutational studies of organophosphorus hydrolase reveal a cryptic and functional allosteric-binding site. Arch. Biochem. Biophys. 442, 169–179...pesticide exposures in female spouses of licensed pesticide applicators in the agricultural health study cohort, J. Occup. Environ. Med. 48 (2006) 1005

  18. Detection of VX contamination in soil through solid-phase microextraction sampling and gas chromatography/mass spectrometry of the VX degradation product bis(diisopropylaminoethyl)disulfide.

    Science.gov (United States)

    Hook, Gary L; Kimm, Gregory; Koch, David; Savage, Paul B; Ding, Bangwei; Smith, Philip A

    2003-04-11

    A solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) sampling and analysis method was developed for bis(diisopropylaminoethyl)disulfide (a degradation product of the nerve agent VX) in soil. A 30-min sampling time with a polydimethylsiloxane-coated fiber and high temperature alkaline hydrolysis allowed detection with 1.0 microg of VX spiked per g of agricultural soil. The method was successfully used in the field with portable GC-MS instrumentation. This method is relatively rapid (less than 1 h), avoids the use of complex preparation steps, and enhances analyst safety through limited use of solvents and decontamination of the soil before sampling.

  19. Comparison of selected skin decontaminant products and regimens against VX in domestic swine.

    Science.gov (United States)

    Bjarnason, S; Mikler, J; Hill, I; Tenn, C; Garrett, M; Caddy, N; Sawyer, T W

    2008-03-01

    An anesthetized domestic swine model was used to compare the efficacy and cross-contamination potential of selected skin decontaminant products and regimens against the chemical warfare agent, VX. Animals topically exposed to 2x, 3x or 5x LD(50) VX showed typical signs of organophosphate nerve agent poisoning, including miosis, salivation, mastication, dysrhythmias, and respiratory distress prior to death. Animals were exposed to 5x LD(50) VX and then decontaminated 45 min later with the reactive skin decontamination lotion (RSDL), Fuller's earth (FE), 0.5% hypochlorite, or soapy water. Survival was 100% when the reactive skin decontamination lotion or FE was utilized, although 50% of Fuller's earth-decontaminated animals exhibited serious signs of VX poisoning. Decontamination of VX-treated animals with 0.5% hypochlorite was less effective but also increased survival. Soapy water was ineffective in preventing lethality. Blood cholinesterase levels were not predictive of clinical outcome in decontaminated animals. The potential of "decontaminated" VX in open wounds to cause poisoning was assessed by vigorously mixing 5x LD(50) VX with the test decontaminants for 5 min and then placing the mixture onto a full-thickness skin wound. Soapy water was ineffective in preventing lethality. Although treatment with dry Fuller's earth prevented death and all signs of organophosphate poisoning, a significant proportion of treated animals decontaminated with Fuller's earth in aqueous suspension exhibited serious signs of organophosphate poisoning, suggesting that live agent may be desorbed from Fuller's earth when it is exposed to a liquid environment. Animals treated with reactive skin decontamination lotion or 0.5% hypochlorite-VX mixtures showed no signs of organophosphate poisoning during the 6- h test period.

  20. Analysis of VX on soil particles using ion trap secondary ion mass spectrometry.

    Science.gov (United States)

    Groenewold, G S; Appelhans, A D; Gresham, G L; Olson, J E; Jeffery, M; Wright, J B

    1999-07-01

    The direct detection of the nerve agent VX (methylphosphonothioic acid, S-[2-[bis(1-methylethyl)amino]ethyl] O-ethyl ester) on milligram quantities of soil particles has been achieved using ion trap secondary ion mass spectrometry (IT-SIMS). VX is highly adsorptive toward a wide variety of surfaces; this attribute makes detection using gas-phase approaches difficult but renders the compound very amenable to surface detection. An ion trap mass spectrometer, modified to perform SIMS, was employed in the present study. A primary ion beam (ReO4-) was fired on axis through the ion trap, where it impacted the soil particle samples. [VX + H]+, [VX + H]+ fragment ions, and ions from the chemical background were sputtered into the gas-phase environment of the ion trap, where they were either scanned out or isolated and fragmented (MS2). At a surface concentration of 0.4 monolayer, intact [VX + H]+, and its fragment ions, were readily observable above background. However, at lower concentrations, the secondary ion signal from VX became obscured by ions derived from the chemical background on the surface of the soil particles. MS2 analysis using the ion trap was employed to improve detection of lower concentrations of VX: detection of the 34S isotopic ion of [VX + H]+, present at a surface concentration of approximately 0.002 monolayer, was accomplished. The study afforded the opportunity to investigate the fragmentation chemistry of VX. Semiempirical calculations suggest strongly that the molecule is protonated at the N atom. Deuterium labeling showed that formation of the base peak ion (C2H4)N(i-C3H7)2+ involves transfer of the amino proton to the phosphonothioate moiety prior to, or concurrent with, C-S bond cleavage. To manage the risk associated with working with the compound, the vacuum unit of the IT-SIMS was located in a hood, connected by cables to the externally located electronics and computer.

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

    Science.gov (United States)

    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.

  2. Ion chemistry of VX surrogates and ion energetics properties of VX: new suggestions for VX chemical ionization mass spectrometry detection.

    Science.gov (United States)

    Midey, Anthony J; Miller, Thomas M; Viggiano, A A; Bera, Narayan C; Maeda, Satoshi; Morokuma, Keiji

    2010-05-01

    Room temperature rate constants and product ion branching ratios have been measured for the reactions of numerous positive and negative ions with VX chemical warfare agent surrogates representing the amine (triethylamine) and organophosphonate (diethyl methythiomethylphosphonate (DEMTMP)) portions of VX. The measurements have been supplemented by theoretical calculations of the proton affinity, fluoride affinity, and ionization potential of VX and the simulants. The results show that many proton transfer reactions are rapid and that the proton affinity of VX is near the top of the scale. Many proton transfer agents should detect VX selectively and sensitively in chemical ionization mass spectrometers. Charge transfer with NO(+) should also be sensitive and selective since the ionization potential of VX is small. The surrogate studies confirm these trends. Limits of detection for commercial and research grade CIMS instruments are estimated at 80 pptv and 5 ppqv, respectively.

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

    Science.gov (United States)

    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.

  4. Simultaneous quantification of VX and its toxic metabolite in blood and plasma samples and its application for in vivo and in vitro toxicological studies.

    Science.gov (United States)

    Reiter, Georg; Mikler, John; Hill, Ira; Weatherby, Kendal; Thiermann, Horst; Worek, Franz

    2011-09-15

    The present study was initiated to develop a sensitive and highly selective method for the simultaneous quantification of the nerve agent VX (O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate) and its toxic metabolite (EA-2192) in blood and plasma samples in vivo and in vitro. For the quantitative detection of VX and EA-2192 the resolution was realized on a HYPERCARB HPLC phase. A specific procedure was developed to isolate both toxic analytes from blood and plasma samples. The limit of detection was 0.1 pg/ml and the absolute recovery of the overall sample preparation procedure was 74% for VX and 69% for EA-2192. After intravenous and percutaneous administration of a supralethal doses of VX in anaesthetised swine both VX and EA-2192 could be quantified over 540 min following exposure. This study is the first to verify the in vivo formation of the toxic metabolite EA-2192 after poisoning with the nerve agent VX. Further toxicokinetic and therapeutic studies are required in order to determine the impact of EA-2192 on the treatment of acute VX poisoning.

  5. Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase 1.

    Science.gov (United States)

    Valiyaveettil, Manojkumar; Alamneh, Yonas; Biggemann, Lionel; Soojhawon, Iswarduth; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2010-12-03

    Paraoxonase 1 (PON1) has been described as an efficient catalytic bioscavenger due to its ability to hydrolyze organophosphates (OPs) and chemical warfare nerve agents (CWNAs). It is the future most promising candidate as prophylactic medical countermeasure against highly toxic OPs and CWNAs. Most of the studies conducted so far have been focused on the hydrolyzing potential of PON1 against nerve agents, sarin, soman, and VX. Here, we investigated the hydrolysis of tabun by PON1 with the objective of comparing the hydrolysis potential of human and rabbit serum purified and recombinant human PON1. The hydrolysis potential of PON1 against tabun, sarin, and soman was evaluated by using an acetylcholinesterase (AChE) back-titration Ellman method. Efficient hydrolysis of tabun (100 nM) was observed with ∼25-40 mU of PON1, while higher concentration (80-250 mU) of the enzyme was required for the complete hydrolysis of sarin (11 nM) and soman (3 nM). Our data indicate that tabun hydrolysis with PON1 was ∼30-60 times and ∼200-260 times more efficient than that with sarin and soman, respectively. Moreover, the catalytic activity of PON1 varies from source to source, which also reflects their efficiency of hydrolyzing different types of nerve agents. Thus, efficient hydrolysis of tabun by PON1 suggests its promising potential as a prophylactic treatment against tabun exposure.

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

    Science.gov (United States)

    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.

  7. Comparison of skin decontamination efficacy of commercial decontamination products following exposure to VX on human skin.

    Science.gov (United States)

    Thors, L; Koch, M; Wigenstam, E; Koch, B; Hägglund, L; Bucht, A

    2017-08-01

    The decontamination efficacy of four commercially available skin decontamination products following exposure to the nerve agent VX was evaluated in vitro utilizing a diffusion cell and dermatomed human skin. The products included were Reactive Skin Decontamination Lotion (RSDL), the Swedish decontamination powder 104 (PS104), the absorbent Fuller's Earth and the aqueous solution alldecontMED. In addition, various decontamination procedures were assessed to further investigate important mechanisms involved in the specific products, e.g. decontamination removal from skin, physical removal by sponge swabbing and activation of degradation mechanisms. The efficacy of each decontamination product was evaluated 5 or 30 min after dermal application of VX (neat or diluted to 20% in water). The RSDL-lotion was superior in reducing the penetration of VX through human skin, both when exposed as neat agent and when diluted to 20% in water. Swabbing with the RSDL-sponge during 2 min revealed decreased efficacy compared to applying the RSDL-lotion directly on the skin for 30 min. Decontamination with Fuller's Earth and alldecontMED significantly reduced the penetration of neat concentration of VX through human skin. PS104-powder was insufficient for decontamination of VX at both time-points, independently of the skin contact time of PS104. The PS104-slurry (a mixture of PS104-powder and water), slightly improved the decontamination efficacy. Comparing the time-points for initiated decontamination revealed less penetrated VX for RSDL and Fuller's Earth when decontamination was initiated after 5 min compared to 30 min post-exposure, while alldecontMED displayed similar efficacy at both time-points. Decontamination by washing with water only resulted in a significant reduction of penetrated VX when washing was performed 5 min after exposure, but not when decontamination was delayed to 30 min post-exposure of neat VX. In conclusion, early initiated decontamination with the

  8. Nerve agent-induced seizures and their pharmacological modulation

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Mumford, Helen; Troyer, John K

    2011-09-25

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

  10. Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

    Science.gov (United States)

    Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

    2012-04-01

    The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

  11. The determination of organophosphonate nerve agent metabolites in human urine by hydrophilic interaction liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Mawhinney, Douglas B; Hamelin, Elizabeth I; Fraser, Rheaclare; Silva, Sathya S; Pavlopoulos, Antonis J; Kobelski, Robert J

    2007-06-01

    A sensitive, robust isotope dilution LC/MS/MS method is presented for the quantitative analysis of human urine for the alkyl methylphosphonic acid metabolites of five organophosphorus nerve agents (VX, rVX or VR, GB or Sarin, GD or Soman, and GF or Cyclosarin). The selective sample preparation method employs non-bonded silica solid-phase extraction and is partially automated. While working with a mobile phase composition that enhances the electrospray ionization process, the hydrophilic interaction chromatography method results in a 5-min injection-to-injection cycle time, excellent peak shapes and adequate retention (k'=3.1). These factors lead to limits of detection for these metabolites as low as 30 pg/mL in a 1-mL sample of human urine. The quality control data (15 and 75 ng/mL) demonstrate accurate (-0.5 to +3.4%) and precise (coefficients of variation of 2.1-3.6%) quantitative results over the clinically relevant urine concentration range of 1-200 ng/mL for a validation set of 20 standard and quality control sets prepared by five analysts over 54 days. The selectivity of the method is demonstrated for a 100-individual reference range study, as well as the analysis of relevant biological samples. The combined sample preparation and analysis portions of this method have a throughput of 288 samples per day.

  12. Non-thermal ablation of rabbit liver VX2 tumor by pulsed high intensity focused ultrasound with ultrasound contrast agent: Pathological characteristics

    Institute of Scientific and Technical Information of China (English)

    Cheng-Wen Zhou; Fa-Qi Li; Yan Qin; Chun-Mei Liu; Xiao-Lin Zheng; Zhi-Biao Wang

    2008-01-01

    AIM:To investigate the pathological characteristics of non-thermal damage induced by pulsed high intensity focused ultrasound (PHIFU) combined with ultrasound contrast agent (UCA),SonoVue (Bracco SpA,Milan,Italy) in rabbit liver VX2 tumor.METHODS:Liver VX2 tumor models were established in 20 rabbits,which were divided randomly into PHIFU combined with ultrasound contrast agent group (PHIFU + UCA group) and sham group.In the PHIFU + UCA group,0.2 mL of SonoVue was injected intravenously into the tumor,followed by ultrasound exposure of Isp 5900 W/cm2.The rabbits were sacrificed one day after ultrasound exposure.Specimens of the exposed tumor tissues were obtained and observed pathologically under light microscope and transmission electron microscope.The remaining tumor tissues were sent for 2,3,5-Triphenyltetrazolium chloride (TTC) staining.RESULTS:Before TTC staining,tumor tissues in both the sham and the PHIFU + UCA groups resembled gray fish meat.After TTC staining,the tumor tissues were uniformly stained red,with a clear boundary between tumor tissue and normal tissue.Histological examination showed signs of tumor cell injury in PHIFU + UCA group,with cytoplasmic vacuoles of various sizes,chromatin margination and karyopyknosis.Electron microscopic examination revealed tumor cell volume reduction,karyopyknosis,chromatin margination,intercellular space widening,the presence of high electron-density apoptotic bodies and vacuoles in cytoplasm.CONCLUSION:The non-thermal effects of PHIFU combined with UCA can be used to ablate rabbit liver VX2 tumors.

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

    Science.gov (United States)

    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.

  14. Chemical analysis of bleach and hydroxide-based solutions after decontamination of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX).

    Science.gov (United States)

    Hopkins, F B; Gravett, M R; Self, A J; Wang, M; Chua, Hoe-Chee; Hoe-Chee, C; Lee, H S Nancy; Sim, N Lee Hoi; Jones, J T A; Timperley, C M; Riches, J R

    2014-08-01

    Detailed chemical analysis of solutions used to decontaminate chemical warfare agents can be used to support verification and forensic attribution. Decontamination solutions are amongst the most difficult matrices for chemical analysis because of their corrosive and potentially emulsion-based nature. Consequently, there are relatively few publications that report their detailed chemical analysis. This paper describes the application of modern analytical techniques to the analysis of decontamination solutions following decontamination of the chemical warfare agent O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate (VX). We confirm the formation of N,N-diisopropylformamide and N,N-diisopropylamine following decontamination of VX with hypochlorite-based solution, whereas they were not detected in extracts of hydroxide-based decontamination solutions by nuclear magnetic resonance (NMR) spectroscopy or gas chromatography-mass spectrometry. We report the electron ionisation and chemical ionisation mass spectroscopic details, retention indices, and NMR spectra of N,N-diisopropylformamide and N,N-diisopropylamine, as well as analytical methods suitable for their analysis and identification in solvent extracts and decontamination residues.

  15. Intercostal nerve blockade for evaluation of local anaesthetic agents.

    Science.gov (United States)

    Bridenbaugh, P O

    1975-02-01

    Bilateral intercostal nerve block provides the opportunity to subject as many as 16 separate peripheral nerves in a single subject to known or unknown local anaesthetic agents in a variety of concentrations, volumes, and additives. It permits the observation of local (e.g., neuritis), clinical (e.g., onset and duration), and systemic (e.g., toxicity and blood concentration) effects of these variables. In double-blind studies, bilateral intercostal nerve block allows the use of each side of the trunk for comparison of two experimental drugs, a new drug against a standard, or two new drugs. Subtle differences in clinical properties as well as simultaneous blood concentrations may be detected in these studies. The advantages of this technique in evaluating local anaesthetic agents are primarily the use of a single subject as his own control while studying may separate peripheral nerves. This aids appreciably in limiting the variable of age, temperature, and perfusion, as well as techniques of administration and evaluation. The constancy of the anatomy of the intercostal nerve provides a highly reliable and reproducible block technique.

  16. Determination of threshold adverse effect doses of percutaneous VX exposure in African green monkeys.

    Science.gov (United States)

    Genovese, Raymond F; Benton, Bernard J; Oubre, John L; Byers, Christopher E; Jakubowski, E Michael; Mioduszewski, Robert J; Settle, Timothy J; Steinbach, Thomas J

    2011-01-11

    Percutaneous exposure to the chemical warfare nerve agent VX was evaluated in African green monkeys (n=9). Doses of VX (7.5-100 μg/kg) were applied to the skin for 60 min and residual agent was quantified (before decontamination) to estimate the absorbed dose. Monkeys were evaluated for the presence or absence of clinical signs of toxicity and blood was sampled periodically (30 min--12 weeks) following exposure to measure the degree of circulating acetylcholinesterase (AChE) inhibition. Monkeys were also evaluated for behavioral changes from VX exposure using a serial probe recognition (SPR) task. The lowest observable adverse effect level (LOAEL) for the production of major clinical signs was determined to be 42.22 μg/kg (absorbed dose estimate=17.36 μg/kg) and the LOAEL for AChE inhibition was 13.33 μg/kg (absorbed dose estimate=6.53 μg/kg). Behavioral performance was unaffected at doses that, while producing substantial AChE inhibition, did not produce clinical signs. VX represents a substantial threat as a contact hazard and these results complement previous studies using the percutaneous route of exposure with VX and extend the findings to a non-human primate species.

  17. Hairy skin exposure to VX in vitro: effectiveness of delayed decontamination.

    Science.gov (United States)

    Rolland, P; Bolzinger, M-A; Cruz, C; Josse, D; Briançon, S

    2013-02-01

    The chemical warfare agents such as VX represent a threat for both military and civilians, which involves an immediate need of effective decontamination systems. Since human scalp is usually unprotected compared to other body regions covered with clothes, it could be a preferential site of exposure in case of terrorist acts. The purpose of this study was to determine if skin decontamination could be efficient when performed more than 1h after exposure. In addition, the impact of hairs in skin contamination was investigated. By using in vitro skin models, we demonstrated that about 75% of the applied quantity of VX was recovered on the skin surface 2h after skin exposition, which means that it is worth decontaminating even if contamination occurred 2h before. The stratum corneum reservoir for VX was quickly established and persistent. In addition, the presence of hairs modified the percutaneous penetration of the nerve agent by binding of VX to hairs. Hair shaft has thus to be taken into account in the decontamination process. Reactive Skin Decontamination Lotion (RSDL) and Fuller's Earth (FE) were active in the skin decontamination 45min post-exposure, but RSDL was more efficient in reducing the amount of VX either in the skin or in the hair.

  18. Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

  19. Comparison of latex body paint with wetted gauze wipes for sampling the chemical warfare agents VX and sulfur mustard from common indoor surfaces.

    Science.gov (United States)

    Hernon-Kenny, Laura A; Behringer, Deborah L; Crenshaw, Michael D

    2016-05-01

    Comparison of solvent-wetted gauze with body paint, a peelable surface sampling media, for the sampling of the chemical warfare agents VX and sulfur mustard from nine surfaces was performed. The nine surfaces sampled are those typical of interior public venues and include smooth, rough, porous, and non-porous surfaces. Overall, solvent-wetted gauze (wipes) performed better for the recovery of VX from non-porous surfaces while body paint (BP) performed better for the porous surfaces. The average percent VX recoveries using wipes and BP, respectively, are: finished wood flooring, 86.2%, 71.4%; escalator handrail, 47.3%, 26.7%; stainless steel, 80.5%, 56.1%; glazed ceramic tile, 81.8%, 44.9%; ceiling tile, 1.77%, 13.1%; painted drywall 7.83%, 21.1%; smooth cement, 0.64%, 10.3%; upholstery fabric, 24.6%, 23.1%; unfinished wood flooring, 9.37%, 13.1%. Solvent-wetted gauze performed better for the recovery of sulfur mustard from three of the relatively non-porous surfaces while body paint performed better for the more porous surfaces. The average percent sulfur mustard recoveries using wipes and BP, respectively, are: finished wood flooring, 30.2%, 2.97%; escalator handrail, 4.40%, 4.09%; stainless steel, 21.2%, 3.30%; glazed ceramic tile, 49.7%, 16.7%; ceiling tile, 0.33%, 11.1%; painted drywall 2.05%, 10.6%; smooth cement, 1.20%, 35.2%; upholstery fabric, 7.63%, 6.03%; unfinished wood flooring, 0.90%, 1.74%.

  20. Ion-molecule reactions of O,S-dimethyl methylphosphonothioate: evidence for intramolecular sulfur oxidation during VX perhydrolysis.

    Science.gov (United States)

    McAnoy, Andrew M; Williams, Jilliarne; Paine, Martin R L; Rogers, Michael L; Blanksby, Stephen J

    2009-12-18

    The alkaline perhydrolysis of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) was investigated by studying the ion-molecule reactions of HOO(-) with O,S-dimethyl methylphosphonothioate in a modified linear ion-trap mass spectrometer. In addition to simple proton transfer, two other abundant product ions are observed at m/z 125 and 109 corresponding to the S-methyl methylphosphonothioate and methyl methylphosphonate anions, respectively. The structure of these product ions is demonstrated by a combination of collision-induced dissociation and isotope-labeling experiments that also provide evidence for their formation by nucleophilic reaction pathways, namely, (i) S(N)2 at carbon to yield the S-methyl methylphosphonothioate anion and (ii) nucleophilic addition at phosphorus affording a reactive pentavalent intermediate that readily undergoes internal sulfur oxidation and concomitant elimination of CH(3)SOH to yield the methyl methylphosphonate anion. Consistent with previous solution phase observations of VX perhydrolysis, the toxic P-O cleavage product is not observed in this VX model system and theoretical calculations identify P-O cleavage to be energetically uncompetitive. Conversely, intramolecular sulfur oxidation is calculated to be extremely exothermic and kinetically accessible explaining its competitiveness with the facile gas phase proton transfer process. Elimination of a sulfur moiety deactivates the nerve agent VX and thus the intramolecular sulfur oxidation process reported here is also able to explain the selective perhydrolysis of the nerve agent to relatively nontoxic products.

  1. Improvements of the fluoride reactivation method for the verification of nerve agent exposure

    NARCIS (Netherlands)

    Degenhardt, C.E.A.M.; Pleijsier, K.; Schans, M.J. van der; Langenberg, J.P.; Preston, K.E.; Solano, M.I.; Maggio, V.L.; Barr, J.R.

    2004-01-01

    One of the most appropriate biomarkers for the verification of organophosphorus nerve agent exposure is the conjugate of the nerve agent to butyrylcholinesterase (BuChE). The phosphyl moiety of the nerve agent can be released from the BuChE enzyme by incubation with fluoride ions, after which the re

  2. Metal organic frameworks for the catalytic detoxification of chemical warfare nerve agents

    Energy Technology Data Exchange (ETDEWEB)

    Hupp, Joseph T.; Farha, Omar K.; Katz, Michael J.; Mondloch, Joseph E.

    2017-04-18

    A method of using a metal organic framework (MOF) comprising a metal ion and an at least bidendate organic ligand to catalytically detoxify chemical warfare nerve agents including exposing the metal-organic-framework (MOF) to the chemical warfare nerve agent and catalytically decomposing the nerve agent with the MOF.

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

    Science.gov (United States)

    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.

  4. M Current-Based Therapies for Nerve Agent Seizures

    Science.gov (United States)

    2013-07-01

    Cholinergic nerve agents cause neuronal hyper-excitability by inhibiting M/KCNQ2/3 potassium channels. 2) Cholinergic seizures can be blocked by drugs ...characterize the effects of M current enhancers on excitabtility and bursting of CA1 pyramidal neurons. Aim 3) To test anticonvulsant action of three M...blocked all EPSCs. Miniature EPSCs (mEPSCs) were recorded by blocking action potentials with 1 μM TTX (Alomone labs, Jerusalem, Israel). All drugs were

  5. Experimental and numerical study of spread and sorption of VX sessile droplets into medium grain-size sand.

    Science.gov (United States)

    D'Onofrio, Terrence G; Navaz, Homayun K; Markicevic, Bojan; Mantooth, Brent A; Sumpter, Kenneth B

    2010-03-02

    The experimental measurement and modeling of liquid chemical agent spread and sorption on a porous substrate are described. Experimental results with the nerve agent O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX) demonstrate that the wetted imprint volume increases, even after the sessile drop volume is exhausted. This indicates the wetted imprint is only partially saturated, and a multiphase flow problem formulation is needed to predict the VX fate in porous substrates. Three characteristics and their changes in time: (i) sessile volume remaining, (ii) wetted imprint area on the sand surface where the droplet is deposited, and (iii) VX penetration depth into sand, are computed numerically and compared to experimentally measured values. A very good qualitative and quantitative agreement was found between the numerical and experimental results. These numerical and experimental methods can be used to determine the spread and sorption of hazardous materials into a variety of substrates.

  6. Diagnosis of Intoxication by the Organophosphate VX: Comparison Between an Electrochemical Sensor and Ellman´s Photometric Method

    OpenAIRE

    Kamil Kuca; Martina Hrabinova; Miroslav Pohanka

    2008-01-01

    An electrochemical sensor is introduced as a tool applicable for diagnosis of intoxication by cholinesterase inhibitors caused by the well-known nerve agent VX. The traditional Ellman method was chosen for comparison with the sensor's analytical parameters. Both methods are based on estimation of blood cholinesterase inhibition as a marker of intoxication. While Ellman´s method provided a limit of detection of 5.2´10-7 M for blood containing VX, the electrochemical sensor was able to de...

  7. 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.

    Science.gov (United States)

    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 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 method is a viable choice for the simultaneous determination of a wide range of degradation products of nerve agents - zwitterionic, monoacid, diacid, and monothioacid chemicals - with excellent performance.

  8. Safety of administration of human butyrylcholinesterase and its conjugates with soman or VX in rats.

    Science.gov (United States)

    Genovese, Raymond F; Sun, Wei; Johnson, Christina C; Ditargiani, Robert C; Doctor, Bhupendra P; Saxena, Ashima

    2010-05-01

    We evaluated the effects of conjugated enzyme-nerve agent product resulting from the inhibition of bioscavenger human serum butyrylcholinesterase (Hu BChE) by nerve agents soman or VX. Rats were trained on a multiple Fixed-Ratio 32, Extinction 30 sec. (FR32, Ext30) schedule of food reinforcement and then injected (i.m.) with Hu BChE (30 mg/kg), equivalent amounts of Hu BChE-soman conjugate (GDC), Hu BChE-VX conjugate, oxotremorine (OXO) (0.316 mg/kg) or vehicle (n = 8, each group). On the day of injection and on 10 subsequent daily sessions, performance was evaluated on the FR32, Ext30 schedule. Neither conjugates nor Hu BChE produced a performance deficit under the schedule. OXO produced a substantial decrease in responding on the day of administration, with complete recovery observed on subsequent sessions. None of the treatments affected circulating acetylcholinesterase (AChE) activity when evaluated 24-72 hr after injection. The dose of Hu BChE produced a 20,000-fold increase above baseline in circulating BChE activity. Pathological evaluation of organ systems approximately 2 weeks following administration of conjugates or Hu BChE alone did not show toxicity. Taken together, these results suggest that Hu BChE - nerve agent conjugates produced following bioscavenger protection against nerve agents soman and VX do not appear to be particularly toxic. These results add to the safety assessment of Hu BChE as a bioscavenger countermeasure against nerve agent exposure.

  9. Hydrolysis of VX on Concrete: Rate of Degradation by Direct Surface Interrogation using an Ion Trap Secondary Ion Mass Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Groenewold, Gary Steven; Appelhans, Anthony David; Gresham, Garold Linn; Olson, John Eric; Rowland, B.; Williams, j.; Jeffery, M. T.

    2002-09-01

    The nerve agent VX (O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate) is lethal at very low levels of exposure, which can occur by dermal contact with contaminated surfaces. Hence, behavior of VX in contact with common urban or industrial surfaces is a subject of acute interest. In the present study, VX was found to undergo complete degradation when in contact with concrete surfaces. The degradation was directly interrogated at submonolayer concentrations by periodically performing secondary ion mass spectrometry (SIMS) analyses after exposure of the concrete to VX. The abundance of the [VX + H]+ ion in the SIMS spectra was observed to decrease in an exponential fashion, consistent with first-order or pseudo-first-order behavior. This phenomenon enabled the rate constant to be determined at 0.005 min-1 at 25 C, which corresponds to a half-life of about 3 h on the concrete surface. The decrease in [VX + H]+ was accompanied by an increase in the abundance of the principal degradation product diisopropylaminoethanethiol (DESH), which arises by cleavage of the P-S bond. Degradation to form DESH is accompanied by the formation of ethyl methylphosphonic acid, which is observable only in the negative ion spectrum. A second degradation product was also implicated, which corresponded to a diisopropylvinylamine isomer (perhaps N,N-diisopropyl aziridinium) that arose via cleavage of the S-C bond. No evidence was observed for the formation of the toxic S-2-diisopropylaminoethyl methylphosphonothioic acid. The degradation rate constants were measured at four different temperatures (24-50 C), which resulted in a linear Arrhenius relationship and an activation energy of 52 kJ mol-1. This value agrees with previous values observed for VX hydrolysis in alkaline solutions, which suggests that the degradation of submonolayer VX is dominated by alkaline hydrolysis within the adventitious water film on the concrete surface.

  10. Toxicokinetics of (±)-VX in hairless guinea pigs and marmosets - in vitro metabolism of (±)-VX

    NARCIS (Netherlands)

    Schans, M.J. van der; Lander, H.J.; Moes, G.W.H.; Wiel, H.J. van der; Langenberg, J.P.; Benschop, H.P.

    2000-01-01

    Although the toxicokinetics of several nerve gases, such as sarin and soman have been thoroughly investigated, the toxicokinetics of (±)-VX are still poorly understood. However, it is important to study the toxicokinetics of (±)-VX because there are several reasons to assume that the behavior of (±)

  11. Microglia as Primary Mediators of Nerve Agent Neuropathy

    Science.gov (United States)

    2010-01-01

    COX-2 expression in brain regions known to be damaged by nerve agents (e.g., hippocampus, amygdala, piriform cortex and thalamus). COX-2 expression was...hippocampal CA3 regions and especially the dentate gyrus (Fig. 1A and 1B) as well as in the amygdala (Fig. 1C) and piriform cortex (Fig. 1D). By 7 days COX... piriform cortex and amygdala also showed substantial increases in the number of COX-2 immunoreactive cells after soman (Fig 3). These cells were somewhat

  12. Interaction of nerve agent antidotes with cholinergic systems.

    Science.gov (United States)

    Soukup, O; Tobin, G; Kumar, U K; Binder, J; Proska, J; Jun, D; Fusek, J; Kuca, K

    2010-01-01

    The poisoning with organophosphorus compounds represents a life threatening danger especially in the time of terroristic menace. No universal antidote has been developed yet and other therapeutic approaches not related to reactivation of acetylcholinesterase are being investigated. This review describes the main features of the cholinergic system, cholinergic receptors, cholinesterases and their inhibitors. It also focuses on the organophosphorus nerve agents, their properties, effects and a large part describes various possibilities in treatments, mainly traditional oxime therapies based on reactivation of AChE. Furthermore, non-cholinesterase coupled antidotal effects of the oximes are thoroughly discussed. These antidotal effects principally include oxime interactions with muscarinic and nicotinic receptors.

  13. Timing of decontamination and treatment in case of percutaneous VX poisoning: a mini review.

    Science.gov (United States)

    Joosen, Marloes J A; van der Schans, Marcel J; Kuijpers, Willem C; van Helden, Herman P M; Noort, Daan

    2013-03-25

    Low volatile organophosphorous nerve agents such as VX, will most likely enter the body via the skin. The pharmacokinetics of drugs such as oximes, atropine and diazepam, are not aligned with the variable and persistent toxicokinetics of the agent. Repeated administration of these drugs showed to improve treatment efficacy compared to a single injection treatment. Because of the effectiveness of continuous treatment, it was investigated to what extent a subchronic pretreatment with carbamate (pyridostigmine or physostigmine combined with either procyclidine or scopolamine) would protect against percutaneous VX exposure. Inclusion of scopolamine in the pretreatment prevented seizures in all animals, but none of the pretreatments affected survival time or the onset time of cholinergic signs. These results indicate that percutaneous poisoning with VX requires additional conventional treatment in addition to the current pretreatment regimen. Decontamination of VX-exposed skin is one of the most important countermeasures to mitigate the effects of the exposure. To evaluate the window of opportunity for decontamination, the fielded skin decontaminant Reactive Skin Decontaminant Lotion (RSDL) was tested at different times in hairless guinea pigs percutaneously challenged with 4× LD50 VX in IPA. The results showed that RSDL decontamination at 15 min after exposure could not prevent progressive blood cholinesterase inhibition and therefore would still require additional treatment. A similar decontamination regimen with RSDL at 90 min showed that it still might effectively increase the time window of opportunity for treatment. In conclusion, the delay in absorption presents a window of opportunity for decontamination and treatment. The continuous release of VX from the skin presents a significant challenge for efficacious therapy, which should ideally consist of thorough decontamination and continuous treatment.

  14. Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Cao Wei [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: zjfurong2008@126.com; Wan Yi [Department of Health Statistics, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Liang Zhihui [Department of Radiology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province 050082 (China); Duan Yunyou; Liu Xi [Department of Ultrasonography, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinshi Road, Xi' an 710038 (China); Wang Zhimin; Liu Yiyong; Zhu Jia; Liu Xiongtao [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China); Zhang Hongxin [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: cawe-001@163.com

    2010-02-15

    Purpose: To evaluate the therapeutic effect of heated (60 deg. C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3 cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 deg. C) (1 mL), lipiodol (60 deg. C) (1 mL) or control (physiological saline (37 deg. C) (1 mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering. Results: The tumor growth rate in the lipiodol (60 deg. C) group (0.92 {+-} 0.21, tumor volume from 1811 {+-} 435 to 1670 {+-} 564 mm{sup 3}) was significantly lower than that in the control group (3.48 {+-} 1.17, tumor volume from 1808 {+-} 756 to 5747 {+-} 1341 mm{sup 3}) (P < 0.05) and in the doxorubicin-lipiodol (37 deg. C) group (1.69 {+-} 0.26, tumor volume from 1881 {+-} 641 to 2428 {+-} 752 mm{sup 3}) (P < 0.05). Consequently, the survival period of the animals in the lipiodol (60 deg. C) group (41.0 {+-} 3.0 days) was significantly greater than that in the doxorubicin-lipiodol (37 deg. C) group (38.0 {+-} 2.5 days) (P < 0.05). On the other hand, there was no statistically significant difference in serum AST levels between the lipiodol (60 deg. C) group (148.2 {+-} 11

  15. Development of a Model for Nerve Agent Inhalation in Conscious Rats

    Science.gov (United States)

    2013-05-23

    Toxicol Mech Meth 14:183–94. Bajgar J. (2004). Organophosphates /nerve agent poisoning : mechanism of action, diagnosis, prophylaxis, and treatment. Adv...See reprint. 15. SUBJECT TERMS Chemical warfare, cholinesterases, inhalation exposure, nerve agents, organophosphates , vapor 16. SECURITY...exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl

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

    Energy Technology Data Exchange (ETDEWEB)

    Koplovitz, I.; Stewart, J.R.

    1994-12-31

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

  17. Fate of chemical warfare agents and toxic indutrial chemicals in landfills

    DEFF Research Database (Denmark)

    Bartelt-Hunt, D.L.; Barlaz, M.A.; Knappe, D.R.U.

    2006-01-01

    ) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS...

  18. Differentiated NSC-34 cells as an in vitro cell model for VX.

    Science.gov (United States)

    Kanjilal, Baishali; Keyser, Brian M; Andres, Devon K; Nealley, Eric; Benton, Betty; Melber, Ashley A; Andres, Jaclynn F; Letukas, Valerie A; Clark, Offie; Ray, Radharaman

    2014-10-01

    The US military has placed major emphasis on developing therapeutics against nerve agents (NA). Current efforts are hindered by the lack of effective in vitro cellular models to aid in the preliminary screening of potential candidate drugs/antidotes. The development of an in vitro cellular model to aid in discovering new NA therapeutics would be highly beneficial. In this regard, we have examined the response of a differentiated hybrid neuronal cell line, NSC-34, to the NA VX. VX-induced apoptosis of differentiated NSC-34 cells was measured by monitoring the changes in caspase-3 and caspase-9 activity post-exposure. Differentiated NSC-34 cells showed an increase in caspase-3 activity in a manner dependent on both time (17-23 h post-exposure) and dose (10-100 nM). The maximal increase in caspase-3 activity was found to be at 20-h post-exposure. Caspase-9 activity was also measured in response to VX and was found to be elevated at all concentrations (10-100 nM) tested. VX-induced cell death was also observed by utilizing annexin V/propidium iodide flow cytometry. Finally, VX-induced caspase-3 or -9 activities were reduced with the addition of pralidoxime (2-PAM), one of the current therapeutics used against NA toxicity, and dizocilpine (MK-801). Overall the data presented here show that differentiated NSC-34 cells are sensitive to VX-induced cell death and could be a viable in vitro cell model for screening NA candidate therapeutics.

