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[PMID]:27773692
[Au] Autor:Myhrer T; Aas P
[Ad] Endereço:Norwegian Defence Research Establishment (FFI), Protection and Societal Security Division, Kjeller, Norway.
[Ti] Título:Pretreatment and prophylaxis against nerve agent poisoning: Are undesirable behavioral side effects unavoidable?
[So] Source:Neurosci Biobehav Rev;71:657-670, 2016 12.
[Is] ISSN:1873-7528
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The threat of chemical warfare agents like nerve agents requires life saving measures of medical pretreatment combined with treatment after exposure. Pretreatment (pyridostigmine) may cause some side effects in a small number of individuals. A comprehensive research on animals has been performed to clarify effects on behavior. The results from these studies are far from unambiguous, since pyridostigmine may produce adverse effects on behavior in animals in relatively high doses, but not in a consistent way. Other animal studies have examined the potential of drugs like physostigmine, galantamine, benactyzine, trihexyphenidyl, and procyclidine, but they all produce marked behavioral impairment at doses sufficient to contribute to protection against a convulsant dose of soman. Attempts have also been made to develop a combination of drugs capable of assuring full protection (prophylaxis) against nerve agents. However, common to all combinations is that they at anticonvulsant doses cause behavioral deficits. Therefore, the use of limited pretreatment doses may be performed without marked side effects followed by post-exposure therapy with a combination of drugs.
[Mh] Termos MeSH primário: Agentes Neurotóxicos/farmacologia
[Mh] Termos MeSH secundário: Animais
Benactizina
Inibidores da Colinesterase
Seres Humanos
Prociclidina
Soman
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cholinesterase Inhibitors); 0 (Nerve Agents); 595EG71R3F (Benactyzine); 96-64-0 (Soman); C6QE1Q1TKR (Procyclidine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180124
[Lr] Data última revisão:
180124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


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[PMID]:28712549
[Au] Autor:Weissberg A; Madmon M; Elgarisi M; Dagan S
[Ad] Endereço:Department of Analytical Chemistry, Israel Institute for Biological Research (IIBR), P.O.B. 19, Ness Ziona, Israel. Electronic address: aviwe@iibr.gov.il.
[Ti] Título:Determination of trace amounts of G-type nerve agents in aqueous samples utilizing "in vial" instantaneous derivatization and liquid chromatography-tandem mass spectrometry.
[So] Source:J Chromatogr A;1512:71-77, 2017 Aug 25.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A methodology for sensitive determination of sarin (GB), soman (GD) and cyclosarin (GF) chemical warfare agents in aqueous media was developed. The method incorporates direct derivatization with 2-[(dimethylamino)methyl]phenol (2-DMAMP), a commercially available, water-soluble reagent, followed by LC-ESI-MS/MS analysis in the positive ion mode. Five derivatization agents were characterized for their MS/MS fragmentation pattern, and their reaction time, temperature and derivatization-reagent amount were optimized. The developed derivatization reaction is simple, fast (1min) and proceeds at ambient temperature. Sample preparation consists of only the addition of the reagent directly into an injection vial prior to LC-ESI(+)-MS/MS analysis. All 2-DMAMP derivatives were stable for at least 48h and had unique tandem mass spectra characterized by common product ions at m/z 230 and 185. Compared with conventional GC-MS or LC-MS methods, simplicity, better sensitivity and informative MS/MS spectra were achieved by this method. Limits of detection (LODs), identification (LOIs), and quantification (LOQs) were determined in tap water and found to be 1pg/ml, 4pg/ml and 4pg/ml respectively. The proposed methodology is appropriate for routine evaluation of contaminated water supplies and has the advantage of a simultaneous analysis of both derivatized G-nerve agents and their intact hydrolysis products within a single LC-MS analysis.
