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Biomedical subjects

J Bajgar

Publications and source records attributed to J Bajgar.

At least 55 records · Page 3Linked to original sources
PubMed1992

Biological monitoring of exposure to nerve agents.

Changes in acetylcholinesterase activity in blood and some organs of rats after intoxication with sarin, soman, VX, and 2-dimethylaminoethyl-(dimethylamido)-phosphonofluoridate (GV), in doses of roughly 2 x LD50 given intramuscularly, were obtained from published data and by experiment. The time course of inhibition of acetylcholinesterase in blood, regions of brain, and diaphragm and the occurrence of signs and symptoms of poisoning (none, salivation, disturbed ventilation and fasciculations, convulsions, or death) were summarised and compared. When blood enzyme activities were 70-100% normal, no obvious signs were seen; at 60-70%, salivation occurred; at less than 30-55%, disturbed ventilation and fasciculations were seen, and at 15-30%, convulsions occurred. Less than 10% was fatal. In experiments with narcotised dogs, the blood acetylcholinesterase activity and the ability to reactivate it with trimedoxime were determined after intoxication by intramuscular administration of the four compounds. It is concluded that acetylcholinesterase activity in the blood corresponds to that in the target organs and can be considered as an appropriate parameter for biological monitoring of exposure to nerve gases. Moreover, determination of reactivation of blood acetylcholinesterase gives more information than simple determination of enzyme activity.

Acetylcholinesterase↗
PubMed1992

Acute toxicities of 2-dialkylaminoalkyl-(dialkylamido)-fluoro-phosphates.

Toxicities expressed as LD50 values of 2-dialkylaminoalkyl-(dialkylamido)-fluorophosphates for rats and mice (i.m. administration) were determined. Rats were more sensitive to these compounds than mice: LD50 values varied from 17 (rats) to 1222 (mice) micrograms/kg. LD50 values at different routes of administration (i.v., i.m., s.c., p.o. and p.c.) for one derivative of this group, 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate, were determined. Depending on the route of administration, LD50 values varied from 11 (i.v.) to 190 (p.o.) micrograms/kg for rats and from 27.6 (i.v.) to 222 (p.o.) micrograms/kg for mice, respectively. Percutaneous toxicity in rats only (LD50 = 1366 micrograms/kg) was determined.

Animals↗
PubMed1992

An evaluation of continual determination of blood cholinesterase activity for inhibition studies.

Simple method of continual monitoring of the rat blood cholinesterase activity in vivo was used to demonstrate its inhibition following i. m. administration of acridine and carbamate inhibitors. Another type of inhibition was demonstrated for different routes of administration of highly toxic organophosphate, VX. Reactivation of the blood cholinesterase was also monitored following intoxication with VX and soman and treated with obidoxime and atropine. This continual determination of cholinesterase activity represents an useful approach to study effects of cholinesterase inhibitors.

Acetylcholinesterase↗
PubMed1992

2-Dialkylaminoalkyl-(dialkylamido)-fluorophosphates: acute toxicities.

Toxicities expressed as LD50 values of 2-dialkylaminoalkyl-(dialkylamid) o-fluorophophates for rats and mice (i. m. administration) were determined. Rats were more sensitive to these compounds than mice: LD50 values varied from 17 to 261 micrograms/kg for rats and from 30.5 to 1222 micrograms/kg for mice, respectively. Different routes of administration in one derivative of this group substituted by methyl groups only were compared. The highest toxicity (lowest LD50 value) in intravenous administration (11 micrograms/kg) and the lowest one in percutaneous (1366 micrograms/kg) were found.

Animals↗
PubMed1992

Changes of acetylcholinesterase activity in hepatectomized rats following soman poisoning.

Acetylcholinesterase activity in the blood, pontomedullar area, basal ganglia of the brain and diaphragm following sublethal soman poisoning (i. m., 31 micrograms/kg) was studied in four groups of rats (n = 6) pretreated as follows: intact, hepatectomized (65 % of resection), sham-operated and narcotized animals. Soman was administered 12 hours following hepatectomy, narcosis or sham-operation, respectively. Except hepatectomized rats, all animals in the groups survived: in hepatectomized rats, 2 animals died. Acetylcholinesterase activity was decreased in each group. The differences among enzyme activities in these groups were not statistically significant for the blood. The highest and significant (p < 0.01) decrease of this activity in the brain parts and diaphragm following hepatectomy was demonstrated. The results indicate that undiminished liver functional capacity is an important factor influencing soman toxicity.

Acetylcholinesterase↗
PubMed1992

Liver and brain DNA contents in acute soman intoxication.

Contents of DNA in the liver and brain parts (cerebellum, pons, hemispheres) of the rat following acute intoxication with soman (i. m., 32 micrograms/kg) were studied. Statistically significant increase of DNA concentrations in the liver and decrease in the hemispheres 1 and 3 hours after the intoxication was demonstrated; in other brain parts studied, no changes were detected. The blood acetylcholinesterase activity was diminished 1 hour after the injection of soman and it was statistically significant 3 days following poisoning. In rats pretreated with atropinee (i. m., 200 mg/kg) and intoxicated with higher dose of soman (i. m., 50 micrograms/kg), specific activity of incorporation of radiolabelled thymidine into DNA was significantly decreased in the liver only. The results suggested that soman except cholinergic effects also influenced metabolism of nucleic acids.

Acute Disease↗
PubMed1991

The influence of inhibitors and other factors on cholinesterases.