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

    Science.gov (United States)

    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

  20. Anticonvulsants for Nerve Agent-Induced Seizures: The Influence of the Therapeutic Dose of Atropine

    Science.gov (United States)

    2007-01-01

    Organophosphorous nerve agents-induced cological Basis of Therapeutics, 10th ed. (Hardman JG, Limbird LE, and ( Gilman seizures and efficacy of atropine...us.army.mil Taylor P (2001) Anticholinesterase agents, in Goodman and Gilman’s The Pharrna-

  1. Cyclooxygenase-2 contributes to VX-induced cell death in cultured cortical neurons.

    Science.gov (United States)

    Tenn, Catherine C; Weiss, M Tracy; Beaup, Claire; Peinnequin, Andre; Wang, Yushan; Dorandeu, Frederic

    2012-04-05

    The link between cell death and increased cyclooxygenases-2 (COX-2) activity has not been clearly established. In this study, we examined whether COX-2 activation contributed to the mechanism of neurotoxicity produced by an organophosphorous nerve agent in cultured rat cortical neurons. Exposure of neuronal cells to the nerve agent, VX resulted in an increase in COX enzyme activity in the culture media. A concentration dependent increase in the activity levels of COX-2 enzyme was observed while there was little to no effect on COX-1. In addition, COX-2 mRNA and protein levels increased several hours post-VX exposure. Pre-treatment of the cortical cells with the COX-2 selective inhibitor, NS 398 resulted in a decrease in both the enzyme activity and prostaglandin (PGE(2) and PGF(2α)) release, as well as in a reduction in cell death. These findings indicate that the increase in COX-2 activity may contribute to the mechanism of VX-induced neurotoxicity in cultured rat cortical neuron.

  2. The effect of blood brain barrier modulation on oxime efficacy in nerve agent poisoning (Abstract)

    NARCIS (Netherlands)

    Joosen, M.; Schans, M.J. van der; Dijk, C.G.M. van; Kuijpers, WC.; Wortelboer, H.M.; Helden, H.P.M. van

    2012-01-01

    One of the shortcomings of current treatment of nerve agent poisoning is that oximes hardly penetrate the blood brain barrier (BBB), whereas nerve agents easily do. Enhancing the efficacy of current oximes in the brain, would therefore provide an attractive approach to improve medical countermeasure

  3. Fast, sensitive and cost-effective detection of nerve agents in the gas phase using a portable instrument and an electrochemical biosensor.

    Science.gov (United States)

    Arduini, Fabiana; Amine, Aziz; Moscone, Danila; Ricci, Francesco; Palleschi, Giuseppe

    2007-07-01

    The nerve agents are chemical warfare agents known to be used during terrorist attacks. An inexpensive and portable system to be used by first responders and military personnel is of interest owing to the continuing threat of possible terrorist attacks. Amperometric biosensors based on cholinesterase inhibition show such potentialities. In this work butyrylcholinesterase was immobilized onto screen-printed electrodes modified with Prussian blue and the nerve agent detection was performed by measuring the residual activity of enzyme. The optimized biosensor was tested with sarin and VX standard solutions, showing detection limits of 12 and 14 ppb (10% of inhibition), respectively. The enzymatic inhibition was also obtained by exposing the biosensors to sarin in gas phase. Two different concentrations of sarin gas (0.1 and 0.5 mg m(-3)) at different incubation times (from 30 s up to 10 min) were tested. It is possible to detect sarin at a concentration of 0.1 mg m(-3) with 30-s incubation time, with a degree of inhibition of 34%, which match the legal limits (immediate danger to life and health).

  4. Behavioral and biochemical evaluation of sub-lethal inhalation exposure to VX in rats.

    Science.gov (United States)

    Genovese, Raymond F; Benton, Bernard J; Lee, Esther H; Shippee, Sara J; Jakubowski, E Michael

    2007-03-22

    We evaluated the effects of low-level inhalation exposures (whole body, 60min duration) to the chemical warfare nerve agent VX (0.016, 0.15, 0.30 or 0.45mg/m(3)) in rats. The range of concentrations was approximately equivalent to 0.02-0.62 times 1.0 LC50. Biochemical effects were assessed by evaluating blood acetylcholinesterase (AChE) activity and by a regeneration assay that quantified the amount of VX (as the G analog) present in blood. Behavioral effects were assessed using a variable-interval 56-s schedule of reinforcement (VI56), in which rats were trained to press a lever to receive a food reward. VI56 training was established before exposure and evaluations continued after exposure. Additionally, after exposure, acquisition and maintenance of an eight-arm radial maze (RAM) task was evaluated in which rats learned to locate the four arms of the maze that presented a single food pellet reward. Behavioral assessments were conducted over approximately 3 months following exposure. Transient miosis was observed following exposure to all concentrations of VX and exposures to the 0.45mg/m(3) concentration also produced mild and temporary signs of toxicity (i.e., slight tremor and ataxia) in some subjects. All concentrations of VX also inhibited circulating AChE and the highest concentration inhibited AChE activity to less than 10% of pre-exposure values. Regenerated VX-G was found in red blood cell (RBC) and plasma blood fractions. In this respect, more VX-G was seen in plasma than RBC. Only small disruptions were observed on the VI56 or RAM following some VX exposures. In general, however, behavioral effects were minor and not clearly systematic. Taken together these results demonstrate that largely asymptomatic exposures to VX vapors in rats can produce substantial biochemical effects while having only minor performance effects on a previously learned behavioral task and on the acquisition of a new behavioral task.

  5. Post-exposure treatment of VX poisoned guinea pigs with the engineered phosphotriesterase mutant C23: a proof-of-concept study.

    Science.gov (United States)

    Worek, Franz; Seeger, Thomas; Reiter, Georg; Goldsmith, Moshe; Ashani, Yacov; Leader, Haim; Sussman, Joel L; Aggarwal, Nidhi; Thiermann, Horst; Tawfik, Dan S

    2014-11-18

    The highly toxic organophosphorus (OP) nerve agent VX is characterized by a remarkable biological persistence which limits the effectiveness of standard treatment with atropine and oximes. Existing OP hydrolyzing enzymes show low activity against VX and hydrolyze preferentially the less toxic P(+)-VX enantiomer. Recently, a phosphotriesterase (PTE) mutant, C23, was engineered towards the hydrolysis of the toxic P(-) isomers of VX and other V-type agents with relatively high in vitro catalytic efficiency (kcat/KM=5×10(6)M(-1)min(-1)). To investigate the suitability of the PTE mutant C23 as a catalytic scavenger, an in vivo guinea pig model was established to determine the efficacy of post-exposure treatment with C23 alone against VX intoxication. Injection of C23 (5mgkg(-1) i.v.) 5min after s.c. challenge with VX (∼2LD50) prevented systemic toxicity. A lower C23 dose (2mgkg(-1)) reduced systemic toxicity and prevented mortality. Delayed treatment (i.e., 15min post VX) with 5mgkg(-1) C23 resulted in survival of all animals and only in moderate systemic toxicity. Although C23 did not prevent inhibition of erythrocyte acetylcholinesterase (AChE) activity, it partially preserved brain AChE activity. C23 therapy resulted in a rapid decrease of racemic VX blood concentration which was mainly due to the rate of degradation of the toxic P(-)-VX enantiomer that correlates with the C23 blood levels and its kcat/KM value. Although performed under anesthesia, this proof-of-concept study demonstrated for the first time the ability of a catalytic bioscavenger to prevent systemic VX toxicity when given alone as a single post-exposure treatment, and enables an initial assessment of a time window for this approach. In conclusion, the PTE mutant C23 may be considered as a promising starting point for the development of highly effective catalytic bioscavengers for post-exposure treatment of V-agents intoxication.

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

    Science.gov (United States)

    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.

  7. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse (II): effects of some currently used skin decontaminants (RSDL and Fuller's earth) against liquid sulphur mustard and VX exposure.

    Science.gov (United States)

    Taysse, L; Dorandeu, F; Daulon, S; Foquin, A; Perrier, N; Lallement, G; Breton, P

    2011-06-01

    Using the hairless mouse screening model presented in the companion paper(1) the aim of this study was to assess two skin decontaminating systems: Fuller's earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg(-1) of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants.

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

    Science.gov (United States)

    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...

  9. Preparation of Oxime HI-6 (Dichloride and DimethanesulphonateŒAntidote against Nerve Agents

    Directory of Open Access Journals (Sweden)

    Kamil Kuca

    2008-05-01

    Full Text Available Because of the threat of misuse of nerve agents as terroristic weapons by the terrorists, animmediate need is felt for the preparation of antidotes on large-scale basis.  HI-6 (dichloride anddimethanesulphonate salt are the most promising acetylcholinesterase reactivators used ascausal antidotes in nerve agents intoxication. In this study, rapid and large-scale preparationof oxime HI-6, the most promising reactivator has been described.

  10. Degradation of paraoxon (VX chemical agent simulant) and bacteria by magnesium oxide depends on the crystalline structure of magnesium oxide.

    Science.gov (United States)

    Sellik, A; Pollet, T; Ouvry, L; Briançon, S; Fessi, H; Hartmann, D J; Renaud, F N R

    2016-11-22

    In this work, our goal was to study the capability of a single metallic oxide to neutralize a chemical agent and to exhibit an antibacterial effect. We tested two types of magnesium oxides, MgO. The first MgO sample tested, which commercial data size characteristic was -325 mesh (MgO-1) destroyed in 3 h, 89.7% of paraoxon and 93.2% of 4-nitrophenol, the first degradation product. The second MgO sample, which commercial data size was <50 nm (MgO-2) neutralized in the same time, 19.5% of paraoxon and 10.9% of 4-nitrophenol. For MgO-1 no degradation products could be detected by GC-MS. MgO-1 had a bactericidal activity on Escherichia coli (6 log in 1 h), and showed a decrease of almost 3 log on a Staphylococcus aureus population in 3 h. MgO-2 caused a decrease of 2 log of a E.coli culture but had no activity against S. aureus. Neither of these two products had an activity on Bacillus subtilis spores. Analytical investigations showed that the real sizes of MgO nanoparticles were 11 nm for MgO-1 and 25 nm for MgO-2. Moreover, their crystalline structures were different. These results highlighted the importance of the size of the nanoparticles and their microscopic arrangements to detoxify chemical products and to inhibit or kill microbial strains.

  11. Activity-based protein profiling reveals broad activity of the nerve agent sarin

    NARCIS (Netherlands)

    Tuin, A.W.; Mol, M.A.E.; Berg, R.M. van den; Fidder, A.; Marel, G.A. van der; Overkleeft, H.S.; Noort, D.

    2009-01-01

    Elucidation of noncholinesterase protein targets of organophosphates, and nerve agents in particular, may reveal additional mechanisms for their high toxicity as well as clues for novel therapeutic approaches toward intoxications with these agents. Within this framework, we here describe the synthes

  12. Capillary gas chromatographic analysis of nerve agents using large volume injections

    NARCIS (Netherlands)

    Degenhardt, C.E.A.M.; Kientz, C.E.

    1996-01-01

    The use of large volume injections has been studied for the verification of intact organophosphorus chemical warfare agents in water samples. As the use of ethyl acetate caused severe detection problems new potential solvents were evaluated. With the developed procedure, the nerve agents sarin, tabu

  13. Toxicokinetics and binding of nerve agents in the presence of scavengers

    NARCIS (Netherlands)

    Schans, M.J. van der; Langenberg, J.P.; Benschop, H.P.

    2004-01-01

    Traditional multidrug therapy of organophosphorus nerve agent poisoning has several drawbacks such as postexposure incapacitation while optimal timing of administration of the drugs is also crucial. A priori, sequestration of the agent before it can reach its physiological targets would provide opti

  14. Design of the SNMP Agent on a NTP server%基于VxWorks操作系统的NTP授时服务器SNMP代理

    Institute of Scientific and Technical Information of China (English)

    张懿范

    2009-01-01

    简单网络管理协议(SNMP)作为TCP/IP相关服务的一部分,是当前最为流行的网络管理协议.本文以NTP网络授时服务器的SNMP代理开发作为核心内容,在VxWorks操作系统中实现了SNMP代理的功能.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mizrahi, Dana M., E-mail: danami@iibr.gov.il [Department of Organic Chemistry, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 74100 (Israel); Saphier, Sigal; Columbus, Ishay [Department of Organic Chemistry, Israel Institute for Biological Research, P.O. Box 19, Ness Ziona 74100 (Israel)

    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{sub 4}){sub 3}PW{sub 12}O{sub 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 ({sup 31}P and {sup 13}C) was utilized both for POM characterization and for decontamination studies monitoring.

  17. Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates.

    Science.gov (United States)

    Chambers, Janice E; Meek, Edward C; Chambers, Howard W

    2016-06-01

    Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain.

  18. 重活化剂抗神经性毒剂中毒作用研究进展%Advances in research on oximes as antagonists of nerve agent

    Institute of Scientific and Technical Information of China (English)

    程凤; 聂志勇; 王永安

    2014-01-01

    Nerve agents (NAs) belong to the class of organic phosphorus compounds which are acetylcholinesterase ( AChE) inhibitors, including soman, sarin, tabun,VX, etc.NAs are extremely toxic and considered as the most danger-ous chemical warfare agents.The current standard treatment for poisoning by nerve agents consists of the combined adminis-tration of anticholinergic drugs such as atropine sulphate, AChE reactivators such as pralidoxime, obidoxime and HI-6 and diazepam for anticonvulsant effects, but oximes are therapeutic antidotes against nerve agent intoxications which exert the therapeutic purposes primarily by reactivating the NAs-inhibited AChE.In this paper, the mechanism of nerve agents, the main working procedure of anti-NAs drugs, the chemical structure of classic reactivator, the corresponding antitoxic action, in vivo and in vitro effects and metabolic kinetics are reviewed.%神经性毒剂属于胆碱酯酶抑制剂类有机磷化合物,主要包括梭曼、沙林、塔崩、维埃克斯( VX )等,这类化合物的毒性极大,被认为是最危险的化学战剂。神经性毒剂中毒的治疗主要根据中毒症状,采用抗胆碱能药物、重活化剂、抗惊厥药物等联合用药,但是其中起根本解毒作用的药物主要是重活化剂,这类药物主要是通过被神经性毒剂抑制的乙酰胆碱酯酶重活化而达到治疗目的。该文对神经性毒剂的作用机制及抗神经性毒剂药物作用的主要环节,经典重活化剂的化学结构与相应的抗毒作用、体内外效应和代谢参数等进行了综述。

  19. Effect of pretreatment with human butyrylcholinesterase scavengers on the toxicokinetics and binding of nerve agents in guinea pigs

    NARCIS (Netherlands)

    Schans, M.J. van der; Pleijsier, K.; Wiel, H.J. van der; Boone, C.M.; Langenberg, J.P.

    2004-01-01

    Human butyrylcholinesterase (HuBuChE) is the most promising scavenger for use as a pretreatment drug against nerve agents. Although in animal studies pretreatment with HuBuChE appeared to improve the survival rate following nerve agent challenges and to alleviate post-exposure incapacitation, the in

  20. Studies on a surface acoustic wave (SAW) dosimeter sensor for organophosphorous nerve agents

    NARCIS (Netherlands)

    Nieuwenhuizen, M.S.; Harteveld, J.L.N.

    1997-01-01

    As a follow-up of previous work on a Surface Acoustic Wave (SAW) sensor for nerve agents, irreversible response effects have been studied in more detail. Surface analytical studies indicated that degradation products are responsible for the effects observed. In addition it was tried to explore these

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

    Science.gov (United States)

    2016-01-01

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

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

    Science.gov (United States)

    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 electrodemodified with an immobilized organophosphorus hydrolase (OPH) layer formed by cross-linkingOPH ...

  3. Estimation of oxime efficacy in nerve agent poisoning: a kinetic approach.

    Science.gov (United States)

    Worek, Franz; Szinicz, Ladislaus; Thiermann, Horst

    2005-12-15

    Standard treatment of poisoning by organophosphorus compounds (OP) includes the administration of an anti-muscarinic, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime). Two oximes, obidoxime and pralidoxime (2-PAM), are presently commercially available, yet, these compounds are considered to be of insufficient efficacy against certain nerve agents, e.g. soman and cyclosarin. In the past decades, numerous new oximes were synthesized and tested for their antidotal efficacy. The available data indicate that two Hagedorn oximes, HI 6 and HLö 7, are promising antidotes against various nerve agents. The efficacy of antidotes against nerve agent poisoning cannot be investigated in humans for ethical reasons. Therefore, it is necessary to use surrogate parameters for the evaluation of oxime efficacy. Reactivation of inhibited AChE is considered to be the main mechanism of action of oximes. Clinical data indicate that changes in erythrocyte AChE activity correlate to neuromuscular function indicating that interactions between AChE, inhibitor and oximes can be investigated in vitro with human erythrocyte AChE. Different theoretical models were used for the evaluation of reactivating efficacy of oximes with nerve agent-inhibited human AChE and for estimating effective oxime concentrations. The calculations demonstrate the marked differences between oximes in dependence of the inhibitor and provide a basis for the estimation of the required oxime dose as well as of dosing intervals.

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

    Science.gov (United States)

    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.

  5. Studies on a surface acoustic wave (SAW) dosimeter sensor for organophosphorous nerve agents

    NARCIS (Netherlands)

    Nieuwenhuizen, M.S.; Harteveld, J.L.N.

    1997-01-01

    As a follow-up of previous work on a Surface Acoustic Wave (SAW) sensor for nerve agents, irreversible response effects have been studied in more detail. Surface analytical studies indicated that degradation products are responsible for the effects observed. In addition it was tried to explore these

  6. Immunomagnetic separation and quantification of butyrylcholinesterase nerve agent adducts in human serum

    NARCIS (Netherlands)

    Sporty, J.L.S.; Lemire, S.W.; Jakubowski, E.M.; Renner, J.A.; Evans, R.A.; Williams, R.F.; Schmidt, J.G.; Schans, M.J. van der; Noort, D.; Johnson, R.C.

    2010-01-01

    A novel method for extracting butyrylcholinesterase (BuChE) from serum as a means of identifying and measuring nerve agent adducts to human BuChE is presented here. Antibutyrylcholinesterase monoclonal antibodies were conjugated to protein-G ferromagnetic particles and mixed with 500 μL serum sample

  7. Novel methods for point-of-care diagnosis of nerve agent exposure (Abstract)

    NARCIS (Netherlands)

    Noort, D.; Schans, M.J. van der; Fidder, A.; Verstappen, D.R.W.; Hulst, A.G.; Mars-Groenendijk, R.

    2012-01-01

    Methods to unequivocally and rapidly assess exposure to nerve agents are highly valuable from a military and security perspective. Within this framework we currently follow two different approaches towards rapid point-of-care diagnosis. Regarding the first approach we hypothesized that proteins in t

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

    Energy Technology Data Exchange (ETDEWEB)

    Dolislager, Frederick [University of Tennessee, Knoxville (UTK); Bansleben, Dr. Donald [U.S. Department of Homeland Security; Watson, Annetta Paule [ORNL

    2010-01-01

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

  9. Functionalized Cellulose: PET Polymer Fibers with Zeolites for Detoxification Against Nerve Agents%Functionalized Cellulose:PET Polymer Fibers with Zeolites for Detoxification Against Nerve Agents

    Institute of Scientific and Technical Information of China (English)

    Agarwal Satya R; Sundarrajan Subramanian; Ramakrishna Seeram

    2012-01-01

    Presently activated carbon is used as an adsorptive material for chemical and biological warfare agents.It possess excellent surface properties such as large surface area,fire-resistance and plenty availability,but has disadvantages such as its heavy weight,low breathability (after adsorption of moisture) and disposal.In this paper,we propose to utilize novel electrospun polymeric nanostructures having zeolites as catalyst materials.In this respective,the electrospun polymer nanofibers would serve as the best possible substitutes to activated carbon based protective clothing applications.This is the first in the literature that reports the integration of these types of catalysts with nanofiberous membranes.Electrospinning of cellulose/polyethylene terephthalate (PET) blend nanofibers has been carried out.Zeolite catalysts (Linde Type A and Mordenite) for the detoxification of nerve agent stimulant-paraoxon,were prepared due to their relative simplicity of synthesis.The catalysts were then coated onto nanofiber membranes and their morphology was confirmed using SEM.This is the first report on the coating of nanofibers with zeolites and their successful demonstration against nerve agent stimulant.The UV absorption spectra clearly show the detoxification ability of the functionalized fibers and their potential to be used in textiles for protection and decontamination.

  10. Optimization of Quantitative Proteomics Using 2-Dimensional Difference Gel Electrophoresis to Characterize Molecular Mechanisms of Chemical Warfare Nerve Agent Exposure in the Rat Brain

    Science.gov (United States)

    2010-11-01

    damaging effects of nerve agents. Currently, one prophylactic (pyridostigmine) and three therapeutic drugs (atropine, pralidoxime chloride, and diazepam ...and J.H. McDonough, Efficacy of biperiden and atropine as anticonvulsant treatment for organophosphorus nerve agent intoxication. Archives of

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

    Science.gov (United States)

    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

  12. Diagnosis of Intoxication by the Organophosphate VX: Comparison Between an Electrochemical Sensor and Ellman´s Photometric Method

    Directory of Open Access Journals (Sweden)

    Kamil Kuca

    2008-09-01

    Full Text Available An electrochemical sensor is introduced as a tool applicable for diagnosis of intoxication by cholinesterase inhibitors caused by the well-known nerve agent VX. The traditional Ellman method was chosen for comparison with the sensor's analytical parameters. Both methods are based on estimation of blood cholinesterase inhibition as a marker of intoxication. While Ellman´s method provided a limit of detection of 5.2´10-7 M for blood containing VX, the electrochemical sensor was able to detect 4.0´10-7 M. Good correlation between both methods was observed (R = 0.92. The electrochemical sensor could be considered a convenient tool for a fast yet accurate method, easily available for field as well as laboratory use. Time and cost savings are key features of the sensor-based assay.

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

    Science.gov (United States)

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

    2008-09-25

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

  14. Selective Real-time Detection of Gaseous Nerve Agent Simulants Using Multiwavelength Photoacoustics

    Science.gov (United States)

    2012-08-15

    Selective real-time detection of gaseous nerve agent simulants using multiwavelength photoacoustics Kristan P. Gurton,* Melvin Felton, and Richard...concentrations. The technique is based on a modified version of conventional laser photoacoustic (PA) spectroscopy, in which optical absorption is typically...spec- troscopic approach [1–4]. One of the more direct methods to implement in prac- tice (without sacrificing sensitivity) is laser photoacoustic

  15. Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

    Science.gov (United States)

    2011-12-01

    Sussman, J.L., Tawfik, D.S. The use of recombinant paraoxonases as bioscavengers for the pretreatment/treatment of organophosphate poisoning , 13th...2006). 10. Bird, S.B., Dawson, A. & Ollis, D. Enzymes and bioscavengers for prophylaxis and treatment of organophosphate poisoning . Front. Biosci...intercepting both existing and emerging organophosphate -based chemical warfare nerve agents (CWNA). The 5 years of performance under this project

  16. Evaluating of the Anticonvulsant Gabapentin against Nerve Agent-Induced Seizures in a Guinea Pig Model

    Science.gov (United States)

    2010-07-01

    this drug or similar compounds of this class (e.g., pregabalin, Lyrica®) would be considered as a replacement for, or a supplement to, diazepam or...L.W., Talbot, B.G., Anderson, D.R. Relationship between reversible acetylcholinesterase inhibition and efficacy against soman lethality. Life Science...treatment of nerve agent seizures: anticholinergics vs diazepam in soman- intoxicated guinea pigs. Epilepsy Research, 2000, 38:1-14. McDonough, J.H

  17. Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

    Science.gov (United States)

    2011-06-01

    biomolecules that can intercept both existing and emerging organo - phosphate-based chemical warfare nerve agents (CWNA). All 5th year milestones have been met...w e have demonstrated the potential of direct ed evolution, combining random and designed mutations based on 3D struct ures, to generate m utants of...I., Harel, M., Rosenberry, T.L. & Sussman, J.L. (2010). “Acetylcholinesterase: From 3D structure to function ” Chem Biol Interact, 187, 10-22

  18. Carbamate nerve agent prophylatics exhibit distinct toxicological effects in the zebrafish embryo model.

    Science.gov (United States)

    Fischer, Audrey; Wolman, Marc; Granato, Michael; Parsons, Michael; McCallion, Andrew S; Proescher, Jody; English, Emily

    2015-01-01

    Pyridostigmine bromide (PB) is an FDA-approved drug for the treatment of myasthenia gravis and a prophylactic pre-treatment for organophosphate nerve agent poisoning. Current methods for evaluating nerve agent treatments include enzymatic studies and mammalian models. Rapid whole animal screening tools for assessing the effects of nerve agent pre-treatment and post-exposure drugs represent an underdeveloped area of research. We used zebrafish as a model for acute and chronic developmental exposure to PB and two related carbamate acetylcholinesterase (AChE) inhibitors, neostigmine bromide (NB) and physostigmine (PS). Lethal doses and gross morphological phenotypes resulting from exposure to sub-lethal doses of these compounds were determined. Quantitative analyses of motility impairment and AChE enzyme inhibition were used to determine optimal dosing conditions for evaluation of the effects of carbamate exposures on neuronal development; ~50% impairment of response to startle stimuli and >50% inhibition of AChE activity were observed at 80 mMPB, 20 mM NB and 0.1 mM PS. PB induced stunted somite length, but no other phenotypic effects were observed. In contrast, NB and PS induced more severe phenotypic morphological defects than PB as well as neurite outgrowth mislocalization. Additionally, NB induced mislocalization of nicotinic acetylcholine receptors, resulting in impaired synapse formation. Taken together, these data suggest that altered patterns of neuronal connectivity contribute to the developmental neurotoxicity of carbamates and demonstrate the utility of the zebrafish model for distinguishing subtle structure-based differential effects of AChE inhibitors, which include nerve agents, pesticides and drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Fully integrated ready-to-use paper-based electrochemical biosensor to detect nerve agents.

    Science.gov (United States)

    Cinti, Stefano; Minotti, Clarissa; Moscone, Danila; Palleschi, Giuseppe; Arduini, Fabiana

    2017-07-15

    Paper-based microfluidic devices are gaining large popularity because of their uncontested advantages of simplicity, cost-effectiveness, limited necessity of laboratory infrastructure and skilled personnel. Moreover, these devices require only small volumes of reagents and samples, provide rapid analysis, and are portable and disposable. Their combination with electrochemical detection offers additional benefits of high sensitivity, selectivity, simplicity of instrumentation, portability, and low cost of the total system. Herein, we present the first example of an integrated paper-based screen-printed electrochemical biosensor device able to quantify nerve agents. The principle of this approach is based on dual electrochemical measurements, in parallel, of butyrylcholinesterase (BChE) enzyme activity towards butyrylthiocholine with and without exposure to contaminated samples. The sensitivity of this device is largely improved using a carbon black/Prussian Blue nanocomposite as a working electrode modifier. The proposed device allows an entirely reagent-free analysis. A strip of a nitrocellulose membrane, that contains the substrate, is integrated with a paper-based test area that holds a screen-printed electrode and BChE. Paraoxon, chosen as nerve agent simulant, is linearly detected down to 3µg/L. The use of extremely affordable manufacturing techniques provides a rapid, sensitive, reproducible, and inexpensive tool for in situ assessment of nerve agent contamination. This represents a powerful approach for use by non-specialists, that can be easily broadened to other (bio)systems.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Watson, A.P.; Munro, N.B. (Oak Ridge National Lab., TN (United States)); Sidell, F.R. (Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)); Leffingwell, S.S. (Centers for Disease Control, Atlanta, GA (United States). Center for Environmental Health and Injury Control)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Watson, A.P.; Munro, N.B. [Oak Ridge National Lab., TN (United States); Sidell, F.R. [Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States); Leffingwell, S.S. [Centers for Disease Control, Atlanta, GA (United States). Center for Environmental Health and Injury Control

    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.

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

    Science.gov (United States)

    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.

  4. Simultaneous measurement of tabun, sarin, soman, cyclosarin, VR, VX, and VM adducts to tyrosine in blood products by isotope dilution UHPLC-MS/MS.

    Science.gov (United States)

    Crow, Brian S; Pantazides, Brooke G; Quiñones-González, Jennifer; Garton, Joshua W; Carter, Melissa D; Perez, Jonas W; Watson, Caroline M; Tomcik, Dennis J; Crenshaw, Michael D; Brewer, Bobby N; Riches, James R; Stubbs, Sarah J; Read, Robert W; Evans, Ronald A; Thomas, Jerry D; Blake, Thomas A; Johnson, Rudolph C

    2014-10-21

    This work describes a new specific, sensitive, and rapid stable isotope dilution method for the simultaneous detection of the organophosphorus nerve agents (OPNAs) tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VR, VX, and VM adducts to tyrosine (Tyr). Serum, plasma, and lysed whole blood samples (50 μL) were prepared by protein precipitation followed by digestion with Pronase. Specific Tyr adducts were isolated from the digest by a single solid phase extraction (SPE) step, and the analytes were separated by reversed-phase ultra high performance liquid chromatography (UHPLC) gradient elution in less than 2 min. Detection was performed on a triple quadrupole tandem mass spectrometer using time-triggered selected reaction monitoring (SRM) in positive electrospray ionization (ESI) mode. The calibration range was characterized from 0.100-50.0 ng/mL for GB- and VR-Tyr and 0.250-50.0 ng/mL for GA-, GD-, GF-, and VX/VM-Tyr (R(2) ≥ 0.995). Inter- and intra-assay precision had coefficients of variation of ≤17 and ≤10%, respectively, and the measured concentration accuracies of spiked samples were within 15% of the targeted value for multiple spiking levels. The limit of detection was calculated to be 0.097, 0.027, 0.018, 0.074, 0.023, and 0.083 ng/mL for GA-, GB-, GD-, GF-, VR-, and VX/VM-Tyr, respectively. A convenience set of 96 serum samples with no known nerve agent exposure was screened and revealed no baseline values or potential interferences. This method provides a simple and highly specific diagnostic tool that may extend the time postevent that a confirmation of nerve agent exposure can be made with confidence.

  5. Evaluation of the benefit of the bispyridinium compound MB327 for the antidotal treatment of nerve agent-poisoned mice.

    Science.gov (United States)

    Kassa, Jiri; Pohanka, Miroslav; Timperley, Christopher M; Bird, Mike; Green, A Christopher; Tattersall, John E H

    2016-06-01

    The potency of the bispyridinium non-oxime compound MB327 [1,1'-(propane-1,3-diyl)bis(4-tert-butylpyridinium) diiodide] to increase the therapeutic efficacy of the standard antidotal treatment (atropine in combination with an oxime) of acute poisoning with organophosphorus nerve agents was studied in vivo. The therapeutic efficacy of atropine alone - or atropine in combination with an oxime, MB327, or both an oxime and MB237 - was evaluated by the determination of LD50 values of several nerve agents (tabun, sarin and soman) in mice with and without treatment. The addition of MB327 increased the therapeutic efficacy of atropine alone, and atropine in combination with an oxime, against all three nerve agents, although differences in the LD50 values only reached statistical significance for sarin. In conclusion, the addition of the compound MB327 to the standard antidotal treatment of acute poisonings with nerve agents was beneficial regardless of the chemical structure of the nerve agent, although at the dose employed, MB327 in combination with atropine, or atropine and an oxime, provided only a modest increase in protection ratio. These results from mice, and previous ones from guinea-pigs, provide consistent evidence for additional, albeit modest, efficacy resulting from the inclusion of the antinicotinic compound MB327 in standard antidotal therapy. Given the typically steep probit slope for the dose-lethality relationship for nerve agents, such modest increases in protection ratio could provide significant survival benefit.

  6. Beginning RPG Maker VX Ace

    CERN Document Server

    Perez, Darrin

    2014-01-01

    Beginning RPG Maker VX Ace takes you through the process of using the RPG Maker VX Ace game development engine to create your very own role playing game. The book has been designed with the complete beginner in mind who has little to no experience with the engine. Tutorials and exercises will take you from installing the software to putting the final touches upon your first project. Game design can be quite a daunting challenge, as it generally involves a large amount of programming know-how on top of having to plan everything out that makes a good game what it is. RPG Maker VX Ace

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. An easy method for the determination of active concentrations of cholinesterase reactivators in blood samples: Application to the efficacy assessment of non quaternary reactivators compared to HI-6 and pralidoxime in VX-poisoned mice.

    Science.gov (United States)

    Calas, André-Guilhem; Dias, José; Rousseau, Catherine; Arboléas, Mélanie; Touvrey-Loiodice, Mélanie; Mercey, Guillaume; Jean, Ludovic; Renard, Pierre-Yves; Nachon, Florian

    2016-03-10

    Organophosphorus nerve agents, like VX, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). AChE inhibited by VX can be reactivated using powerful nucleophilic molecules, most commonly oximes, which are one major component of the emergency treatment in case of nerve agent intoxication. We present here a comparative in vivo study on Swiss mice of four reactivators: HI-6, pralidoxime and two uncharged derivatives of 3-hydroxy-2-pyridinaldoxime that should more easily cross the blood-brain barrier and display a significant central nervous system activity. The reactivability kinetic profile of the oximes is established following intraperitoneal injection in healthy mice, using an original and fast enzymatic method based on the reactivation potential of oxime-containing plasma samples. HI-6 displays the highest reactivation potential whatever the conditions, followed by pralidoxime and the two non quaternary reactivators at the dose of 50 mg/kg bw. But these three last reactivators display equivalent reactivation potential at the same dose of 100 μmol/kg bw. Maximal reactivation potential closely correlates to surviving test results of VX intoxicated mice.

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

    Science.gov (United States)

    2011-03-18

    inhibition, Michaelis - Menten constants, and rates of reactivation for wild-type and V146H/ L363E hCE1 against racemic cyclosarin and stereoisomers of...0017441.t002 Table 3. Inhibition and Michaelis - Menten constants for wild-type and V146H/L363E hCE1 against stereoisomers of sarin and soman model...6 | Issue 3 | e17441 where Km was the nerve agent model Michaelis - Menten constant, k2 the unimolecular phosphonylation rate constant, v the remaining

  10. Reactivation of nerve agent-inhibited human acetylcholinesterase by obidoxime, HI-6 and obidoxime+HI-6: Kinetic in vitro study with simulated nerve agent toxicokinetics and oxime pharmacokinetics.

    Science.gov (United States)

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

    2016-03-28

    Despite extensive research for decades no effective broad-spectrum oxime for the treatment of poisoning by a broad range of nerve agents is available. Previous in vitro and in vivo data indicate that the combination of in service oximes could be beneficial. To investigate the ability of obidoxime, HI-6 and the combination of both oximes to reactivate inhibited human AChE in the presence of sarin, cyclosarin or tabun we adopted a dynamic in vitro model with real-time and continuous determination of AChE activity to simulate inhalation nerve agent exposure and intramuscular oxime administration. The major findings of this kinetic study are that the extent and velocity of reactivation is dependent on the nerve agent and the oxime-specific reactivating potency. The oxime-induced reactivation of inhibited human AChE in the presence of nerve agents is markedly impaired and the combination of obidoxime and HI-6 had no additive effect but could broaden the spectrum. In conclusion, these data indicate that a combination of obidoxime and HI-6 would be beneficial for the treatment of poisoning by a broad spectrum of nerve agents and could present an interim solution until more effective and broad-spectrum reactivators are available.

  11. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    Science.gov (United States)

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period.

  12. Immobilization of Russian VX skin depots by localized cooling: implications for decontamination and medical countermeasures.

    Science.gov (United States)

    Mikler, J; Tenn, C; Worek, F; Reiter, G; Thiermann, H; Garrett, M; Bohnert, S; Sawyer, T W

    2011-09-25

    The chemical weapon nerve agent known as Russian VX (VR) is a potent organophosphorus (OP) compound that is much less studied than its VX analogue with respect to toxicity, as well as to the effectiveness of several known countermeasures against it. An anaesthetized domestic swine model was utilized to assess several approaches in mitigating its toxicity, including the utility of cooling VR treated skin to increase the therapeutic window for treatment. The 6h LD₅₀ for VR topically applied on the ear was 100 μg/kg. Treatment of VR exposed animals (5 × LD₅₀) with pralidoxime (2PAM) very poorly regenerated inhibited blood cholinesterase activity, but was partially effective in preventing signs of OP poisoning and increasing survival. In contrast, treatment with the Hagedorn oxime HI-6 reactivated cholinesterase, eliminated all signs of poisoning and prevented death. Decontamination with the Reactive Skin Decontaminant Lotion (RSDL) 15 min after VR exposure was completely effective in preventing death. Cooling of the VR exposure sites for 2 or 6h prevented signs of OP poisoning and death during the cooling period. However, these animals died very quickly after the cessation of cooling, unless they were treated with oxime or decontaminated with RSDL. Blood analyses showed that cooling of agent exposure sites delayed the entry of VR into the bloodstream. Medical treatment with HI-6 and to a lesser extent 2PAM, or decontamination with RSDL are effective in protecting against the toxic effects of cutaneous exposure to VR. Immobilizing this agent (and related compounds) within the dermal reservoir by cooling the exposure sites, dramatically increases the therapeutic window in which these medical countermeasures are effective.

  13. Quantification of VX vapor in ambient air by liquid chromatography isotope dilution tandem mass spectrometric analysis of glass bead filled sampling tubes.

    Science.gov (United States)

    Evans, Ronald A; Smith, Wendy L; Nguyen, Nam-Phuong; Crouse, Kathy L; Crouse, Charles L; Norman, Steven D; Jakubowski, E Michael

    2011-02-15

    An analysis method has been developed for determining low parts-per-quadrillion by volume (ppqv) concentrations of nerve agent VX vapor actively sampled from ambient air. The method utilizes glass bead filled depot area air monitoring system (DAAMS) sampling tubes with isopropyl alcohol extraction and isotope dilution using liquid chromatography coupled with a triple-quadrupole mass spectrometer (LC/MS/MS) with positive ion electrospray ionization for quantitation. The dynamic range was from one-tenth of the worker population limit (WPL) to the short-term exposure limit (STEL) for a 24 L air sample taken over a 1 h period. The precision and accuracy of the method were evaluated using liquid-spiked tubes, and the collection characteristics of the DAAMS tubes were assessed by collecting trace level vapor generated in a 1000 L continuous flow chamber. The method described here has significant improvements over currently employed thermal desorption techniques that utilize a silver fluoride pad during sampling to convert VX to a higher volatility G-analogue for gas chromatographic analysis. The benefits of this method are the ability to directly analyze VX with improved selectivity and sensitivity, the injection of a fraction of the extract, quantitation using an isotopically labeled internal standard, and a short instrument cycle time.