[Mh] Termos MeSH primário: Substâncias para a Guerra Química/química
Cromatografia Líquida/métodos
Agentes Neurotóxicos/química
Espectrometria de Massas em Tandem/métodos
Poluentes Químicos da Água/química
[Mh] Termos MeSH secundário: Cromatografia Gasosa-Espectrometria de Massas
Hidrólise
Limite de Detecção
Sarina/química
Soman/química
Espectrometria de Massas em Tandem/instrumentação
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chemical Warfare Agents); 0 (Nerve Agents); 0 (Water Pollutants, Chemical); 96-64-0 (Soman); B4XG72QGFM (Sarin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE


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[PMID]:28531843
[Au] Autor:Baygildiev T; Zatirakha A; Rodin I; Braun A; Stavrianidi A; Koryagina N; Rybalchenko I; Shpigun O
[Ad] Endereço:Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, GSP-1, Moscow 119991, Russia.
[Ti] Título:Rapid IC-MS/MS determination of methylphosphonic acid in urine of rats exposed to organophosphorus nerve agents.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1058:32-39, 2017 Jul 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A direct approach for the determination of a specific hydrolysis product of organophosphorus nerve agents such as methylphosphonic acid (MPA) in urine by ion chromatography and tandem mass spectrometry (IC-MS/MS) has been developed. The first advantage of the proposed approach is a rapid and simple sample preparation, which does not require a large sample volume, complicated and laborious preconcentration and derivatization steps, and takes less than 7min per sample. The second advantage is the fast and selective IC determination of MPA carried out on a noncommercial anion exchanger based on a poly(styrene-co-divinylbenzene) (PS-DVB) substrate with a high degree of crosslinking and a covalently-bonded branched functional layer, which enables complete resolution of MPA from major urine matrix components and allows one to overcome matrix effects. Hyphenation of IC with tandem mass spectrometry results in highly sensitive and reliable MPA determination with the lowest detection limit (4ngmL ) reported so far for HPLC determination of MPA in urine. The proposed approach is successfully applied for the analysis of urine from rats exposed to nonlethal doses of organophosphorus nerve agents such as sarin, soman, and VR in up to 13days after initial exposure, which shows the possibility to verify the nerve agent exposure after a long period of time.
[Mh] Termos MeSH primário: Agentes Neurotóxicos/metabolismo
Compostos Organofosforados/urina
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Limite de Detecção
Modelos Lineares
Compostos Organofosforados/metabolismo
Compostos Organotiofosforados/administração & dosagem
Compostos Organotiofosforados/metabolismo
Ratos
Reprodutibilidade dos Testes
Sarina/administração & dosagem
Sarina/metabolismo
Soman/administração & dosagem
Soman/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nerve Agents); 0 (Organophosphorus Compounds); 0 (Organothiophosphorus Compounds); 0 (S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate); 329W4YM10Z (methylphosphonic acid); 96-64-0 (Soman); B4XG72QGFM (Sarin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE


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[PMID]:28418831
[Au] Autor:Kassa J; Korábecný J; Nepovimová E
[Ad] Endereço:Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic. kassa@pmfhk.cz.
[Ti] Título:The Evaluation of Benefit of Newly Prepared Reversible Inhibitors of Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological Pretreatment of Soman-Poisoned Mice.
[So] Source:Acta Medica (Hradec Kralove);60(1):37-43, 2017.
[Is] ISSN:1211-4286
[Cp] País de publicação:Czech Republic
[La] Idioma:eng
[Ab] Resumo:AIM: The ability of four newly prepared reversible inhibitors of acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and currently used carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated. METHODS: The evaluation of the effect of pharmacological pretreatment is based on the identification of changes of soman-induced toxicity that was evaluated by the assessment of its LD50 value and its 95% confidence limit using probitlogarithmical analysis of death occurring within 24 h after administration of soman. RESULTS: 6-chlorotacrine was only able to markedly protect mice against acute toxicity of soman. In addition, the pharmacological pretreatment with 6-chlorotacrine or compound 2 was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. The other newly prepared reversible inhibitors of acetylcholinesterase (7-phenoxytacrine, compound 1) as well as commonly used pyridostigmine did not influence the efficacy of antidotal treatment. CONCLUSION: These findings demonstrate that pharmacological pretreatment of somanpoisoned mice can be promising and useful in the case of administration of 6-chlorotacrine and partly compound 2.
