Experts and Doctors on chemical warfare agents in Hradec Králové, Královéhradecký, Czech Republic

Summary

Locale: Hradec Králové, Královéhradecký, Czech Republic
Topic: chemical warfare agents

Top Publications

  1. Kassa J, Karasova J. A comparison of the potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to counteract tabun-induced neurotoxicity in rats. Toxicology. 2007;229:136-44 pubmed
    ..Due to their neuroprotective effects, both newly developed oximes (especially K075) appear to be more suitable oximes for the antidotal treatment of acute tabun poisonings than the oxime HI-6. ..
  2. Soukup O, Tobin G, Kumar U, Binder J, Proska J, Jun D, et al. Interaction of nerve agent antidotes with cholinergic systems. Curr Med Chem. 2010;17:1708-18 pubmed
    ..Furthermore, non-cholinesterase coupled antidotal effects of the oximes are thoroughly discussed. These antidotal effects principally include oxime interactions with muscarinic and nicotinic receptors. ..
  3. Kassa J. [Effect of diazepam on the effectiveness of antidote therapy in eliminating the acute lethal effects of soman in mice]. Cas Lek Cesk. 2001;140:497-9 pubmed
  4. Kassa J, Krejèová G. Neuroprotective effects of currently used antidotes in tabun-poisoned rats. Pharmacol Toxicol. 2003;92:258-64 pubmed
  5. Kassa J, Karasova J. The evaluation of the neuroprotective effects of bispyridinium oximes in tabun-poisoned rats. J Toxicol Environ Health A. 2007;70:1556-67 pubmed
    ..Due to its neuroprotective effects, trimedoxime may be considered to be more suitable oxime for the antidotal treatment of acute tabun exposure than currently used oximes (obidoxime, HI-6) and the newly synthesized oxime K075. ..
  6. Bajgar J, Sevelová L, Krejcova G, Fusek J, Vachek J, Kassa J, et al. Biochemical and behavioral effects of soman vapors in low concentrations. Inhal Toxicol. 2004;16:497-507 pubmed
    ..Summarizing, long-term effects (4 wk) were observed after inhalation exposure of guinea pigs to sublethal concentrations of soman. ..
  7. Pohanka M, Stetina R, Svobodová H, Ruttkay Nedecky B, Jilkova M, Sochor J, et al. Sulfur mustard causes oxidative stress and depletion of antioxidants in muscles, livers, and kidneys of Wistar rats. Drug Chem Toxicol. 2013;36:270-6 pubmed publisher
    ..Significant OS, depletion of low-molecular-mass antioxidants, increase in caspase activity, and some other processes related to SM action were determined. Moreover, we infer a principal role of OS in the tested organs. ..
  8. Kassa J. Therapeutic and neuroprotective efficacy of pharmacological pretreatment and antidotal treatment of acute tabun or soman poisoning with the emphasis on pretreatment drug PANPAL. Arh Hig Rada Toksikol. 2006;57:427-34 pubmed
  9. Kassa J, Jun D, Kuca K. The reactivating and therapeutic efficacy of oximes to counteract Russian VX poisonings. Int J Toxicol. 2006;25:397-401 pubmed
    ..Thus, the oxime HI-6 seems to be the most suitable oxime for the antidotal treatment of acute poisonings with Russian VX as in the case of VX, sarin, cyclosarin, and soman poisonings...

More Information

Publications47

  1. 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...
  2. 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...
  3. 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...
  4. 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
  5. Kassa J, Sepsova V, Musilek K, Horova A. The evaluation of the reactivating and therapeutic efficacy of three novel bispyridinium oximes (K454, K456, K458) in comparison with the oxime K203 and trimedoxime in tabun-poisoned rats and mice. Toxicol Mech Methods. 2013;23:94-8 pubmed publisher
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. 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. ..
  10. Kassa J, Koupilová M. Neuroprotective effects of antidotes in soman-poisoned rats. Acta Medica (Hradec Kralove). 1999;42:127-31 pubmed
  11. 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. ..
  12. 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
  13. 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. ..
  14. 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. ..
  15. 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...
  16. Kassa J, Karasova J, Sepsova V, Caisberger F. The benefit of combinations of oximes for the reactivating and therapeutic efficacy of antidotal treatment of sarin poisoning in rats and mice. Basic Clin Pharmacol Toxicol. 2011;109:30-4 pubmed publisher
  17. 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. ..
  18. 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...
  19. 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...
  20. Kassa J, Misik J, Karasova J. Evaluation of the potency of two novel bispyridinium oximes (K456, K458) in comparison with oxime K203 and trimedoxime to counteract tabun-induced neurotoxicity in rats. Basic Clin Pharmacol Toxicol. 2013;113:201-8 pubmed publisher
  21. 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. ..
  22. 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...
  23. 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. ..
  24. Kassa J, Karasova J, Caisberger F, Bajgar J. The influence of combinations of oximes on the reactivating and therapeutic efficacy of antidotal treatment of soman poisoning in rats and mice. Toxicol Mech Methods. 2009;19:547-51 pubmed publisher
  25. 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...
  26. 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...
  27. 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...
  28. 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. ..
  29. 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. ..
  30. 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. ..
  31. 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
  32. 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. ..
  33. Kassa J, Karasova J, Kuca K, Musilek K. A comparison of the reactivating and therapeutic efficacy of newly developed oximes (K347, K628) with commonly used oximes (obidoxime, HI-6) against tabun in rats and mice. Drug Chem Toxicol. 2010;33:227-32 pubmed publisher
  34. 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. ..
  35. 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...
  36. Kassa J, Misik J, Karasova J. A comparison of the potency of a novel bispyridinium oxime K203 and currently available oximes (obidoxime, HI-6) to counteract the acute neurotoxicity of sarin in rats. Basic Clin Pharmacol Toxicol. 2012;111:333-8 pubmed publisher
  37. 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
  38. 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