  14. Pengembangan Software Game Menggunakan RPG Maker VX

    OpenAIRE

    Beny

    2010-01-01

    Dalam Tugas Akhir ini dibahas mengenai perancangan game Role Playing Game (RPG) menggunakan RPG Maker VX. Software RPG Maker VX ini digunakan untuk mempermudah dalam pembuatan perangkat lunak game atau software game. Objektif utama adalah mengembangkan permainan atau game menggunakan RPG Maker VX sehingga menghasilkan perangkat lunak game atau software game yang berbasis RPG. 072406137

  15. Pengembangan Software Game Menggunakan RPG Maker VX

    OpenAIRE

    Beny

    2010-01-01

    Dalam Tugas Akhir ini dibahas mengenai perancangan game Role Playing Game (RPG) menggunakan RPG Maker VX. Software RPG Maker VX ini digunakan untuk mempermudah dalam pembuatan perangkat lunak game atau software game. Objektif utama adalah mengembangkan permainan atau game menggunakan RPG Maker VX sehingga menghasilkan perangkat lunak game atau software game yang berbasis RPG. 072406137

  16. Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection.

    Science.gov (United States)

    Wille, Timo; Neumaier, Katharina; Koller, Marianne; Ehinger, Christina; Aggarwal, Nidhi; Ashani, Yacov; Goldsmith, Moshe; Sussman, Joel L; Tawfik, Dan S; Thiermann, Horst; Worek, Franz

    2016-09-06

    The recent attacks with the nerve agent sarin in Syria reveal the necessity of effective countermeasures against highly toxic organophosphorus compounds. Multiple studies provide evidence that a rapid onset of antidotal therapy might be life-saving but current standard antidotal protocols comprising reactivators and competitive muscarinic antagonists show a limited efficacy for several nerve agents. We here set out to test the newly developed phosphotriesterase (PTE) mutant C23AL by intravenous (i.v.), intramuscular (i.m.; model for autoinjector) and intraosseous (i.o.; model for intraosseous insertion device) application in an in vivo guinea pig model after VX challenge (∼2LD50). C23AL showed a Cmax of 0.63μmolL(-1) after i.o. and i.v. administration of 2mgkg(-1) providing a stable plasma profile up to 180min experimental duration with 0.41 and 0.37μmolL(-1) respectively. The i.m. application of C23AL did not result in detectable plasma levels. All animals challenged with VX and subsequent i.o. or i.v. C23AL therapy survived although an in part substantial inhibition of erythrocyte, brain and diaphragm AChE was detected. Theoretical calculation of the time required to hydrolyze in vivo 96.75% of the toxic VX enantiomer is consistent with previous studies wherein similar activity of plasma containing catalytic scavengers of OPs resulted in non-lethal protection although accompanied with a variable severity of cholinergic symptoms. The relatively low C23AL plasma level observed immediately after its i.v. or i.o load, point at a possible volume of distribution greater than the guinea pig plasma content, and thus underlines the necessity of in vivo experiments in antidote research. In conclusion the i.o. application of PTE is efficient and resulted in comparable plasma levels to the i.v. application at a given time. Thus, i.o. vascular access systems could improve the post-exposure PTE therapy of nerve agent poisoning.

  17. Determination of VX-G analogue in red blood cells via gas chromatography-tandem mass spectrometry following an accidental exposure to VX.

    Science.gov (United States)

    McGuire, Jeffrey M; Taylor, James T; Byers, Christopher E; Jakubowski, Edward M; Thomson, Sandra M

    2008-01-01

    A sensitive method for determining exposure to the chemical warfare agent VX is described in which the biomarker ethyl methylphosphonofluoridate (VX-G) is measured in red blood cells (RBCs) following treatment with fluoride ion using isotope-dilution gas chromatography-tandem mass spectrometry. The analyte was isolated via solid-phase extraction and detected using ammonia chemical ionization in the multiple reaction monitoring mode. A good linear relationship was obtained in the quantitative concentration range of 4 ng/mL to 1000 ng/mL with an absolute detection limit of VX vapor. Detection and quantitation of VX-G were possible in samples taken as late as 27 days following exposure.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2014-04-07

    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.

  20. A Comparative Toxidrome Analysis of Human Organophosphate and Nerve Agent Poisonings Using Social Media.

    Science.gov (United States)

    Reddy, D S; Colman, E

    2017-02-26

    Here we utilized social media to compare the toxidrome of three lethal chemical exposures worldwide. YouTube videos were the main source from which the data were collected, but published reports and news were also utilized to fill in some gaps. All videos were organized in a database detailing symptoms and severity of each victim, along with demographics such as approximate age and gender. Each symptom was rated as mild, moderate, or severe and corresponding pie graphs for each incident were compared. The videos displayed symptoms ranging from mild to severe cholinergic toxicity and life-threatening convulsions. Social media may represent an important resource in developing a viable approach to the early detection and identification of chemical exposure, reinforce our preparedness for better antidotes, long-term follow up, and training about deadly chemical nerve agent attacks.

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

    Science.gov (United States)

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

    2015-03-04

    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.

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

    Science.gov (United States)

    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.

  3. Continuum Model for Decontamination of Chemical Warfare Agent from a Rubbery Polymer using the Maxwell-Stefan Formulation

    Science.gov (United States)

    Varady, Mark; Bringuier, Stefan; Pearl, Thomas; Stevenson, Shawn; Mantooth, Brent

    Decontamination of polymers exposed to chemical warfare agents (CWA) often proceeds by application of a liquid solution. Absorption of some decontaminant components proceed concurrently with extraction of the CWA, resulting in multicomponent diffusion in the polymer. In this work, the Maxwell-Stefan equations were used with the Flory-Huggins model of species activity to mathematically describe the transport of two species within a polymer. This model was used to predict the extraction of the nerve agent O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate (VX) from a silicone elastomer into both water and methanol. Comparisons with experimental results show good agreement with minimal fitting of model parameters from pure component uptake data. Reaction of the extracted VX with sodium hydroxide in the liquid-phase was also modeled and used to predict the overall rate of destruction of VX. Although the reaction proceeds more slowly in the methanol-based solution compared to the aqueous solution, the extraction rate is faster due to increasing VX mobility as methanol absorbs into the silicone, resulting in an overall faster rate of VX destruction.

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

    Science.gov (United States)

    2016-04-01

    molecules in either the environment or the food supply could indicate a compliance breach, even if the actual CWA levels were not high enough to cause...Vasudev, K.; Rao , M.V.V. Quantification of Organophosphate Insecticides and Herbicides in Vegetable Samples Using the “Quick Easy Cheap Effective

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

    Science.gov (United States)

    2013-01-01

    times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic...Doctor, M.P. Nambiar, Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase

  6. Non-enzymatic pretreatment of nerve agent (soman) poisoning: A brief state-of-the-art review

    NARCIS (Netherlands)

    Helden, H.P.M. van; Joosen, M.J.A.; Philippens, I.H.C.H.M.

    2011-01-01

    The rapid onset of toxic signs following nerve agent intoxication and the apprehension that current therapy (atropine, oxime, diazepam) may not prevent brain damage, requires supportive pretreatment. Since the current pretreatment drug pyridostigmine fails in protecting brain-AChE, more effective pr

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

    Directory of Open Access Journals (Sweden)

    Moshiri Mohammd

    2012-11-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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.

  9. Percutaneous toxicity and decontamination of soman, VX, and paraoxon in rats using detergents.

    Science.gov (United States)

    Misík, Jan; Pavliková, Růžena; Kuča, Kamil

    2013-06-01

    Highly toxic organophosphorus compounds (OPs) were originally developed for warfare or as agricultural pesticides. Today, OPs represent a serious threat to military personnel and civilians. This study investigates the in vivo decontamination of male Wistar rats percutaneously exposed to paraoxon and two potent nerve agents--soman (GD) and VX. Four commercial detergents were tested as decontaminants--Neodekont(TM), Argos(TM), Dermogel(TM), and FloraFree(TM). Decontamination performed 2 min after exposure resulted in a higher survival rate in comparison with non-decontaminated controls. The decontamination effectiveness was expressed as protective ratio (PR, median lethal dose of agent in decontaminated animals divided by the median lethal dose of agent in untreated animals). The highest decontamination effectiveness was consistently achieved with Argos(TM) (PR=2.3 to 64.8), followed by Dermogel(TM) (PR=2.4 to 46.1). Neodekont(TM) and FloraFree(TM) provided the lowest decontamination effectiveness, equivalent to distilled water (PR=1.0 to 43.2).

  10. Simultaneous quantification of soman and VX adducts to butyrylcholinesterase, their aged methylphosphonic acid adduct and butyrylcholinesterase in plasma using an off-column procainamide-gel separation method combined with UHPLC-MS/MS.

    Science.gov (United States)

    Liu, Chang-Cai; Huang, Gui-Lan; Xi, Hai-Ling; Liu, Shi-Lei; Liu, Jing-Quan; Yu, Hui-Lan; Zhou, Shi-Kun; Liang, Long-Hui; Yuan, Ling

    2016-11-15

    This work describes a novel and sensitive non-isotope dilution method for simultaneous quantification of organophosphorus nerve agents (OPNAs) soman (GD) and VX adducts to butyrylcholinesterase (BChE), their aged methylphosphonic acid (MeP) adduct and unadducted BChE in plasma exposed to OPNA. OPNA-BChE adducts were isolated with an off-column procainamide-gel separation (PGS) from plasma, and then digested with pepsin into specific adducted FGES(*)AGAAS nonapeptide (NP) biomarkers. The resulting NPs were detected by UHPLC-MS/MS MRM. The off-column PGS method can capture over 90% of BChE, MeP-BChE, VX-BChE and GD-BChE from their respective plasma materials. One newly designed and easily synthesized phosphorylated BChE nonapeptide with one Gly-to-Ala mutation was successfully reported to serve as internal standard instead of traditional isotopically labeled BChE nonapeptide. The linear range of calibration curves were from 1.00-200ngmL(-1) for VX-NP, 2.00-200ngmL(-1) for GD-NP and MeP-NP (R(2)≥0.995), and 3.00-200ngmL(-1) for BChE NP (R(2)≥0.990). The inter-day precision had relative standard deviation (%RSD) of VX-NP, GD-NP, MeP-NP and BChE NP, respectively. OPNA-exposed quality control plasma samples were characterized as part of method validation. Investigation of plasma samples unexposed to OPNA revealed no baseline values or interferences. Using the off-column PGS method combined with UHPLC-MS/MS, VX-NP and GD-NP adducts can be unambiguously detected with high confidence in 0.10ngmL(-1) and 0.50ngmL(-1) of exposed human plasma respectively, only requiring 0.1mL of plasma sample and taking about four hours without special sample preparation equipment. These improvements make it a simple, sensitive and robust PGS-UHPLC-MS/MS method, and this method will become an attractive alternative to immunomagnetic separation (IMS) method and a useful diagnostic tool for retrospective detection of OPNA exposure with high confidence. Furthermore, using the developed

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

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  12. The fragmentation pathways of protonated Amiton in the gas phase: towards the structural characterisation of organophosphorus chemical warfare agents by electrospray ionisation tandem mass spectrometry.

    Science.gov (United States)

    Ellis-Steinborner, Simon; Ramachandran, Aravind; Blanksby, Stephen J

    2006-01-01

    Amiton (O,O-diethyl-S-[2-(diethylamino)ethyl] phosphorothiolate), otherwise known as VG, is listed in schedule 2 of the Chemical Weapons Convention (CWC) and has a structure closely related to VX (O-ethyl-S-(2-diisopropylamino)ethylmethylphosphonothiolate). Fragmentation of protonated VG in the gas phase was performed using electrospray ionisation ion trap mass spectrometry (ESI-ITMS) and revealed several characteristic product ions. Quantum chemical calculations provide the most probable structures for these ions as well as the likely unimolecular mechanisms by which they are formed. The decomposition pathways predicted by computation are consistent with deuterium-labeling studies. The combination of experimental and theoretical data suggests that the fragmentation pathways of VG and analogous organophosphorus nerve agents, such as VX and Russian VX, are predictable and thus ESI tandem mass spectrometry is a powerful tool for the verification of unknown compounds listed in the CWC.

  13. Development of Reactive Topical Skin Protectants against Sulfur Mustard and Nerve Agents

    Science.gov (United States)

    1997-06-01

    mL) (%) (g/mL) Method Blank 0.49 lLg/mL 0.48 ig/mL ND,’ 100 mg Fe 20 3 contamination contamination < 0.5 I.ig/_mL E297 -MB Lab Control 0.91 Fig/mL ND...ND, ND, no Fe 20 3 , no spike contamination < 0.5 [tg/mL < 0.5 jig/mL < 0.5 ig/mL E297 -LC Lab Control Spike 3.36 Lg/mL 83.4% 3.29 jig/mL 81.6% ND...no Fe20 3, 4 plL VX < 0.5 i~g/mL E297 -LCS Sample 1 0.5 [ig/mL 12.4% ND, ND, ND, 100 mg Fe 20 3, < 0.5 jig/mL < 0.5 .Lg/mL < 0.5 [ig/mL 4 [IL VX E297

  14. Electrochemical sensor for organophosphate pesticides and nerve agents using zirconia nanoparticles as selective sorbents.

    Science.gov (United States)

    Liu, Guodong; Lin, Yuehe

    2005-09-15

    An 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 the strong affinity of zirconia for 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 pH of the reaction medium have been optimized. The stripping voltammetric response is highly linear over the 5-100 ng/mL (ppb) methyl parathion range examined (2-min adsorption), with a detection limit of 3 ng/mL and good precision (RSD = 5.3%, n = 10). The detection limit was improved to 1 ng/mL by using 10-min adsorption time. The promising stripping voltammetric performances open new opportunities for fast, simple, and sensitive analysis of OPs in environmental and biological samples. These findings can lead to a widespread use of electrochemical sensors to detect OP contaminates.

  15. Structural Analysis and Bioengineering of Thermostable Pyrococcus furiosus Prolidase for the Optimization of Organophosphorus Nerve Agent Detoxification

    Science.gov (United States)

    2012-04-26

    12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS prolidase, organophosphate , OP nerve agent, thermostable enzyme, Pyrococcus furiosus...Singh, 2009). Annually, there are an estimated 3 million poisonings and 300,000 human deaths owing to OP compounds (Singh, 2009). There is a need... organophosphate anhydrolase/prolidase. Biochemistry, 49, 547-59. Wang, Q., Sun, M., Zhang, H. & Huang, C. 1998. Purification and properties of soman

  16. Ionization Mechanism of the Ambient Pressure Pyroelectric Ion Source (APPIS) and Its Applications to Chemical Nerve Agent Detection

    OpenAIRE

    Neidholdt, Evan L.; Beauchamp, J. L.

    2009-01-01

    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 su...

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

    Science.gov (United States)

    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.

  18. Analysis of Trace VX in Acidified VX Hydrolysate Samples

    Science.gov (United States)

    2009-07-01

    reformation. 2. EXPERIMENTAL PROCEDURES 2.1 Materials Tribasic potassium phosphate (K3P04, >98%, lot 097K0010), sodium carbonate (Na2C03, lot...reservoir was removed. Any water droplets in the cartridge were removed with a disposable pipet. n. VX was eluted by adding 2 ml_ of 90:10...Column temperature 50-200 °C (5 min) @ 20 °C /min; 200-230 °C @ 3 °C /min; 230-260 °C @ 30 °C/min; post-run 260 °C (7 min) Carrier gas Helium

  19. Cholinesterase reactivators: the fate and effects in the organism poisoned with organophosphates/nerve agents.

    Science.gov (United States)

    Bajgar, J; Kuca, K; Jun, D; Bartosova, L; Fusek, J

    2007-12-01

    Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinergics that antagonize the effects of accumulated acetylcholine at the cholinergic synapses and cholinesterase reactivators (oximes) reactivating inhibited AChE. Anticonvulsants such as diazepam are also used to treat convulsions. Though there are experimental data on a good therapeutic effects of reactivators, some attempts to underestimate the role of reactivators as effective antidotes against OP poisoning have been made. Some arguments on the necessity of their administration following OP poisoning are discussed. Their distribution patterns and some metabolic and pharmacological effects are described with the aim to resolve the question on their effective use, possible repeated administration in the treatment of OP poisoning, their peripheral and central effects including questions on their penetration through the blood brain barrier as well as a possibility to achieve their effective concentration for AChE reactivation in the brain. Reactivation of cholinesterases in the peripheral and central nervous system is described and it is underlined its importance for the survival or death of the organism poisoned with OP. Metabolization and some other effects of oximes (not connected with AChE reactivation) are discussed (e.g. forming of the phosphonylated oxime, parasympatholytic action, hepatotoxicity, behavioral changes etc.). An universality of oximes able to reactivate AChE inhibited by all OP is questioned and therefore, needs of development of new oximes is underlined.

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

    Science.gov (United States)

    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.

  1. Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study.

    Science.gov (United States)

    Khan, Md Abdul Shafeeuulla; Ganguly, Bishwajit

    2012-05-01

    Oximate anions are used as potential reactivating agents for OP-inhibited AChE because of they possess enhanced nucleophilic reactivity due to the α-effect. We have demonstrated the process of reactivating the VX-AChE adduct with formoximate and hydroxylamine anions by applying the DFT approach at the B3LYP/6-311 G(d,p) level of theory. The calculated results suggest that the hydroxylamine anion is more efficient than the formoximate anion at reactivating VX-inhibited AChE. The reaction of formoximate anion and the VX-AChE adduct is a three-step process, while the reaction of hydroxylamine anion with the VX-AChE adduct seems to be a two-step process. The rate-determining step in the process is the initial attack on the VX of the VX-AChE adduct by the nucleophile. The subsequent steps are exergonic in nature. The potential energy surface (PES) for the reaction of the VX-AChE adduct with hydroxylamine anion reveals that the reactivation process is facilitated by the lower free energy of activation (by a factor of 1.7 kcal mol(-1)) than that of the formoximate anion at the B3LYP/6-311 G(d,p) level of theory. The higher free energy of activation for the reverse reactivation reaction between hydroxylamine anion and the VX-serine adduct further suggests that the hydroxylamine anion is a very good antidote agent for the reactivation process. The activation barriers calculated in solvent using the polarizable continuum model (PCM) for the reactivation of the VX-AChE adduct with hydroxylamine anion were also found to be low. The calculated results suggest that V-series compounds can be more toxic than G-series compounds, which is in accord with earlier experimental observations.

  2. Role of the P-F bond in fluoride-promoted aqueous VX hydrolysis: an experimental and theoretical study.

    Science.gov (United States)

    Marciano, Daniele; Columbus, Ishay; Elias, Shlomi; Goldvaser, Michael; Shoshanim, Ofir; Ashkenazi, Nissan; Zafrani, Yossi

    2012-11-16

    Following our ongoing studies on the reactivity of the fluoride ion toward organophosphorus compounds, we established that the extremely toxic and environmentally persistent chemical warfare agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) is exclusively and rapidly degraded to the nontoxic product EMPA (ethyl methylphosphonic acid) even in dilute aqueous solutions of fluoride. The unique role of the P-F bond formation in the reaction mechanism was explored using both experimental and computational mechanistic studies. In most cases, the "G-analogue" (O-ethyl methylphosphonofluoridate, Et-G) was observed as an intermediate. Noteworthy and of practical importance is the fact that the toxic side product desethyl-VX, which is formed in substantial quantities during the slow degradation of VX in unbuffered water, is completely avoided in the presence of fluoride. A computational study on a VX-model, O,S-diethyl methylphosphonothioate (1), clarifies the distinctive tendency of aqueous fluoride ions to react with such organophosphorus compounds. The facility of the degradation process even in dilute fluoride solutions is due to the increased reactivity of fluoride, which is caused by the significant low activation barrier for the P-F bond formation. In addition, the unique nucleophilicity of fluoride versus hydroxide toward VX, in contrast to their relative basicity, is discussed. Although the reaction outcomes were similar, much slower reaction rates were observed experimentally for the VX-model (1) in comparison to VX.

  3. Measurement of breakthrough volumes of volatile chemical warfare agents on a poly(2,6-diphenylphenylene oxide)-based adsorbent and application to thermal desorption-gas chromatography/mass spectrometric analysis.

    Science.gov (United States)

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2015-09-04

    To establish adequate on-site solvent trapping of volatile chemical warfare agents (CWAs) from air samples, we measured the breakthrough volumes of CWAs on three adsorbent resins by an elution technique using direct electron ionization mass spectrometry. The trapping characteristics of Tenax(®) TA were better than those of Tenax(®) GR and Carboxen(®) 1016. The latter two adsorbents showed non-reproducible breakthrough behavior and low VX recovery. The specific breakthrough values were more than 44 (sarin) L/g Tenax(®) TA resin at 20°C. Logarithmic values of specific breakthrough volume for four nerve agents (sarin, soman, tabun, and VX) showed a nearly linear correlation with the reciprocals of their boiling points, but the data point of sulfur mustard deviated from this linear curve. Next, we developed a method to determine volatile CWAs in ambient air by thermal desorption-gas chromatography (TD-GC/MS). CWA solutions that were spiked into the Tenax TA(®) adsorbent tubes were analyzed by a two-stage TD-GC/MS using a Tenax(®) TA-packed cold trap tube. Linear calibration curves for CWAs retained in the resin tubes were obtained in the range between 0.2pL and 100pL for sarin, soman, tabun, cyclohexylsarin, and sulfur mustard; and between 2pL and 100pL for VX and Russian VX. We also examined the stability of CWAs in Tenax(®) TA tubes purged with either dry or 50% relative humidity air under storage conditions at room temperature or 4°C. More than 80% sarin, soman, tabun, cyclohexylsarin, and sulfur mustard were recovered from the tubes within 2 weeks. In contrast, the recoveries of VX and Russian VX drastically reduced with storage time at room temperature, resulting in a drop to 10-30% after 2 weeks. Moreover, we examined the trapping efficiency of Tenax TA(®) adsorbent tubes for vaporized CWA samples (100mL) prepared in a 500mL gas sampling cylinder. In the concentration range of 0.2-2.5mg/m(3), >50% of sarin, soman, tabun, cyclohexylsarin, and HD were

  4. VX

    Science.gov (United States)

    ... e.g., Salmonella species, Escherichia coli O157:H7, Shigella ) Francisella tularensis (tularemia) Key Facts About Tularemia Frequently ... salmonellosis) Salmonella Typhi (typhoid fever) Salmonellosis ( Salmonella species) Shigella (shigellosis) Shigellosis ( Shigella ) Smallpox (variola major) Smallpox Basics ...

  5. What to Do After You've Gotten the Smallpox Vaccine

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  6. Side Effects of Smallpox Vaccination

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  7. Someone You Are Close to May Get the Smallpox Vaccine: What You Should Know and Do

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  8. Smallpox Vaccination Information for Women Who Are Pregnant or Breastfeeding

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  9. Smallpox Vaccine Overview

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  10. Live Virus Smallpox Vaccine

    Science.gov (United States)

    ... Agent and Organophosphate Pesticide Poisoning Sarin Soman Tabun VX Nicotine Case Definition: Nicotine Poisoning Nitrogen mustard (HN- ... Poisoning Unidentified chemical Vesicants/blister agents Vomiting agents VX Facts About VX Case Definition: Nerve Agents or ...

  11. Decontamination of VX, GD, and HD on a surface using modified vaporized hydrogen peroxide.

    Science.gov (United States)

    Wagner, George W; Sorrick, David C; Procell, Lawrence R; Brickhouse, Mark D; Mcvey, Iain F; Schwartz, Lewis I

    2007-01-30

    Vaporized hydrogen peroxide (VHP) has proven efficacy for biological decontamination and is a common gaseous sterilant widely used by industry. Regarding chemical warfare agent decontamination, VHP is also effective against HD and VX, but not GD. Simple addition of ammonia gas to VHP affords reactivity toward GD, while maintaining efficacy for HD (and bioagents) and further enhancing efficacy for VX. Thus, modified VHP is a broad-spectrum CB decontaminant suitable for fumigant-type decontamination scenarios, i.e., building, aircraft, and vehicle interiors and sensitive equipment. Finally, as an interesting aside to the current study, commercial ammonia-containing cleaners are also shown to be effective surface decontaminants for GD, but not for VX or HD.

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

    Science.gov (United States)

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

    2017-08-01

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

  13. Variants of Phosphotriesterase for the Enhanced Detoxification of the Chemical Warfare Agent VR.

    Science.gov (United States)

    Bigley, Andrew N; Mabanglo, Mark F; Harvey, Steven P; Raushel, Frank M

    2015-09-08

    The V-type organophosphorus nerve agents are among the most hazardous compounds known. Previous efforts to evolve the bacterial enzyme phosphotriesterase (PTE) for the hydrolytic decontamination of VX resulted in the identification of the variant L7ep-3a, which has a kcat value more than 2 orders of magnitude higher than that of wild-type PTE for the hydrolysis of VX. Because of the relatively small size of the O-ethyl, methylphosphonate center in VX, stereoselectivity is not a major concern. However, the Russian V-agent, VR, contains a larger O-isobutyl, methylphosphonate center, making stereoselectivity a significant issue since the SP-enantiomer is expected to be significantly more toxic than the RP-enantiomer. The three-dimensional structure of the L7ep-3a variant was determined to a resolution of 2.01 Å (PDB id: 4ZST ). The active site of the L7ep-3a mutant has revealed a network of hydrogen bonding interactions between Asp-301, Tyr-257, Gln-254, and the hydroxide that bridges the two metal ions. A series of new analogues that mimic VX and VR has helped to identify critical structural features for the development of new enzyme variants that are further enhanced for the catalytic detoxification of VR and VX. The best of these mutants has been shown to have a reversed stereochemical preference for the hydrolysis of VR-chiral center analogues. This mutant hydrolyzes the two enantiomers of VR 160- and 600-fold faster than wild-type PTE hydrolyzes the SP-enantiomer of VR.

  14. In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs

    Science.gov (United States)

    2010-01-01

    peripheral tissues and the blood components . A “+” sign was assigned for each of the peripheral tissues or blood com- ponents, when an oxime treatment...reactivation by oxime treatments in peripheral tissues and blood components following exposure to GB, GF, VR, and VXa. A. Peripheral tissues (diaphragm...tissues (A) or blood components (B), an oxime treatm ign. When an oxime treatment did not significantly reactivate a nerve agent-inhib ll four nerve

  15. Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX.

    Science.gov (United States)

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

    2016-11-25

    Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy.

  16. Analysis of Urinary Metabolites of Nerve and Blister Chemical Warfare Agents

    Science.gov (United States)

    2014-08-01

    Warfare Agents GA Tabun , ethyl dimethylphosphoramidate GB Sarin, isopropyl methylphosphonofluoridate GD Soman, pinacolyl methylphosphonofluoridate...and their metabolites Agent Metabolite GA, Tabun O P O N CN Ethyl Dimethylphosphoroamidate, EDMAP, GA Acid HO P O N CN GB, Sarin P O

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

    Science.gov (United States)

    2010-01-01

    collection chamber. A 2-h normalization period was allowed to pass before commencing the continuous collec- tion of dialysate samples at IS-min intervals...volume per sample = 22.5 ~l) in 250-1li micro centrifuge tubes. Baseline dialysate samples were taken for 60 min (four IS-min frac- tions) prior...a SAL/SAL control group, an AMN/SAL control group, and four AMN/nerve agent groups (sarin, soman, VR, orVX). EEG recording and dialysate col

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

    Science.gov (United States)

    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.

  19. Reactivation of VX-inhibited AChE by novel oximes having two oxygen atoms in the linker.

    Science.gov (United States)

    Kuca, Kamil; Cabal, Jiri; Jun, Daniel; Musilek, Kamil; Soukup, Ondrej; Pohanka, Miroslav; Pejchal, Jaroslav; Oh, Kyung-Ae; Yang, Garp Yeol; Jung, Young-Sik

    2010-07-01

    Two newly developed AChE reactivators possessing two oxime groups in 4-position of the pyridinium rings with linkers CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) were tested for their potency to reactivate VX-inhibited AChE. Their reactivation potency was compared with currently available oximes such as pralidoxime, obidoxime and HI-6. Appropriate constants (affinity towards the intact and inhibited enzyme, reactivation rate) characterizing the reactivation process were determined. According to the data obtained, a new oxime with CH(2)O(CH(2))(2)OCH(2) linker reached as high reactivation potency as HI-6. The percentage of reactivation of the oxime with CH(2)O(CH(2))(2)OCH(2) linker was comparable to that of obidoxime at a concentration 10(-3)M. Hence, these oximes may be worthy of future development for the treatment of nerve agent intoxications, especially, with lipophilic agents such as soman and cyclosarin.

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

    Directory of Open Access Journals (Sweden)

    Tetsade Piermartiri

    2015-11-01

    Full Text Available 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.

  1. Retrospective detection of exposure to nerve agents: Analysis of phosphofluoridates originating from fluoride-induced rectivation of phospylated BuChE

    NARCIS (Netherlands)

    Schans, M.J. van der; Polhuijs, M.; Dijk, C. van; Degenhardt, C.E.A.M.; Pleijsier, K.; Langenberg, J.P.; Benschop, H.P.

    2004-01-01

    The utility was explored of a new approach to detect retrospectively exposure to nerve agents by means of conversion of the inhibitor moiety bound to the active site of the enzyme BuChE in plasma with fluoride ions into a phosphofluoridate which is subsequently analyzed by means of gas chromatograph

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

    NARCIS (Netherlands)

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

    2010-01-01

    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 spectromet

  3. Low level nose-only exposure to the nerve agent soman: Toxicokinetics of soman stereoisomers and cholinesterase inhibition in atropinized guinea pigs

    NARCIS (Netherlands)

    Benschop, H.P.; Trap, H.C.; Spruit, H.E.T.; Wiel, H.J. van der; Langenberg, J.P.; Jong, L.P.A. de

    1998-01-01

    In order to initiate a quantitative basis for the toxicology of low level exposure to nerve agents, the toxicokinetics of soman stereoisomers during nose-only exposure for 5 h to 20 ppb (160 μg/m3) of C(±)P(±)- soman in air were studied in restrained, anesthetized, and atropinized guinea pigs. The c

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

    Science.gov (United States)

    2011-01-01

    Reactions contained Mutazyme II reaction buffer, 125 ng/μL of each primer, 40mM dNTP mix, and 2.5U of Mutazyme II DNA polymerase. Initial DNA template...there was interest in determining the relative activity of recombi - nant Ph1prol compared to Pf prol and Phprol against G- type nerve agent simulants DFP

  5. [Trials of in vitro propagation of the scrapie agent in mouse nerve cells].

    Science.gov (United States)

    Markovits, P; Dormont, D; Delpech, B; Court, L; Latarjet, R

    1981-11-02

    We attempted to propagate the Scrapie agent in vitro in glia and neuroblastoma cells of Mice. Four out of seven assays of infection were positive, i.e. after several passages in vitro yielding at most a 10(9) fold final dilution of the original material, the extracts of each of the four cultures, when injected intracerebrally into CD1 Mice, produced a deadly disease displaying the clinical and pathological signs characteristic of Scrapie.

  6. Prophylaxis with human serum butyrylcholinesterase protects guinea pigs exposed to multiple lethal doses of soman or VX.

    Science.gov (United States)

    Saxena, Ashima; Sun, Wei; Fedorko, James M; Koplovitz, Irwin; Doctor, Bhupendra P

    2011-01-01

    Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a bioscavenger for the prophylaxis of organophosphorus (OP) nerve agent toxicity in humans. It is estimated that a dose of 200mg will be required to protect a human against 2×LD(50) of soman. To provide data for initiating an investigational new drug application for the use of this enzyme as a bioscavenger in humans, we purified enzyme from Cohn fraction IV-4 paste and initiated safety and efficacy evaluations in mice, guinea pigs, and non-human primates. In mice, we demonstrated that a single dose of enzyme that is 30 times the therapeutic dose circulated in blood for at least four days and did not cause any clinical pathology in these animals. In this study, we report the results of safety and efficacy evaluations conducted in guinea pigs. Various doses of Hu BChE delivered by i.m. injections peaked at ∼24h and had a mean residence time of 78-103h. Hu BChE did not exhibit any toxicity in guinea pigs as measured by general observation, serum chemistry, hematology, and gross and histological tissue changes. Efficacy evaluations showed that Hu BChE protected guinea pigs from an exposure of 5.5×LD(50) of soman or 8×LD(50) of VX. These results provide convincing data for the development of Hu BChE as a bioscavenger that can protect humans against all OP nerve agents.

  7. Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970.

    Science.gov (United States)

    Hall, Amy B; Newsome, Dave; Wang, Yuxin; Boucher, Diane M; Eustace, Brenda; Gu, Yong; Hare, Brian; Johnson, Mac A; Milton, Sean; Murphy, Cheryl E; Takemoto, Darin; Tolman, Crystal; Wood, Mark; Charlton, Peter; Charrier, Jean-Damien; Furey, Brinley; Golec, Julian; Reaper, Philip M; Pollard, John R

    2014-07-30

    Platinum-based DNA-damaging chemotherapy is standard-of-care for most patients with lung cancer but outcomes remain poor. This has been attributed, in part, to the highly effective repair network known as the DNA-damage response (DDR). ATR kinase is a critical regulator of this pathway, and its inhibition has been shown to sensitize some cancer, but not normal, cells in vitro to DNA damaging agents. However, there are limited in vivo proof-of-concept data for ATR inhibition. To address this we profiled VX-970, the first clinical ATR inhibitor, in a series of in vitro and in vivo lung cancer models and compared it with an inhibitor of the downstream kinase Chk1. VX-970 markedly sensitized a large proportion of a lung cancer cell line and primary tumor panel in vitro to multiple DNA damaging drugs with clear differences to Chk1 inhibition observed. In vivo VX-970 blocked ATR activity in tumors and dramatically enhanced the efficacy of cisplatin across a panel of patient derived primary lung xenografts. The combination led to complete tumor growth inhibition in three cisplatin-insensitive models and durable tumor regression in a cisplatin-sensitive model. These data provide a strong rationale for the clinical evaluation of VX-970 in lung cancer patients.

  8. Extraction and Analysis of V-Type Agents (VX, RVX, CVX, and VM) from Various Food Matrices by Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry

    Science.gov (United States)

    2015-12-01

    Various agent quantities, ranging from 1.7 to 3.1 mg, were spiked into food samples. The Agent Chemistry Branch at the U.S. Army Edgewood Chemical...available and affordable, such as solid-phase extraction cartridges12–20 or QuEChERS systems ( Quick , Easy, Cheap, Effective, Rugged, and Safe);21–29...laboratory.9,30–35 This document reports the efforts of the Agent Chemistry Team from the Research and Technology Directorate of the U.S. Army Edgewood

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

    Science.gov (United States)

    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

  10. Median lethal dose determination for percutaneous exposure to soman and VX in guinea pigs and the effectiveness of decontamination with M291 SDK or SANDIA foam.

    Science.gov (United States)

    Clarkson, Edward D; Schulz, Susan M; Railer, Roy F; Smith, Kelly H

    2012-08-03

    Soman (GD) and VX are chemical warfare agents that can be absorbed through the skin. We determined the median lethal dose (MLD) for the cutaneous application of GD and VX in anesthetized haired guinea pigs and then tested the ability of a currently fielded decontamination kit, the M291 Skin Decontamination Kit (SDK), and decontaminating foam made by SANDIA Labs to decontaminate areas that have been exposed to cutaneous applications of GD and VX. The fur of guinea pigs was clipped on the left flank 24h prior to exposure. Animals were anesthetized and 5 min later neat GD or neat VX was applied. The MLD for percutaneous exposure to GD was 11.6 mg/kg, and to VX it was 0.10mg/kg. To test the ability of the M291 SDK, either GD or VX was applied and removed 1 min later with the pads of the M291 SDK clasped in a pair of forceps and wiped across the flank of the animal. The MLDs for GD and VX removed with the M291 SDK pads were 76.9 mg/kg and 0.87 mg/kg, respectively. When neat GD or neat VX was applied and removed 1 min later in the same manner with gauze soaked in SANDIA foam (MDF-100), the MLDs were 412 mg/kg and 10.4 mg/kg respectively. These data demonstrate that GD and VX are significantly less potent when applied cutaneously than previously reported for subcutaneous injections and indicate that improvement is needed on the limited protective ratio provided by the M291 SDK.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Meyerhoff James L

    2011-07-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

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

    2003-02-01

    1 The anti-tussive effects, of the local anaesthetic, lidocaine and carcainium chloride (RSD931) have been investigated in guinea-pigs and rabbits. 2 Pre-treatment of guinea-pigs with aerosols of lidocaine or RSD931 at 0.1, 1.0 and 10 mg ml(-1) reduced the number of citric acid-induced coughs by 9.3, 32.6 and 40.9% (P>0.05) for lidocaine and by 25.3% (P>0.05), 40.4% (P>0.05) and 97.6% (Plidocaine or RSD931 at 10.0 and 30.0 mg ml(-1) reduced the number of capsaicin-evoked coughs by 42.2 and 10.3% (P>0.05) (lidocaine) and by 25% (P>0.05) and 76.9% (PLidocaine had little effect on the latency of cough onset at either 10.0 or 30.0 mg ml(-1), however, RSD at 30.0 mg ml(-1) significantly (PLidocaine at 10.0 mg ml(-1) also significantly (P0.05) effects on discharges in bronchial C-fibres originating from bronchial C-fibre endings, capsaicin-evoked discharges of either pulmonary or bronchial C-fibre endings or on capsaicin-evoked bronchoconstriction. In contrast, lidocaine (10.0 mg ml(-1)) significantly (PLidocaine also significantly (Pactions of RSD931 are mediated via inhibition of discharges in Adelta-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.