[Mh] Termos MeSH primário: Inibidores da Colinesterase/farmacologia
Compostos de Piridínio/farmacologia
Soman/envenenamento
[Mh] Termos MeSH secundário: Animais
Quimioterapia Combinada
Seres Humanos
Isoquinolinas
Masculino
Camundongos
Compostos de Piridínio/administração & dosagem
Brometo de Piridostigmina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1,10-bis(pyridinium)decane); 0 (1,8-bis(4-tert-butylpyridinium)oct-1,8-diyl); 0 (1,8-bis(isoquinolinium)-oct-1,8-diyl); 0 (Cholinesterase Inhibitors); 0 (Isoquinolines); 0 (Pyridinium Compounds); 96-64-0 (Soman); KVI301NA53 (Pyridostigmine Bromide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.14712/18059694.2017.45


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[PMID]:28109985
[Au] Autor:Althaus AL; McCarren HS; Alqazzaz A; Jackson C; McDonough JH; Smith CD; Hoffman E; Hammond RS; Robichaud AJ; Doherty JJ
[Ad] Endereço:Drug Discovery, Sage Therapeutics, Inc., Cambridge, MA, USA. Electronic address: alison.althaus@sagerx.com.
[Ti] Título:The synthetic neuroactive steroid SGE-516 reduces status epilepticus and neuronal cell death in a rat model of soman intoxication.
[So] Source:Epilepsy Behav;68:22-30, 2017 Mar.
[Is] ISSN:1525-5069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Organophosphorus nerve agents (OPNAs) are irreversible inhibitors of acetylcholinesterase that pose a serious threat to public health because of their use as chemical weapons. Exposure to high doses of OPNAs can dramatically potentiate cholinergic synaptic activity and cause status epilepticus (SE). Current standard of care for OPNA exposure involves treatment with cholinergic antagonists, oxime cholinesterase reactivators, and benzodiazepines. However, data from pre-clinical models suggest that OPNA-induced SE rapidly becomes refractory to benzodiazepines. Neuroactive steroids (NAS), such as allopregnanolone, retain anticonvulsant activity in rodent models of benzodiazepine-resistant SE, perhaps because they modulate a broader variety of GABA receptor subtypes. SGE-516 is a novel, next generation NAS and a potent and selective GABA receptor positive allosteric modulator (PAM). The present study first established that SGE-516 reduced electrographic seizures in the rat lithium-pilocarpine model of pharmacoresistant SE. Then the anticonvulsant activity of SGE-516 was investigated in the soman-intoxication model of OPNA-induced SE. SGE-516 (5.6, 7.5, and 10mg/kg, IP) significantly reduced electrographic seizure activity compared to control when administered 20min after SE onset. When 10mg/kg SGE-516 was administered 40min after SE onset, seizure activity was still significantly reduced compared to control. In addition, all cohorts of rats treated with SGE-516 exhibited significantly reduced neuronal cell death as measured by FluoroJade B immunohistochemistry. These data suggest synthetic NASs that positively modulate both synaptic and extrasynaptic GABA receptors may be candidates for further study in the treatment of OPNA-induced SE.