Literature survey dealing with cholinesterases and effects of highly toxic organophosphorus compounds suitable for use as chemical weapons is given in introductory part of this work. There are nerve paralytical agents (NPA)--sarin, soman, VX and a model compound O-ethyl-S-(2-dimethylaminoethyl)-methyl-phosphonothioate (EDMM). On the base of described scheme of intoxication with NPA, inhibition effect on cholinesterases, preferably on AChE as the most important factor involved in the mechanism of acute intoxication with NPA was studied. Intoxication of mice or rats with sarin and soman (2 x LD50) showed that time course of poisoning is faster than that for VX or EDMM. Inhibition of AChE in the blood was in good correlation with symptoms of intoxication and also with inhibition of AChE in the brain. The differences between inhibition effect of soman preferably uniform character of inhibition in the brain parts) and sarin (selective inhibition in the brain parts, with maximum in the frontal cortex and pontomedullar area) were observed. This selectivity was most marked for VX and EDMM intoxication (maximal inhibition in the part of the pontomedullar area containing reticular formation). The dose causing inhibition effect in the brain was assessed to be about 1% of the dose administered. The study of the effect of antidotal therapy (combination of atropine and reactivator) in vivo showed in mice and rats intoxicated with sarin non-uniform increase of AChE activity in the pontomedullar part depending on the dose and type of reactivator. The most marked effect was observed for methoxime. It was demonstrated that there exists good correlation between survival of experimental animals and the rest AChE activity in the pontomedullar part of the brain. AChE activity level critical for survival or death of the organism poisoned with NPA was assessed from these experiments; it was about 1-5% of normal values. By means of original method allowing continual monitoring of AChE activity in the blood, similar AChE reactivation was demonstrated, with highest effect for trimedoxime and methoxime. Using continual determination of the blood AChE activity following sarin, soman, VX and EDMM intoxication demonstrated that only a part of the dose administered caused inhibition effect in the blood; this part was determined to be practically 100% (i. v. administration); for other routes of administration this ratio was as follows: 50-80% (i. m.), 20-40% (i. p.), 6-16% (p. o.) and 1-5% (p. c.), respectively. Using this continual monitoring, the detoxication of sarin and soman was demonstrated. Detoxication of VX and EDMM was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
PubMed1991

Efficacy of various pretreatment and therapy regimens against soman lethality in mice.

The efficacy of a number of drug pretreatment combinations in protecting mice against lethal effects of soman was determined. Pyridostigmine peroral pretreatment followed by intramuscular postpoisoning therapy with atropine, obidoxime and/or trimedoxime, and diazepam protected mice against the lethal action of soman. Combination of pyridostigmine with trihexyphenidyl, benactyzine and bis-(4-hydroxyiminomethyl) pyridinium-methane dichloride improved prophylactic action even further.

Animals↗
PubMed1991

Molecular forms of hippocampal acetylcholinesterase and their changes following septal lesions in the rat.

Changes of acetylcholinesterase activity and its molecular forms, extracted by Triton X-100 and separated by polyacrylamide gel electrophoresis, were studied in the rat hippocampus following septal lesions. Detection of acetylcholinesterase was made densitometrically. While the total activity of acetylcholinesterase was decreased, its molecular forms exhibited a different pattern of changes: the heavy forms were decreased, while the light ones were increased. The results support the view that different acetylcholinesterase molecular forms serve different regulatory mechanisms.

Acetylcholinesterase↗
PubMed1989

Inhibition of multiple molecular forms of human brain acetylcholinesterase by different types of inhibitors.

The inhibition of soluble human AChE and its molecular forms following the electrophoretic separation in polyacrylamide gel to four in vitro inhibitors was studied. Also I50 constants pointing on inhibitory concentration responsible of 50% inhibition have been determined as its negative decade logarithm (pI50). Molecular AChE forms were determined to be of various sensitivity. Those of higher molecular weight showed the maximum sensitivity to the action of all inhibitors used. Of them, the most efficient was O-pinacolyl-methylfluorophosphonate which showed the fluctuation of pI50 values from 9.20 to 6.39. Tacrin was the lesser inhibitor (pI50 values ranging from 5.57 to 3.80). The comparison of mean pl50 values of individual forms with experimentally measured value for AChE without electrophoretic separation pointed on a good correlation. The in vitro inhibition of soluble human brain AChE correlated well with the toxicity of substances tested in vivo in rat. The obtained results are remarquable in that various AChE molecular forms should have a different physiologic functions each, and they confirm the cerebral AChE inhibition is of crucial significance for the toxic effect of various inhibitors.

Acetylcholinesterase↗
PubMed1987

[Use of sheep erythrocytes and plasma for the determination of neuroparalytic substances in vitro].

A simple method of the determination of nerve-paralytic substances is presented, based on the use of ram erythrocytes and plasma with the determination of cholinesterase inhibition. Dichlorvos administered at the rate of 94.64 ng per litre induced 50% inhibition of acetylcholinesterase in the erythrocytes; administration of dichlorvos at the rate of 243.82 ng per litre caused a 50% inhibition of butyrylcholinesterase in the plasma.

Acetylcholinesterase↗
PubMed1987

Protective effect of bis-pyridinium compounds on the rat brain acetylcholinesterase inhibition by carbamate in vitro.

The inhibition of the rat brain acetylcholinesterase by quaternary bis-pyridinium compounds and the protection against acetylcholinesterase inhibition by 3-diethyl-aminophenyl-N-methylcarbamate methiodide was studied with three bis-pyridinium compounds. These compounds have two pyridinium rings connected by a dimethylether link and alkyl groups in position 4 of both pyridinium rings. Toxogonin was used as a reference compound. Bis-pyridinium compounds studied are weak reversible inhibitors of acetylcholinesterase (I50 from 10(-4) to 10(-3) M) and exert also the ability to protect acetylcholinesterase against inhibition by 3-diethyl-aminophenyl-N-methylcarbamate methiodide in vitro at a concentration of 0.1 mM. Negligible protection was obtained with Toxogonin.

Animals↗