Vojenské Zdravotnické Listy, 2001 (vol. 70), Suppl.1
THE 6th CZECH AND SLOVAK INTERNATIONAL TOXICOLOGICAL CONFERENCE IN HRADEC KRÁLOVÉ FROM 3rd TO 5th SEPTEMBER 2001
Josef Fusek
MMSL 2001, 70(S1):1 
The Toxicological Section of the Czech Association for Experimental and Clinical Pharmacology and Toxicology of the Czech Purkyně Medical Association, the Toxicological Section of the Slovak Pharmacological Association, the Slovak Medical Association and the Purkyně Military Medical Academy in Hradec Králové held the 6th Czech and Slovak International Toxicological Conference in Hradec Králově from 3rd to 5th September 2001. The Conference took place on the occasion of two important anniversaries ...
TOXICOKINETICS OF NERVE AGENTS
Hendrik P. Benschop, Leo P.A. De Jong
MMSL 2001, 70(S1):2-12
Toxicokinetic studies of nerve agents deal with the in vivo absorption, distribution, and elimination of these agents as a function of animal species, route of administration, dose and time after administration. Such studies provide a quantitative basis for toxicodynamic studies of nerve agents, which should result in causal treatment of intoxications with these agents. While toxicodynamic studies of nerve agents have been intensively pursued since WW II, toxicokinetic studies were only initiated in the last two decennia of the twentieth century. The late start of the latter type of research was caused by the long held but uncorrect assumption...
CRYSTAL STRUCTURE OF HUMAN BUTYRYLCHOLINESTERASE: A KEY STEP FOR ENGINEERING OF CATALYTIC SCAVENGERS AGAINST ORGANOPHOSPHATE POISONING
Patrick Masson, Florian Nachon, Oksana Lockridge
MMSL 2001, 70(S1):13
Enzymes capable of degrading highly toxic organophosphate (OP) esters are emerging as safe and efficient means for destruction of nerve agent stockpiles, remediation of contaminated areas, decontamination of materials. Stoichiometric and catalytic biological scavengers are also promising alternative medical countermeasures against poisoning by nerve agents. Different OP-degrading enzymes are potential candidates for pretreatment, decontamination of skin, mucosa and open wounds or for treatment as supplement to current therapy. Here we will focus on human butyrylcholinesterase (BuChE, EC.3.1.1.8). Our goal is to engineer cholinesterase-based enzymes,...
METHODS FOR RETROSPECTIVE DETECTION OF EXPOSURE TO TOXIC SCHEDULED CHEMICALS: AN OVERVIEW
Daan Noort, Hendrik P. Benschop, Leo P.A. de Jong
MMSL 2001, 70(S1):14-17
Methods to analyze toxic scheduled chemicals (TSC) and their decomposition products in environmental samples have been developed and are widely used. However, methods for such analyses in biological samples have only recently been developed. Retrospective detection of exposure to TSC can be useful for various reasons. First of all, such analytical methods can be used to establish firmly whether casualties have indeed been exposed to these chemicals, whereas dosimetry of the exposure will be a starting point for medical treatment of the intoxication. Second, these methods will be useful for verification of alleged non-adherence to the Chemical Weapons...
RELATIONSHIP BETWEEN TOXICITY AND IN VIVO ANTICHOLINESTERASEPOTENCY IN NERVE AGENTS POISONING
Jiří Bajgar, Josef Fusek, Jiří Kassa, Josef Vachek
MMSL 2001, 70(S1):18-20
Using originally developed method for monitoring of rat blood acetylcholinesterase activity, the toxicity and half-times of enzyme inhibition in vivo were compared following intoxication with highly toxic organophosphates of O-alkyl S-2-dialkylaminoethyl methyl phosphonothiolate type. A linear relationship between these two parameters was demonstrated. On the other hand, similar correlation for sarin and soman was not found. It suggests that mechanism of the toxic effect ofphosphonofluoridates covers more reactions in comparison with phosphonothiolates.
ALTERNATIVE METHODS TO STUDY OP EFFECTS: CELL LINES OR BRAIN CAPILLARY
I Svensson, B Karlsson, L Johansson, A Göransson-Nyberg, G Cassel
MMSL 2001, 70(S1):21
Organophosphates are compounds that are commonly used as pesticides and furthermore conceivable as chemical warfare agents. These compounds are also used for medical treatment in diseases like glaucoma and Alzheimer’s. All of the promising leads to date are based on observations made from in vivo studies conducted in animals and humans, and therefore have a strong mechanistic foundation. A current basic shift in the ethical, scientific and commercial engagement for alternatives to animal experimentation have engaged scientists from academia and industry to the development of alternative, non-animal test methods for assessing the toxic...
A COMPARISON OF THE EFFICACY OF PHARMACOLOGICAL PRETREATMENTS AGAINST SOMAN IN MICE
Jiří Kassa, Josef Vachek, Jiří Bajgar, Josef Fusek
MMSL 2001, 70(S1):22-25
The ability of Czech original mixed pharmacological pretreatment, designated PANPAL (pyridostigmine in combination with benactyzine and trihexyphenidyle) to increase the resistance of soman-exposed mice in the case of non-treated or treated poisoning was compared to the currently used pharmacological pretreatment involving pyridostigmine alone. A significant decrease in the LD50 values of soman in the case of non-treated poisoning of mice was observed when the rats were pretreated with PANPAL. On the other hand, the pharmacological pretreatment with pyridostigmine alone was practically ineffective to protect mice against soman-induced acute toxicity....