[Mh] Termos MeSH primário: Anticonvulsivantes/farmacologia
Morte Celular/efeitos dos fármacos
Moduladores GABAérgicos/farmacologia
Neurônios/efeitos dos fármacos
Neurotransmissores/farmacologia
Convulsões/tratamento farmacológico
Soman
Estado Epiléptico/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Anticonvulsivantes/uso terapêutico
Convulsivantes
Moduladores GABAérgicos/uso terapêutico
Masculino
Neurotransmissores/uso terapêutico
Pilocarpina
Ratos
Ratos Sprague-Dawley
Convulsões/induzido quimicamente
Estado Epiléptico/induzido quimicamente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Convulsants); 0 (GABA Modulators); 0 (Neurotransmitter Agents); 01MI4Q9DI3 (Pilocarpine); 96-64-0 (Soman)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170123
[St] Status:MEDLINE


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[PMID]:27799295
[Au] Autor:Miller SL; Aroniadou-Anderjaska V; Pidoplichko VI; Figueiredo TH; Apland JP; Krishnan JK; Braga MF
[Ad] Endereço:Departments of Anatomy, Physiology, and Genetics (S.L.M., V.A.-A., V.I.P., T.H.F., J.K.S.K., M.F.M.B.) and Psychiatry (V.A.-A., M.F.M.B.), and Program in Neuroscience (S.L.M., V.A.-A., M.F.M.B.), F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Mar
[Ti] Título:The M1 Muscarinic Receptor Antagonist VU0255035 Delays the Development of Status Epilepticus after Organophosphate Exposure and Prevents Hyperexcitability in the Basolateral Amygdala.
[So] Source:J Pharmacol Exp Ther;360(1):23-32, 2017 Jan.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Exposure to organophosphorus toxins induces seizures that progress to status epilepticus (SE), which can cause brain damage or death. Seizures are generated by hyperstimulation of muscarinic receptors, subsequent to inhibition of acetylcholinesterase; this is followed by glutamatergic hyperactivity, which sustains and reinforces seizure activity. It has been unclear which muscarinic receptor subtypes are involved in seizure initiation and the development of SE in the early phases after exposure. Here, we show that pretreatment of rats with the selective M receptor antagonist, VU0255035 [N-(3-oxo-3-(4-(pyridine-4-yl)piperazin-1-yl)propyl)-benzo[c][1,2,5]thiadiazole-4 sulfonamide], significantly suppressed seizure severity and prevented the development of SE for about 40 minutes after exposure to paraoxon or soman, suggesting an important role of the M receptor in the early phases of seizure generation. In addition, in in vitro brain slices of the basolateral amygdala (a brain region that plays a key role in seizure initiation after nerve agent exposure), VU0255035 blocked the effects produced by bath application of paraoxon-namely, a brief barrage of spontaneous inhibitory postsynaptic currents, followed by a significant increase in the ratio of the total charge transferred by spontaneous excitatory postsynaptic currents over that of the inhibitory postsynaptic currents. Furthermore, paraoxon enhanced the hyperpolarization-activated cation current I in basolateral amygdala principal cells, which could be one of the mechanisms underlying the increased glutamatergic activity, an effect that was also blocked in the presence of VU0255035. Thus, selective M antagonists may be an efficacious pretreatment in contexts in which there is risk for exposure to organophosphates, as these antagonists will delay the development of SE long enough for medical assistance to arrive.
[Mh] Termos MeSH primário: Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos
Paraoxon/toxicidade
Receptor Muscarínico M1/antagonistas & inibidores
Soman/toxicidade
Estado Epiléptico/induzido quimicamente
Estado Epiléptico/prevenção & controle
Sulfonamidas/farmacologia
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Animais
Complexo Nuclear Basolateral da Amígdala/patologia
Complexo Nuclear Basolateral da Amígdala/fisiopatologia
Masculino
Ratos
Ratos Sprague-Dawley
Estado Epiléptico/patologia
Estado Epiléptico/fisiopatologia
Sinapses/efeitos dos fármacos
Sinapses/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(3-oxo-3-(4-(pyridin-4-yl)piperazin-1-yl)propyl)benzo(c)(1,2,5)thiadiazole-4-sulfonamide); 0 (Receptor, Muscarinic M1); 0 (Sulfonamides); 0 (Thiadiazoles); 96-64-0 (Soman); Q9CX8P80JW (Paraoxon)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161102
[St] Status:MEDLINE


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[PMID]:27718463
[Au] Autor:Liu CC; Huang GL; Xi HL; Liu SL; Liu JQ; Yu HL; Zhou SK; Liang LH; Yuan L
[Ad] Endereço:State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China; Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing 102205, China.
