Experts and Doctors on chemical warfare agents in Hradec Králové, Královéhradecký, Czech Republic
Locale: Hradec Králové, Královéhradecký, Czech Republic
Topic: chemical warfare agents
- Bajgar J, Hajek P, Zdarova J, Kassa J, Paseka A, Slizova D, et al. A comparison of tabun-inhibited rat brain acetylcholinesterase reactivation by three oximes (HI-6, obidoxime, and K048) in vivo detected by biochemical and histochemical techniques. J Enzyme Inhib Med Chem. 2010;25:790-7 pubmed publisher..AChE activity in the pontomedullar area and frontal cortex seems to be the most important for the therapeutic effect of the reactivators. HI-6 was not a good reactivator for the treatment of tabun intoxication...
- Kassa J, Karasova J. A comparison of the potency of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) to counteract soman-induced neurotoxicity in rats. Drug Chem Toxicol. 2007;30:117-31 pubmed..The oxime HI-6 is still the best acetylcholinesterase reactivator for the antidotal treatment of acute poisonings with soman...
- Kuca K, Cabal J, Kassa J, Jun D, Hrabinova M. In vitro potency of H oximes (HI-6, HLö-7), the oxime BI-6, and currently used oximes (pralidoxime, obidoxime, trimedoxime) to reactivate nerve agent-inhibited rat brain acetylcholinesterase. J Toxicol Environ Health A. 2006;69:1431-40 pubmed..More than one oxime may be necessary for the antidotal treatment of nerve agent-exposed individuals...
- Musilek K, Jun D, Cabal J, Kassa J, Gunn Moore F, Kuca K. Design of a potent reactivator of tabun-inhibited acetylcholinesterase--synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203). J Med Chem. 2007;50:5514-8 pubmed
- Kuca K, Cabal J, Kassa J. A comparison of the efficacy of a bispyridinium oxime--1,4-bis-(2-hydroxyiminomethylpyridinium) butane dibromide and currently used oximes to reactivate sarin, tabun or cyclosarin-inhibited acetylcholinesterase by in vitro methods. Pharmazie. 2004;59:795-8 pubmed..Thus, oxime K033 seems to be a relatively efficacious broad spectrum acetylcholinesterase reactivator and, therefore, could be useful if no information about the type of nerve agent used was available. ..
- Patocka J, Fusek J. Chemical agents and chemical terrorism. Cent Eur J Public Health. 2004;12 Suppl:S75-7 pubmed..High-toxic chemical substances can fall in terrorist hands through wide range of sources. Potentially misused types of chemical compounds are discussed in this article. ..
- Sevelová L, Vachek J. Effect of methoxime combined with anticholinergic, anticonvulsant or anti-HCN drugs in tabun-poisoned mice. Acta Medica (Hradec Kralove). 2003;46:109-12 pubmed..We established that anticholinergic drug option in the therapeutic mixture of methoxime and anticholinergic drug did not cause the difference in the antidotal treatment effectivities. ..
- Bajgar J, Bartosova L, Kuca K, Jun D, Fusek J. Changes of cholinesterase activities in the rat blood and brain after sarin intoxication pretreated with butyrylcholinesterase. Drug Chem Toxicol. 2007;30:351-9 pubmed..These results demonstrate protective effects of EqBuChE pretreatment in rats intoxicated with sublethal concentrations of sarin by inhalation. ..
- Kassa J, Koupilová M. Neuroprotective effects of antidotes in soman-poisoned rats. Acta Medica (Hradec Kralove). 1999;42:127-31 pubmed
- Kassa J. [Comparison of the effects of BI-6, a new asymmetric bipyridine oxime, with HI-6 oxime and obidoxime in combination with atropine on soman and fosdrine toxicity in mice]. Ceska Slov Farm. 1999;48:44-7 pubmed..At the equi-effective level which respects the toxicity of the oxime and is therefore more important for practical use, it is a therapeutically weaker reactivator of acetylcholinesterase than HI-6. ..
- Kassa J. [The effect of pharmacologic prophylaxis with Panpal on acetylcholinesterase activity in the diaphragm and various parts of the brain in rats during treated and untreated Soman poisoning]. Cas Lek Cesk. 1998;137:299-302 pubmed
- Kassa J. [Comparison of the effect of selected cholinesterase reactivators combined with atropine on soman and fosdrin toxicity in mice]. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl. 1995;38:63-6 pubmed..These findings suggest that HI-6 has definite advantage over obidoxime as well as tetroxime in the treatment of poisoning with not only highly toxic organophosphates but also organophoshorus insecticides. ..
- Gorecki L, Korabecny J, Musilek K, Nepovimova E, Malinak D, Kucera T, et al. Progress in acetylcholinesterase reactivators and in the treatment of organophosphorus intoxication: a patent review (2006-2016). Expert Opin Ther Pat. 2017;27:971-985 pubmed publisher..The importance of detection of OP also has to be taken into consideration. Especially, with the fast spreading toxic effect when death can occur within minutes. ..
- Kuca K, Musilek K, Pohanka M, Dohnal V, Patocka J. Reactivation potency of the acetylcholinesterase reactivator obidoxime is limited. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009;153:259-62 pubmed..It is also needed by the fact that clinical findings considering this oxime are controversial...
- Bajgar J. Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication. Acta Medica (Hradec Kralove). 2010;53:207-11 pubmed..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. ..
- Kassa J, Kunesova G. The benefit of combination of oximes for the neuroprotective efficacy of antidotal treatment of sarin-poisoned rats. Toxicol Mech Methods. 2012;22:260-7 pubmed publisher..Thus, both tested combinations of oximes in combination with atropine bring a small benefit for the neuroprotective efficacy of antidotal treatment of acute sarin poisonings...