  14. Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

    Science.gov (United States)

    Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2017-03-01

    Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

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

    Science.gov (United States)

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

    2016-11-16

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

  16. HONEY Ⅲ 昂达VX848

    Institute of Scientific and Technical Information of China (English)

    紫头盔

    2007-01-01

    经过一段时间的精心准备,昂达时尚HONEY系列的第三款产品VX848也上市了,在延续HONEY系列产品一贯设计风格的同时,又加入了黑、蓝为主打的"蓝调"风情元素,并首次融人流行的点触式按键,一触即蓝,时尚养眼。除了支持MP3、WMA、WAV格式的音乐播放之外,VX848还支持24fps的视频播放,而价格却仅为449元(2GByte),性价比不俗。

  17. VX Toxicity in the Gottingen Minipig

    Science.gov (United States)

    2016-02-01

    Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law , no person...following the onset of sustained prostration and remained on until death or just prior to euthanasia . Data Analysis The LD50 estimate was...Cerasoli, D. M., Federko, J. M., Luo, C., Saxena, A., Doctor , B. P., and Olson, C. (2005). Protection against soman or VX poisoning by human

  18. Methodology and biological monitoring of exposure to chemical warfare agents

    Energy Technology Data Exchange (ETDEWEB)

    Shih, M.L.; Smith, J.R.; McMonagle, J.D. [Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)

    1995-06-01

    In the past few years, our institute has developed several GC/MS methods for the detection of the breakdown products of toxic organophosphonates (soman, sarin, GF) and vesicant sulfur mustard in biological samples. Recently we developed a modified GC/MS method for VX and are continually working on the methodology for lewisite and tabun. The purpose is to have an analytical tool to verify the exposure of chemical warfare agents in humans. Analytical procedures for quantitating the hydrolyzed phosphonic acids from nerve agents in environmental samples have been reported by many analysts. For more complex matrices such as biological samples, there is not yet a method reported. To make these polar acids amenable to gas chromatographic analysis a prior derivatization is needed. We found the pentafluorobenzyl ester derivatives of the phosphonates are suitable for verification and pharmacokinetic studies in biological samples. This method may also serve as an alternative method for confirmation purposes in environmental samples.

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

    Directory of Open Access Journals (Sweden)

    Casey M. Theriot

    2011-01-01

    Full Text Available 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.

  20. Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes.

    Science.gov (United States)

    Ekström, F J; Astot, C; Pang, Y-P

    2007-09-01

    Organophosphorus compound-based nerve agents inhibit the essential enzyme acetylcholinesterase (AChE) causing acute toxicity and death. Clinical treatment of nerve-agent poisoning is to use oxime-based antidotes to reactivate the inhibited AChE. However, the nerve agent tabun is resistant to oximes. To design improved oximes, crystal structures of a tabun-conjugated AChE in complex with different oximes are needed to guide the structural modifications of known antidotes. However, this type of structure is extremely challenging to obtain because both deamidation of the tabun conjugate and reactivation of AChE occur during crystallographic experiments. Here we report, for the first time, the crystal structures of Ortho-7 and HLö-7 in complex with AChE that is conjugated to an intact tabun. These structures were determined by our new strategy of combining crystallographic and mass spectrometric analyses of AChE crystals. The results explain the relative reactivation potencies of the two oximes and offer insights into improving known medical antidotes.

  1. Reactions of VX, HD, and their simulants with NaY and AgY zeolites. Desulfurization of VX on AgY

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, G.W.; Bartram, P.W.

    1999-11-09

    The room-temperature reactions of the chemical warfare agents VX (O-ethyl S-2-(diisopropylamino)-ethyl methylphosphonothioate), HD (2,2{prime}-dichloroethyl sulfide, or mustard), and their common simulants, O,S-diethyl phenylphosphonothioate (DEPPT) and 2-chloroethyl phenyl sulfide (CEPS), with NaY and silver-exchanged (AgY) zeolites have been studied using solid-state magic angle spinning NMR. VX hydrolyzes via exclusive cleavage of the P{single{underscore}bond}S bond on both NaY and AgY to yield ethyl methylphosphonate (EMPA). The reaction is significantly faster on AgY than on NaY, suggesting catalysis by silver. On AgY, an intermediate silver salt of EMPA is apparently formed which is slowly converted to ethyl 2-(diisopropylamino)ethyl methylphosphonate (QB, the desulfurized analogue of VX) in about a 78% yield. DEPPT similarly hydrolyzes via P{single{underscore}bond}S cleavage on AgY to yield an apparent silver salt of ethyl phenylphosphonate, which does not undergo further reaction to the desulfurized analogue. No reaction is observed for DEPPT on NaY. HD on AgY forms both vinyl sulfide and the cyclic ether 1,4-thioxane. HD reacts faster on NaY to exclusively form the CH-TG sulfonium ion (HOCH{sub 2}CH{sub 2}SCH{sub 2}CH{sub 2}S{sup +}[CH{sub 2}CH{sub 2}OH]{sub 2}). CEPS also reacts faster on NaY, forming 2-hydroxyethyl phenyl sulfide. On AgY, CEPS does not give the vinyl product, but does yield the ether product PhSCH{sub 2}CH{sub 2}OCH{sub 2}CH{sub 2}SPh. A mechanism is proposed for the silver-catalyzed hydrolysis of VX, the desulfurization of the cleaved thiol, and the formation of QB.

  2. Cerium oxide for the destruction of chemical warfare agents: A comparison of synthetic routes

    Energy Technology Data Exchange (ETDEWEB)

    Janoš, Pavel, E-mail: pavel.janos@ujep.cz [Faculty of the Environment, University of Jan Evangelista Purkyně, Králova Výšina 7, 400 96 Ústí nad Labem (Czech Republic); Henych, Jiří [Faculty of the Environment, University of Jan Evangelista Purkyně, Králova Výšina 7, 400 96 Ústí nad Labem (Czech Republic); Institute of Inorganic Chemistry AS CR v.v.i., 25068 Řež (Czech Republic); Pelant, Ondřej; Pilařová, Věra; Vrtoch, Luboš [Faculty of the Environment, University of Jan Evangelista Purkyně, Králova Výšina 7, 400 96 Ústí nad Labem (Czech Republic); Kormunda, Martin [Faculty of Sciences, University of Jan Evangelista Purkyně, České Mládeže 8, 400 96 Ústí nad Labem (Czech Republic); Mazanec, Karel [Military Research Institute, Veslařská 230, 637 00 Brno (Czech Republic); and others

    2016-03-05

    Highlights: • Four synthetic routes were compared to prepare the nanoceria-based reactive sorbents. • The sorbents prepared by homogeneous hydrolysis destroy efficiently the soman and VX nerve agents. • Toxic organophosphates are converted to less-dangerous products completely within a few minutes. • Surface non-stoichiometry and −OH groups promote the destruction by the S{sub N}2 mechanism. - Abstract: Four different synthetic routes were used to prepare active forms of cerium oxide that are capable of destroying toxic organophosphates: a sol–gel process (via a citrate precursor), homogeneous hydrolysis and a precipitation/calcination procedure (via carbonate and oxalate precursors). The samples prepared via homogeneous hydrolysis with urea and the samples prepared via precipitation with ammonium bicarbonate (with subsequent calcination at 500 °C in both cases) exhibited the highest degradation efficiencies towards the extremely dangerous nerve agents soman (O-pinacolyl methylphosphonofluoridate) and VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) and the organophosphate pesticide parathion methyl. These samples were able to destroy more than 90% of the toxic compounds in less than 10 min. The high degradation efficiency of cerium oxide is related to its complex surface chemistry (presence of surface −OH groups and surface non-stoichiometry) and to its nanocrystalline nature, which promotes the formation of crystal defects on which the decomposition of organophosphates proceeds through a nucleophilic substitution mechanism that is not dissimilar to the mechanism of enzymatic hydrolysis of organic phosphates by phosphotriesterase.

  3. The Utility of Human Plasma-Derived Butyrylcholinesterase (huBuChE) as a Therapeutic Measure in the Absence of Pre-Treatment or Conventional Post-Poisoning Therapies Against Nerve Agent

    Science.gov (United States)

    2011-10-01

    Human butyrylcholinesterase (huBuChE) has investigational new drug (IND) status in the U.S. as a pretreatment against organophosphate poisoning in humans...huBuChE) as a therapeutic measure in the absence of pre-treatment or conventional post- poisoning therapies against nerve agent. PRINCIPAL...absence of pre- treatment or conventional post- poisoning therapies against nerve agent. 5a. CONTRACT NUMBER W81WXH-10- -0044 5b. GRANT NUMBER 5c

  4. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit.

    Science.gov (United States)

    Byrn, Randal A; Jones, Steven M; Bennett, Hamilton B; Bral, Chris; Clark, Michael P; Jacobs, Marc D; Kwong, Ann D; Ledeboer, Mark W; Leeman, Joshua R; McNeil, Colleen F; Murcko, Mark A; Nezami, Azin; Perola, Emanuele; Rijnbrand, Rene; Saxena, Kumkum; Tsai, Alice W; Zhou, Yi; Charifson, Paul S

    2015-03-01

    VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m(7)GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). VX-787 was highly efficacious in both prophylaxis and treatment models of mouse influenza and was superior to the neuraminidase inhibitor, oseltamivir, including in delayed-start-to-treat experiments, with 100% survival at up to 96 h postinfection and partial survival in groups where the initiation of therapy was delayed up to 120 h postinfection. At different doses, VX-787 showed a 1-log to >5-log reduction in viral load (relative to vehicle controls) in mouse lungs. Overall, these favorable findings validate the PB2 subunit of the viral polymerase as a drug target for influenza therapy and support the continued development of VX-787 as a novel antiviral agent for the treatment of influenza infection.

  5. Research progress in antidotes of nerve agents in the USA%美国神经性毒剂救治研究进展

    Institute of Scientific and Technical Information of China (English)

    程晋; 但国蓉; 赵远鹏; 王健; 叶枫; 赵吉清; 邹仲敏

    2015-01-01

    Nerve agent not only inhibit acetylcholinesterase ( AChE) at an early stage, but also induce prolonged and progressive neuroinflammation and delayed neurodegeneration.Recently, the US National Institute of Health ( NIH) has sponsored some major programs of toxic mechanisms and treatment of nerve agents, which aims at the development of quick and effective treatment to acute intoxication and delayed effect.The experimentally effective new antidotes mainly include AChE-targeting drugs, broad-spectrum reactivators and scavengers, antiinflamatory and nerve protection drugs.%神经性毒剂除了在早期抑制乙酰胆碱酯酶( AChE)外,也导致长期的进行性神经炎和迟发神经退行性病变。近年来,美国国立卫生研究院资助了多项神经性毒剂中毒机制和治疗药物的研究,旨在快速高效对抗神经性毒剂急性中毒及远后效应。正在研制的治疗药物主要包括AChE靶向药物、广谱重活化剂和生物清除剂、抗炎及神经保护药。

  6. Colling Wipe Samples for VX Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Koester, C; Hoppes, W G

    2010-02-11

    This standard operating procedure (SOP) provides uniform procedures for the collection of wipe samples of VX residues from surfaces. Personnel may use this procedure to collect and handle wipe samples in the field. Various surfaces, including building materials (wood, metal, tile, vinyl, etc.) and equipment, may be sampled based on this procedure. The purpose of such sampling is to determine whether or not the relevant surfaces are contaminated, to determine the extent of their contamination, to evaluate the effectiveness of decontamination procedures, and to determine the amount of contaminant that might present as a contact hazard.

  7. Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Capacio, B.R.; Harris, L.W.; Anderson, D.R.; Lennox, W.J.; Gales, V.

    1992-12-31

    The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepan, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. AH compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (micrometer ol/kg) values and peak effect tunes were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepwn, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock MES and subcutaneous pentylenetetrazol (scMET)). I serve agents, anticonvulsants, diazepam, accelerating rotarod, motor performance.

  8. A rapid and sensitive technique for assessing exposure to VX via GC-MS-MS analysis.

    Science.gov (United States)

    McGuire, Jeffrey M; Byers, Christopher E; Hulet, Stanley W; Jakubowski, Edward M; Thomson, Sandra A

    2008-01-01

    A rapid and sensitive method for the determination of the chemical warfare agent VX in plasma taken from Göttingen minipigs has been developed using isotope-dilution gas chromatography-tandem mass spectrometry (GC-MS-MS). Chromatographic separation was achieved on a 5% diphenyl/95% dimethyl polysiloxane capillary column with a total run time of about 11 min. The analyte was detected using ammonia chemical ionization in the multiple reaction monitoring mode, following a simple extraction with 10% 2-propanol in hexane. A good linear relationship was obtained in the quantitative concentration range of 10 ng/mL to 1000 ng/mL (r(2) = 0.9998) with an average slope of 1.275 +/- 0.037 (n = 7), and an absolute detection limit of 0.4 pg on column. The average recovery for VX was 95% in saline in the concentration range of 50-100 ng/mL. The method was successfully applied to the analysis of VX in minipig plasma in a preliminary toxicokinetic study.

  9. The limitations of diazepam as a treatment for nerve agent-induced seizures and neuropathology in rats: comparison with UBP302.

    Science.gov (United States)

    Apland, James P; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Rossetti, Franco; Miller, Steven L; Braga, Maria F M

    2014-11-01

    Exposure to nerve agents induces prolonged status epilepticus (SE), causing brain damage or death. Diazepam (DZP) is the current US Food and Drug Administration-approved drug for the cessation of nerve agent-induced SE. Here, we compared the efficacy of DZP with that of UBP302 [(S)-3-(2-carboxybenzyl)willardiine; an antagonist of the kainate receptors that contain the GluK1 subunit] against seizures, neuropathology, and behavioral deficits induced by soman in rats. DZP, administered 1 hour or 2 hours postexposure, terminated the SE, but seizures returned; thus, the total duration of SE within 24 hours after soman exposure was similar to (DZP at 1 hour) or longer than (DZP at 2 hours) that in the soman-exposed rats that did not receive the anticonvulsant. Compared with DZP, UBP302 stopped SE with a slower time course, but dramatically reduced the total duration of SE within 24 hours. Neuropathology and behavior were assessed in the groups that received anticonvulsant treatment 1 hour after exposure. UBP302, but not DZP, reduced neuronal degeneration in a number of brain regions, as well as neuronal loss in the basolateral amygdala and the CA1 hippocampal area, and prevented interneuronal loss in the basolateral amygdala. Anxiety-like behavior was assessed in the open field and by the acoustic startle response 30 days after soman exposure. The results showed that anxiety-like behavior was increased in the DZP-treated group and in the group that did not receive anticonvulsant treatment, but not in the UBP302-treated group. The results argue against the use of DZP for the treatment of nerve agent-induced seizures and brain damage and suggest that targeting GluK1-containing receptors is a more effective approach.

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

    Science.gov (United States)

    2014-11-01

    Neuroscience 221:157–169. Bajgar J (2005) Complex view on poisoning with nerve agents and organophosphates . Acta Med (Hradec Kralove) 48:3–21. Braga MF...Coubard S, Béracochéa D, Collombet JM, Philippin JN, Krazem A, Liscia P, Lallement G, and Piérard C (2008) Long-term consequences of soman poisoning in mice...Baubichon D, Masqueliez C, Lallement G, and Collombet JM (2007) Long-term behavioral con- sequences of soman poisoning in mice. Neurotoxicology 28:508–519

  11. High Power Experiments in VX-10

    Science.gov (United States)

    Squire, Jared; Chang-Diaz, Franklin; Araya-Chacon, Gonzalo; Jacobson, Verlin; Glover, Tim; McCaskill, Greg; Vera, Jerry; Baity, Wally; Carter, Mark; Goulding, Rick

    2004-11-01

    In the Advanced Space Propulsion Laboratory VASIMR experiment (VX-10) we have measured a plasma flux to input gas rate ratio near 100power levels up to 10 kW. The plasma source is being developed to supply a dense target with a high degree of ionization for ICRF acceleration of the flow in an expanding magnetic field. An upgrade to 20 kW helicon operations is underway. Recent results at Oak Ridge National Laboratory show enhanced efficiency operation with a high power density, over 5 kW in a 5 cm diameter tube. Our helicon is presently 9 cm in diameter, so comparable power densities will be achieved in VX-10. We have operated with a Boswell double-saddle antenna design with a magnetic cusp just upstream of the antenna. Recently we have converted to a double-helix half-turn antenna. ICRF experiments have been performed as 1.5 kW that show significant plasma flow acceleration, doubling the flow velocity. A 10 kW ICRF upgrade is underway. Results from high total power ( ˜ 30 kW) experiments with this new helicon antenna and ICRF acceleration are presented.

  12. The Pulsation Spectrum of VX Hydrae

    Science.gov (United States)

    Templeton, M. R.; Samolyk, G.; Dvorak, S.; Poklar, R.; Butterworth, N.; Gerner, H.

    2009-10-01

    We present the results of a two-year, multisite observing campaign investigating the high-amplitude δ Scuti star VX Hydrae during the 2006 and 2007 observing seasons. The final data set consists of nearly 8500 V-band observations spanning HJD 2453763.6 to 2454212.7 (2006 January 28 to 2007 April 22). Separate analyses of the two individual seasons of data yield 25 confidently detected frequencies common to both data sets, of which two are pulsation modes, and the remaining 23 are Fourier harmonics or beat frequencies of these two modes. The 2006 data set had five additional frequencies with amplitudes less than 1.5 mmag, and the 2007 data had one additional frequency. Analysis of the full 2006–2007 data set yields 22 of the 25 frequencies found in the individual seasons of data. There are no significant peaks in the spectrum other than these between 0 and 60 cycles day-1. The frequencies of the two main pulsation modes derived from the 2006 and 2007 observing seasons individually do not differ at the level of 3σ, and thus we find no conclusive evidence for period change over the span of these observations. However, the amplitude of changed significantly between the two seasons, while the amplitude of remained constant; amplitudes of the Fourier harmonics and beat frequencies of f1 also changed. Similar behavior was seen in the 1950s, and it is clear that VX Hydrae undergoes significant amplitude changes over time.

  13. Chemical Warfare Agent Degradation and Decontamination

    Energy Technology Data Exchange (ETDEWEB)

    Talmage, Sylvia Smith [ORNL; Watson, Annetta Paule [ORNL; Hauschild, Veronique [U.S. Environmental Protection Agency; Munro, Nancy B [ORNL; King, J. [U.S. Army Environmental Center

    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.

  14. Exhaust Plume Measurements of the VASIMR VX-200

    Science.gov (United States)

    Longmier, Benjamin; Bering, Edgar, III; Squire, Jared; Glover, Tim; Chang-Diaz, Franklin; Brukardt, Michael

    2008-11-01

    Recent progress is discussed in the development of an advanced RF electric propulsion concept: the Variable Specific Impulse Magnetoplasma Rocket (VASIMR) VX-200 engine, a 200 kW flight-technology prototype. Results from high power Helicon only and Helicon with ICRH experiments are performed on the VX-200 using argon plasma. Recent measurements of axial plasma density and potential profiles, magnetic field-line shaping, charge exchange, and force measurements taken in the plume of the VX-200 exhaust are made within a new 125 cubic meter cryo-pumped vacuum chamber and are presented in the context of RF plasma thruster physics.

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

    OpenAIRE

    Mumford, Helen; Troyer, John K.

    2011-01-01

    Poisoning by nerve agents via the percutaneous (p.c.) route is an issue because the slow absorption of agent could result in poisoning which outlasts the protection provided by conventional pharmacological therapy. The bioscavenger approach is based on the concept of binding nerve agent in the bloodstream, thus preventing nerve agent from reaching the target tissues and inhibiting acetylcholinesterase activity. One bioscavenger that has been extensively studied is human butyrylcholinesterase ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Wymore, Troy W [ORNL; Langan, Paul [ORNL; Smith, Jeremy C [ORNL; Field, Martin J. [Institut de Biologie Structurale Jean-Pierre Ebel; Parks, Jerry M [ORNL

    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.

  17. Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

    Science.gov (United States)

    Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay

    2014-09-16

    Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators.

  18. Formation of pyrophosphate-like adducts from nerve agents sarin, soman and cyclosarin in phosphate buffer: implications for analytical and toxicological investigations.

    Science.gov (United States)

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

    2011-01-15

    Phosphate buffer is frequently used in biological, biochemical and biomedical applications especially when pH is to be controlled around the physiological value of 7.4. One of the prerequisites of a buffer compound among good buffering capacity and pH stability over time is its non-reactivity with other constituents of the solution. This is especially important for quantitative analytical or toxicological assays. Previous work has identified a number of amino alcohol buffers like TRIS to react with G-type nerve agents sarin, soman and cyclosarin to form stable phosphonic diesters. In case of phosphate buffer we were able to confirm not only the rapid hydrolysis of these agents to the respective alkyl methylphosphonates but also the formation of substantial amounts of pyrophosphate-like adducts (phosphorylated methylphosphonates), which very slowly hydrolyzed following zero-order kinetics. This led to a complex mixture of phosphorus containing species with changing concentrations over time. We identified the molecular structure of these buffer adducts using 1D ¹H-³¹P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates of adduct formation are fast enough to compete with hydrolysis in aqueous solution and to yield substantial amounts of buffer adduct over the course of just a couple of minutes. Possible reaction mechanisms are discussed with respect to the formation and subsequent hydrolysis of the pyrophosphate-like compounds as well as the increased rate of hydrolysis of the nerve agent to the corresponding alkyl methylphosphonates. In summary, the use of phosphate buffer for the development of new assays with sarin, soman and cyclosarin is discouraged. Already existing protocols should be carefully reexamined on an individual basis.

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

    Science.gov (United States)

    Thiermann, Horst; Worek, Franz; Kehe, Kai

    2013-12-01

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

  20. Photocatalytic oxidation of VX-simulation substance.

    Science.gov (United States)

    Kozlova, E; Vorontsov, A; Rima, G; Lion, C; Preis, S

    2007-01-01

    Experimental studies of photocatalytic oxidation (PCO) of VX-gas simulation substance cysteamine-S-phosphate sodium salt (NaHPO3S-CH2-CH2-NH2, CPSS) at various initial concentrations and pH were undertaken. PCO ultimately resulted in complete mineralisation of CPSS. The PCO byproducts of CPSS include acetate, oxalate and trace amounts of formate ions. The formation rates of acetate and phosphate were equal to the rate of degradation of CPSS, which indicates easy breakage of P-S, C-S and C-N bonds. Sulphate was formed more slowly due to stepwise oxidation of reduced sulphur. Amino group, generally transformed to ammonia, was partially oxidised to nitrite and nitrate in alkaline media. The fastest mineralisation in terms of both TOC degradation and phosphate formation was observed in neutral media. Under neutral media conditions, the PCO rate increased linearly with the CPSS concentration increase. The maximum efficiency by TOC degradation was observed as large as 77 mg per Wh of incident UV flux with quantum efficiency 3.8%.

  1. The pulsation spectrum of VX Hydrae

    CERN Document Server

    Templeton, M R; Dvorak, S; Poklar, R; Butterworth, N; Gerner, H

    2009-01-01

    We present the results of a two-year, multisite observing campaign investigating the high-amplitude delta Scuti star VX Hydrae during the 2006 and 2007 observing seasons. The final data set consists of nearly 8500 V-band observations spanning HJD 2453763.6 to 2454212.7 (2006 January 28 to 2007 April 22). Separate analyses of the two individual seasons of data yield 25 confidently-detected frequencies common to both data sets, of which two are pulsation modes, and the remaining 23 are Fourier harmonics or beat frequencies of these two modes. The 2006 data set had five additional frequencies with amplitudes less than 1.5 mmag, and the 2007 data had one additional frequency. Analysis of the full 2006-2007 data set yields 22 of the 25 frequencies found in the individual seasons of data. There are no significant peaks in the spectrum other than these between 0 and 60 c/d. The frequencies of the two main pulsation modes derived from the 2006 and 2007 observing seasons individually do not differ at the level of 3-si...

  2. Wearable Atmospheric Pressure Plasma Fabrics Produced by Knitting Flexible Wire Electrodes for the Decontamination of Chemical Warfare Agents

    Science.gov (United States)

    Jung, Heesoo; Seo, Jin Ah; Choi, Seungki

    2017-01-01

    One of the key reasons for the limited use of atmospheric pressure plasma (APP) is its inability to treat non-flat, three-dimensional (3D) surface structures, such as electronic devices and the human body, because of the rigid electrode structure required. In this study, a new APP system design—wearable APP (WAPP)—that utilizes a knitting technique to assemble flexible co-axial wire electrodes into a large-area plasma fabric is presented. The WAPP device operates in ambient air with a fully enclosed power electrode and grounded outer electrode. The plasma fabric is flexible and lightweight, and it can be scaled up for larger areas, making it attractive for wearable APP applications. Here, we report the various plasma properties of the WAPP device and successful test results showing the decontamination of toxic chemical warfare agents, namely, mustard (HD), soman (GD), and nerve (VX) agents.

  3. Dual-Function Metal-Organic Framework as a Versatile Catalyst for Detoxifying Chemical Warfare Agent Simulants.

    Science.gov (United States)

    Liu, Yangyang; Moon, Su-Young; Hupp, Joseph T; Farha, Omar K

    2015-12-22

    The nanocrystals of a porphyrin-based zirconium(IV) metal-organic framework (MOF) are used as a dual-function catalyst for the simultaneous detoxification of two chemical warfare agent simulants at room temperature. Simulants of nerve agent (such as GD, VX) and mustard gas, dimethyl 4-nitrophenyl phosphate and 2-chloroethyl ethyl sulfide, have been hydrolyzed and oxidized, respectively, to nontoxic products via a pair of pathways catalyzed by the same MOF. Phosphotriesterase-like activity of the Zr6-containing node combined with photoactivity of the porphyrin linker gives rise to a versatile MOF catalyst. In addition, bringing the MOF crystals down to the nanoregime leads to acceleration of the catalysis.

  4. Hand-held analyser based on microchip electrophoresis with contactless conductivity detection for measurement of chemical warfare agent degradation products

    Science.gov (United States)

    Duran, Karolina-Petkovic; Zhu, Yonggang; Chen, Chuanpin; Swallow, Anthony; Stewart, Robert; Hoobin, Pam; Leech, Patrick; Ovenden, Simon

    2008-12-01

    This paper reports on the development of a hand-held device for on-site detection of organophosphonate nerve agent degradation products. This field-deployable analyzer relies on efficient microchip electrophoresis separation of alkyl methylphosphonic acids and their sensitive contactless conductivity detection. Miniaturized, low-powered design is coupled with promising analytical performance for separating the breakdown products of chemical warfare agents such as Soman, Sarin and VX . The detector has a detection limit of about 10 μg/mL and has a good linear response in the range 10-300 μg/mL concentration range. Applicability to environmental samples is demonstrated .The new hand-held analyzer offers great promise for converting conventional ion chromatography or capillary electrophoresis sophisticated systems into a portable forensic laboratory for faster, simpler and more reliable on-site screening.

  5. VX Her: Eclipsing Binary System or Single Variable Star

    Science.gov (United States)

    Perry, Kathleen; Castelaz, Michael; Henson, Gary; Boghozian, Andrew

    2015-01-01

    VX Her is a pulsating variable star with a period of .4556504 days. It is believed to be part of an eclipsing binary system (Fitch et al. 1966). This hypothesis originated from Fitch seeing VX Her's minimum point on its light curve reaching a 0.7 magnitude fainter than normal and remaining that way for nearly two hours. If VX Her were indeed a binary system, I would expect to see similar results with a fainter minimum and a broader, more horizontal dip. Having reduced and analyzed images from the Southeastern Association for Research in Astronomy Observatory in Chile and Kitt Peak, as well as images from a 0.15m reflector at East Tennessee State University, I found that VX Her has the standard light curve of the prototype variable star, RR Lyrae. Using photometry, I found no differing features in its light curve to suggest that it is indeed a binary system. However, more observations are needed in case VX Her is a wide binary.

  6. The success rate of bupivacaine and lidocaine as anesthetic agents in inferior alveolar nerve block in teeth with irreversible pulpitis without spontaneous pain

    Directory of Open Access Journals (Sweden)

    Masoud Parirokh

    2015-05-01

    Full Text Available Objectives Achieving adequate anesthesia with inferior alveolar nerve blocks (IANB is of great importance during dental procedures. The aim of the present study was to assess the success rate of two anesthetic agents (bupivacaine and lidocaine for IANB when treating teeth with irreversible pulpitis. Materials and Methods Sixty volunteer male and female patients who required root canal treatment of a mandibular molar due to caries participated in the present study. The inclusion criteria included prolonged pain to thermal stimulus but no spontaneous pain. The patients were randomly allocated to receive either 2% lidocaine with 1:80,000 epinephrine or 0.5% bupivacaine with 1:200,000 epinephrine as an IANB injection. The sensitivity of the teeth to a cold test as well as the amount of pain during access cavity preparation and root canal instrumentation were recorded. Results were statistically analyzed with the Chi-Square and Fischer's exact tests. Results At the final step, fifty-nine patients were included in the study. The success rate for bupivacaine and lidocaine groups were 20.0% and 24.1%, respectively. There was no significant difference between the two groups at any stage of the treatment procedure. Conclusions There was no difference in success rates of anesthesia when bupivacaine and lidocaine were used for IANB injections to treat mandibular molar teeth with irreversible pulpitis. Neither agent was able to completely anesthetize the teeth effectively. Therefore, practitioners should be prepared to administer supplemental anesthesia to overcome pain during root canal treatment.

  7. Corrector VX-809 stabilizes the first transmembrane domain of CFTR.

    Science.gov (United States)

    Loo, Tip W; Bartlett, M Claire; Clarke, David M

    2013-09-01

    Processing mutations that inhibit folding and trafficking of CFTR are the main cause of cystic fibrosis (CF). A potential CF therapy would be to repair CFTR processing mutants. It has been demonstrated that processing mutants of P-glycoprotein (P-gp), CFTR's sister protein, can be efficiently repaired by a drug-rescue mechanism. Many arginine suppressors that mimic drug-rescue have been identified in the P-gp transmembrane (TM) domains (TMDs) that rescue by forming hydrogen bonds with residues in adjacent helices to promote packing of the TM segments. To test if CFTR mutants could be repaired by a drug-rescue mechanism, we used truncation mutants to test if corrector VX-809 interacted with the TMDs. VX-809 was selected for study because it is specific for CFTR, it is the most effective corrector identified to date, but it has limited clinical benefit. Identification of the VX-809 target domain will help to develop correctors with improved clinical benefits. It was found that VX-809 rescued truncation mutants lacking the NBD2 and R domains. When the remaining domains (TMD1, NBD1, TMD2) were expressed as separate polypeptides, VX-809 only increased the stability of TMD1. We then performed arginine mutagenesis on TM6 in TMD1. Although the results showed that TM6 had distinct lipid and aqueous faces, CFTR was different from P-gp as no arginine promoted maturation of CFTR processing mutants. The results suggest that TMD1 contains a VX-809 binding site, but its mechanism differed from P-gp drug-rescue. We also report that V510D acts as a universal suppressor to rescue CFTR processing mutants.

  8. Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

    Science.gov (United States)

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

    2015-05-15

    Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals.

  9. The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT

    Directory of Open Access Journals (Sweden)

    X.-L. Qi

    2012-01-01

    Full Text Available Blood supply is crucial for rapid growth of a malignant tumor; medical imaging can play an important role in evaluating the vascular characterstics of tumors. Magnetic resonance imaging (MRI and micro-computed tomography (CT are able to detect tumors and measure blood volumes of microcirculation in tissue. In this study, we used MR imaging and micro-CT to assess the microcirculation in a VX2 tumor model in rabbits. MRI characterization was performed using the intravascular contrast agent Clariscan (NC100150-Injection; micro-CT with Microfil was used to directly depict blood vessels with diameters as low as 17 um in tissue. Relative blood volume fraction (rBVF in the tumor rim and blood vessel density (rBVD over the whole tumor was calculated using the two imaging methods. Our study indicates that rBVF is negatively related to the volume of the tumor measured by ultrasound (R=0.90. rBVF in the tissue of a VX2 tumor measured by MRI in vivo was qualitatively consistent with the rBVD demonstrated by micro-CT in vitro (R=0.97. The good correlation between the two methods indicates that MRI studies are potentially valuable for assessing characteristics or tumor vascularity and for assessing response to therapy noninvasively.

  10. Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770.

    Science.gov (United States)

    Gentzsch, Martina; Ren, Hong Y; Houck, Scott A; Quinney, Nancy L; Cholon, Deborah M; Sopha, Pattarawut; Chaudhry, Imron G; Das, Jhuma; Dokholyan, Nikolay V; Randell, Scott H; Cyr, Douglas M

    2016-09-01

    Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Steven L., E-mail: stevenmiller17@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Aroniadou-Anderjaska, Vassiliki, E-mail: vanderjaska@usuhs.edu [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Figueiredo, Taiza H., E-mail: taiza.figueiredo.ctr@usuhs.edu [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Prager, Eric M., E-mail: eric.prager683@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Almeida-Suhett, Camila P., E-mail: camilapalmeida@gmail.com [Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Program in Neuroscience, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (United States); Apland, James P., E-mail: james.p.apland.civ@mail.mil [Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010 (United States); 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

  12. Capture of nerve agents and mustard gas analogues by hydrophobic robust MOF-5 type metal-organic frameworks.

    Science.gov (United States)

    Montoro, Carmen; Linares, Fátima; Procopio, Elsa Quartapelle; Senkovska, Irena; Kaskel, Stefan; Galli, Simona; Masciocchi, Norberto; Barea, Elisa; Navarro, Jorge A R

    2011-08-10

    In this communication, a series of observations and data analyses coherently confirms the suitability of the novel metal-organic framework (MOF) [Zn(4)(μ(4)-O)(μ(4)-4-carboxy-3,5-dimethyl-4-carboxy-pyrazolato)(3)] (1) in the capture of harmful volatile organic compounds (VOCs). It is worthy of attention that 1, whose crystal structure resembles that of MOF-5, exhibits remarkable thermal, mechanical, and chemical stability, as required if practical applications are sought. In addition, it selectively captures harmful VOCs (including models of Sarin and mustard gas, which are chemical warfare agents), even in competition with ambient moisture (i.e., under conditions mimicking operative ones). The results can be rationalized on the basis of Henry constant and adsorption heat values for the different essayed adsorbates as well as H(2)O/VOC partition coefficients as obtained from variable-temperature reverse gas chromatography experiments. To further strengthen the importance of 1, its performance in the capture of harmful VOCs has been compared with those of well-known materials, namely, a MOF with coordinatively unsaturated metal sites, [Cu(3)(btc)(2)] and the molecular sieve active carbon Carboxen. The results of this comparison show that coordinatively unsaturated metal sites (preferential guest-binding sites) are ineffective for the capture of VOCs in the presence of ambient moisture. Consequently, we propose that the driving force of the VOC-MOF recognition process is mainly dictated by pore size and surface hydrophobicity. © 2011 American Chemical Society

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

    DEFF Research Database (Denmark)

    Hakonen, Aron; Rindzevicius, Tomas; Schmidt, Michael Stenbæk;

    2016-01-01

    we demonstrate that surface-enhanced Raman scattering (SERS) can be used for sensitive detection of femtomol quantities of two nerve gases, VX and Tabun, using a handheld Raman device and SERS substrates consisting of flexible gold-covered Si nanopillars. The substrate surface exhibits high droplet...

  14. Outward Motions of SiO Masers around VX Sgr

    Indian Academy of Sciences (India)

    J. B. Su; Z.-Q. Shen; X. Chen; D. R. Jiang

    2014-09-01

    We report the proper motions of SiO maser features around VX Sgr from the two-epoch VLBA observations (2006 December 15 and 2007 August 19). The majority of maser feature activities show a trend of outward motions. It is consistent with our previous finding that the outflow may play an important role for SiO maser pumping.

  15. Spectroscopic measurements of electron temperature on VX-10

    Science.gov (United States)

    Sciamma, Ella; Lee, Charles; Bengtson, Roger; Jacobson, Verlin; Lavagni-Bolanos, Frank; McCaskill, Greg

    2004-11-01

    We have made spectroscopic measurements at several locations in the VX-10 experiment in the near UV, visible, and near IR spectral region. We estimate electron temperatures using a collisional radiative model. Residual gas analysis is also performed with plasma discharges. Quantitative estimates of plasma composition are also discussed.

  16. Nerve biopsy

    Science.gov (United States)

    Biopsy - nerve ... A nerve biopsy is most often done on a nerve in the ankle, forearm, or along a rib. The health care ... feel a prick and a mild sting. The biopsy site may be sore for a few days ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

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

    2015-03-20

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

  19. Evaluation of Chemical Warfare Agent Percutaneous Vapor Toxicity: Derivation of Toxicity Guidelines for Assessing Chemical Protective Ensembles.

    Energy Technology Data Exchange (ETDEWEB)

    Watson, A.P.

    2003-07-24

    Percutaneous vapor toxicity guidelines are provided for assessment and selection of chemical protective ensembles (CPEs) to be used by civilian and military first responders operating in a chemical warfare agent vapor environment. The agents evaluated include the G-series and VX nerve agents, the vesicant sulfur mustard (agent HD) and, to a lesser extent, the vesicant Lewisite (agent L). The focus of this evaluation is percutaneous vapor permeation of CPEs and the resulting skin absorption, as inhalation and ocular exposures are assumed to be largely eliminated through use of SCBA and full-face protective masks. Selection of appropriately protective CPE designs and materials incorporates a variety of test parameters to ensure operability, practicality, and adequacy. One aspect of adequacy assessment should be based on systems tests, which focus on effective protection of the most vulnerable body regions (e.g., the groin area), as identified in this analysis. The toxicity range of agent-specific cumulative exposures (Cts) derived in this analysis can be used as decision guidelines for CPE acceptance, in conjunction with weighting consideration towards more susceptible body regions. This toxicity range is bounded by the percutaneous vapor estimated minimal effect (EME{sub pv}) Ct (as the lower end) and the 1% population threshold effect (ECt{sub 01}) estimate. Assumptions of exposure duration used in CPE certification should consider that each agent-specific percutaneous vapor cumulative exposure Ct for a given endpoint is a constant for exposure durations between 30 min and 2 hours.