[Ti] Título: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.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1036-1037:57-65, 2016 Nov 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo: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 for VX-NP, 2.00-200ngmL for GD-NP and MeP-NP (R ≥0.995), and 3.00-200ngmL for BChE NP (R ≥0.990). The inter-day precision had relative standard deviation (%RSD) of <8.89%, and the accuracy ranged between 88.9-120%. The limit of detection was calculated to be 0.411, 0.750, 0.800 and 1.43ngmL for 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 and 0.50ngmL 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 method, the adducted BChE levels from VX and GD-exposed (0.10-100ngmL ) plasma samples were completely characterized, and the fact that VX being more active and specific to BChE than GD was re-confirmed.
[Mh] Termos MeSH primário: Butirilcolinesterase/sangue
Substâncias para a Guerra Química/farmacocinética
Inibidores da Colinesterase/sangue
Compostos Organofosforados/sangue
Compostos Organotiofosforados/sangue
Soman/sangue
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Butirilcolinesterase/isolamento & purificação
Inibidores da Colinesterase/isolamento & purificação
Cromatografia Líquida de Alta Pressão/instrumentação
Cromatografia Líquida de Alta Pressão/métodos
Desenho de Equipamento
Géis/química
Seres Humanos
Limite de Detecção
Compostos Organofosforados/isolamento & purificação
Compostos Organotiofosforados/isolamento & purificação
Procainamida/química
Soman/isolamento & purificação
Espectrometria de Massas em Tandem/instrumentação
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Chemical Warfare Agents); 0 (Cholinesterase Inhibitors); 0 (Gels); 0 (Organophosphorus Compounds); 0 (Organothiophosphorus Compounds); 329W4YM10Z (methylphosphonic acid); 96-64-0 (Soman); 9A4381183B (VX); EC 3.1.1.8 (Butyrylcholinesterase); L39WTC366D (Procainamide)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161009
[St] Status:MEDLINE


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[PMID]:27639501
[Au] Autor:Worek F; Seeger T; Neumaier K; Wille T; Thiermann H
[Ad] Endereço:Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany. Electronic address: franzworek@bundeswehr.org.
[Ti] Título:Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.
[So] Source:Toxicol Lett;262:12-16, 2016 Nov 16.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo: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.
[Mh] Termos MeSH primário: Substâncias para a Guerra Química/toxicidade
Baratas/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Arsenicais
Vesícula/induzido quimicamente
Vesícula/patologia
Substâncias para a Guerra Química/química
Inibidores da Colinesterase/toxicidade
Feminino
Masculino
Gás de Mostarda/toxicidade
Agentes Neurotóxicos/toxicidade
Compostos Organofosforados/toxicidade
Projetos Piloto
Sarina/toxicidade
Soman/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Arsenicals); 0 (Chemical Warfare Agents); 0 (Cholinesterase Inhibitors); 0 (Nerve Agents); 0 (Organophosphorus Compounds); 0N54LGU5WS (lewisite); 96-64-0 (Soman); B4XG72QGFM (Sarin); T8KEC9FH9P (Mustard Gas); VM36F9N236 (cyclohexyl methylphosphonofluoridate)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160919
[St] Status:MEDLINE


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[PMID]:27509164
[Au] Autor:Ash T; Debnath T; Banu T; Das AK
[Ad] Endereço:Department of Spectroscopy, Indian Association for the Cultivation of Science , Jadavpur, Kolkata-700032, India.
[Ti] Título:Exploration of Unimolecular Gas-Phase Detoxication Pathways of Sarin and Soman: A Computational Study from the Perspective of Reaction Energetics and Kinetics.