USE AND RISKS OF ANTICONVULSANT THERAPY IN NERVE AGENTS POISONINGS IN COMBAT CONDITIONS
S. Rump, M. Kowalczyk, O. Antkowiak, E. Gidynska, E. Galecka
MMSL 2001, 70(S1):26-29
Centrally mediated seizures are one of the toxic signs that occur following poisoning with a very toxic organophosphate (OP) soman (pinacolyl methyl phosphonofluoridate). They are belived to be primarily due to hyperactivity of the cholinergic system as a result of decreased acetylcholinesterase (AChE; EC 3.1.1.7) activity and increased endogenous acetylcholine (ACh) level at central neuronal synapses.This convulsive activity creates a problem for medical management and, if uncontrolled, can lead to brain damage. A combined regimen of prophylaxis and therapy, consisting of pretreatment with pyridostygmine and treatment with atropine and oxime...
EFFICACY OF BIPERIDEN AND HI-6 AS A PROPHYLACTIC COMBINATION AGAINST CONVULSIONS PRODUCED BY A HIGHLY TOXIC ORGANOPHOSPHORUS COMPOUND
Ivan Samnaliev
MMSL 2001, 70(S1):30-32
Inhibition of enzyme acetylcholinesterase (AChE, EC 3.1.1.7.) at central nervous system by highly toxic organophosphorus compounds (OPC) causes a cholinergic crisis which is the most probable “trigger” mechanism for the convulsive activity observed after intoxication. It is known that the convulsions produced by OPC may cause brain damages and long-term effects with neurobehavioral, cognitive and neuromuscular disturbances (McLeod, 1985; USAMRICD report, 1998). Therefore the abolishment of convulsions plays a very important role in the prophylactic of organophosphorus poisoning. Significant attention has been paid to this problem during...
PHARMACOKINETIC STUDIES ON THREE REACTIVATORS OF CHOLINESTERASE
T. K. Ivanov, Ch. D. Dishovski, E. I. Tzerovski, I. J. Petrova
MMSL 2001, 70(S1):33-34
The drug therapy on intoxication with organophosphoric compounds (OPC) included mainly combination of cholinesterase reactivators and cholinolytics (4). A variety 'Of bispyridinium mono- and dioximes have been synthesized over several years in order to improve the treatment of poisoning with highly toxic organophosphates. The “H” -oximes (HI-6 and HLo-7) synthesized by Prof. Hagedorn are the most popular now.Some of the pyridine-heterocyclic oximes, synthesized in Military Medical Academy, Sofia have good protective effect against OPC intoxication. Very important is their anticonvulsive action (3)....
GENOTOXIC EFFECTS OF SOMAN AND OXIME HI-6: THE INDUCTION OF DNA BREAKS AND MICRONUCLEI IN MICE AND CHINESE HAMSTERS
Rudolf Štětina, Radka Nečasová, Petr Šmerák, Ivo Bárta
MMSL 2001, 70(S1):35-37
Soman applied i.m. at doses corresponding to 20% Or 60% Of LD50 did not induce DNA breaks, but only endonuclease III sensitive sites (representing oxidised pyrimidines or abasic sites) in the DNA of lymphocytes and liver cells of male MNRI mice and Chinese hamsters. Significant amount of micronuclei was induced also in polychromatophilic erythrocytes in bone marrow. Neither of these effects was found after application of same doses of sarin related to its toxicity in vivo. Intramuscular application of 2% or 20% LD50 HI-6 oxime induced single strand DNA breaks and endonuclease III sensitive sites. Micronuclei were induced...
QUATERNARY KETOXIMES - NEW PERSPECTIVE COMPOUNDS FOR HYDROLYSIS OF TOXIC ORGANOPHOSPHATES
Radek Cibulka, František Hampl, Hana Kotoučová, Ondřej Páv, Alexandra Šilhánková, František Liška
MMSL 2001, 70(S1):38-40
Micellar systems made of amphiphilic quaternary pyridinium and quinolinium ketoximes readily hydrolyze 4-nitrophenyl diphenyl phosphate. and/or 1-(1-naphtylazo)napht-2-yl diphenyl phosphate, simulants of toxic organophosphates. Reactivity of these functional surfactants towards phosphates depends strongly on the position of their nucleophilic oxime function relative to micellar surface.
DEVELOPMENT OF MEANS FOR THE DECONTAMINATION OF SUPERTOXIC LETHAL CHEMICAL WARFARE AGENTS ON HUMAN SKIN
Jiří Matoušek, Jiří Cabal
MMSL 2001, 70(S1):41-46
Main features Of the R&D resulting in the new mean for primary decontamination based on the sorption-mechanical principle introduced into the Czech Army's individual decon packet IPB-80 and into the Czech Civil Protection first aid kit ZPJ-80, and in the upgrading of sets for secondary decontamination PCHB-6O-P and PCHP-60-P are presented. First results of research on universal solution for decontamination of human skin are shown.
NATURAL CHOLINOTOXINS
Jiří Patočka, Olga Benešová
MMSL 2001, 70(S1):47-49
Natural toxins represent interesting and recently very studied group of substances with great practical meaning. Especially toxins with targeting to cholinergic nervous system, which plays an important role in many physiological and behavioral functions in animals, represent meaningful group of neurotoxins with wide spectrum of clinical use. These Cholinotoxins are the aim of this paper.
NATURAL CHOLINOTOXINS AND PROGRESS IN PSYCHOPHARMACOLOGY
Olga Benešová, Jiří Patočka
MMSL 2001, 70(S1):50-52
The paper reviews the impact of natural cholinotoxin research on the recent knowledge of brain cholinergic neurotransmission, which represents the biological background for learning and memory processes as well as for various psychiatric disorders. Several natural cholinotoxins helped to analyze cholinergic receptor functions on molecular level; others served as models for the synthesis of agents with perspective use in psychopharmacology.