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Multitasking Programming Based on VxWorks%基于VxWorks的多任务程序设计

    Institute of Scientific and Technical Information of China (English)

    武华; 刘军伟

    2011-01-01

    Vx Works is a real-time .multitasking embedded operating system, it had been used in many fields such as aerospace, aeronautics and communication. With the continuous complexity of function and improvement of performance requirements of embedded systems, the rational design of multitask procedure plays an important role in embedded system software. Analyze multitasking schedule under VxWorks, introduce the key point of multitasking programming on multitasking priority allocation, the communication mode between tasks and interrupt handling, present multitasking programming procedure and methods with an application example of PC communication, the design is reasonable and reliable in practice, which can also give some reference in design of multitasking programming based on VxWorks.%VxWorks是一种嵌入式实时多任务操作系统,以其良好的可靠性和卓越的实时性被广泛地应用在航天、航空、通信等领域中.随着嵌入式系统功能的不断复杂和性能需求的不断提高,多任务程序的合理设计对嵌入式系统软件的稳定、可靠运行起着重要的作用.文中对VxWorks下的多任务调度机制进行分析,然后介绍多任务程序设计过程中任务优先级的设置、多任务间通信、中断处理等关键要点,结合FC通信的应用实例给出多任务程序设计的步骤和方法,在实际应用中验证了设计的合理性和可靠性,为基于VxWorks的多任务程序设计提供一定的参考.

  2. Photodynamic therapy for implanted VX2 tumor in rabbit brains

    Science.gov (United States)

    Li, Fei; Feng, Hua; Lin, Jiangkai; Zhu, Gang; Chen, Zhi; Li, Cong-yan

    2005-07-01

    To evaluate the therapeutic effect and the safety of single photodynamic therapy (PDT) with hematoporphyrin derivative produced in China, 60 New Zealand adult rabbits with VX2 tumor implanted into the brain were divided randomly into non-PDT-group and PDT-group. 36 rabbits of the PDT-group were performed photodynamic therapy. The survival time, neurological deteriorations, intracranial pressure (ICP), histology, pathology, tumor volume and brain water content were measured. Other 12 rabbits were received hematoporphyrin derivative and light irradiation of the normal brain. The ICP, histology, pathology, and brain water content were measured. The result indicated that Simple PDT may elongate the average survival time of the rabbits with VX2 tumors significantly; kill tumor cells; cause transient brain edema and increase ICP, but it is safe to be used in treating brain tumor.

  3. VX-702获得阳性结果

    Institute of Scientific and Technical Information of China (English)

    王吉云

    2005-01-01

    VX-702(Ⅰ)是美国Vertex制药公司的一种口服p38MAP激酶抑制剂。其Ⅱa期临床试验的初步结果显示,此药用于接受经皮冠状动脉介入治疗(PCI)的急性冠状动脉综合征患者前景良好。

  4. Syria’s Chemical Weapons: Issues for Congress

    Science.gov (United States)

    2013-09-12

    regime of President Bashar al Asad possesses stocks of nerve (sarin, VX ) and blister (mustard gas) agents , possibly weaponized into bombs, shells...largest in the world” during a June 2012 interview.16 Damascus possesses mustard blister agent , sarin nerve agent , and VX nerve agent , according to...chemical weapons stockpile. Syria also has several hundred metric tons of mustard agent in ready-to-use form and several tens of metric tons of VX . The

  5. Nerve Agent Sensing Biopolymer Wipe

    Science.gov (United States)

    2003-04-01

    minutes. Polymer synthesis is complete in less than 10 minutes. The CO2 evolved during the reaction of water and isocyanate lifts the foam to a...concrete, stone and asphalt . Excessive dirt or any material that significantly masks clear viewing of the sensor polymer may invalidate sensor

  6. Prophylaxis Against Nerve Agent Intoxications

    Directory of Open Access Journals (Sweden)

    Jiri Patocka

    2006-11-01

    Full Text Available The acute toxicity of organophosphates is usually attributed to their irreversible inhibitionof an enzyme acetylcholinesterase that hydrolyses the neurotransmitter acetylcholine. Theresultant increase in concentration of acetylcholine at the cholinergic synapses of the peripheraland central nervous system, and neuromuscular junction is manifested by over-stimulation ofthe cholinergic neurotransmission. Current antidotal regimens for organophosphate poisoningconsisting of a post-exposure therapy with anticholinergics such as atropine, acetylcholinesterasereactivators (oximes, benzodiazepines have some limitations. Therefore, effective prophylaxisbefore intoxication is of a special interest. Four fundamental prophylactic methods are: (iprotection of acetylcholinesterase against irreversible inhibition by organophosphates usingdifferent reversible inhibitors, (ii protection against neurotoxic effect of organophosphates usingbenzodiazepines, memantine, NMDA receptor blockers, (iii administration of cholinesterasepreparations of different sources (sometimes commercially available at present acting asbioscavengers, and (iv gene therapy being a new treatment modality under intensive researchusing enzymes hydrolysing/splitting organophosphates with the aim to eliminate toxic agentbefore it is transported to the target organs.

  7. 八重洲YAESU VX-3R新机发布

    Institute of Scientific and Technical Information of China (English)

    黎海

    2007-01-01

    日本八重洲公司(YAESU)在2007年6月份,正式发布一款新型的微型业余手持电台,型号是VX-3R。在经历长达10年的微型业余机制作经验的积累和沉淀后,从一代的VX-1R到二代的VX-2R,再到如今的VX-3R,这已是八重洲公司十年磨一剑的第三代产品。

  8. Performance Measurements and Technology Demonstration of the VASIMR® VX-200

    Science.gov (United States)

    Longmier, B. W.; Bering, E. A.; Squire, J. P.; Glover, T. W.; Cassady, L. D.; Ilin, A. V.; Carter, M. D.; Olsen, C. S.; McCaskill, G. E.; Chang Díaz, F.

    2010-12-01

    Recent progress is discussed in the development of an advanced RF electric propulsion engine: the VAriable Specific Impulse Magnetoplasma Rocket (VASIMR®) VX-200, a 200 kW flight-technology prototype. This device is the only known industrial application of the physics of the aurora borealis. Results are presented from first stage only and first stage with booster stage experiments that were performed on the VX-200 using between 60 mg/s and 150 mg/s argon propellant. The plasma source is a helicon discharge that uses whistler mode waves near the lower hybrid frequency. The booster stage uses electromagnetic ion cyclotron wave absorption to accelerate the ions. Measurements of ion flux, ion energy, plasma density and potential gradients, and force density profiles taken in the exhaust plume of the VX-200 are made within a 150 cubic meter vacuum chamber and are presented in the context of individual stage and total engine performance. Measurements include detailed pitch angle scans of the accelerated ions and plasma parameter maps of the exhaust plume. An emphasis will be given to our ability to probe wave-particle interactions in the exhaust plume. We are now in a position to conduct more detailed auroral simulation studies and are actively seeking collaborators.

  9. Chemical profiling of chemical warfare agents for forensic purposes

    NARCIS (Netherlands)

    Noort, D.; Reuver, L.P.J. de; Fidder, A.; Tromp, M.; Verschraagen, M.

    2010-01-01

    A program has been initiated towards the chemical profiling of chemical warfare agents, in order to support forensic investigations towards synthesis routes, production sites and suspect chemical suppliers. Within the first stage of the project various chemical warfare agents (VX, sulfur mustard, sa

  10. Using Metal Complex Ion-Molecule Reactions in a Miniature Rectilinear Ion Trap Mass Spectrometer to Detect Chemical Warfare Agents

    Science.gov (United States)

    Graichen, Adam M.; Vachet, Richard W.

    2013-06-01

    The gas-phase reactions of a series of coordinatively unsaturated [Ni(L)n]y+ complexes, where L is a nitrogen-containing ligand, with chemical warfare agent (CWA) simulants in a miniature rectilinear ion trap mass spectrometer were investigated as part of a new approach to detect CWAs. Results show that upon entering the vacuum system via a poly(dimethylsiloxane) (PDMS) membrane introduction, low concentrations of several CWA simulants, including dipropyl sulfide (simulant for mustard gas), acetonitrile (simulant for the nerve agent tabun), and diethyl phosphite (simulant for nerve agents sarin, soman, tabun, and VX), can react with metal complex ions generated by electrospray ionization (ESI), thereby providing a sensitive means of detecting these compounds. The [Ni(L)n]2+ complexes are found to be particularly reactive with the simulants of mustard gas and tabun, allowing their detection at low parts-per-billion (ppb) levels. These detection limits are well below reported exposure limits for these CWAs, which indicates the applicability of this new approach, and are about two orders of magnitude lower than electron ionization detection limits on the same mass spectrometer. The use of coordinatively unsaturated metal complexes as reagent ions offers the possibility of further tuning the ion-molecule chemistry so that desired compounds can be detected selectively or at even lower concentrations.

  11. Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

    Science.gov (United States)

    Veit, Guido; Avramescu, Radu G; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E; Hegedus, Tamas; Verkman, Alan S; Lukacs, Gergely L

    2014-07-23

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF.

  12. Degradation of VX surrogate profenofos on surfaces via in situ photo-oxidation.

    Science.gov (United States)

    Petrick, Lauren M; Sabach, Sara; Dubowski, Yael

    2013-08-06

    Surface degradation of profenofos (PF), a VX nerve gas surrogate, was investigated using in situ photo-oxidation that combines simple instrumentation and ambient gases (O2 and H2O) as a function of exposure conditions ([O3], [OH], UV light λ = 185 and/or 254 nm, relative humidity) and PF film surface density (0.38-3.8 g m(-2)). PF film 0.38 g m(-2) fully degraded after 60 min of exposure to both 254 and 185 nm UV light in humidified air and high ozone. The observed pseudo-first-order surface reaction rate constant (kobs = 0.075 ± 0.004 min(-1)) and calculated hydroxyl concentration near the film surface ([OH]g = (9 ± 2) × 10(7) molecules cm(-3)) were used to determine the second-order rate constant for heterogeneous reaction of PF and OH (k(OH)PF = (5 ± 1) × 10(-12) cm(3) molec(-1) s(-1)). PF degradation in the absence of 185 nm light or without humidity was lower (70% or 90% degradation, respectively). With denser PF films ranging from 2.3 to 3.8 g m(-2), only 80% degradation was achieved until the PF droplet was redissolved in acetonitrile which allowed >95% PF degradation. Surface product analysis indicated limited formation of the nontoxic phosphoric acid ester but the formation of nonvolatile chemicals with increased hydrophilicity and addition of OH.

  13. Evaporation and Degradation of a Sessile Droplet of VX on an Impermeable Surface

    Science.gov (United States)

    2017-09-01

    methylphosphonic acid and VX-pyro) and hydrophobic (VX-disulfide) components occurs. The hydrophilic components make up the core of the droplet and the...hydrophobic component comprises the shell. Continuum models of the process suggest that experimental observations cannot be reproduced without accounting...1 2. METHODS AND MATERIALS .............................................................................5 2.1

  14. Pharmacology of airway afferent nerve activity

    Directory of Open Access Journals (Sweden)

    Carr Michael J

    2001-05-01

    Full Text Available Abstract Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology.

  15. VxWorks实时操作系统的定制方法

    Institute of Scientific and Technical Information of China (English)

    李丽颖; 李彦峰; 韩广志; 苗丽娟

    2016-01-01

    VxWorks实时操作系统具有良好的可裁剪性和可扩展性,在Tornado集成开发环境下,开发者可以根据应用程序的需要,选择VxWorks系统的组成.利用Tornado定制VxWorks的方法,简单方便,但具有局限性——不能扩展组件选项、不能修改组件源码、不能细粒度裁剪等.针对以上缺陷,本文系统地提出一种定制VxWorks的方法,包括对VxWorks的扩展、修改、裁剪,操作简便、安全可靠.

  16. Pumping Mechanisms for SiO Masers around VX Sgr

    Indian Academy of Sciences (India)

    J. B. Su; Z.-Q. Shen; X. Chen; Jiyune Yi; D. R. Jiang; Y. J. Yun

    2011-03-01

    VX Sgr, a semi-regular variable, is a red giant star with intense SiO maser emission at 43 GHz. The pumping mechanism of the circumstellar SiO masers has been controversial for decades since its discovery. In order to pursue this long-standing problem further, we have carried out simultaneous VLBA observations of two 7 mm SiO masers at five epochs in about two years. We present relatively aligned = 1 and = 2, = 1-0 SiO maser maps and discuss the dominant pumping mechanism, which may be epoch dependent or a combination of both mechanisms.

  17. Pumping Mechanisms for SiO Masers around VX Sgr

    Science.gov (United States)

    Su, J. B.; Shen, Z.-Q.; Chen, X.; Yi, Jiyune; Jiang, D. R.; Yun, Y. J.

    2011-06-01

    VX Sgr, a semi-regular variable, is a red giant star with intense SiO maser emission at 43 GHz. The pumping mechanism of the circumstellar SiO masers has been controversial for decades since its discovery. In order to pursue this long-standing problem further, we have carried out simultaneous VLBA observations of two 7 mm SiO masers at five epochs in about two years. We present relatively aligned υ = 1 and υ = 2, J = 1-0 SiO maser maps and discuss the dominant pumping mechanism, which may be epoch dependent or a combination of both mechanisms.

  18. 金嗓子AV控制中心VX-700

    Institute of Scientific and Technical Information of China (English)

    钱志远

    2004-01-01

    金嗓子总会出一些惊世之作,这新近推出的AV控制中心VX-700又是一例。该机集中了所有最新音频格式解码功能,采用两片32bit的高速浮点DSP芯片,全部八个声道都用MDS+型D/A变换器,并对每个音箱

  19. 华硕VX7再续奢华

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    自2006年华硕携手兰博基尼推出VX系列"跑车本"以来,旗下每款产品的上市,都会迅速在消费者和媒体圈中引发轰动。如今,VX系列"跑车本"再从兰博基尼经典超跑Murcielago LP640身上汲取最新灵感,重磅推出一款黑、橙双色的VX7。

  20. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Bruce A Stanton

    Full Text Available P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF. Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770.F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR.The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.

  1. STUDY EXPERIENCE AND ESTABLISHMENT OF METASTATIC RABBIT MODEL WITH VX-2 CARCINOMA IN LIVER%兔肝VX2移植癌模型的建立

    Institute of Scientific and Technical Information of China (English)

    陈利平; 文天夫

    2011-01-01

    [目的]制作VX-2兔肝移植癌模型.[方法]新西兰白兔10只,采用VX-2瘤株动物自身接种传代.采用瘤组织块包埋法,均接种于肝左叶.[结果]2周后均顺利成瘤,该瘤在肝组织中呈浸润式生长.[结论]成功建立了兔VX-2移植性肝癌模型,为肝癌治疗的基础及临床研究提供了成熟的大型实验动物肝癌模型.%[Objective]To establish a metastatic rabbit VX-2 liver tumor model.[Methods]10 New-Zealand white rabbits were inoculated with VX-2 carcinoma in the left lobe of the liver by implantation.[Results]The tumor was successfully established two weeks later.The tumor grew in the liver tissue and infiltrated into the normal liver tissue.[Conclusion]It is successful to establish a modified metastatic rabbit VX-2 liver carcinma model, and it makes it possible to gain a reliable mature large animal model of tumor for the basic and clinical study of therapy of liver carcinoma.

  2. Exploring the physicochemical properties of oxime-reactivation therapeutics for cyclosarin, sarin, tabun, and VX inactivated acetylcholinesterase.

    Science.gov (United States)

    Esposito, Emilio Xavier; Stouch, Terry R; Wymore, Troy; Madura, Jeffry D

    2014-01-21

    The inactivation of acetylcholinesterase (AChE) by organophosphorus agent (OP) compounds is a serious problem regardless of how the individual was exposed. The reactivation of OP-inactivated AChE is dependent on the OP conjugate, and commonly a specific oxime is better at reactivating a specific OP conjugate than several diverse OP conjugates. The presented research explores the physicochemical properties needed for the reactivation of OP-inactivated AChE. Four different OPs, cyclosarin, sarin, tabun, and VX, were analyzed using the same set of oxime reactivators. A trial descriptor pool of semiempirical, traditional, and molecular interaction field descriptors was used to construct an ensemble of QSAR models for each OP-conjugate pair. Based on the molecular information and the cross-validation ability, individual QSAR models were selected to be part of an OP-conjugate consensus model. The OP-conjugate specific models provide important insight into the physicochemical properties required to reactivate the OP conjugates of interest. The reactivation of AChE inactivated with either cyclosarin or tabun requires the oxime therapeutic to possess an overall polar-positive surface area. Oxime therapeutics for the reactivation of sarin-inactivated AChE are conformationally dependent while oxime reverse therapeutics for VX require a compact region with a highly hydrophilic region and two positively charged pyridine rings.

  3. MR diffusion-weighted imaging of rabbit liver VX-2 tumor

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; Quan-Liang Shang; Wei-Zhou Hu; Su-Wen Yuan; En-Hua Xiao; Jun Xiang; Ke-Li Tang; Ke Jin; Shi-Jian Yi; Qiang Yin; Rong-Hua Yan; Zhong He

    2005-01-01

    AIM: To investigate the implanting method of rabbit liver VX-2 tumor and its MR diffusion-weighted imaging (DWI) characteristics.METHODS: Thirty-five New Zealand rabbits were included in the study. VX-2 tumor was implanted subcutaneously in 14 rabbits and intrahepatically in 6 for pre-experiments. VX-2 tumor was implanted intrahepatically in 12 rabbits for experiment and three were used as the control group. DWI, T1- and T2-weighted of MR1 were performed periodically in 15 rabbits for experiment before and after implantation. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance was calculated byanalysis of variance (ANOVA) of the randomized block design using SPSS10.0 software. RESULTS: The successful rate of subcutaneous implantation of VX-2 tumor was 29% (4/14) while that of intrahepatic implantation of it was 33% (2/6) in the preexperiment. The successful rate of intrahepatic implantation of VX-2 tumor in the experiment was 83% (10/12) and 15 tumors grew in 10 successfully implanted rabbits. The DWT signal of VX-2 tumor was high and became lower when the b value increased step by step. The signal of VX-2 tumor on the map of ADC was low. When the b value was 100 or 300 s/mm2, the ADC value of normal group and VX-2 tumor group was respectively 2.57±0.26, 1.73±0.31, 1.87±0.25 and 1.57±0.23 mm2/s. Their distinction was significant (F= 43.26, P<0.01), the tumor ADC value between b values 100 and 300 s/mm2 wassignificant (Tukey HSP, P<0.05) and the ADC value between VX-2 tumor and normal liver was also significant (Tukey HSP, P<0.01). VX-2 tumor developed quickly and metastasized early to all body, especially to the lung, liver, lymph nodes of mediastinum, etc.CONCLUSION: The DWI signal of rabbit VX-2 tumor has its characteristics on MR DWI and DWI plays an important role in diagnosing and discovering VX-2 tumor.

  4. 昂达新品“VX610W加强版”%ONDA VX610W Enhanced Version

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    国内数码领进品牌昂达电子近期推出首款A10处理芯片平板——vx610w加强版。它搭载1.5GHz主频、新一代多核技术、7.0英寸高清触摸屏、2160P超高清、3D视频、超长续航时间、双向画面输出显示等,8GB售价499元,性价比相当高。

  5. Recent Experimental Results in the VX-10 Device

    Science.gov (United States)

    Squire, J. P.; Díaz, F. R. Chang; Jacobson, V. T.; McCaskill, G. E.; McCoy, J. E.; Petro, A. J.; Baity, F. W.; Bengtson, R. D.; Bering, E. A.; Garret, J. A.; Glover, T. W.

    2000-10-01

    In the VASIMR engine, neutral gas is ionized using a helicon type source and the ions are subsequently accelerated via ICRF power injection. The experimental device in the ASPL is targeting a total RF power level of 10 kW and is called VX-10. RF power is available with 3 kW at 25 MHz for the helicon source and 100 kW at 3 MHz for ICRF. Experiments with light gasses (hydrogen, deuterium, and helium) are performed. The VX-10 3-magnet system is capable of a maximum B field of 2 T and has flexible axial profile shaping capability. Diagnostics in the plasma exhaust include an RF compensated Langmuir probe, a Mach probe, Retarding Potential Analyzer (RPA), newly installed density interferometer and an ion gauge neutral pressure measurement. Parametric (e.g. magnetic field, gas flow, and RF power) studies are presented. Data indicate ion heating to more than 1 eV and acceleration by the magnetic exhaust with the helicon alone. ICRF experiments are beginning and initial data are presented.

  6. Light Curve and Orbital Period Analysis of VX Lac

    Science.gov (United States)

    Yılmaz, M.; Nelson, R. H.; Şenavcı, H. V.; İzci, D.; Özavcı, İ.; Gümüş, D.

    2017-04-01

    In this study, we performed simultaneously light curve and radial velocity, and also period analyses of the eclipsing binary system VX Lac. Four color (BVRI) light curves of the system were analysed using the W-D code. The results imply that VX Lac is a classic Algol-type binary with a mass ratio of q=0.27, of which the less massive secondary component fills its Roche lobe. The orbital period behaviour of the system was analysed by assuming the light time effect (LITE) from a third body. The O-C analysis yielded a mass transfer rate of dM/dt=1.86×10-8Mȯyr-1 and the minimal mass of the third body to be M3=0.31Mȯ. The residuals from mass transfer and the third body were also analysed because another cyclic variation is seen in O-C diagram. This periodic variation was examined under the hypotheses of stellar magnetic activity and fourth body.

  7. The Global Auroral Imaging Access (GAIA) VxO Program

    Science.gov (United States)

    Spanswick, E.; Donovan, E.; Syrjaesuo, M.; Kauristie, K.; Mende, S.; Frey, H.; Germany, G.; Roberts, A.; Lummerzheim, D.; Marple, S.; Honary, F.; Weatherwax, A.; Moen, J.; Manuel, J.; Sandahl, I.

    2006-12-01

    The Global Auroral Imaging Access virtual observatory (herein GAIA-VxO) is being developed as a clearing house for data related to remote sensing of auroral precipitation. GAIA-VxO is a truly international program. Researchers in Finland, the UK, Canada, and the US have agreed to contribute work on different modules of the overall GAIA system. These include summary browsers, mirror sites, and a data distribution system. GAIA will stage summary and full-resolution data from satellite-borne and ground-based auroral imagers, as well as meridian scanning photometers, and imaging and single-beam riometers. GAIA will provide ready access to data from the THEMIS, NORSTAR, and MIRACLE ASIs, as well, numerous other programs. GAIA has at its heart a relational data base, and protocols for production of summary data (we currently have more than 7,000,000 summary images on our prototype web page http://gaia-vxo.org). In this talk, we present an overview of the GAIA concept and architecture. We discuss how GAIA will draw on the efforts of researchers from different countries, with different programmatic constraints and scientific and operational objectives. Finally, we provide some insights into how GAIA will form an integral part of the evolving Living With a Star Data Environment.

  8. The 2006-2007 Observing Campaign On VX Hydrae

    Science.gov (United States)

    Templeton, Matthew R.; Samolyk, G.; Dvorak, S.; Poklar, R.; Butterworth, N.; Gerner, H. S.

    2009-12-01

    We present the results of the 2006-2007 observing campaign on the double-mode delta Scuti star VX Hydrae. Nearly 8800 V-band CCD observations were obtained during the two observing seasons. Although the data were taken with small telescopes (0.3-m or less, using consumer-grade CCD cameras), the data quality is very high, enabling the detection of variability at the millimagnitude level at some frequencies. Analysis of the data yields only two primary pulsation frequencies: f(0) = 4.4765 c/d, and f(1) = 5.7899 c/d. The two modes have comparable amplitude, although the amplitude of f(1) appears to have increased slightly from 2006 to 2007 by 0.01 mag. Only two pulsation modes are detected, but at least 18 additional linear combination frequencies are also clearly detected, some having amplitudes as low as 1 mmag, resulting in an incredibly rich Fourier spectrum. We discuss the evidence for amplitude variation in VX Hydrae, along with prospects for future study of this and other similar delta Scuti stars by AAVSO observers.

  9. Use of a hand-portable gas chromatograph-toroidal ion trap mass spectrometer for self-chemical ionization identification of degradation products related to O-ethyl S-(2-diisopropylaminoethyl) methyl phosphonothiolate (VX).

    Science.gov (United States)

    Smith, Philip A; Lepage, Carmela R Jackson; Savage, Paul B; Bowerbank, Christopher R; Lee, Edgar D; Lukacs, Michael J

    2011-04-01

    The chemical warfare agent O-ethyl S-(2-diisopropylaminoethyl) methyl phosphonothiolate (VX) and many related degradation products produce poorly diagnostic electron ionization (EI) mass spectra by transmission quadrupole mass spectrometry. Thus, chemical ionization (CI) is often used for these analytes. In this work, pseudomolecular ([M+H](+)) ion formation from self-chemical ionization (self-CI) was examined for four VX degradation products containing the diisopropylamine functional group. A person-portable toroidal ion trap mass spectrometer with a gas chromatographic inlet was used with EI, and both fixed-duration and feedback-controlled ionization time. With feedback-controlled ionization, ion cooling (reaction) times and ion formation target values were varied. Evidence for protonation of analytes was observed under all conditions, except for the largest analyte, bis(diisopropylaminoethyl)disulfide which yielded [M+H](+) ions only with increased fixed ionization or ion cooling times. Analysis of triethylamine-d(15) provided evidence that [M+H](+) production was likely due to self-CI. Analysis of a degraded VX sample where lengthened ion storage and feedback-controlled ionization time were used resulted in detection of [M+H](+) ions for VX and several relevant degradation products. Dimer ions were also observed for two phosphonate compounds detected in this sample.

  10. Reevaluation of 1999 Health-Based Environmental Screening Levels (HBESLs) for Chemical Warfare Agents

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Annetta Paule [ORNL; Dolislager, Fredrick G [ORNL

    2007-05-01

    This report evaluates whether new information and updated scientific models require that changes be made to previously published health-based environmental soil screening levels (HBESLs) and associated environmental fate/breakdown information for chemical warfare agents (USACHPPM 1999). Specifically, the present evaluation describes and compares changes that have been made since 1999 to U.S. Environmental Protection Agency (EPA) risk assessment models, EPA exposure assumptions, as well as to specific chemical warfare agent parameters (e.g., toxicity values). Comparison was made between screening value estimates recalculated with current assumptions and earlier health-based environmental screening levels presented in 1999. The chemical warfare agents evaluated include the G-series and VX nerve agents and the vesicants sulfur mustard (agent HD) and Lewisite (agent L). In addition, key degradation products of these agents were also evaluated. Study findings indicate that the combined effect of updates and/or changes to EPA risk models, EPA default exposure parameters, and certain chemical warfare agent toxicity criteria does not result in significant alteration to the USACHPPM (1999) health-based environmental screening level estimates for the G-series and VX nerve agents or the vesicant agents HD and L. Given that EPA's final position on separate Tier 1 screening levels for indoor and outdoor worker screening assessments has not yet been released as of May 2007, the study authors find that the 1999 screening level estimates (see Table ES.1) are still appropriate and protective for screening residential as well as nonresidential sites. As such, risk management decisions made on the basis of USACHPPM (1999) recommendations do not require reconsideration. While the 1999 HBESL values are appropriate for continued use as general screening criteria, the updated '2007' estimates (presented below) that follow the new EPA protocols currently under development

  11. Reactivity of Dual-Use Decontaminants with Chemical Warfare Agents

    Science.gov (United States)

    2016-07-01

    decrease the logistical burden associated with transport and storage of decontaminants. The experiments in this study were focused on evaluating...propanediammonium dichloride, isopropanol, inert ingredients/water, hydrogen peroxide, diacetin Decontaminant formulated for chemical warfare agents F...potassium bisulfate, potassium sulfate, dipotassium peroxodisulfate, magnesium carbonate Acidic oxidative chemistry, used for VX laboratory waste

  12. Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; En-Hua Xiao; Jian-Bin Liu; Zhong He; Ke Jin; Cong Ma; Jun Xiang; Jian-Hua Xiao; Wei-Jian Chen

    2008-01-01

    AIM: To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC)on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. METHODS: Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and StTept Avidin-Biotin Complex (SABC)immunohistochemical staining. RESULTS" The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P<0. 001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P<0. 001). PCNA and nm23 expression in the VX-2 tumor periphery first increased and then decreased (P<0. 001 and P=0. 03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm2, there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P<0. 001), and PCNA expression in VX-2 tumor periphery influenced the ADC. CONCLUSION: The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

  13. Analysis of Patent Databases Using VxInsight

    Energy Technology Data Exchange (ETDEWEB)

    BOYACK,KEVIN W.; WYLIE,BRIAN N.; DAVIDSON,GEORGE S.; JOHNSON,DAVID K.

    2000-12-12

    We present the application of a new knowledge visualization tool, VxInsight, to the mapping and analysis of patent databases. Patent data are mined and placed in a database, relationships between the patents are identified, primarily using the citation and classification structures, then the patents are clustered using a proprietary force-directed placement algorithm. Related patents cluster together to produce a 3-D landscape view of the tens of thousands of patents. The user can navigate the landscape by zooming into or out of regions of interest. Querying the underlying database places a colored marker on each patent matching the query. Automatically generated labels, showing landscape content, update continually upon zooming. Optionally, citation links between patents may be shown on the landscape. The combination of these features enables powerful analyses of patent databases.

  14. An in vitro and in vivo Evaluation of the Efficacy of Recombinant Human Liver Prolidase as a Catalytic Bioscavenger of Chemical Warfare Nerve Agents

    Science.gov (United States)

    2015-01-01

    preparation used in the previous study (Costante et al., 2012) was 70 to 80% pure and its gel image was not shown. In vivo protection offered by rhProlidase... monkeys . Chem Biol Interact 157–158:205–210. Lenz DE, Yeung D, Smith JR, et al. (2007). Stoichiometric and catalytic scavengers as protection against nerve...rhesus monkeys against soman toxicity. Toxicol Appl Pharmacol 117:189–193. Yokoyama K, Araki S, Murata K, et al. (1998). Chronic neurobehavioral and

  15. Measuring the Distance of VX Sagittarii with SiO Maser Proper Motions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We report on 43 GHz v=1, J=1-0 SiO maser proper motions in the circumstellar envelope of the M-type semi-regular variable star VX Sgr, observed by Very Long Baseline Array (VLBA) at 3 epochs during 1999 April-May. Applying the statistical parallax analysis to these proper motions, we estimated a distance of VX Sgr of 1.57±0.27 kpc, which is consistent with that based on the proper motions of H2O masers, or on the assumption that VX Sgr belongs to the Sgr OB1 association. At this distance, VX Sgr can be classified as a red supergiant. Comparing the statistical parallax method with those of model fitting and annual parallax, we think that the statistical parallax method may be a good way of estimating SiO maser distances at present.

  16. VX-8GR 双波段手持收发信机

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    YaeSUVX-8R手持收发信机包含了四个频段——50、144、222和440MHz——并提供了GPS接收机和蓝牙耳机的功能。现在,VX-8R已经被VX-8DR这款功能更强大的四波段收发信机所取代,我们今天要对这一产品线中的新成员,VX-8GR(以下简称8GR)进行评测。VX-8GR是一台双波段(144/440MHZ)收发信机,具有宽频率范围的接受能力和5W的发射功率。

  17. Measuring the Distance of VX Sagittarii with SiO Maser Proper Motions

    Science.gov (United States)

    Chen, Xi; Shen, Zhi-Qiang; Xu, Ye

    2007-08-01

    We report on 43 GHz v=1, J=1--0 SiO maser proper motions in the circumstellar envelope of the M-type semi-regular variable star VX Sgr, observed by Very Long Baseline Array (VLBA) at 3 epochs during 1999 April--May. Applying the statistical parallax analysis to these proper motions, we estimated a distance of VX Sgr of 1.57±0.27 kpc, which is consistent with that based on the proper motions of H2O masers, or on the assumption that VX Sgr belongs to the Sgr OB1 association. At this distance, VX Sgr can be classified as a red supergiant. Comparing the statistical parallax method with those of model fitting and annual parallax, we think that the statistical parallax method may be a good way of estimating SiO maser distances at present.

  18. A poloidal field control system based on VxWorks in HT-7 Tokamak

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; LUO Jia-Rong; WANG Hua-Zhong

    2004-01-01

    The PF (Poloidal Field) control system is one of the most important control systems in HT-7 Tokamak.Most of parameters such as plasma current, plasma horizontal position and plasma vertical position will be monitored.For the purpose of long-pulse discharge and the more precise control to plasma, the real-time operation system VxWorks is applied, instead of the behindhand and unbefitting DOS operation system. This paper describes the development process of HT-7 PF control system based on VxWorks on Intel X86 platforms. The method of using hardware cards in VxWorks, and the network communication with other operation systems are discussed especially. Results of the comparison between VxWorks and DOS operation systems are given too.

  19. Assessment of hepatic VX2 tumors of rabbits with second harmonic imaging under high and low acoustic pressures

    Institute of Scientific and Technical Information of China (English)

    Wen-Hua Du; Wei-Xiao Yang; Xiang Wang; Xiu-Qin Xiong; Yi Zhou; Tao Li

    2003-01-01

    AIM: To investigate the possible clinical application value of second harmonic imaging under low acoustic pressure.METHODS: Six New Zealand rabbits, averaging 2.7±0.4kg, were selected and operated upon to construct hepatic VX2 tumor carrier model. Hepatic VX2 tumors were imaged with B mode Ultrasonography (US), and second harmonic imaging (SHI) under high mechanic index (1.6) and low mechanic index (0.1). Echo agent was intravenously injected through ear vein at a dose of 0.01 mL/kg under B mode US and high MI SHI, and 0.05 mL/kg under low MI SHI, and then the venous channel was cleaned with sterilized saline.All the images were recorded by magnetic optics (MO),and they were analyzed further by at least two independent experienced sonographers.RESULTS: Totally 6 hypoechoic and 3 hyperechoic lesions were found in the six carrier rabbits with a mean size about 2.1±0.4 under B mode ultrasound, they were oval or round in shape with a clear outline or a hypoechoic halo at the margin of the lesions. Contrast agent could not change the echogenicity of the lesions under B mode US and SHI under high acoustic pressure. However, it could greatly increase the real time visualization sensitivity of the lesions with SHI under low acoustic pressure.CONCLUSION: Our results suggest that contrast enhanced SHI with low MI and a bubble non-destructive method would be much more helpful than conventional SHI in our future clinical applications.

  20. Molecular modeling and residue interaction network studies on the mechanism of binding and resistance of the HCV NS5B polymerase mutants to VX-222 and ANA598.

    Science.gov (United States)

    Xue, Weiwei; Jiao, Pingzu; Liu, Huanxiang; Yao, Xiaojun

    2014-04-01

    Hepatitis C virus (HCV) NS5B protein is an RNA-dependent RNA polymerase (RdRp) with essential functions in viral genome replication and represents a promising therapeutic target to develop direct-acting antivirals (DAAs). Multiple nonnucleoside inhibitors (NNIs) binding sites have been identified within the polymerase. VX-222 and ANA598 are two NNIs targeting thumb II site and palm I site of HCV NS5B polymerase, respectively. These two molecules have been shown to be very effective in phase II clinical trials. However, the emergence of resistant HCV replicon variants (L419M, M423T, I482L mutants to VX-222 and M414T, M414L, G554D mutants to ANA598) has significantly decreased their efficacy. To elucidate the molecular mechanism about how these mutations influenced the drug binding mode and decreased drug efficacy, we studied the binding modes of VX-222 and ANA598 to wild-type and mutant polymerase by molecular modeling approach. Molecular dynamics (MD) simulations results combined with binding free energy calculations indicated that the mutations significantly altered the binding free energy and the interaction for the drugs to polymerase. The further per-residue binding free energy decomposition analysis revealed that the mutations decreased the interactions with several key residues, such as L419, M423, L474, S476, I482, L497, for VX-222 and L384, N411, M414, Y415, Q446, S556, G557 for ANA598. These were the major origins for the resistance to these two drugs. In addition, by analyzing the residue interaction network (RIN) of the complexes between the drugs with wild-type and the mutant polymerase, we found that the mutation residues in the networks involved in the drug resistance possessed a relatively lower size of topology centralities. The shift of betweenness and closeness values of binding site residues in the mutant polymerase is relevant to the mechanism of drug resistance of VX-222 and ANA598. These results can provide an atomic-level understanding about

  1. Supporting Real-Time Computer Vision Workloads using OpenVX on Multicore+GPU Platforms

    Science.gov (United States)

    2015-05-01

    workloads specified using OpenVX to be supported in a predictable way. I. INTRODUCTION In the automotive industry today, vision-based sensing through cameras...Supporting Real-Time Computer Vision Workloads using OpenVX on Multicore+GPU Platforms Glenn A. Elliott, Kecheng Yang, and James H. Anderson...Department of Computer Science, University of North Carolina at Chapel Hill Abstract—In the automotive industry, there is currently great interest in

  2. Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle.