[So] Source:Chem Res Toxicol;29(9):1439-57, 2016 Sep 19.
[Is] ISSN:1520-5010
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A mechanistic investigation has been carried out to explore all possible gas phase unimolecular isomerization as well as decomposition pathways of toxic organophosphorus compounds (OPCs), namely, sarin (GB) and soman (GD), which are better known as nerve agents. We have identified a total of 13 detoxication pathways for sarin, where the α-H, ß-H, and γ-H take part in the H-transfer process. However, for soman, due to the presence of ω-H, three additional detoxication pathways are obtained, where the ω-H is involved in the H-transfer process. Among all the pathways, the D3 decomposition pathway, where the phosphorus oxoacid derivative and alkene are generated via the formation of a six-membered ring in the transition state, is identified as the most feasible pathway from the perspective of both activation barrier and reaction enthalpy values. Moreover, we have studied the feasibility of the isomerization and decomposition pathways by performing the reaction kinetics in the temperature range of 300 K-1000 K using the one-dimensional Rice-Ramsperger-Kassel-Marcus (RRKM) master equation. From the RRKM calculation also, D3 pathway is confirmed as the most feasible pathway for both OPCs. The rate constant values associated with the D3 pathway within the temperature range of 600 K-700 K imply that the degradation of the OPCs is possible within this temperature range via the D3 pathway, which is in good agreement with the earlier reported experimental result. It is also observed that at higher temperature range (∼900 K), the increased rate constant values of other detoxication pathways indicate that along with D3, all other pathways become more or less equally feasible. Therefore, the entire work provides a widespread idea about the kinetic as well as thermodynamic feasibility of the explored detoxication pathways of the titled OPCs.
[Mh] Termos MeSH primário: Sarina/metabolismo
Soman/metabolismo
Termodinâmica
[Mh] Termos MeSH secundário: Gases
Cinética
Estrutura Molecular
Transição de Fase
Sarina/química
Sarina/toxicidade
Soman/química
Soman/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gases); 96-64-0 (Soman); B4XG72QGFM (Sarin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160811
[St] Status:MEDLINE
[do] DOI:10.1021/acs.chemrestox.6b00132


  10 / 1292 MEDLINE  
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[PMID]:27287416
[Au] Autor:Joosen MJ; Vester SM; Hamelink J; Klaassen SD; van den Berg RM
[Ad] Endereço:TNO, CBRN Protection, P.O. Box 45, 2280 AA Rijswijk, The Netherlands. Electronic address: Marloes.joosen@tno.nl.
[Ti] Título:Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.
[So] Source:Chem Biol Interact;259(Pt B):115-121, 2016 Nov 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes.
[Mh] Termos MeSH primário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Agentes Neurotóxicos/envenenamento
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética
Acetilcolinesterase/sangue
Acetilcolinesterase/metabolismo
Animais
Atropina/metabolismo
Atropina/uso terapêutico
Barreira Hematoencefálica/efeitos dos fármacos
Barreira Hematoencefálica/metabolismo
Encéfalo/enzimologia
Encéfalo/metabolismo
Cães
Células Madin Darby de Rim Canino
Masculino
Oximas/metabolismo
Oximas/uso terapêutico
Compostos de Piridínio/metabolismo
Compostos de Piridínio/uso terapêutico
Quinolinas/farmacologia
Quinolinas/uso terapêutico
Ratos
Ratos Wistar
Convulsões/induzido quimicamente
Convulsões/tratamento farmacológico
Convulsões/metabolismo
Soman/toxicidade
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Nerve Agents); 0 (Oximes); 0 (Pyridinium Compounds); 0 (Quinolines); 7C0697DR9I (Atropine); 96-64-0 (Soman); EC 3.1.1.7 (Acetylcholinesterase); HUV88P6SJS (asoxime chloride); J58862DTVD (tariquidar)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160612
[St] Status:MEDLINE



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