- Kassa J, Karasova J, Tesarova S, Musilek K, Kuca K, Jung Y. A comparison of neuroprotective efficacy of the oxime K203 and its fluorinated analogue (KR-22836) with obidoxime in Tabun-poisoned rats. Basic Clin Pharmacol Toxicol. 2010;107:861-7 pubmed publisher..Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime...
- Pohanka M, Adam V, Kizek R. An acetylcholinesterase-based chronoamperometric biosensor for fast and reliable assay of nerve agents. Sensors (Basel). 2013;13:11498-506 pubmed publisher..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. ..
- Kassa J, Bajgar J. Therapeutic efficacy of obidoxime or HI-6 with atropine against intoxication with some nerve agents in mice. Acta Medica (Hradec Kralove). 1996;39:27-30 pubmed..4 Higher doses of both oximes showed significantly more effective therapeutic efficacy against all nerve agents studied...
- Kuca K, Musilek K, Jun D, Pohanka M, Ghosh K, Hrabinova M. Oxime K027: novel low-toxic candidate for the universal reactivator of nerve agent- and pesticide-inhibited acetylcholinesterase. J Enzyme Inhib Med Chem. 2010;25:509-12 pubmed publisher..In the case of cyclosarin- and soman-inhibited AChE, oxime K027 did not reach sufficient reactivation potency. ..
- Kuca K, Jun D, Bajgar J. Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro. Drug Chem Toxicol. 2007;30:31-40 pubmed..Moreover, oxime HI-6 (the most effective one) was not able to reactivate tabun- and soman-inhibited AChE. Due to this fact, it could be designated as a partially broad-spectrum reactivator...
- Kuca K, Cabal J, Jun D, Hrabinova M. In vitro evaluation of acetylcholinesterase reactivators as potential antidotes against tabun nerve agent poisonings. Drug Chem Toxicol. 2006;29:443-9 pubmed..In most cases, the reactivation bell-shaped curve is obtained. The most potent AChE reactivators are selected and provided for further experiments during our development process...
- Kassa J, Kuca K, Cabal J. A comparison of the potency of trimedoxime and other currently available oximes to reactivate tabun-inhibited acetylcholinesterase and eliminate acute toxic effects of tabun. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005;149:419-23 pubmed..The oxime HI-6, so efficacious against soman, does not seem to be sufficiently effective oxime to reactivate tabun-inhibited acetylcholinesterase and to counteract acute lethal effects of tabun...
- Kuca K, Juna D, Musilek K. Structural requirements of acetylcholinesterase reactivators. Mini Rev Med Chem. 2006;6:269-77 pubmed..It is shown that there are several structural fragments possibly involving in the structure of proposed AChE reactivators. Finally, an attempt of a future course of new AChE reactivators development is discussed. ..
- Bartosova L, Kunesova G, Kuca K, Vachek J. Therapeutic efficacy of different antidotal mixtures against poisoning with GF-agent in mice. Acta Medica (Hradec Kralove). 2004;47:249-51 pubmed..The present findings show that all four combinations of oxime with anticholinergic drug decrease the GF-agent toxicity more than twofold regardless of the time of treatment administration. ..
- Kassa J, Krejcova G, Samnaliev I. A comparison of the neuroprotective efficacy of pharmacological pretreatment and antidotal treatment in soman-poisoned rats. Acta Medica (Hradec Kralove). 2003;46:101-7 pubmed..The pharmacological pretreatment containing pyridostigmine and biperiden appears to be more efficacious to eliminate soman-induced neurotoxic sings than PANPAL. ..
- Kassa J, Fusek J. Effect of Panpal pretreatment and antidotal treatment (HI-6 plus benactyzine) on respiratory and circulatory function in soman-poisoned rats. Hum Exp Toxicol. 1997;16:563-9 pubmed
- Bajgar J. Protective effect of reversible cholinesterase inhibitors (tacrine, pyridostigmine) and eqbuche against VX poisoning and brain acetylcholinesterase inhibition in rats. Acta Medica (Hradec Kralove). 2008;51:223-8 pubmed..Tacrine alone or in other combinations has had no better prophylactic effect in comparison with these combinations containing pyridostigmine. Equine butyrylcholinesterase, also protected against VX poisoning very effectively. ..
- Kassa J, Karasova J, Tesarova S, Kuca K, Musilek K. A comparison of the ability of newly-developed bispyridinium oxime K203 and currently available oximes (trimedoxime, obidoxime, HI-6) to counteract the acute neurotoxicity of soman in rats. Toxicol Mech Methods. 2010;20:445-51 pubmed publisher..Thus, the oxime K203 does not provide any beneficial effect for the antidotal treatment of acute poisoning with soman and the oxime HI-6 should be still considered to be the best oxime for antidotal treatment of acute soman poisonings. ..
- Bajgar J, Fusek J, Bartosova L, Jun D, Kuca K. Evaluation of reactivation test in anaesthetized dogs with experimental intoxication with nerve agents. J Appl Toxicol. 2006;26:439-43 pubmed..Thus, the reactivation efficacy of obidoxime during nerve agent intoxication indicates that its repeated administration could be easily monitored using the reactivation test...
- Sevelová L, Bajgar J, Saxena A, Doctor B. Protective effect of equine butyrylcholinesterase in inhalation intoxication of rats with sarin: determination of blood and brain cholinesterase activities. Inhal Toxicol. 2004;16:531-6 pubmed
- Kassa J, Koupilová M, Herink J, Vachek J. The long-term influence of low-level sarin exposure on behavioral and neurophysiological functions in rats. Acta Medica (Hradec Kralove). 2001;44:21-7 pubmed