    Science.gov (United States)

    Jih, Kang-Yang; Hwang, Tzyh-Chang

    2013-03-12

    Vx-770 (Ivacaftor), a Food and Drug Administration (FDA)-approved drug for clinical application to patients with cystic fibrosis (CF), shifts the paradigm from conventional symptomatic treatments to therapeutics directly tackling the root of the disease: functional defects of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel caused by pathogenic mutations. The underlying mechanism for the action of Vx-770 remains elusive partly because this compound not only increases the activity of wild-type (WT) channels whose gating is primarily controlled by ATP binding/hydrolysis, but also improves the function of G551D-CFTR, a disease-associated mutation that abolishes CFTR's responsiveness to ATP. Here we provide a unified theory to account for this dual effect of Vx-770. We found that Vx-770 enhances spontaneous, ATP-independent activity of WT-CFTR to a similar magnitude as its effects on G551D channels, a result essentially explaining Vx-770's effect on G551D-CFTR. Furthermore, Vx-770 increases the open time of WT-CFTR in an [ATP]-dependent manner. This distinct kinetic effect is accountable with a newly proposed CFTR gating model depicting an [ATP]-dependent "reentry" mechanism that allows CFTR shuffling among different open states by undergoing multiple rounds of ATP hydrolysis. We further examined the effect of Vx-770 on R352C-CFTR, a unique mutant that allows direct observation of hydrolysis-triggered gating events. Our data corroborate that Vx-770 increases the open time of WT-CFTR by stabilizing a posthydrolytic open state and thereby fosters decoupling between the gating cycle and ATP hydrolysis cycle. The current study also suggests that this unique mechanism of drug action can be further exploited to develop strategies that enhance the function of CFTR.

  3. 基于VxWorks的人机界面图形开发系统设计%Design of Human-Machine Interface Library Based on VxWorks

    Institute of Scientific and Technical Information of China (English)

    刘东涛; 肖峰

    2011-01-01

    针对当前嵌入式实时系统VxWorks图形界面开发支持较弱的缺点,结合海军多功能标准台项目,分析了VxWorks实时操作系统下国内外主流图形开发系统的设计原理,采用了基于控件技术的层次化设计和面向对象的设计方法,实现了一种在VxWorks实时操作系统下具有自主知识产权的人机界面图形开发系统JARI EGK.通过多个项目中的应用验证,JARI EGK在功能和性能方面能够满足基于VxWorks实时系统的窗口图形界面开发要求.%According to the disadvantages of graphics interface design under the real-time embedded operation systems VxWorks, and combining with the Multifunction Console projects, this paper analyzes the design principle of graphical user interface library at home and abroad, and adopts the architecture of hierarchical design and object-oriented programming. One kind of graphical user interface library(JARI_EGK) which possesses independent intellectual property rights is realized and used successfully. Through applied to many projects, JARI_EGK is proved to satisfy the requirement of developing graphical interfaces based on Vx Works real-time system.

  4. 基于VxWorks的多页面程序框架设计%The design of multipage graphical interfaces frame based on VxWorks

    Institute of Scientific and Technical Information of China (English)

    韩邦杰; 刘桢; 袁志毅

    2012-01-01

    In the development of embedded systems, we need some user friendly interfaces to carry out some man machine conversation operations. This paper introduces a design of multipage graphical interfaces frame based on VxWorks. Operating system of VxWorks and its multimedia library (WindML) are introduced briefly, and some key points of the development of graphical interfaces frame are discussed particularly. We also bring forward a way of the design of multipage graphical frame interfaces. Our design takes advantage of multitasking environment of VxWorks and plenty of API functions of WindML. The design is very available and significative in practice.%在嵌入式应用开发过程中,有时需要友好的用户界面来完成一些人机互动操作.本文介绍在VxWorks操作系统下的多页面图形界面程序框架的设计,对VxWorks操作系统和其自带的多媒体库(WindML)做了简要介绍,重点讨论了图形界面开发过程中的关键问题,提出了多页面图形界面程序框架的设计方法.本设计充分利用VxWorks操作系统处理多任务能力强的优势以及WindML提供的丰富API函数,在实际中有一定的应用价值和参考意义.

  5. Memory Allocation Algorithm based on VxWorks%一种基于VxWorks的内存分配算法

    Institute of Scientific and Technical Information of China (English)

    朱筱菲; 黄凤岗

    2006-01-01

    研究了VxWorks系统内存分配算法,指出了常用内存管理算法的局限性,在此基础上,提出了一种改进的内存分配算法.改进的内存分配算法包括优化的内存块分配算法和快速高效的动态内存分配算法,两者结合使用将会有效提高嵌入式系统的性能.对改进内存算法的实现作了详细的介绍.

  6. Decontamination of Chemical/Biological Warfare (CBW) Agents Using an Atmospheric Pressure Plasma Jet (APPJ)

    Science.gov (United States)

    Herrmann, Hans W.

    1998-11-01

    The atmospheric pressure plasma jet (APPJ) is a non-thermal, high pressure, uniform glow discharge that produces a high velocity effluent stream of highly reactive chemical species. The discharge operates on a feedstock gas (e.g. He/O_2/H_2O) which flows between an outer, grounded, cylindrical electrode and an inner, coaxial electrode powered at 13.56 MHz RF. While passing through the plasma, the feedgas becomes excited, dissociated or ionized by electron impact. Once the gas exits the discharge volume, ions and electrons are rapidly lost by recombination, but the fast-flowing effluent still contains metastables (e.g. O2*, He*) and radicals (e.g. O, OH). These reactive species have been shown to be effective neutralizers of surrogates for anthrax spores, mustard blister agent and VX nerve gas. Unlike conventional, wet decontamination methods, the plasma effluent does not cause corrosion of most surfaces and does not damage wiring, electronics, nor most plastics. This makes it highly suitable for decontamination of high value sensitive equipment such as is found in vehicle interiors (i.e. tanks, planes...) for which there is currently no good decontamination technique. Furthermore, the reactive species rapidly degrade into harmless products leaving no lingering residue or harmful byproducts. Physics of the APPJ will be discussed and results of surface decontamination experiments using simulant and actual CBW agents will be presented.

  7. Galantamine is a novel post-exposure therapeutic against lethal VX challenge.

    Science.gov (United States)

    Hilmas, Corey J; Poole, Melissa J; Finneran, Kathryn; Clark, Matthew G; Williams, Patrick T

    2009-10-15

    The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 microg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).

  8. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias.

    Science.gov (United States)

    Fei, Fei; Stoddart, Sonia; Groffen, John; Heisterkamp, Nora

    2010-05-01

    The emergence of resistance to tyrosine kinase inhibitors due to point mutations in Bcr/Abl is a challenging problem for Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) patients, especially for those with the T315I mutation, against which neither nilotinib or dasatinib shows significant activity. VX-680 is a pan-Aurora kinase inhibitor active against all Bcr/Abl proteins but has not been extensively examined in preclinical models of Ph-positive ALL. Here, we have tested VX-680 for the treatment of Bcr/Abl-positive ALL when leukemic cells are protected by the presence of stroma. Under these conditions, VX-680 showed significant effects on primary human Ph-positive ALL cells both with and without the T315I mutation, including ablation of tyrosine phosphorylation downstream of Bcr/Abl, decreased viability, and induction of apoptosis. However, drug treatment of human Ph-positive ALL cells for 3 days followed by drug removal allowed the outgrowth of abnormal cells 21 days later, and on culture of mouse Bcr/Abl ALL cells on stroma with lower concentrations of VX-680, drug-resistant cells emerged. Combined treatment of human ALL cells lacking the T315I mutation with both VX-680 and dasatinib caused significantly more cytotoxicity than each drug alone. We suggest that use of VX-680 together with a second effective drug as first-line treatment for Ph-positive ALL is likely to be safer and more useful than second-line treatment with VX-680 as monotherapy for drug-resistant T315I Ph-positive ALL.

  9. Experimental Therapeutics Against the Toxic and Lethal Effects Resulting from Acute Exposure to Nerve Agents Without Carbamate Pretreatment in Guinea Pigs

    Science.gov (United States)

    2010-09-01

    The "Bradypnea" stage was generally preceded by episodes of ataxic or dyspneic breathing. Seizures and convulsions typically continued during...acute agent exposure. These included oro-facial movements (indicative of immoderate secretion), mild degree of dystonia/ ataxia , and a short period of...periods of acute cholinergic effects (mucoid-salivary secretion, dystonia, ataxia , tremors and fasciculations) were seen shortly after intoxication

  10. SNMP在嵌入式操作系统(VxWorks)中的实现%SNMP's Realization in Embedded Operating System (VxWorks)

    Institute of Scientific and Technical Information of China (English)

    金松; 郭兴旺

    2004-01-01

    简要分析了UCD-SNMP协议栈源码,并在此基础上介绍了SNMP简单网络管理协议在嵌入式操作系统的(VxWorks)的实现,从而提出了在各种嵌入式操作系统实现SNMP的方法.

  11. VxWorks下实时多任务程序的实现%Real-Time Multitasking Program realization based on VxWorks

    Institute of Scientific and Technical Information of China (English)

    李洪亮; 侯朝桢; 周绍生

    2008-01-01

    本文介绍了Vxworks操作系统的技术特点,给出了一种VxWorks操作系统下实现实时多任务程序的一种方法,并利用软件逻辑分析仪WindView对程序运行结果进行了分析.

  12. Vascularity of hepatic VX2 tumors of rabbits: Assessment with conventional power Doppler US and contrast enhanced harmonic power Doppler US

    Institute of Scientific and Technical Information of China (English)

    Wen-Hua Du; Wei-Xiao Yang; Xiang Wang; Xiu-Qin Xiong; Yi Zhou; Tao Li

    2003-01-01

    AIM: To investigate the characteristics of the vascularity ofhepatic metastasis.METHODS: Six New Zealand rabbits, weighing averagely2.7±0.4 kg, were selected and operated to establish hepaticVX2 tumor carrier model. Hepatic VX2 tumors were thenimaged with conventional B mode US, second harmonicimaging (SHI), color Doppler flow imaging (CDFI), powerDoppler imaging (PDI) and harmonic PDI by a transducerS8 connected to HP-5 500 ultrasound system. A kind of selfmade echo contrast agent was intravenously injected at adose of 0.01 mL/kg through ear vein, and then the venouspassage was cleaned with sterilized saline.RESULTS: Totally, 6 hypoechoic lesions and 3 hyperechoiclesions were found in the six carrier rabbits with a mean sizeabout 2.1±0.4 cm under conventional B mode ultrasound, theywere oval or round in shape with a dear outline or a hypoechoichalo at the margin of the lesions. Contrast agent could notchange the echogenicity of the lesions under conventional Bmode and SHI, however, it could greatly increase the flowsensitivity of the lesions under PDI and harmonic PDI. Nutrientartery of these metastatic lesions might also be well depictedunder contrast enhanced PDI and harmonic PDI.CONCLUSION: Our result suggested that contrast enhancedPDI, especially harmonic PDI, was a promised method inthe detection of vascularity of hepatic tumor nodules.

  13. Ge{sup 4+} doped TiO{sub 2} for stoichiometric degradation of warfare agents

    Energy Technology Data Exchange (ETDEWEB)

    Stengl, Vaclav, E-mail: stengl@iic.cas.cz [Department of Solid State Chemistry, Institute of Inorganic Chemistry AS CR v.v.i., 250 68 Rez (Czech Republic); Grygar, Tomas Matys [Department of Solid State Chemistry, Institute of Inorganic Chemistry AS CR v.v.i., 250 68 Rez (Czech Republic); Oplustil, Frantisek; Nemec, Tomas [Military Technical Institute of Protection Brno, Veslarska 230, 628 00 Brno (Czech Republic)

    2012-08-15

    Highlights: Black-Right-Pointing-Pointer We prepared nanodisperse Ge{sup 4+} doped titania by a novel synthesis method. Black-Right-Pointing-Pointer Synthesis does not involve organic solvents, organometallics nor thermal processes. Black-Right-Pointing-Pointer The prepared materials are efficient in removal of chemical warfare agents. Black-Right-Pointing-Pointer Ge{sup 4+} doping improves rate of removal of soman and agent VX by TiO{sub 2}. - Abstract: Germanium doped TiO{sub 2} was prepared by homogeneous hydrolysis of aqueous solutions of GeCl{sub 4} and TiOSO{sub 4} with urea. The synthesized samples were characterized by X-ray diffraction, scanning electron microscopy, EDS analysis, specific surface area (BET) and porosity determination (BJH). Ge{sup 4+} doping increases surface area and content of amorphous phase in prepared samples. These oxides were used in an experimental evaluation of their reactivity with chemical warfare agent, sulphur mustard, soman and agent VX. Ge{sup 4+} doping worsens sulphur mustard degradation and improves soman and agent VX degradation. The best degree of removal (degradation), 100% of soman, 99% of agent VX and 95% of sulphur mustard, is achieved with sample with 2 wt.% of germanium.

  14. Ulnar nerve dysfunction

    Science.gov (United States)

    Neuropathy - ulnar nerve; Ulnar nerve palsy; Mononeuropathy; Cubital tunnel syndrome ... neuropathy occurs when there is damage to the ulnar nerve. This ... syndrome may result. When damage destroys the nerve covering ( ...

  15. Cutaneous nerve entrapment syndrome

    Institute of Scientific and Technical Information of China (English)

    DongFuhui

    2004-01-01

    The cutaneous nerve entrapment syndrome is named that, the cutaneous nerve's functional disorder caused by some chronic entrapment, moreover appears a series of nerve's feeling obstacle,vegetative nerve function obstacle, nutrition obstacle, even motor function obstacle in various degree.

  16. Nerve biopsy (image)

    Science.gov (United States)

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  17. Vagus Nerve Stimulation

    Science.gov (United States)

    Vagus nerve stimulation Overview By Mayo Clinic Staff Vagus nerve stimulation is a procedure that involves implantation of a device that stimulates the vagus nerve with electrical impulses. There's one vagus nerve on ...

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

    Science.gov (United States)

    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.

  19. Yaesu VX-7R手持收发信机

    Institute of Scientific and Technical Information of China (English)

    王冉宁(编译)

    2013-01-01

    YAESU的新款对讲机VX-7R,外观看起来与前身VX-5R非常相似。此款机器曾在《OST》杂志1999年5月刊上被杰伊·梅比(NUOX)评测。VX-7R比VX-5R更长更宽,但它们的区别不是很明显,这就需要你仔细地给它来个初次检验。尽管如此,我第一次打开包装看到新的对讲机时,发现一些足够微妙的变化,这激起发了我对它的探索。VX-5R的使用者不会花费很长时间注意到它的提高。

  20. High Power Electric Propulsion Using The VASIMR VX-200: A Flight Technology Prototype

    Science.gov (United States)

    Bering, Edgar, III; Longmier, Benjamin; Glover, Tim; Chang-Diaz, Franklin; Squire, Jared; Brukardt, Michael

    2008-11-01

    The Variable Specific Impulse Magnetoplasma Rocket (VASIMR) is a high power magnetoplasma rocket, capable of Isp/thrust modulation at constant power. The plasma is produced by a helicon discharge. The bulk of the energy is added by ion cyclotron resonance heating (ICRH.) Axial momentum is obtained by adiabatic expansion of the plasma in a magnetic nozzle. Thrust/specific impulse ratio control in the VASIMR is primarily achieved by the partitioning of the RF power to the helicon and ICRH systems, with the proper adjustment of the propellant flow. Ion dynamics in the exhaust were studied using probes, gridded energy analyzers (RPA's), microwave interferometry and optical techniques. Results are summarize from high power ICRH experiments performed on the VX-100 using argon plasma during 2007, and on the VX-200 using argon plasma during 2008. The VX-100 has demonstrated ICRH antenna efficiency >90% and a total coupling efficiency of ˜75%. The rocket performance parameters inferred by integrating the moments of the ion energy distribution corresponds to a thrust of 2 N at an exhaust velocity of 20 km/s with the VX-100 device. The new VX-200 machine is described.

  1. Treatability study report for remediation of chemical warfare agent contaminated soils using peroxysulfate ex-situ treatment. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Pugh, J.R.; Grinstead, J.H.; Farley, J.A.; Enlow, P.D.; Kelly, D.A.

    1996-07-01

    This laboratory scale study examines the feasibility of using peroxysulfate based oxidants to remediate soils contaminated with GB, Hi, and VX. The project was conducted with chemical warfare agent simulants. The study concludes that peroxysulfates, and particularly peroxydisulfate, can degrade chemical warfare agent simulants in soil and recommends continuing research.

  2. 基于Pentium处理器VxWorks实时操作系统BSP的设计

    Institute of Scientific and Technical Information of China (English)

    张勇

    2016-01-01

    针对Pentium处理器目标机上VxWorks操作系统的研发,BSP和设备驱动程序的设计是一个关键环节和难点。文章对BSP和驱动程序设计中的理论和关键技术进行了分析研究,应用风河公司开发的Tornado集成开发环境,设计了VxWorks下的BSP。在此基础上,开发完成基于VxWorks和Pentium处理器的通用开发平台。

  3. 细说VX-8R之蓝牙应用

    Institute of Scientific and Technical Information of China (English)

    杨法

    2009-01-01

    @@ YAESU新款上市的VX-8R提供了蓝牙传输和APRS GPS传输的新特性,本文就VX-8R的蓝牙音频应用进行比较详细的介绍. VX-8R是业余电台界第一部具备内置蓝牙功能的手持式对讲机.蓝牙音频传输功能在移动电话上早已被广泛应用,由于其通过无线电波传输的方式使得耳机摆脱传统传输线的困扰而广受前卫用户的喜爱.

  4. Acute Toxicity and Efficacy of Current Medical Countermeasures against VM in Guinea Pigs: A Comparison to VX and VR

    Science.gov (United States)

    2013-05-01

    O, Skopec F, and Bajgar J. (1996) Toxicities of o- alkyl s-(2-dialkylaminoethyl) methyl phosphonothiolates (V-compounds). Acta. Medica (Hradec...specificity of organophosphorus nerve agents. Chem-Bio. Interact . 157-158: 293-303. 8. Maxwell DM, Brecht KM, and Koplovitz I (1997

  5. Evaluation of RSDL, M291 SDK, 0.5% Bleach, 1% Soapy Water and SERPACWA. Part 1: Challenge with VX

    Science.gov (United States)

    2009-06-01

    destroyed, U.S. soldiers became exposed to nerve agents. It has been suggested that this exposure may have contributed to the Gulf War Syndrome ... Clipper System (Hazard Technology, Millersville, MD 21108) using Oster Brand clippers (model: Golden A5) with a number 40 CryogenX blade. Animals were

  6. Median Lethal Doses Associated with Intravenous Exposure to the Optically Pure Enantiomers of VX in Guinea Pigs

    Science.gov (United States)

    2017-03-01

    number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD- MM -YYYY) XX-03-2017 2. REPORT TYPE Final 3. DATES COVERED (From...Biperiden and Atropine as Anticonvulsant Treatment for Organophosphorus Nerve Agent Intoxication. Arch. Toxicol. 2000, 74, 165–172. 8 van der

  7. The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure.

    Science.gov (United States)

    Joosen, M J A; van den Berg, R M; de Jong, A L; van der Schans, M J; Noort, D; Langenberg, J P

    2017-04-01

    The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first phase the effect of various decontamination regimens on levels of free VX in skin and plasma were studied as well as on blood cholinesterase levels. Animals were exposed to 0.5 mg/kg VX and were not decontaminated (control), decontaminated with RSDL once at 15 or 90 min after exposure or three times at 15, 25 and 35 (10-min interval) or 15, 45 and 75 min after exposure (30-min interval). There was no significant effect of any of the decontamination regimens on the 6-h survival rate of the animals. However, all animals that had been decontaminated 15 min after exposure, showed a survival rate of more than 90%, compared to 50-60% in animals that were not decontaminated or decontaminated at 90 min after exposure. In the second phase of the study, hairless guinea pigs were exposed to 1 mg/kg VX on the shoulder, followed either by decontamination with RSDL (10 min interval), conventional treatment on indication of clinical signs or a combination thereof. It appeared that a thorough, repeated decontamination alone could not save the majority of the animals. A 100% survival rate was observed in the group that received a combination of decontamination and treatment. In conclusion, the effects of VX exposure could be influenced by various RSDL decontamination regimens. The results in freely moving animals showed that skin decontamination, although not fully effective in removing all VX from the skin and skin depot is crucial to support pharmacological intervention.

  8. In vitro evaluation of Aurora kinase inhibitor—VX680—in formulation of PLA-TPGS nanoparticles

    Science.gov (United States)

    Thuy Duong Le, Thi; Thu Ha, Phuong; Hai Yen Tran, Thi; Nguyen, Dac Tu; Nguyen, Hoai Nam; Khanh Bui, Van; Nhung Hoang, My

    2016-06-01

    Polymeric nanoparticles prepared from poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) were used as potential drug carries with many advantages to overcome the disadvantages of insoluble anticancer drugs and enhance blood circulation time and tissues. VX680 is an Aurora kinase inhibitor and is also the foremost Aurora kinase inhibitor to be studied in clinical trials. In this study, we aimed to investigate whether VX680-loaded PLA-TPGS nanoparticles (VX680-NPs) are able to effectively increase the toxicity of chemotherapy. Accordingly, we first synthesized VX680-loaded nanoparticles and NP characterizations of morphology, mean size, zeta potential, and encapsulation efficiency were spherical shape, 63 nm, -30 mV and 76%, respectively. Then, we investigated the effects on HeLa cells. The cell cytotoxicity was evaluated by the xCELLigence real-time cell analyzer allowing measurement of changes in electrical impedance on the surface of the E-plate. Analysis of nucleus morphology and level of histone H3 phosphorylation was observed by confocal fluorescence scanning microscopy. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Our results showed that VX680-NPs reduced cell viability with IC50 value lower 3.4 times compared to free VX680. Cell proliferation was inhibited by VX680-NPs accompanied by other effects such as high abnormal changes of nucleus, a decrease of phospho-histone H3 at Ser10 level, an increase of polyploid cells and resulted in higher apoptotic cells. These results demonstrated that VX680-NPs had more cytotoxicity than as treated with VX680 alone. Thus, VX680-NPs may be considered as promising drug delivery system for cancer treatment.

  9. Fate of chemical warfare agents and toxic industrial chemicals in landfills.

    Science.gov (United States)

    Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

    2006-07-01

    One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

  10. 优派首款曲面显示器VX3271-scw上市

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    优派(View Sonic)推出旗下首款曲面显示器VX3271-SCW。VX3271-SCW,曲率达到3000R.是目前已上市曲面显示最大曲率.采用全新符合人体工程学的曲面设计,更贴合人眼生理曲线构造,缓解观看者的眼部疲劳。

  11. 精品系列系列精品ONDA昂达VX818

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    在昂达的系列产品线中,8系向来是他们主打的精品系列,最近推出的VX818更是一款实在的精品。昂达VX818的外观非常简洁,采用成熟稳重的黑色为主色调,表面光滑继腻,手感良好。

  12. Preliminary Effects of Real-World Factors on the Recovery and Exploitation of Forensic Impurity Profiles of a Nerve-Agent Simulant from Office Media

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Decomposition kinetics of dimethyl methylphospate(chemical agent simulant) by supercritical water oxidation

    Institute of Scientific and Technical Information of China (English)

    Bambang VERIANSYAH; Jae-Duck KIM; Youn-Woo LEE

    2006-01-01

    Supercritical water oxidation (SCWO) has been drawing much attention due to effectively destroy a large variety of high-risk wastes resulting from munitions demilitarization and complex industrial chemical. An important design consideration in the development of supercritical water oxidation is the information of decomposition rate. In this paper, the decomposition rate of dimethyl methylphosphonate(DMMP), which is similar to the nerve agent VX and GB(Sarin) in its structure, was investigated under SCWO conditions. The experiments were performed in an isothermal tubular reactor with a H2O2 as an oxidant. The reaction temperatures were ranged from 398 to 633 ℃ at a fixed pressure of 24 MPa. The conversion of DMMP was monitored by analyzing total organic carbon (TOC) on the liquid effluent samples. It is found that the oxidative decomposition of DMMP proceeded rapidly and a high TOC decomposition up to 99.99% was obtained within 11 s at 555℃. On the basis of data derived from experiments, a global kinetic equation for the decomposition of DMMP was developed. The model predictions agreed well with the experimental data.

  14. 基于VxWorks系统的路由器固件研究%Study of router firmware based on VxWorks system

    Institute of Scientific and Technical Information of China (English)

    丛培欣

    2016-01-01

    This paper analyzed the characteristics of MemFS file system based on VxWorks system of router firmware,by using binwalk software tools of Kali Linux system and procedures written by myself,and the corresponding router firmware files are extracted.Provide ideas and technical support for the subsequent router firmware rewriting.%本文通过kali linux系统的binwalk软件工具及自行编写程序,识别并分析了基于VxWorks的MemFS文件系统的路由器固件的文件特征,同时提取了相应路由器的固件文件.为后续路由器固件重写提供思路及技术支持.

  15. 基于VxWorks实现自动发送彩信嵌入式设计%Embedded automatic MMS sender with VxWorks

    Institute of Scientific and Technical Information of China (English)

    韩正伟; 裴昌幸; 朱畅华; 林成保

    2005-01-01

    在ARM微处理器硬件平台上,应用WindRiver公司的Tornado集成开发环境,实现基于VxWorks的自动发送彩信的嵌入式应用系统。该系统使用现有CDMA网络,根据设定的参数发送彩信到特定的移动终端用户。

  16. Application research of vehicle management system based on VxWorks%VxWorks在飞行器管理系统中的应用研究

    Institute of Scientific and Technical Information of China (English)

    汤小明; 李引娟; 程农

    2011-01-01

    提出了一种操作系统分级调度模型,该模型能够将多个传统子系统综合到一个应用平台中,并能保证各子系统在时间上相互独立.结合实时操作系统VxWorks,论述了该模型的最佳实践方法辅助时钟法,并对VxWorks的启动、存储管理,中断与异常管理等进行了详细论述.采用该模型在飞行器管理系统中将飞行控制系统、导航系统、数传模块以及任务管理系统等传统的子系统进行了综合,并给出了在某系统中的具体应用和性能评估,实验结果表明了该系统具有高性能、增量开发与部署的能力.%A hierarchical scheduling model of operating system is proposed, which make a number of traditional subsystems integrated to one application platform and isolated in temporal domain. Based on the real-time operating system VxWorks, the best practical method,the auxiliary clock scheduling algorithm is provided. The start-up, memory management, interrupt and exception management in VxWorks is depicted as well. And then the flight control system, navigation system, data transmission system and mission management system are integrated into one platform of vehicle management system by this hierarchical scheduling model. In the end, the performance evaluation is conducted, which indicates this project has features of high performance, incremental development and deployment.

  17. Prolonged Inhibition of Motor Activity Following Repeated Exposure to Low Levels of Chemical Warfare Agent VX

    Science.gov (United States)

    2005-10-01

    Anxious mice tend to avoid the brightly lit center of the maze, and display thigmotaxis (wall following), in which they closely walk along the...analysis of the mouse open field test: effects of diazepam , chlordiazepoxide and an extremely low frequency pulsed magnetic field, Neurosci Biobehav

  18. Establishing VxWorks TrueFFS File System with NOR Flash%用NOR Flash建立VxWorks TrueFFS文件系统

    Institute of Scientific and Technical Information of China (English)

    邵富杰; 徐云宽

    2012-01-01

    This paper describes the method to establish the TrueFFS file system of embedded real-time operating system VxWorks, taking SST39VF1601 NOR Flash as an example. Firstly, DOS file system is configured, including the TrueFFS core component and the translation layer according to the technology used by SST39VF1601. Secondly, MTD layer and Socket layer Drivers are written. Lastly, the VxWorks DOS file system is mounted on a TrueFFS Flash drive, and simple test is carried out.%详细说明了嵌入式系统中常用的NOR Flash存储器建立Vxworks TrueFFS文件系统的方法。首先配置完整的DOS文件系统支持,包含核心TrueFFS组件和翻译层组件;然后编写MTD层和Socket层驱动程序;最后在TrueFFS的NOR Flash驱动上挂接VxWorksDOS文件系统,并进行了简单的测试。

  19. The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure

    NARCIS (Netherlands)

    Joosen, M.J.A.; Berg, R.M. van den; Jong, A.L. de; Schans, M.J. van der; Noort, D.; Langenberg, J.P.

    2017-01-01

    The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless

  20. 男人的MP3,全新昂达VX303来了!

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    <正>昂达VX系列最新成员,延续了VX系列高水准的音质表现,信噪比及FM收音效果更上层楼 全新上市的昂达VX303是ONDA最新推出的 一款音乐欣赏专用高保真MP3播放器,昂 达VX303拥有全新设计的硬朗外观,延续了VX 系列MP3一贯的高水平音质表现水准。 作为最新一代VX系列MP3播放器,昂达 VX303又有多项技术进步:比如支持SRS专利环 绕音效;首次采用国内领先水准的喷釉工艺GE (通用电气)ABS材质骨架,表面光亮耐磨,手 感光滑细腻;以及具备超低的背景噪音和顶级的 FM收音效果。

  1. [Effect of aurora inhibitor VX-680 on proliferation and apoptosis of CML cells].

    Science.gov (United States)

    Yin, Yue; Sun, Hui-Yan; Li, Xiao-Lin; Xiao, Feng-Jun; Wang, Li-Sheng

    2014-12-01

    This study was aimed to explore the effect of VX-680, an aurora inhibitor, on proliferation and apoptosis of K562, KCL22 cell lines and CD34⁺ cells from chronic myeloid leukemia (CML) patients in vitro. The proliferation of K562 and KCL22 cell was detected by CCK-8 method. Apoptosis of cells was detected by Annexin V-PI labeling and flow cytometry. The colony forming ability of bone marrow CD34⁺ cells derived from CML patients and donors was determined by the colony forming test. The results showed that the treatment of K562, KCL22 and CML CD34⁺ cells with VX-680 of 20-100 nmol/L for 3 days could obviously inhibit the cell proliferation in a concentration-dependent manner (P VX-680 treatment significantly induced apoptosis of K562 and KCL22 cells. Compared to bone marrow CD34⁺ cells derived from the healthy donors, the colony forming ability of CML CD34⁺ cells derived from bone marrow of CML patients was remarkably reduced (P VX-680, an aurora inhibitor, can inhibit the proliferation and induce apoptosis of CML cells in vitro.

  2. VizieR Online Data Catalog: 22GHz observations of VX Sgr (Murakawa+, 2003)

    Science.gov (United States)

    Murakawa, K.; Yates, J. A.; Richards, A. M. S.; Cohen, R. J.

    2012-07-01

    The 22-GHz H2O maser emission from VX Sgr was observed on 1994 26 and 1999 January 16 for 5 and 7hr, respectively, in both left and right circular polarization, using 5 antennas of MERLIN. (3 data files).

  3. Use of Auroral Processes in Spacecraft Propulsion: A VASIMR VX-100 Status Report

    Science.gov (United States)

    Brukardt, M.; Bering, E. A.; Chang-Diaz, F. R.; Squire, J. P.; Glover, T. W.; Cassady, L. D.; Jacobson, V. T.; Chancery, W. J.; Longmier, B. W.

    2007-12-01

    Plasma physics has found an increasing range of practical industrial applications, including the development of electric spacecraft propulsion systems. One of these systems, the Variable Specific Impulse Magnetoplasma Rocket (VASIMR) engine, applies several important physical processes occurring in the magnetosphere. These processes include the mechanisms involved in the ion acceleration and heating that occur in the Birkeland currents of an auroral arc system. Auroral current region processes that are applied in VASIMR include lower hybrid heating, parallel electric field acceleration and ion cyclotron acceleration. This paper will focus on using two physics demonstration model VASIMR's to study ion cyclotron heating (ICRH). Prior to VASIMR, laboratory simulation of electromagnetic ion cyclotron wave heating has been difficult owing to the difficulty in obtaining efficient antenna coupling for this mode and to the fact that the ions involved only pass through the acceleration region once. The VX-50 and VX-100 VASIMR's use(d) a helicon antenna with 20 kW of power to generate plasma. Both devices then use(d) an RF booster stage that uses left hand polarized slow mode waves launched from the high field side of the resonance. The VX-50 used 2 to 4 MHz waves with 30 kW of power. The VX-100 operates at ~500 kHz, with up to 100 kW of available ICRH power. This paper will summarize results from high power ICRH experiments performed on the VX-50 using deuterium, neon and argon plasma during 2006 and will present preliminary results from the VX-100. Emphasis will be placed on results obtained since the last Fall meeting We have demonstrated ion cyclotron acceleration of a dense (>1019/m3) plasma flow using all three gasses. ICRH loading measurements are consistent with efficient (90%) RF coupling to the plasma. The ICRH experiments have demonstrated that an energy boost of over 500 eV is possible. Early VX-100 results indicate that it should be possible to obtain an exhaust

  4. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Genovese, Mark C; Yang, Fang; Østergaard, Mikkel;

    2016-01-01

    OBJECTIVE: To assess early effects on joint structures of VX-509 in combination with stable disease-modifying antirheumatic drug (DMARD) therapy using MRI in adults with rheumatoid arthritis (RA). METHODS: This phase II, placebo-controlled, double-blind, dose-ranging study randomised patients...... synovitis scores were significantly different from placebo for all VX-509 doses (pTreatment was generally well tolerated. CONCLUSIONS: VX-509 plus a DMARD reduced the signs and symptoms of RA in patients with an inadequate response to a DMARD...... alone. MRI responses were detected at week 12. Treatment was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01754935; results....

  5. Thermochemical ablation therapy of VX2 tumor using a permeable oil-packed liquid alkali metal.

    Directory of Open Access Journals (Sweden)

    Ziyi Guo

    Full Text Available Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors.Permeable oil-packed sodium-potassium (NaK was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluated using the Fluke Ti400 Thermal Imager. The thermochemical effect of the NaK-oil mixture on VX2 tumors was evaluated by performing perfusion CT scans both before and after treatment in 10 VX2 rabbit model tumors. VX2 tumors were harvested from two rabbits immediately after treatment to assess their viability using trypan blue and hematoxylin and eosin (H.E. staining.The injection of the NaK-oil mixture resulted in significantly higher heat in the ablation areas. The permeable oil controlled the rate of heat released during the NaK reaction with water in the living tissue. Perfusion computed tomography and its parameter map confirmed that the NaK-oil mixture had curative effects on VX2 tumors. Both trypan blue and H.E. staining showed partial necrosis of the VX2 tumors.The NaK-oil mixture may be used successfully to ablate tumor tissue in vivo. With reference to the controlled thermal and chemical lethal injury to tumors, using a liquid alkali in ablation is potentially an effective and safe method to treat malignant tumors.

  6. Research on the nanocrystal FeVxOy catalysts for new reaction from propane to propylene and CO

    Science.gov (United States)

    Li, Yanhua; Chen, Shu; Xu, Aixin; Ma, Fei; Chen, Fang; Lu, Weimin

    2014-11-01

    The FeVxOy catalysts, used for selective oxidation of propane to propylene and CO, were prepared via sol-gel method using F-127 as chelating agent. And the catalyst with V/Fe (molar ratio) = 0.1 showed quite good selectivity of propylene and CO and the sum of them can be more than 90%. The catalysts were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Raman, H2-TPR and NH3-TPD. The relationship between the structure and catalytic properties was also preliminarily discussed. The results indicated that chemical interaction took place between the vanadium and iron, which could be referred to Vsbnd Osbnd Fe bonds and the formation of Fe(VO4). Meanwhile, with the increase of vanadium content, the distribution of all the elements proportion and valence state on the surface of the catalysts as well as the acid amount and acid sites changed immensely. All of these affected the catalytic performance and improve the selectivity of CO and inhibit that of CO2.

  7. Therapeutic efifcacy and bone marrow protection of the mdr1 gene and over-dose chemotherapy with doxorubicin for rabbits with VX2 hepatocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yi Wang; Xian-Qing Jin; Shan Wang; Qiao Wang; Qing Luo; Xiao-Ji Luo

    2006-01-01

    BACKGROUND: Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efifcacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits. METHODS: The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efifcacy of over-dose chemotherapy were observed. RESULTS:The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efifciency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26±1.03)×104/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00±46.75 d) of the rabbits was extended (P CONCLUSIONS:The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be

  8. The neurochemistry of peripheral nerve regeneration

    Science.gov (United States)

    Benga, Andreea; Zor, Fatih; Korkmaz, Ahmet; Marinescu, Bogdan; Gorantla, Vijay

    2017-01-01

    Peripheral nerve injuries (PNIs) can be most disabling, resulting in the loss of sensitivity, motor function and autonomic control in the involved anatomical segment. Although injured peripheral nerves are capable of regeneration, sub-optimal recovery of function is seen even with the best reconstruction. Distal axonal degeneration is an unavoidable consequence of PNI. There are currently few strategies aimed to maintain the distal pathway and/or target fidelity during regeneration across the zone of injury. The current state of the art approaches have been focussed on the site of nerve injury and not on their distal muscular targets or representative proximal cell bodies or central cortical regions. This is a comprehensive literature review of the neurochemistry of peripheral nerve regeneration and a state of the art analysis of experimental compounds (inorganic and organic agents) with demonstrated neurotherapeutic efficacy in improving cell body and neuron survival, reducing scar formation and maximising overall nerve regeneration. PMID:28615804

  9. Confocal Raman Microspectroscopy: The Measurement of VX Depth Profiles in Hairless Guinea Pig Skin and the Evaluation of RSDL

    Science.gov (United States)

    2015-02-01

    neurotransmitter acetylcholine. This neurotransmitter then accumulates at synaptic sites, causing cholinergic system hyperactivity. Symptoms of VX...The use of clipped haired guinea pigs was initially planned in this project. Using training animals from the Veterinary Medicine and Surgery

  10. Characteristics and pathological mechanism on magnetic resonance diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate dynamic characteristics and pathological mechanism of signal in rabbit VX-2 tumor model on diffusion-weighted imaging (DWI) after chemoembolization.METHODS: Forty New Zealand rabbits were included in the study and forty-seven rabbit VX-2 tumor models were raised by implanting directly and intrahepatically after abdominal cavity opened. Forty VX-2 tumor models from them were divided into four groups. DWI was performed periodically and respectively for each group after chemoembolization. All VX-2 tumor samples of each group were studied by pathology. The distinction of VX-2tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance between different time groups, different area groups or different b-value groups was calculated by using SPSS12.0 software.RESULTS: Under b-value of 100 s/mm2, ADC values were lowest at 16 h after chemoembolization in area of VX-2 tumor periphery, central, and normal liver parenchyma around tumor, but turned to increase with further elongation of chemoembolization treatment. The distinction of ADC between different time groups was significant respectively (F = 7.325, P < 0.001; F = 2.496,P < 0.048; F = 6.856, P < 0.001). Cellular edema in the area of VX-2 tumor periphery or normal liver parenchyma around tumor, increased quickly in sixteen h after chemoembolization but, from the 16th h to the 48th h, cellular edema in the area of normal liver parenchyma around tumor decreased gradually and that in the area of VX-2 tumor periphery decreased lightly at, and then increased continually. After chemoembolization, Cellular necrosis in the area of VX-2 tumor periphery was more significantly high than that before chemoembolization. The areas of dead cells in VX-2 tumors manifested low signal and high ADC value, while the areas of viable cells manifested high signal and low ADC value.CONCLUSION: DWI is able to detect and differentiate tumor necrotic areas from viable

  11. Furthering the Enzymatic Destruction of Nerve Agents

    Science.gov (United States)

    2002-01-01

    0.1 mg of CoCl2⋅6H2O, 0.1 mg of ZnSO4⋅7H2O, 0.02 mg of H3BO3, 0.01 mg of Na2MoO4⋅ 2H2O , 0.01 mg of CuSO4 , and 1 g of O O...mg of thiamine, 6 mg of MgSO4⋅7H2O, 3 mg of nitrilotriacetic acid, 48 mg of K2SO4, 1 mg of MnSO4⋅H2O, 2.8 mg of FeSO4⋅7H2O, 0.1 mg of CaCl2⋅ 2H2O

  12. Assessment of hepatic VX2 tumors with combined percutaneous transhepatic lymphosonography and contrast-enhanced ultrasonographic imaging

    Institute of Scientific and Technical Information of China (English)

    Cun Liu; Ping Liang; Yang Wang; Pei Zhou; Xin Li; Zhi-Yu Han; Shao-Ping Liu

    2008-01-01

    AIM: To evaluate the feasibility and efficacy of percutaneous transhepatic lymphosonography (PTL) as a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits and to evaluate combined PTL and routine contrast-enhanced ultrasonographic imaging for the diagnosis of liver cancer.METHODS: Ten rabbits with VX2 tumor were included in this study.SonoVue (0.1 mL/kg) was injected into each rabbit v/a an ear vein for contrast-enhanced ultrasonographic imaging,and 0.5 mL SonoVue was injected into the normal liver parenchyma near the VX2 tumor for PTL.Images and/or movie clips were stored for further analysis.RESULTS: Ultrasonographic imaging showed VX2 tumors ranging 5-19 mm in the liver of rabbits.The VX2 tumor was hyperechoic and hypoechoic to liver parenchyma at the early and later phase,respectively.The hepatic lymph vessels were visualized immediately after injection of contrast medium and continuously visualized with SonoVue(R) during PTL.The boundaries of VX2 tumors were hyperechoic to liver parenchyma and the tumors.There was a significant difference in the values for the boundaries of VX2 tumors after injection compared with the liver normal parenchyma and the tumor parenchyma during PTL.CONCLUSION: PTL is a novel method for the detection of tumor lymphangiogenesis in hepatic VX2 of rabbits.Combined PTL and contrast-enhanced ultrasonographic imaging can improve the diagnosis of liver cancer.

  13. 有板有眼 昂达VX611W豪华版(8GB)

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    这是MID,还是平板电脑?搭载了Android OS v2.3.4系统,拥有7英寸主流尺寸屏幕的昂达(ONDA)VX61OW豪华版让MI无法定义,但VX610W却是国产7英寸Android设备中少有让MI赞不绝口之作。

  14. OpenVX-based Python Framework for real-time cross platform acceleration of embedded computer vision applications

    Directory of Open Access Journals (Sweden)

    Ori Heimlich

    2016-11-01

    Full Text Available Embedded real-time vision applications are being rapidly deployed in a large realm of consumer electronics, ranging from automotive safety to surveillance systems. However, the relatively limited computational power of embedded platforms is considered as a bottleneck for many vision applications, necessitating optimization. OpenVX is a standardized interface, released in late 2014, in an attempt to provide both system and kernel level optimization to vision applications. With OpenVX, Vision processing are modeled with coarse-grained data flow graphs, which can be optimized and accelerated by the platform implementer. Current full implementations of OpenVX are given in the programming language C, which does not support advanced programming paradigms such as object-oriented, imperative and functional programming, nor does it have runtime or type-checking. Here we present a python-based full Implementation of OpenVX, which eliminates much of the discrepancies between the object-oriented paradigm used by many modern applications and the native C implementations. Our open-source implementation can be used for rapid development of OpenVX applications in embedded platforms. Demonstration includes static and real-time image acquisition and processing using a Raspberry Pi and a GoPro camera. Code is given as supplementary information. Code project and linked deployable virtual machine are located on GitHub: https://github.com/NBEL-lab/PythonOpenVX.

  15. 基于 VxWorks 的网卡驱动程序开发%Programming of Network Adapter Driver Based on VxWorks

    Institute of Scientific and Technical Information of China (English)

    张宇坤; 袁冬莉; 黄鑫鑫; 姚建勋

    2013-01-01

      VxWorks 是一种运行在目标机上的可剪裁的高性能嵌入式实时操作系统,集成了标准 TCP/ IP 网络功能。但其支持的网卡型号有限,限制了网络资源的使用,网络驱动开发就显出其重要性。 VxWorks 特有的增强网络驱动(END)包含有一个多路复用层模块(MUX)将驱动程序细化,这个模块赋予了驱动独立性,使得开发者专注于驱动本身的开发,因此选择使用这种驱动模式为 intel82567网卡成功实现驱动。这种特有的驱动模式在应用的过程中确实体现出其高效性,不用关心底层的转换和协议处理,对需要进行短周期 END 型网络驱动的开发有参考价值。%VxWorks is a scalable embedded real-time operating system with great performance,which is run in the target. And the stand-ard TCP/ IP protocol is integrated within the system. As only a few network adapters support the system,which limits the use of cyber source,the designing of network driver in VxWorks systems becomes vital. The MUX included in END is able to refine the driver pro-gram,which helps the designer to focus on developing the driver and gives the drive independence,so use this driving mode for successful implementation of intel82567 NIC driver. This special driving mode reflects the efficiency in the application process with no care about the underlying drive conversion and protocol processing,and may have a reference value for the short period designing of END.

  16. Biochemical engineering nerve conduits using peptide amphiphiles.

    Science.gov (United States)

    Tan, Aaron; Rajadas, Jayakumar; Seifalian, Alexander M

    2012-11-10

    Peripheral nerve injury is a debilitating condition. The gold standard for treatment is surgery, requiring an autologous nerve graft. Grafts are harvested from another part of the body (a secondary site) to treat the affected primary area. However, autologous nerve graft harvesting is not without risks, with associated problems including injury to the secondary site. Research into biomaterials has engendered the use of bioartificial nerve conduits as an alternative to autologous nerve grafts. These include synthetic and artificial materials, which can be manufactured into nerve conduits using techniques inspired by nanotechnology. Recent evidence indicates that peptide amphiphiles (PAs) are promising candidates for use as materials for bioengineering nerve conduits. PAs are biocompatible and biodegradable protein-based nanomaterials, capable of self-assembly in aqueous solutions. Their self-assembly system, coupled with their intrinsic capacity for carrying bioactive epitopes for tissue regeneration, form particularly novel attributes for biochemically-engineered materials. Furthermore, PAs can function as biomimetic materials and advanced drug delivery platforms for sustained and controlled release of a plethora of therapeutic agents. Here we review the realm of nerve conduit tissue engineering and the potential for PAs as viable materials in this exciting and rapidly advancing field. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Butyrylcholinesterase as a Therapeutic Drug for Protection Against Percutaneous VX

    Science.gov (United States)

    2010-01-01

    Larison, D.M. Maxwell, M.R. Murphy, M. Schutz, K. Waibel, A.D. Wolfe A.D., Cholinesterases as scavengers for organophosphorous compounds: protection...scavengers for organophosphorous agents, in: J. Massoulie, F. Bacou, E. Barnard, A. Chatonnet, B.P. Doctor, D.M. Quinn (Eds.), Cholinesterases: Structure

  18. A Novel Minimally Invasive Technique to Create a Rabbit VX2 Lung Tumor Model for Nano-Sized Image Contrast and Interventional Studies

    OpenAIRE

    Takashi Anayama; Takahiro Nakajima; Michael Dunne; Jinzi Zheng; Christine Allen; Brandon Driscoll; Douglass Vines; Shaf Keshavjee; David Jaffray; Kazuhiro Yasufuku

    2013-01-01

    BACKGROUND: The rabbit VX2 lung cancer model is a large animal model useful for preclinical lung cancer imaging and interventional studies. However, previously reported models had issues in terms of invasiveness of tumor inoculation, control of tumor aggressiveness and incidence of complications. PURPOSE: We aimed to develop a minimally invasive rabbit VX2 lung cancer model suitable for imaging and transbronchial interventional studies. METHODS: New Zealand white rabbits and VX2 tumors were u...

  19. Effects of Herbal vX on libido and sexual activity in premenopausal and postmenopausal women.

    Science.gov (United States)

    Waynberg, J; Brewer, S

    2000-01-01

    This study investigated the possibility of an alternative to chemical medication in the treatment of sexual dysfunction in healthy women. The efficacy of a unique herbal formulation of Muira puama and Ginkgo biloba (Herbal vX) was assessed in 202 healthy women complaining of low sex drive. Various aspects of their sex life were rated before and after 1 month of treatment. Responses to self-assessment questionnaires showed significantly higher average total scores from baseline in 65% of the sample after taking the supplement. Statistically significant improvements occurred in frequency of sexual desires, sexual intercourse, and sexual fantasies, as well as in satisfaction with sex life, intensity of sexual desires, excitement of fantasies, ability to reach orgasm, and intensity of orgasm. Reported compliance and tolerability were good. These initial findings support the strong anecdotal evidence for the benefits of Herbal vX on the female sex drive. A double-blind study is planned to further research these results.

  20. 双核芯双无损 昂达VX868

    Institute of Scientific and Technical Information of China (English)

    柠檬草; 黄新乐

    2007-01-01

    VX868是昂达HONEY系列的最新精品,外观上延续了HONEY系列一触即蓝的时尚风格精致的亚克力面板和铝合金底壳,材质高档,26万色2.8英寸QVGA高清TFT彩屏同时还支持FLV视频和FLAC、APE双无损格式。

  1. Photometric and Polarimetric Activity of the Herbig Ae Star VX Cas

    Science.gov (United States)

    Shakhovskoi, D. N.; Rostopchina, A. N.; Grinin, V. P.; Minikulov, N. Kh.

    2003-04-01

    We present the results of our simultaneous photometric and polarimetric observations of the Herbig Ae/Be star VX Cas acquired in 1987 2001. The star belongs to the UX Ori subtype of young variable stars and exhibits a rather low level of photometric activity: only six Algol-like minima with amplitudes ΔV>1m were recorded in 15 years of observations. Two of these minima, in 1998 and 2001, were the deepest in the history of the star’s photometric studies, with V amplitudes of about 2m. In each case, the dimming was accompanied by an increase in the linear polarization in agreement with the law expected for variable circumstellar extinction. The highest V polarization was about 5%. Observations of VX Cas in the deep minima revealed a turnover of the color tracks, typical of stars of this type and due to an increased contribution from radiation scattered in the circumstellar disk. We separated the observed polarization of VX Cas into interstellar (P is) and intrinsic (P in) components. Their position angles differ by approximately 60°, with P is dominating in the bright state and P in dominating during the deep minima. The competition of these two polarization components leads to changes in both the degree and position angle of the polarization during the star’s brightness variations. Generally speaking, in terms of the behavior of the brightness, color indices, and linear polarization, VX Cas is similar to other UX Ori stars studied by us earlier. A number of episodes of photometric and polarimetric activity suggest that, in their motion along highly eccentric orbits, circumstellar gas and dust clouds can enter the close vicinity of the star (and be disrupted there).

  2. Metabolomic Analysis of Liver Tissue from the VX2 Rabbit Model of Secondary Liver Tumors

    OpenAIRE

    Ibarra, R.; Dazard, J-E.; Y. Sandlers; Rehman, F; Abbas, R.; Kombu, R.; Zhang, G-F; Brunengraber, H; Sanabria, J.

    2014-01-01

    Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+...

  3. Repeated Exposure to Sublethal Doses of the Organophosphorus Compound VX Activates BDNF Expression in Mouse Brain

    Science.gov (United States)

    2012-01-01

    cresyl/-4 H-1: 3: 2-benzodioxa- phosphorin-2-oxide (CBDP) on organophosphate poisoning and its therapy. Arch. Toxicol. 42, 207–216. French, S. J... organophosphates or other environmental insults, have a greater FIG. 4. Mice that received repeated exposure to low levels of VX (0.2 LD50 and 0.4 LD50...to neuro- behavioral deficits and neuropathology. Although exposure to organophosphates such as pesticides has been shown to affect the expression of

  4. 气势如虹——昂达VX797HD MP4

    Institute of Scientific and Technical Information of China (English)

    周梦迎; 罗观(摄影)

    2009-01-01

    众多高清播放产品都在朝着大尺寸屏幕发展,昂达(ONDA)推出的VX797HD MP4脱颖而出成为众人关注的焦点,这和它7.0英寸超大尺寸的显示屏幕有着很大关系。

  5. Impact of microbubble enhanced, pulsed, focused ultrasound on tumor circulation of subcutaneous VX2 cancer

    Institute of Scientific and Technical Information of China (English)

    Li Peijing; Zhu Mei; Xu Yali; Zhao Yang; Gao Shunji; Liu Zheng; Gao Yun-hua

    2014-01-01

    Background Intravascular microbubble-enhanced acoustic cavitation is capable of disrupting the vascular walls of capillaries and small vessels.This study was designed to investigate the impact of microbubble-enhanced,pulsed and focused ultrasound (MEUS) on the blood perfusion of subcutaneous VX2 tumors in rabbits.Methods Subcutaneous VX2 cancers in twenty New Zealand rabbits were treated by combining high-pressure amplitude,pulsed and focused therapeutic ultrasound (TUS) and intravenous microbubble injections.The TUS transducer was operated with a peak negative pressure of 4.6 MPa and a duty cycle of 0.41%.Controls were subcutaneous VX2 cancers treated with TUS or microbubbles only.Contrast-enhanced ultrasound (CEUS) and intravenous Evans Blue (EB) perfusion were performed to assess the tumor circulation.The tumor microvascular disruption was assessed by histological examination.Results CEUS showed that the tumor circulation almost vanished after MEUS treatment.The average peak grayscale value (GSV) of tumor CEUS dropped significantly from 84.1±22.4 to 15.8±10.8 in the MEUS-treated tumors but no significant GSV changes were found in tumors in the two control groups.The mean tumor EB content of the MEUS-treated tumors was significantly lower than that of the controls.Histological examination found scattered tumor microvascular disruption with intercellular edema after MEUS treatment.Conclusion The tumor circulation of VX2 cancers can be arrested or significantly reduced by MEUS due to microvascular disruption.

  6. Infrared Complex Optical Constants of GB, GF, HD, HN1, and VX

    Science.gov (United States)

    2014-04-01

    31 23. Imaginary refractive index of VX from ECBC (blue trace) and the PNNL database (black trace) expanded to the region near 1300 cm 1...been shown to give satisfactory performance when compared with other peak-picking methods for evaluating the positions of peaks in polystyrene ...9, which is an expanded view of the baselines in the fingerprint region of the GB absorption index spectra from ECBC and PNNL. The ellipsometer

  7. Sentinel Node Mapping of VX2 Carcinoma in Rabbit Thigh with CT Lymphography Using Ethiodized Oil

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jin; Kim, Young Hoon; Lee, Kyoung Ho; Park, Ji Hoon [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Hye Seung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Jung, Seung Chai [Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Joo, Seung-Moon [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720 (Korea, Republic of)

    2014-07-01

    To assess the feasibility of computed tomography (CT) lymphography using ethiodized oil for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh. This experiment received approval from the institutional animal use and care administrative advisory committee. Twenty-three rabbits with VX2 carcinoma in the thigh underwent CT before and after (1 hour, 2 hour) peritumoral injection of 2 mL ethiodized oil. After the CT examination, sentinel nodes were identified by peritumoral injection of methylene blue and subsequently removed. The retrieved sentinel and non-sentinel lymph nodes were investigated with radiographic and pathologic examinations. Based on the comparison of CT findings with those of radiographic and pathologic examinations, the diagnostic performance of CT for sentinel node identification was assessed. All 23 rabbits showed 53 ethiodized oil retention nodes on post-injection CT and specimen radiography, and 52 methylene blue-stained nodes at the right femoroiliac area. Of the 52 blue-stained sentinel nodes, 50 nodes demonstrated ethiodized oil retention. Thus, the sentinel node detection rate of CT was 96% (50 of 52). On pathologic examination, 28 sentinel nodes in 17 rabbits (nodes/rabbit, mean ± standard deviation, 1.7 ± 0.6) harbored metastasis. Twenty seven of the 28 metastatic sentinel nodes were found to have ethiodized oil retention. Computed tomography lymphography using ethiodized oil may be feasible for sentinel node mapping in experimentally induced VX2 carcinoma in the rabbit thigh.

  8. Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

    Science.gov (United States)

    Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

    2012-10-01

    Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

  9. Cellular Imaging Using Equivalent Cross-Relaxation Rate Technique in Rabbit VX-2 Tumor Model.

    Science.gov (United States)

    Nishiofuku, Hideyuki; Matsushima, Shigeru; Taguchi, Osamu; Inaba, Yoshitaka; Yamaura, Hidekazu; Sato, Yozo; Tanaka, Toshihiro; Kichikawa, Kimihiko

    2011-01-01

    Equivalent cross-relaxation rate (ECR) imaging (ECRI) is a measurement technique that can be used to quantitatively evaluate changes in structural organization and cellular density by MRI. The aim of this study was to evaluate the correlation between the ECR value and cellular density in the rabbit VX2 tumor model. Five rabbits implanted with 10 VX2 tumors in the femur muscles were included in this study. We adopted the off-resonance technique with a single saturation transfer pulse frequency of 7 ppm downfield from water resonance. The ECR value was defined as the percentage of signal loss between the unsaturated and saturated images. ECR images were constructed based on the percentage of the ECR value. Pathological specimens were divided into 34 areas and classified into two groups: the viable group and the necrotic group. ECR values were measured and compared between groups. The correlation between the ECR value and cellular density was then determined. The mean ECR value was significantly higher in the viable group than in the necrotic group (61.2% vs. 35.8%). The area under the curve that calculated by receiver operating characteristic curve was 0.991 at 7 ppm. The regression graph showed a linear relationship between the ECR value and cellular density; the correlation coefficient (r) was 0.858. There is a strong association between the ECR value and cellular density in VX2 tumors and so ECRI could be a potentially useful technique for accurately depicting viable and necrotic areas.

  10. Design and Implementation of UAV's Simulator based on VxWorks%基于 VxWorks 的无人机模拟器设计与实现

    Institute of Scientific and Technical Information of China (English)

    薛艳峰; 薛鹏

    2015-01-01

    无人机模拟器通过模拟与地面发控设备的电气接口及逻辑关系和无人机空中飞行全过程实现了对无人机的模拟,是一套用于飞行协同训练及地面发控设备检查的地面辅助设备。该设备采用基于 CPCI 总线结构、VxWorks 操作系统的计算机,实现了串口通信、UDP 网络通信、图形人机交互界面等功能。%UAV simulator is a set of ground support equipment, used to flying Cooperative training and testing of ground control device. The device achieved by simulation of electrical interface and logic relation between of UAV and ground control device, and it also can simulate the whole process of air flight of UAV. The equipment adopts the embedded computer, which uses CPCI bus structure and Vx-Works operating system. It has the function of serial communication and UDP network communication, and of graphic human-machine interface.

  11. Design of TIS Gateway Based on VxWorks Platform%基于VxWorks平台的TIS网关设计

    Institute of Scientific and Technical Information of China (English)

    王榕; 许磊; 姚敏立

    2006-01-01

    战术信息系统(TIS)具有集成的战术通信、导航定位和网内识别功能.由于其工作在Lx (960-1215 MHz)频段,无法完成信息的超视距实时传输,限制了其在超视距机动作战中的应用.TIS网关是实现TIS信息和指控信息的超视距实时传输的关键设备.该文构建了一个基于VxWorks实时操作系统的TIS网关,利用VxWorks丰富而标准的sockets编程接口和多任务机制,通过同步卫星为中继的数据链路,实现了TIS信息和指控信息的超视距实时传输,解决了信息的超视距实时传输问题.

  12. Development Technology of VxWorks Graphical Interfaces Based on Tilcon%基于Tilcon的VxWorks图形界面开发技术

    Institute of Scientific and Technical Information of China (English)

    张士福

    2011-01-01

    In view of the problem that the development of graphical interface is difficult in embedded system,this paper introduces the Tilcon as an ideal development tool of graphical interface, analyzes the operating principle and main characteristics of the tool, puts forward the method to develop the VxWorks graphical interface based on Tilcon, presents an application example of graphical interface,analyzes and illuminates the program development method and program operational flow based on Tilcon.%针对嵌入式系统下图形界面开发困难的问题,介绍了一种理想的图形界面开发工具Tilcon,分析了该工具的工作原理和主要特点,提出了基于Tilcon的VxWorks图形界面开发方法,给出了一个图形界面应用实例,对基于Tilcon的程序开发方法和程序运行流程进行了分析和说明。

  13. Aurora激酶抑制剂VX-680对慢性髓系白血病细胞增殖及凋亡的影响%Effect of Aurora Inhibitor VX-680 on Proliferation and Apoptosis of CML Cells

    Institute of Scientific and Technical Information of China (English)

    尹玥; 孙慧燕; 李晓林; 肖凤君; 王立生

    2014-01-01

    本研究探讨Aurora激酶抑制剂VX-680在体外对白血病细胞系K562、KCL22和慢性髓系白血病(CML)患者骨髓CD34+细胞的增殖和凋亡的影响.利用CCK-8法观察VX-680对K562和KCL22细胞的增殖作用,细胞计数方法测定VX-680对CML的CD34+细胞增殖影响,Annexin V-PI凋亡检测试剂盒、流式细胞术分析VX-680对K562、KCL22细胞凋亡效应,集落形成试验检测VX-680对CML及正常供者(donor)的骨髓CD34+细胞集落形成能力影响.结果表明,Aurora激酶抑制剂VX-680(20-100 nmol/L)在处理细胞第3天时能明显抑制K562和KCL22细胞增殖(P<0.01),并能抑制CML患者骨髓CD34+细胞增殖,而且随着剂量增加,抑制作用增强;VX-680(20nmoL/L)作用K562和KCL22细胞3天时可诱导细胞凋亡(P<0.01);集落形成试验表明,CML患者骨髓CD34+细胞在VX-680的体外处理下集落形成能力较正常骨髓CD34+细胞明显下降(P<0.01).结论:Aurora激酶抑制剂VX-680在体外对慢性髓系白血病细胞有抑制增殖和促进凋亡的作用.

  14. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors.

    Science.gov (United States)

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-11-08

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy.

  15. Thermo-sensitive composite hydrogels based on poloxamer 407 and alginate and their therapeutic effect in embolization in rabbit VX2 liver tumors

    Science.gov (United States)

    Huang, Lili; Shen, Ming; Li, Rongxin; Zhang, Xiangyu; Sun, Ying; Gao, Pei; Fu, Hao; Liu, Hongqiang; He, Yang; Du, Yuqing; Cao, Jun; Duan, Yourong

    2016-01-01

    Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5°C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy. PMID:27602579

  16. Neutrophils express oncomodulin and promote optic nerve regeneration

    National Research Council Canada - National Science Library

    Kurimoto, Takuji; Yin, Yuqin; Habboub, Ghaith; Gilbert, Hui-Ya; Li, Yiqing; Nakao, Shintaro; Hafezi-Moghadam, Ali; Benowitz, Larry I

    2013-01-01

    .... In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve...

  17. Nerve conduction velocity

    Science.gov (United States)

    ... to measure the speed of the nerve signals. Electromyography (recording from needles placed into the muscles) is ... Often, the nerve conduction test is followed by electromyography (EMG). In this test, needles are placed into ...

  18. Common peroneal nerve dysfunction

    Science.gov (United States)

    ... toe-out movements Tests of nerve activity include: Electromyography (EMG, a test of electrical activity in muscles) Nerve ... Peroneal neuropathy. In: Preston DC, Shapiro BE, eds. Electromyography and Neuromuscular Disorders . 3rd ed. Philadelphia, PA: Elsevier; ...

  19. The Physics of Nerves

    CERN Document Server

    Heimburg, Thomas

    2010-01-01

    The accepted model for nerve pulse propagation in biological membranes seems insufficient. It is restricted to dissipative electrical phenomena and considers nerve pulses exclusively as a microscopic phenomenon. A simple thermodynamic model that is based on the macroscopic properties of membranes allows explaining more features of nerve pulse propagation including the phenomenon of anesthesia that has so far remained unexplained.

  20. 基于VxWo rks的数据融合系统的设计与实现%Design and realization of data fusion system based on VxWorks

    Institute of Scientific and Technical Information of China (English)

    刘雄杰; 杨剑锋; 郭成城

    2016-01-01

    为满足在复杂海洋环境下获取更加及时、准确与可靠的目标信息数据的要求,提出一种基于VxWorks的数据融合系统的设计方案。采用Tornado集成开发环境,结合VxWorks嵌入式实时操作系统,进行实时多任务的数据处理平台开发,实现对雷达与船舶自动识别系统(AIS)目标数据的融合处理,描述相关算法及系统在VxWorks中的实现。通过实验验证了该系统的可行性、稳定性与可靠性。%To get accurate and reliable data in real time ,a design scheme of data fusion system based on VxWorks was presen‐ted .The Tornado integrated development environment was established ,and VxWorks embedded real‐time operating system was combined .The real‐time multitask data processing platform was constructed ,and based on these ,the fusion processing of the target data of the radar and the ship automatic identification system (AIS) was implemented .Related algorithms and the realiza‐tion of the system in VxWorks were also described .The feasibility ,stability and reliability of the system were verified by simula‐tion and experiment .

  1. Delisting toxicity evaluation of HTH and oxone(trade name) decontaminated VX. Final report, July 1989-March 1990

    Energy Technology Data Exchange (ETDEWEB)

    Manthei, J.H.; Heitkamp, D.H.; Buettner, L.C.; Lawrence-Beckett, E.M.; Samuel, J.B.

    1992-07-01

    The acute percutaneous (bare skin) LD50 was determined for EA 2192 in the rabbit. Also established were the effective doses (ED50s) for the major toxic signs observed. Dermal, Department of Transportation (DOT), tests with rabbits indicated that VX/HTH decontaminated waste is a Class B poison after being aged only 24 hr following initiation of the decontamination procedure. The same reaction, when allowed to age through about 2 half-lives (28-30 days), was no longer a Class B poison and was nonhazardous by Code of Maryland Regulations (COMAR) toxicity criteria. The DOT tests with OXONE decontaminated/neutralized VX showed this solution to be less than a Class B poison by all three routes of administration (rat oral, rat inhalation, and rabbit dermal) after only 24-hr aging and a nonhazardous material by COMAR toxicity criteria.... vx, Rat, Half-life, ED50, EA 2192, Rabbit, COMAR, Decontaminated/Neutralized, HTH, OXONE, LD50.

  2. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch

    2005-01-01

    at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...... glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen......-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical...

  3. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch;

    2005-01-01

    at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...... glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen......-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical...

  4. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1.

    Science.gov (United States)

    Ren, Hong Yu; Grove, Diane E; De La Rosa, Oxana; Houck, Scott A; Sopha, Pattarawut; Van Goor, Fredrick; Hoffman, Beth J; Cyr, Douglas M

    2013-10-01

    Cystic fibrosis (CF) is a fatal genetic disorder associated with defective hydration of lung airways due to the loss of chloride transport through the CF transmembrane conductance regulator protein (CFTR). CFTR contains two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory domain, and its channel assembly requires multiple interdomain contacts. The most common CF-causing mutation, F508del, occurs in NBD1 and results in misfolding and premature degradation of F508del-CFTR. VX-809 is an investigational CFTR corrector that partially restores CFTR function in people who are homozygous for F508del-CFTR. To identify the folding defect(s) in F508del-CFTR that must be repaired to treat CF, we explored the mechanism of VX-809 action. VX-809 stabilized an N-terminal domain in CFTR that contains only MSD1 and efficaciously restored function to CFTR forms that have missense mutations in MSD1. The action of VX-809 on MSD1 appears to suppress folding defects in F508del-CFTR by enhancing interactions among the NBD1, MSD1, and MSD2 domains. The ability of VX-809 to correct F508del-CFTR is enhanced when combined with mutations that improve F508del-NBD1 interaction with MSD2. These data suggest that the use of VX-809 in combination with an additional CFTR corrector that suppresses folding defects downstream of MSD1 may further enhance CFTR function in people with F508del-CFTR.

  5. Assessment of tumor angiogenesis: dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA in a rabbit Vx-2 tumor model.

    Science.gov (United States)

    Kassner, Andrea; Thornhill, Rebecca E; Liu, Fang; Winter, Patrick M; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2010-01-01

    The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K(i) values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p = 0.018). When PNs and Gd-DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd-DTPA data (p = 0.34). The mean K(i) for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis.

  6. Classification of VxOyq Clusters by △=2yl+q-5x

    Institute of Scientific and Technical Information of China (English)

    Yan-ping Ma; Yan-xia Zhao; Zi-yu Li; Xun-lei Ding; Sheng-gui He

    2011-01-01

    Vanadium oxide clusters VxOyq (x≤8,q=0,+1) are classified according to the oxidation index (A=2y+q-5x) of each cluster.Density functional calculations indicate that clusters with the same oxidation index tend to have similar bonding characters,electronic structures,and reactivities.This general rule leads to the findings of new possible ground state structures for V2O6 and V3O6+ clusters.This successful application of the classification method on vanadium oxide clusters proves that this method is very effective in studying the bonding properties of early transition metal oxide clusters.

  7. Untersuchung der Mira-Sterne RT Boo, TV Peg und VX Aur

    Science.gov (United States)

    Raetz, Kerstin; Berthold, Thomas

    2015-02-01

    The light-change of the Mira stars RT Boo, TV Peg and VX Aur was analyzed on three ways for a long time. In the first period I estimated the brightness of the variables on sky monitoring photo plates (red spectral range) from Sonneberg Observatory with Argelander¥s Method, in the last years I measured scanned photo plates with a photometry program and in addition I used visual observations from A.A.V.S.O. for the analysis. The behavior of the periods of the tree stars from 1965 to 2013 is described here.

  8. 昂达VX-606 MP3播放器 音乐宝囊

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    昂达的板卡类产品在“装机一族”心中一直占有较高的地位,而它推出的几款MP3播放器在市场上也有不错的”战绩”.尤其是前段时间引领低价风暴的512MB版本的VX-505.更是以极高的性价比受到消费者的广泛关注。

  9. VX CAD/CAM 2009版发布会成功举行

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009年4月30日,VX公司在上海隆重推出了第14个版本VX CAD/CAM 2009版,此版本超过26个大项的新增功能全部来自世界各地用户的需求,并且软件研发的重点在于更好的匹配CAD/CAM一体化的无缝工作,以提高产品设计的易用性及加工效率。

  10. Quantum Griffiths Phase Inside the Ferromagnetic Phase of Ni1 -xVx

    Science.gov (United States)

    Wang, Ruizhe; Gebretsadik, Adane; Ubaid-Kassis, Sara; Schroeder, Almut; Vojta, Thomas; Baker, Peter J.; Pratt, Francis L.; Blundell, Stephen J.; Lancaster, Tom; Franke, Isabel; Möller, Johannes S.; Page, Katharine

    2017-06-01

    We study by means of bulk and local probes the d -metal alloy Ni1 -xVx close to the quantum critical concentration, xc≈11.6 %, where the ferromagnetic transition temperature vanishes. The magnetization-field curve in the ferromagnetic phase takes an anomalous power-law form with a nonuniversal exponent that is strongly x dependent and mirrors the behavior in the paramagnetic phase. Muon spin rotation experiments demonstrate inhomogeneous magnetic order and indicate the presence of dynamic fluctuating magnetic clusters. These results provide strong evidence for a quantum Griffiths phase on the ferromagnetic side of the quantum phase transition.

  11. Effects of deep heating provided by therapeutic ultrasound on demyelinating nerves

    OpenAIRE

    2016-01-01

    [Purpose] Physiotherapeutic heating agents are classified into two groups: superficial-heating agents and deep-heating agents. Therapeutic ultrasound is a deep-heating agent used to treat various musculosketal disorders. Numerous studies have attempted to determine the impact of ultrasound on healthy nerve conduction parameters. However, the instantaneous effects of deep heating via ultrasound on demyelinating nerves do not appear to have been described previously. The present study aimed to ...

  12. Structure-activity relationship of nerve-highlighting fluorophores.

    Directory of Open Access Journals (Sweden)

    Summer L Gibbs

    Full Text Available Nerve damage is a major morbidity associated with numerous surgical interventions. Yet, nerve visualization continues to challenge even the most experienced surgeons. A nerve-specific fluorescent contrast agent, especially one with near-infrared (NIR absorption and emission, would be of immediate benefit to patients and surgeons. Currently, there are only three classes of small molecule organic fluorophores that penetrate the blood nerve barrier and bind to nerve tissue when administered systemically. Of these three classes, the distyrylbenzenes (DSBs are particularly attractive for further study. Although not presently in the NIR range, DSB fluorophores highlight all nerve tissue in mice, rats, and pigs after intravenous administration. The purpose of the current study was to define the pharmacophore responsible for nerve-specific uptake and retention, which would enable future molecules to be optimized for NIR optical properties. Structural analogs of the DSB class of small molecules were synthesized using combinatorial solid phase synthesis and commercially available building blocks, which yielded more than 200 unique DSB fluorophores. The nerve-specific properties of all DSB analogs were quantified using an ex vivo nerve-specific fluorescence assay on pig and human sciatic nerve. Results were used to perform quantitative structure-activity relationship (QSAR modeling and to define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo fluorescence were tested for in vivo nerve specificity in mice to assess the effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB fluorophores with the highest nerve to muscle ratio were tested in pigs to confirm scalability.

  13. Consequence Management: A Disconnect Between National Security Policy and Force Structure?

    Science.gov (United States)

    2001-03-15

    the highly toxic nerve agent VX, an amount sufficient to kill over 15,000.8 So while the global community believed the madness of the cult had been...effective VX nerve agent chemical attack? How do you rapidly dispose of the thousands of dead to prevent the associated problems? To prevent widespread...fully provide the requested assistance. Meanwhile, the biological agent continues its deadly rampage irrespective of the frenzied American effort

  14. Imaging the trigeminal nerve

    Energy Technology Data Exchange (ETDEWEB)

    Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093, Lisboa (Portugal)], E-mail: borgalexandra@gmail.com; Casselman, Jan [Department of Radiology, A. Z. St Jan Brugge and A. Z. St Augustinus Antwerpen Hospitals (Belgium)

    2010-05-15

    Of all cranial nerves, the trigeminal nerve is the largest and the most widely distributed in the supra-hyoid neck. It provides sensory input from the face and motor innervation to the muscles of mastication. In order to adequately image the full course of the trigeminal nerve and its main branches a detailed knowledge of neuroanatomy and imaging technique is required. Although the main trunk of the trigeminal nerve is consistently seen on conventional brain studies, high-resolution tailored imaging is mandatory to depict smaller nerve branches and subtle pathologic processes. Increasing developments in imaging technique made possible isotropic sub-milimetric images and curved reconstructions of cranial nerves and their branches and led to an increasing recognition of symptomatic trigeminal neuropathies. Whereas MRI has a higher diagnostic yield in patients with trigeminal neuropathy, CT is still required to demonstrate the bony anatomy of the skull base and is the modality of choice in the context of traumatic injury to the nerve. Imaging of the trigeminal nerve is particularly cumbersome as its long course from the brainstem nuclei to the peripheral branches and its rich anastomotic network impede, in most cases, a topographic approach. Therefore, except in cases of classic trigeminal neuralgia, in which imaging studies can be tailored to the root entry zone, the full course of the trigeminal nerve has to be imaged. This article provides an update in the most recent advances on MR imaging technique and a segmental imaging approach to the most common pathologic processes affecting the trigeminal nerve.

  15. Paraoxonase activity against nerve gases measured by capillary electrophoresis and characterization of human serum paraoxonase (PON1) polymorphism in the coding region (Q192R).

    Science.gov (United States)

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2009-02-01

    An analytical method for determining paraoxonase activity against sarin, soman and VX was established. We used capillary electrophoresis to measure directly the hydrolysis products: alkyl methylphosphonates. After enzymatic reaction of human serum paraoxonase (PON1) with nerve gas, substrate was removed with dichloromethane, and alkyl methylphoshphonates were quantified by capillary electrophoresis of reversed osmotic flow using cationic detergent and sorbic acid. This method was applied to the characterization of human serum PON1 polymorphism for nerve gas hydrolytic activity in the coding region (Q192R). PON1-192 and PON1-55 genotypes were determined by their gel electrophoretic fragmentation pattern with restriction enzymes after polymerase chain reaction (PCR) of blood leukocyte genomic DNA. Frequencies of genotypes among 63 members of our institutes with PON1-192 and PON1-55 were 9.5% ((192)QQ), 30.1% ((192)QR) and 44.4% ((192)RR), and 82.5% ((55)LL), 17.5% ((55)LM) and 0% ((55)MM), respectively. (192)Q and (192)R enzymes were purified from the respective genotype human plasma, using blue agarose affinity chromatography and diethyl amino ethane (DEAE) anion exchange chromatography. V(max) and K(m) were measured using Lineweaver-Burk plots for hydrolytic activities against sarin, soman and VX at pH 7.4 and 25 degrees C. For sarin and soman, the V(max) for (192)Q PON1 were 3.5- and 1.5-fold higher than those for (192)R PON1; and k(cat)/K(m) for (192)Q PON1 were 1.3- and 2.8-fold higher than those for (192)R PON1. For VX, there was little difference in V(max) and k(cat)/K(m) between (192)Q and (192)R PON1, and VX hydrolyzing activity was significantly lower than those for sarin and soman. PON1 hydrolyzed sarin and soman more effectively than paraoxon.

  16. Characteristics of liver on magnetic resonance diffusion-weighted imaging: Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

    Institute of Scientific and Technical Information of China (English)

    You-Hong Yuan; En-Hua Xiao; Jian-Bin Liu; Zhong He; Ke Jin; Cong Ma; Jun Xiang; Jian-Hun Xiao; Wei-Jian Chen

    2008-01-01

    AIM: To investigate dynamical and image pathological characteristics of the liver on magnetic resonance (MR) diffusion-weighted imaging (DWI) in the rabbit VX-2 tumor model.METHODS: Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1-and T2-weighted of magnetic resonance imaging (MRI) were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically.RESULTS: The rate of lump detected by DWI, T1WI and T2WI was 78.7%,10.7% and 53.5% (χ2= 32.61, P<0.001) on the 7th d after implantation and 95.8%,54.3% and 82.9% (χ2= 21.50, P<0.001) on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal on the map of apparent diffusion coefficient (ADC). The signal of VX tumors did not decrease on the 7th d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually distinct and

  17. Intrahepatic transneedle inoculation of VX2 particles for obtaining a solitary hepatic tumor in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jin Han; Choi, Jong Cheol; Shin, Tae Beom; Park, Byeong Ho [Dong-A University, School of Medicine, Busan (Korea, Republic of)

    2005-07-15

    The purpose of this study was to develop a large animal (rabbit) model which has a proper solitary intrahepatic tumor with lower leakage rates through less traumatic methods. Consequently, we evaluated tumor progression following the intrahepatic inoculation of VX2 cells into New Zealand white rabbits to acquire baseline data on the progression of a VX2 tumor. Twenty New Zealand white rabbits, each weighting 2.5-3 kg, were selected for this study. A 1 mm{sup 3} VX2 tumor fragment was created and then minced to enable the particles to pass through a 21 G needle mounting in a tuberculin syringe with 0.1 ml of normal saline. The minced VX2 tumor particles were injected into the subcapsular parenchyma of the left hepatic lobe. A 21 G needle was used to avoid penetrating large hepatic vessels. In order to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route, a purse-string suture around the puncture site was made using black silk 4-0. The tumor particles were then injected through the center of the suture. While removing the needle, the suture was tightened to prevent hemorrhage or leakage of the VX2 tumor cells through the injection route. Finally, the injection site was covered with a Surgical patch. The inoculated intrahepatic VX2 tumors were then imaged with a 16 channel multidetector CT every week for the duration of the study. The CT images covered from the lung apex to the pelvic floor. Two radiologists evaluated the size, location, and peritoneal seeding of the tumors as well as metastasis of other organs. Three rabbits were sacrificed as random beginning in the second week, and this process continued on a weekly basis for the duration of the study. The CT images and pathologic findings for the sacrificed rabbits were correlated. The inoculated intrahepatic VX2 tumors were not visible in the first week. By the second week 66.7% were visible on CT images and by the third week all tumors were visible. Of the twenty rabbits, three (15

  18. Nerve conduction and excitability studies in peripheral nerve disorders

    DEFF Research Database (Denmark)

    Krarup, Christian; Moldovan, Mihai

    2009-01-01

    PURPOSE OF REVIEW: The review is aimed at providing information about the role of nerve excitability studies in peripheral nerve disorders. It has been known for many years that the insight into peripheral nerve pathophysiology provided by conventional nerve conduction studies is limited. Nerve...

  19. 一种针对VxWorks系统的通用软件故障注入方法%A Common Software Fault Injection Method for VxWorks Systems

    Institute of Scientific and Technical Information of China (English)

    范文豪; 马捷中; 孙姜燕

    2011-01-01

    针对VxWorks下的系统提出了一种通用的基于软件的故障注入方法,给出了故障注入工具的架构和故障模型.故障注入工具使用TCP/IP协议与目标机进行通信,并在目标机上驻留一小部分程序,利用中断的性质完成故障的注入.实验在VMware虚拟机上完成,表明该方法能有效地将故障注入到VxWorks平台下的设备中,以供系统容错性能的评价和改进.%A common software fault injection method for VxWorks-based systems is given. It has framework of fault injection tool and fault model. The fault injection tool uses TCP/IP protocol to communication and injects fault by property of interruption. It resides a part of program in target system. Experiments are done on VMware virtual machine. The result indicates that the method can inject fault effectively into VxWorks-based equipment for evaluation and improvement of fault tolerance.

  20. High-field magnetization of Heusler compound Fe2Mn1 -xVxSi

    Science.gov (United States)

    Hiroi, Masahiko; Tazoko, Tomoya; Sano, Hiroaki; Shigeta, Iduru; Koyama, Keiichi; Kondo, Akihiro; Kindo, Koich; Manaka, Hirotaka; Terada, Norio

    2017-01-01

    Fe2MnSi exhibits a ferromagnetic transition at TC˜230 K and another transition to a phase with antiferromagnetic components at TA˜60 K. By substituting V for Mn, so as to obtain Fe2Mn1 -xVxSi , TA is revealed to decrease with x and then vanish around x ˜0.2 . In this study, the phase boundary of the transition at TA in the high-field range is found for 0 ≤x ≤0.15 with pulsed fields up to ˜70 T. The magnetization of Fe2Mn1 -xVxSi slowly increases even at the highest field of ˜70 T, though it occurs more gradually as x increases. We compare the magnetization for 0 ≤x ≤0.20 at 62 T with the Slater-Pauling rule, which holds when a Heusler compound is a half-metal, and find fairly good agreement. This suggests an intimate relation between the high-field phase and the half-metallic electronic structure, and that at the high-field limit the phase approaches the half-metallic state, which has been predicted by band-structure calculations.

  1. HI-6 assisted catalytic scavenging of VX by acetylcholinesterase choline binding site mutants.

    Science.gov (United States)

    Maček Hrvat, Nikolina; Žunec, Suzana; Taylor, Palmer; Radić, Zoran; Kovarik, Zrinka

    2016-11-25

    The high toxicity of organophosphorus compounds originates from covalent inhibition of acetylcholinesterase (AChE), an essential enzyme in cholinergic neurotransmission. Poisonings that lead to life-threatening toxic manifestations require immediate treatment that combines administration of anticholinergic drugs and an aldoxime as a reactivator of AChE. An alternative approach to reduce the in vivo toxicity of OPs focuses on the use of bioscavengers against the parent organophosphate. Our previous research showed that AChE mutagenesis can enable aldoximes to substantially accelerate the reactivation of OP-enzyme conjugates, while dramatically slowing down rates of OP-conjugate dealkylation (aging). Herein, we demonstrate an efficient HI-6-assisted VX detoxification, both ex vivo in human blood and in vivo in mice by hAChE mutants modified at the choline binding site (Y337A and Y337A/F338A). The catalytic scavenging of VX in mice improved therapeutic outcomes preventing lethality and resulted in a delayed onset of toxicity symptoms.

  2. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    Photochemical bond- ing required clear access 5 mm proximal and dis- tal to coaptation sites. As a result, the maximum achievable nerve gap before...rodents for nerve gap reconstruction. Induction and maintenance anesthesia was achieved using isoflurane (Baxter Healthcare Corp., Deerfield, Ill...injury, nerve gap , nerve wrap, PTB, photosealing, Rose Bengal, amnion, nerve conduit, crosslinking, allograft, photochemistry. 3. Accomplishments

  3. The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer.

    Science.gov (United States)

    Xiang, Zhiming; Liang, Qianwen; Liang, Changhong; Zhong, Guimian

    2014-12-01

    Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P 0.05). However, the quantitative parameter of them were significantly positively correlated (P liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer.

  4. Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner.

    Science.gov (United States)

    Eckford, Paul D W; Li, Canhui; Ramjeesingh, Mohabir; Bear, Christine E

    2012-10-26

    The cystic fibrosis transmembrane conductance regulator (CFTR) acts as a channel on the apical membrane of epithelia. Disease-causing mutations in the cystic fibrosis gene can lead to CFTR protein misfolding as in the case of the F508del mutation and/or channel dysfunction. Recently, a small molecule, VX-770 (ivacaftor), has shown efficacy in restoring lung function in patients bearing the G551D mutation, and this has been linked to repair of its channel gating defect. However, these studies did not reveal the mechanism of action of VX-770 in detail. Normally, CFTR channel activity is regulated by phosphorylation, ATP binding, and hydrolysis. Hence, it has been hypothesized that VX-770 modifies one or more of these metabolic events. In this study, we examined VX-770 activity using a reconstitution system for purified CFTR protein, a system that enables control of known regulatory factors. We studied the consequences of VX-770 interaction with CFTR incorporated in planar lipid bilayers and in proteoliposomes, using a novel flux-based assay. We found that purified and phosphorylated CFTR was potentiated in the presence of Mg-ATP, suggesting that VX-770 bound directly to the CFTR protein, rather than associated kinases or phosphatases. Interestingly, we also found that VX-770 enhanced the channel activity of purified and mutant CFTR in the nominal absence of Mg-ATP. These findings suggest that VX-770 can cause CFTR channel opening through a nonconventional ATP-independent mechanism. This work sets the stage for future studies of the structural properties that mediate CFTR gating using VX-770 as a probe.

  5. Enhancing tissue permeability with MRI guided preclinical focused ultrasound system in rabbit muscle: From normal tissue to VX2 tumor.

    Science.gov (United States)

    Sun, Yao; Xiong, Xiaobing; Pandya, Darpan; Jung, Youngkyoo; Mintz, Akiva; Hayasaka, Satoru; Wadas, Thaddeus J; Li, King C P

    2017-06-28

    High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, (111)In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of (111)In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24h after systematic delivery of (111)In-DOTA-IA in VX2 tumors pretreated by pHIFU compared

  6. Preclinical Activity of VX-787, a First-in-Class, Orally Bioavailable Inhibitor of the Influenza Virus Polymerase PB2 Subunit

    OpenAIRE

    2014-01-01

    VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m7GTP) cap-binding site of PB2. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compou...

  7. Suprascapular nerve palsy.

    Science.gov (United States)

    Moskowitz, E; Rashkoff, E S

    1989-11-01

    Isolated traumatic suprascapular nerve palsy without associated fracture is a rare occurrence. Localized segmental muscle atrophy limited to the supraspinatus and infraspinatus muscles associated with weakness in initiating abduction and in external rotation of the shoulder should suggest the diagnosis. Electromyography will confirm the diagnosis by excluding nerve root and brachial plexus involvement with denervation potentials limited to the supraspinatus and infraspinatus muscles.

  8. Imaging the hypoglossal nerve

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Pedro [Department of Radiology, Centro Hospitalar de Lisboa Central-Hospital de Sao Jose, Rua Jose Antonio Serrano, 1150-199 Lisboa Codex (Portugal)], E-mail: tojais.pedro@gmail.com

    2010-05-15

    The hypoglossal nerve is a pure motor nerve. It provides motor control to the intrinsic and extrinsic tongue muscles thus being essential for normal tongue movement and coordination. In order to design a useful imaging approach and a working differential diagnosis in cases of hypoglossal nerve damage one has to have a good knowledge of the normal anatomy of the nerve trunk and its main branches. A successful imaging evaluation to hypoglossal diseases always requires high resolution studies due to the small size of the structures being studied. MRI is the preferred modality to directly visualize the nerve, while CT is superior in displaying the bony anatomy of the neurovascular foramina of the skull base. Also, while CT is only able to detect nerve pathology by indirect signs, such as bony expansion of the hypoglossal canal, MRI is able to visualize directly the causative pathological process as in the case of small tumors, or infectious/inflammatory processes affecting the nerve. The easiest way to approach the study of the hypoglossal nerve is to divide it in its main segments: intra-axial, cisternal, skull base and extracranial segment, tailoring the imaging technique to each anatomical area while bearing in mind the main disease entities affecting each segment.

  9. Detection of human butyrylcholinesterase-nerve gas adducts by liquid chromatography-mass spectrometric analysis after in gel chymotryptic digestion.

    Science.gov (United States)

    Tsuge, Kouichiro; Seto, Yasuo

    2006-06-21

    To verify the exposure to nerve gas, a method for detecting human butyrylcholinesterase (BuChE)-nerve gas adduct was developed using LC-electrospray mass spectrometry (ESI-MS). Purified human serum BuChE was incubated with sarin, soman or VX, and the adduct was purified by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and digested in gel by treatment with chymotrypsin. The resulting peptide mixture was subjected to LC-ESI-MS. From the chymotryptic digest of untreated human BuChE, one peak corresponding to the peptide fragment containing the active center serine residue was detected on the extracted ion chromatogram at m/z 948.5, and the sequence was ascertained to be "GESAGAASVSL" by MS/MS analysis. From the chymotryptic digest of the human BuChE-sarin adduct, a singly charged peptide peak was detected on the extracted ion chromatogram at m/z 1,069.5, and the sequence was ascertained to be "GEXAGAASVSL" by MS/MS analysis (X denotes isopropylmethylphosphonylated serine). The difference in molecular weight (120.0 Da) between the active center peptide fragments corresponding to the untreated BuChE and BuChE-sarin adduct was assumed to be derived from the addition of an isopropyl methylphosphonyl moiety to the serine residue. The formation of human BuChE adducts with soman, VX and an aged soman adduct was confirmed by detecting the respective active center peptide fragments using LC-ESI-MS. To apply the established method to an actual biological sample, human serum was incubated with VX, and the adduct was purified by procainamide affinity chromatography followed by SDS-PAGE. After chymotryptic in gel digestion, the ethylphosphonylated active center peptide fragment could be detected, and the structure of the residue was ascertained by LC-ESI-MS analysis.

  10. Biological and artificial nerve conduit for repairing peripheral nerve defect

    Institute of Scientific and Technical Information of China (English)

    Xuetao Xie; Changqing Zhang

    2006-01-01

    OBJECTIVE: Recently, with the development of biological and artificial materials, the experimental and clinical studies on application of this new material-type nerve conduit for treatment of peripheral nerve defect have become the hotspot topics for professorial physicians.DATA SOURCES: Using the terms "nerve conduits, peripheral nerve, nerve regeneration and nerve transplantation" in English, we searched Pubmed database, which was published during January 2000 to June 2006, for the literatures related to repairing peripheral nerve defect with various materials. At the same time, we also searched Chinese Technical Scientific Periodical Database at the same time period by inputting" peripheral nerve defect, nerve repair, nerve regeneration and nerve graft" in Chinese.STUDY SELECTION: The materials were firstly selected, and literatures about study on various materials for repairing peripheral nerve defect and their full texts were also searched. Inclusive criteria: nerve conduits related animal experiments and clinical studies. Exclusive criteria: review or repetitive studies.DATA EXTRACTION: Seventy-nine relevant literatures were collected and 30 of them met inclusive criteria and were cited.DATA SYNTHESTS: Peripheral nerve defect, a commonly seen problem in clinic, is difficult to be solved. Autogenous nerve grafting is still the gold standard for repairing peripheral nerve defect, but because of its application limitation and possible complications, people studied nerve conduits to repair nerve defect. Nerve conduits consist of biological and artificial materials.CONCLUSION: There have been numerous reports about animal experimental and clinical studies of various nerve conduits, but nerve conduit, which is more ideal than autogenous nerve grafting, needs further clinical observation and investigation.

  11. Acupuncture Treatment for Optic Nerve Contusion

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Optic nerve contusion is a commonly-seen eye injury, which is mostly caused by traffic accident, collision, and falling. Early diagnosis and timely emergency treatment can make such patients restore vision to a certain extent. Otherwise, there may appear optic atrophy or loss of vision. At present, in the treatment of this disease, cortical hormone, dehydrating agent, vasodilator, vitamin, energy mixture and neurotrophic agent, or surgical operation can all give certain therapeutic effect. In the recent 5 years, the Department of Ophthalmology of the Hospital Affiliated to Hubei College of Traditional Chinese Medicine has adopted acupuncture for treatment of optic nerve contusion, and obtained quite good therapeutic results. Some typical cases are reported in the following.

  12. Mechanical, electronic and thermodynamic properties of full Heusler compounds Fe2VX(X = Al, Ga)

    Science.gov (United States)

    Khalfa, M.; Khachai, H.; Chiker, F.; Baki, N.; Bougherara, K.; Yakoubi, A.; Murtaza, G.; Harmel, M.; Abu-Jafar, M. S.; Omran, S. Bin; Khenata, R.

    2015-11-01

    The electronic structure, mechanical and thermodynamic properties of Fe2VX, (with X = Al and Ga), have been studied self consistently by employing state-of-the-art full-potential linearized approach of augmented plane wave plus local orbitals (FP-LAPW + lo) method. The exchange-correlation potential is treated with the local density and generalized gradient approximations (LDA and GGA). Our predicted ground state properties such as lattice constants, bulk modulus and elastic constants appear more accurate when we employed the GGA rather than the LDA, and these results are in very good agreement with the available experimental and theoretical data. Further, thermodynamic properties of Fe2VAl and Fe2VGa are predicted with pressure and temperature in the ranges of 0-40 GPa and 0-1500 K using the quasi-harmonic Debye model. We have obtained successfully the variations of the heat capacities, primitive cell volume and volume expansion coefficient.

  13. Time Variation of SiO Masers in VX Sagittarii over an Optically Quiescent Phase

    Science.gov (United States)

    Kamohara, Ryuichi; Deguchi, Shuji; Miyoshi, Makoto; Shen, Zhi-Qiang

    2005-04-01

    The time variation of SiO masers in a semi-regular variable, VX Sgr, was investigated in the period between 1994 and 2004 when the optical light curve exhibited an ˜6-yr quiescent phase intercepting a regularly pulsating era. The quiescent period occurred with a delay of several years after a decrease in the SiO maser flux. VLBA observations of SiO masers made during this period showed no drastic spatial variation except for emission features being shifted from south-west to north-east. The SiO maser flux decrease, and a succeeding optical quiescent phase, may indicate that the stellar mass-loss rate diminished over a few years around 1994. A SiO maser flare occurring in 1999 may be a reminiscence of a final gas blow, which resulted in the optically quiescent period.

  14. Make a 2D RPG in a weekend with RPG maker VX Ace

    CERN Document Server

    Perez, Darrin

    2015-01-01

    Make a 2D RPG in a Weekend shows you how to create your very own dungeon crawler game in RPG Maker VX Ace in a single weekend. The entire process, from start to finish, is covered within this book. You will see a variety of dungeon maps and events, all broken down for your convenience. One of the hardest parts of game development is actually finishing a game, but it is also one of the most important steps on the way to becoming a game developer. If you have yet to finish a game, this book will give you the confidence and resources you need to finally be able to create your very own RPG. Once

  15. High-frequency VLBI Imaging of Sgr A* and VX Sgr

    Science.gov (United States)

    Lu, R.-S.; Krichbaum, T. P.; Zensus, A. J.

    VLBI observations at millimeter wavelengths provide unprecedented high angular resolution and allow to image regions, which are self-absorbed at longer wavelengths. Here we present new results from a multi-frequency VLBA monitoring of SgrA* at 22, 43, and 86 GHz performed on 10 consecutive days in May 2007. We discuss the source structure of Sgr A* through the analysis of the closure phase and closure amplitude, of which the latter improves the calibration accuracy and shows indications of a non-Gaussian brightness distribution at the highest frequency. We also present preliminary maps of the maser emission lines (v=1, J=1-0, and J=2-1) in the circumstellar SiO maser of VX Sgr. This will put new constraints on the kinematics and the pumping mechanisms of SiO masers.

  16. Immediate post-dosing paralysis following severe soman and VX toxicosis in guinea pigs.

    Science.gov (United States)

    Bide, R W; Schofield, L; Risk, D J

    2005-01-01

    There have been numerous studies of the central nervous system (CNS) involvement in organophosphate (OP) poisoning showing status epilepticus and/or 'electrographic seizures'. Brain damage has been demonstrated as 'neuronal necrosis' primarily in the cortex, thalamus and hippocampus. To the authors' knowledge there have been no reports of partial/total paralysis following close upon OP exposure although delayed paralysis has been reported. This report summarizes the immediate, OP induced paralytic events recorded in guinea pigs during development of the Canadian reactive skin decontaminant lotion (RSDL). As part of the development work, supra-lethal cutaneous doses of OP were applied to large numbers of guinea pigs followed by decontamination with the RSDL or predecessor lotions and solvents. Soman (pinacolyl methylphosphonofluoridate; GD) challenges were applied to 1277 animals and S-(2-diisopropyl-aminoethyl) methylphosphorothiolate (VX) challenges to 108. The classic sequence of clinical signs--ptyalism, tremors, fasciculations, convulsions, apnea and flaccid paralysis before death--was seen in the 658 animals that died and in many of the survivors. Eighty-four of 688 survivors of GD and 4 of 39 survivors of VX showed random paralysis of various distal regions following recovery from an insult which produced convulsions and/or flaccid paralysis. Because the experiments were designed to assess the decontamination procedures, there were no apparent relationships between the amounts of OP applied and the sequellae recorded. The observations of paralysis were also incidental to the prime focus of the experiments. Because of this, only ten animals paralysed following GD exposure were examined for histological effects. The pathologist diagnosed 'encephalomalacia' and 'focal necrotic lesions' in the cerebral cortex and 'focal necrotic lesions' in one spinal cord. Of the 84 guinea pigs paralysed after GD challenge, one was not decontaminated and the decontaminants used

  17. Transcatheter Arterial Embolization of Renal VX-2 Carcinoma: Ethiodol-Ethanol Capillary Embolization Combined with Carboplatin

    Energy Technology Data Exchange (ETDEWEB)

    Konya, Andras; Pelt, Carolyn S. Van; Wright, Kenneth C. [The University of Texas MD Anderson Cancer Center, Hoston (United States); Choi, Byung Gil [The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-04-15

    We wanted to determine whether transcatheter Ethiodol-based capillary embolization in combination with carboplatin could improve the efficiency of a 1:1 Ethiodol-ethanol mixture (EEM) to ablate kidneys that been inoculated with VX-2 carcinoma. The right kidney in 34 New Zealand white rabbits were inoculated with fresh VX-2 tumor fragments. One week later, the kidneys were subjected to transarterial treatment (4-5 rabbits/group): Saline infusion (Group 1); carboplatin infusion (5 or 10 mg, Groups 2A and 2B); carboplatin- Ethiodol (CE) alone (Group 3) and followed by main renal artery occlusion with ethanol (RAO) (Group 4); carboplatin-EEM (C-EEM) followed by RAO (Group 5); carboplatin infusion followed by EEM plus RAO (Group 6); and EEM followed by RAO (Group 7). The animals were followed for up to 3-weeks. The treated kidneys were evaluated angiographically and macroscopically. The kidneys that showed successful embolization macroscopically were entirely cut into serial sections, and these were examined microscopically. Histologically, the kidneys were evaluated on the basis of the residual tumor found in the serial sections. The results obtained with carboplatin infusion alone (Groups 2A and 2B) and CE without RAO (Group 3) were similar to those of the control animals (Group 1). Kidneys from Groups 4-7 demonstrated macroscopically successful embolization with histologically proven complete renal parenchyma infarction; however, some residual tumor was evident in all but one animal. None of the Ethiodol-based modalities combined with locoregional carboplatin were more efficacious for tumor ablation than EEM alone.

  18. Changes in nerve microcirculation following peripheral nerve compression

    Institute of Scientific and Technical Information of China (English)

    Yueming Gao; Changshui Weng; Xinglin Wang

    2013-01-01

    Following peripheral nerve compression, peripheral nerve microcirculation plays important roles in regulating the nerve microenvironment and neurotrophic substances, supplying blood and oxygen and maintaining neural conduction and axonal transport. This paper has retrospectively analyzed the articles published in the past 10 years that addressed the relationship between peripheral nerve compression and changes in intraneural microcirculation. In addition, we describe changes in different peripheral nerves, with the aim of providing help for further studies in peripheral nerve microcirculation and understanding its protective mechanism, and exploring new clinical methods for treating peripheral nerve compression from the perspective of neural microcirculation.

  19. Arsenic trioxide treatment of rabbit liver VX-2 carcinoma via hepatic arterial cannulationinduced apoptosis and decreased levels of survivin in the tumor tissue

    OpenAIRE

    LI, HONG; Gong, Jian; Jiang, Xuyuan; Shao, Haibo

    2013-01-01

    Aim To investigate the role of tumor apoptosis-inhibitory protein survivin in arsenic trioxide-induced apoptosis in VX-2 carcinoma in the rabbit liver by means of transcatheter arterial chemoembolization. Methods Sixteen rabbits with 32 implanted hepatic VX-2 tumors were randomly divided into two groups. The experimental group received 2 mg of arsenic trioxide and 1 mL of ultra-fluid lipiodol co-injected via hepatic arterial cannulation and the control group received o...

  20. Research on the Developing of Embedded%基于MPC860/VxWorks的嵌入式系统开发

    Institute of Scientific and Technical Information of China (English)

    韩雪琴; 丁汉清

    2007-01-01

    本文介绍了嵌入式处理器MPC860与嵌入式实时操作系统VxWorks的特点,描述了基于MPC860/VxWorks嵌入式系统开发的流程:使用BDM调试器烧写bootrom文件,使用FTP下载vxworks内核镜像,使用Tornado集成开发环境下载与调试应用程序.

  1. Ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury.

    Science.gov (United States)

    Ma, Junxiong; Li, Wenxian; Tian, Ruifeng; Lei, Wei

    2010-07-05

    Searching for effective drugs which are capable of promoting nerve regeneration after nerve injuries has gained extensive attention. Ginsenoside Rg1 (GRg1) is one of the bioactive compounds extracted from ginseng. GRg1 has been shown to be neuroprotective in many in vitro studies, which raises the possibility of using GRg1 as a neuroprotective agent after nerve injuries. However, such a possibility has never been tested in in vivo studies. The present study was designed to investigate the efficacy of GRg1 in promoting nerve regeneration after nerve crush injury in rats. All rats were randomly divided into four groups (n=8 in each group) after crush injury and were intraperitoneally administrated daily for 4 weeks with 1mg/kg, or 5mg/kg GRg1 (low or high dose GRg1 groups), or 100mug/kg mecobalamin or normal saline, respectively. The axonal regeneration was investigated by retrograde labeling and morphometric analysis. The motor functional recovery was evaluated by electrophysiological studies, behavioral tests and histological appearance of the target muscles. Our data showed that high dose GRg1 achieved better axonal regeneration and functional recovery than those achieved by low dose GRg1 and mecobalamin. The final outcome of low dose GRg1 and mecobalamin was similar in both morphological and functional items, which was significantly better than that in saline group. These findings show that GRg1 is capable of promoting nerve regeneration after nerve injuries, suggesting the possibility of developing GRg1 a neuroprotective drug for peripheral nerve repair applications.

  2. 基于VxWorks的密度反馈控制系统的基本性能分析%Fundamental Performance Analysis for Density Feedback Control System Based on VxWorks

    Institute of Scientific and Technical Information of China (English)

    赵大政; 罗家融

    2004-01-01

    从任务执行时间和实时性两个方面分析了基于Windows与VxWorks双操作系统的HT-7超导托卡马克装置上等离子体密度反馈控制系统(DFCS)的特点,并和基于Windows与Linux下的系统进行了比较.结果表明:基于Windows与VxWroks双操作系统的DFCS具有更好的实时性、更为精确的控制效果以及更加稳定的控制过程.

  3. Design of A Solenoid Valve Control System Based on VxWorks%一种基于 VxWorks 的电磁阀控制系统设计

    Institute of Scientific and Technical Information of China (English)

    张星; 刘巍; 张建国; 付道俊

    2016-01-01

    Solenoid valves are widely used in various control fields .As the control demand enhances ,designing a sole-noid valve control system with real-timing ,accuracy and reliability becomes a key question .This paper proposes a solenoid valve control system based on VxWorks ,describes its hardware and software design in detail .The result of tests shows that the control system is of high performance .%电磁阀广泛应用于各控制领域,随着对控制要求的不断提高,实时、准确、可靠的阀控系统是一大难题。论文提出一种基于 VxWorks 的阀件控制系统,详细介绍了其软硬件设计,并验证了其高性能。

  4. Damaged axillary nerve (image)

    Science.gov (United States)

    Conditions associated with axillary nerve dysfunction include fracture of the humerus (upper arm bone), pressure from casts or splints, and improper use of crutches. Other causes include systemic disorders that cause neuritis (inflammation of ...

  5. Diabetes and nerve damage

    Science.gov (United States)

    Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... In people with diabetes, the body's nerves can be damaged by decreased blood flow and a high blood sugar level. This condition is ...

  6. Sacral nerve stimulation.

    Science.gov (United States)

    Matzel, K E; Stadelmaier, U; Besendörfer, M

    2004-01-01

    The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure) and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

  7. Diabetic Nerve Problems

    Science.gov (United States)

    ... at the wrong times. This damage is called diabetic neuropathy. Over half of people with diabetes get ... you change positions quickly Your doctor will diagnose diabetic neuropathy with a physical exam and nerve tests. ...

  8. Axillary nerve dysfunction

    Science.gov (United States)

    ... is the nerve that helps control the deltoid muscles of the shoulder and the skin around it. A problem with ... can cause difficulty moving your arm. The deltoid muscle of the shoulder may show signs of muscle atrophy . Tests that ...

  9. Degenerative Nerve Diseases

    Science.gov (United States)

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many of these diseases are genetic. Sometimes the cause is a medical ...

  10. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    la Cour, M; Kiilgaard, Jens Folke; Eysteinsson, T

    2000-01-01

    To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide....

  11. 基于MPC860和VxWorks的硬件防火墙设计及实现%Design and implementation of hardware firewall based on MPC860 and VxWorks

    Institute of Scientific and Technical Information of China (English)

    李正熙; 于兴晗; 杨扬; 朱兴

    2007-01-01

    介绍了一款以MPC860 PowerQUICCTM(Quad Unit Integrated Communications Controller)嵌入式通信控制器为核心、嵌入式操作系统VxWorks为操作系统,带有内容过滤功能的硬件防火墙设计与实现,详细阐明各种相关原理和关键技术.

  12. Conjoined lumbosacral nerve roots

    Directory of Open Access Journals (Sweden)

    Atila Yılmaz

    2012-03-01

    Full Text Available Lumbosacral nerve root anomalies are a rare group ofcongenital anatomical anomalies. Various types of anomaliesof the lumbosacral nerve roots have been documentedin the available international literature. Ttheseanomalies may consist of a bifid, conjoined structure, ofa transverse course or of a characteristic anastomizedappearance. Firstly described as an incidental findingduring autopsies or surgical procedures performed forlumbar disk herniations and often asymptomatic, lumbosacralnerve root anomalies have been more frequentlydescribed in the last years due to the advances made inradiological diagnosis.

  13. Design of a fast boot method of VxWorks embedded system based on NOR Flash%一种基于Flash的VxWorks操作系统快速引导方法设计

    Institute of Scientific and Technical Information of China (English)

    肖二宁; 张兴明; 李晗; 魏帅

    2016-01-01

    Pointing to the condition that the embedded system is lack of NVRAM and the write& read speed request is not strict,a fast boot method of operation system based on Flash is designed on the platform of Vxworks operating system,the method uses NOR Flash storage for taking place of NVRAM to store boot information,and a 1+1 fault-tolerant mechanism is used. The test results show that it realizes the fast boot of operation system,and can effectively reduce the erase frequency, extend the service life of Flash,improves the system stability.%针对在嵌入式系统中缺少NVRAM并对读写速度要求不是很高的情况下,以VxWorks操作系统Workbench3.1为平台,设计了一种基于Flash的VxWorks操作系统快速引导方法,该方法通过用NOR Flash存储器代替NVRAM保存引导信息,并运用了1+1容错机制,经验证,该方法实现了VxWorks操作系统的快速引导,并有效降低了Flash的擦除频率,延长了Flash寿命,提高了系统的稳定性。

  14. The stabilization effect of the substituted atoms and the magnetism for intermetallic compounds YFe12-xVx

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Based on the density functional theory(DFT),using linearized augmented plane wave and improved local orbital(APW+lo),the structures and energies of Y,Fe,V,FeV,YFe12-xVx,and Y2Fe17 are optimized and calculated.It is explained that the pure YFe12 with ThMn12-type structure does not exist,and replacing a small fraction of vanadium can stabilize the structure.The local magnetic moments reveal that the decrease of magnetization of YFe12-xVx does not only correspond to a simple dilution of the iron sublattice magnetization,but also reduce the Fe moments as well with increasing vanadium content.

  15. Experimental Study of Multi-slice Spiral CT Perfusion Imaging in VX2 Soft-tissue Tumor of Rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jingfeng; WANG Renfa; WANG Min; LI Yonggang; YANG Haitao

    2006-01-01

    An experimental animal model of malignant soft-tissue tumor was established to investigate the applied value of multi-slice spiral CT perfusion imaging preliminarily. Ten New Zealand white rabbits which were implanted with VX2 tumor in either proximal thigh were subjected to CT plain scan and perfusion scan two weeks later respectively, then the original perfusion images were transmitted to AW4.0 Workstation. The functional maps and perfusion parameters including blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS) were computed and analyzed. All the values of BF, BV and PS in VX2 soft-tissue tumors were obviously higher while the MTT-values were lower than those in the normal muscular tissues significantly. It was suggested that multi-slice spiral CT perfusion imaging is an accurate, convenient and relatively safe functional imaging technique, and can give a quantitative assessment to angiogenesis and blood perfusion of soft-tissue tumors.

  16. 基于VxWorks操作系统的虚拟进程调度设计

    Institute of Scientific and Technical Information of China (English)

    殷锡亮

    2013-01-01

    介绍了实时操作系统的概念,以及应用的场景,提出了在数字通信网络中使用VxWorks实时操作系统的必要性,并基于Vx-Works实时操作系统设计了一种分组Round-Robin调度算法。阐明了任务运行的流程,提出了在任务下创建虚拟进程来使一个任务可以处理不同的响应,说明了虚拟进程运行时如何在三种状态之间进行切换,以及虚拟进程的通用处理流程。

  17. 配备最小USB接收器 罗技VX Nano激光无线鼠标

    Institute of Scientific and Technical Information of China (English)

    激谈

    2007-01-01

    8月17日,罗技推出一款笔记本电脑专用鼠标—VX Nan激光无线鼠标。VX Nano沿袭了VX系列鼠标一贯的卓越性能表现,并特别配备了全球最小的超便携无线USB接收器,同时配合MicroGear精确滚轮及一系列专为笔记本电脑用户定制的细节设计,为频繁出行的笔记本电脑用户带来全面的便携移动解决方案。

  18. Spectroscopic and catalytic investigations of VxOy/SBA-15 and magnesium vanadate model catalysts for selective propene oxidation

    OpenAIRE

    Walter, Anke

    2011-01-01

    The objective of the present work was elucidating structure-activity relationships concerning the individual role of vanadium sites in selective propene oxidation. Two suitable vanadium oxide model catalyst systems were employed: vanadium oxides supported on SBA-15, “VxOy/SBA-15”, and various magnesium vanadate phases. Detailed investigations on the preparation, thermal stability, structure, and structural evolution under reducing and propene oxidizing condition were conducted. Various in sit...

  19. Bioevaluation study of 32P-CP-PLLA particle brachytherapy in a rabbit VX2 lung tumor model.

    Science.gov (United States)

    Xu, Yu ping; Yang, Min; Pan, Dong hui; Wang, Li zhen; Liu, Lu; Huang, Peilin; Shao, Guoqiang

    2012-04-01

    The purpose of this study was to investigate the therapy effects of intratumoral administration of (32)P-CP-PLLA particles in a rabbit VX2 lung tumor model. 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of (32)P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent (18)F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, (18)F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last (18)F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination. Bremsstrahlung SPECT images study indicated that there was no leakage of (32)P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and (32)P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (pCP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Anatomical study of sciatic nerve and common peroneal nerve compression

    Institute of Scientific and Technical Information of China (English)

    Mingzhao Jia; Qing Xia; Jinmin Sun; Qiang Zhou; Weidong Wang

    2008-01-01

    BACKGROUND: Many diseases of the common peroneal nerve are a result of sciatic nerve injury. The present study addresses whether anatomical positioning of the sciatic nerve is responsible for these injuries. OBJECTIVE: To analyze anatomical causes of sciatic nerve and common peroneal nerve injury by studying the relationship between the sciatic nerve and piriformis. DESIGN, TIME AND SETTING: Observe and measure repeatedly. The experiment was conducted in the Department of Anatomy, Tianjin Medical College between January and June 2005. MATERIALS: Fifty-two adult cadavers 33 males and 19 females, with a total of 104 hemispheres, and fixed with formaldehyde, were provided by Tianjin Medical College and Tianjin Medical University. METHODS: A posterior cut was made from the lumbosacral region to the upper leg, fully exposing the piriformis and path of the sciatic nerve. MAIN OUTCOME MEASURES: (1) Anatomical characteristics of the tibial nerve and common peroneal nerve. (2) According to different areas where the sciatic nerve crosses the piriformis, the study was divided into two types--normal and abnormal. Normal is considered to be when the sciatic nerve passes through the infrapiriform foramen. Remaining pathways are considered to be abnormal. (3) Observe the relationship between the suprapiriform foramen, infrapiriform foramen, as well as the superior and inferior space of piriformis. RESULTS: (1) The nerve tract inside the common peroneal nerve is smaller and thinner, with less connective tissue than the tibial nerve. When pathological changes or variations of the piriformis, or over-abduction of the hip joint, occur, injury to the common peroneal nerve often arises due to blockage and compression. (2) A total of 76 hemispheres (73.08%) were normal, 28 were abnormal (26.92%). The piriformis can be injured, and the sciatic nerve can become compressed, when the hip joint undergoes intorsion, extorsion, or abduction. (3) The structures between the infrapiriform and