Biomedical subjects

J Bajgar

Publications and source records attributed to J Bajgar.

At least 37 records · Page 2Linked to original sources

PubMed1996

Therapeutic efficacy of obidoxime or HI-6 with atropine against intoxication with some nerve agents in mice.

1 The toxicity of pinacolyl methylphosphonofluoridate (soman, GD), cyclohexyl methylphosphonofluoridate (cyclohe xylsarin, GF) and 2-dimethylaminoethyl-(dimethylamido)-phosphonofluoridate (GV) and the therapeutic efficacy of two oximes (obidoxime and HI-6) in combination with atropine against mentioned nerve agents were evaluated in mice. 2 The 24-h i.m. LD50 of GD was 101 micrograms/kg (99.5-104.0), LD50 of GF was 170 micrograms/kg (151.0-190.0 and LD50 of GV was 25.2 micrograms/kg (23.0-27.7). 3 The efficacy of two oximes, obidoxime (15 and 30 mg/kg) or HI-6 (15 and 30 mg/kg) in combination with atropine (21 mg/kg) was tested. HI-6 was significantly more effective in reducing mortality than obidoxime following poisoning with all three nerve agents. 4 Higher doses of both oximes showed significantly more effective therapeutic efficacy against all nerve agents studied.

Animals↗

PubMed1996

Toxicities of O-alkyl S-(2-dialkylaminoethyl) methyl phosphonothiolates (V-compounds).

Toxicities expressed as LD50 values of O-alkyl S-(2-dialkylaminoethyl) methyl phosphonothiolates in different species and different routes of administration were determined. Rats were more sensitive to these compounds than mice, rabbits and guinea-pigs were more sensitive than mice and rats. The most sensitive to these compounds were dogs. LD50 values varied in a wide range, however, a decrease of toxicity was observed in the following rank: i.v., i.m., s.c., i.p., p.o. and p.c., respectively. Depending on the route of administration, LD50 values varied from 5 g/kg (i.m., dogs) through tens of microgram/kg for the most part of compounds and routes of administration to hundreds, rarely thousands of g/kg (some chemicals, p.c. administration).

Animals↗

PubMed1996

Present views on toxidynamics of soman poisoning.

This paper summarizes present views on effects of soman (O-pinacolyl methylphosphonofluoridate) and on possibilities of treatment of intoxication with this highly toxic compound. Simultaneously, it indicates the problems need to be solved. On this base only, it will be possible to improve the therapy of soman intoxication which is not sufficiently effective at present.

Animals↗

PubMed1995

Differential reactivation by HI-6 in vivo of paraoxon-inhibited rat brain acetylcholinesterase molecular forms.

The effects of the cholinesterase reactivator HI-6, [1-(((4-(aminocarbonyl)-piridinio)methoxy)methyl-2-(hydroxy- imino)methyl pyridinium dichloride], on paraoxon-inhibited brain acetylcholinesterase (AChE) and its molecular forms were studied in rats. Treatment with paraoxon (0.25 mg/kg s.c.) caused approx. 60% inhibition of total AChE from frontal cerebral cortex, while that including HI-6 (140 mg/kg i.m.) and atropine (50 mg/kg i.m.) reduced such inhibition to only 25%. Two molecular forms of the enzyme, 10S and 4S, corresponding to globular tetrameric (G4) and monomeric (G1), were detected by sucrose gradient sedimentation. In paraoxon treated rats the G4 form was inhibited by approx. 65% while G1 only by 35%. The G4 form was considerably and selectively reactivated by HI-6 while the G1 form was not reactivated at all. The data show that HI-6 penetrates the blood-brain barrier and reactivates the molecular forms preferentially inhibited by paraoxon and involved in synaptic neurotransmission.

Animals↗

PubMed1995

Differential inhibition of rat brain acetylcholinesterase molecular forms by 7-methoxytacrine in vitro.

The effects of 7-methoxytacrine (7-MEOTA), a less toxic derivative of tetrahydroaminoacridine, on the activity of acetylcholinesterase (AChE) molecular forms were investigated in vitro. AChE molecular forms were separated by sucrose gradient sedimentation from homogenates of the frontal cerebral cortex prepared with buffer containing Triton X-100 (soluble + membrane-bound enzyme). Two molecular forms, namely 10S and 4S corresponding to globular tetrameric (G4) and monomeric (G1) forms, respectively, were detected; their molecular weights were 220,000 and 54,000 Da. A significantly higher sensitivity to 7-MEOTA of G4 than of G1 forms was observed. The Ki values were 0.21 +/- 0.07 microM for the former and 0.70 +/- 0.15 microM for the latter. The differential inhibition of AChE molecular forms by 7-MEOTA is discussed in relation to its possible clinical application for treatment of disorders such as Alzheimer's disease, in which a reduction of brain cholinergic neurotransmission is believed to play a role.

Acetylcholinesterase↗

PubMed1995

Comparison of the efficacy of HI-6 and obidoxime against cyclohexyl methylphosphonofluoridate (GF) in rats.

1. The efficacy of HI-6 and obidoxime in combination with atropine on cyclohexyl methylphosphonofluoridate (GF)-induced cholinergic and stressogenic effects in rats was studied. 2. HI-6 sufficiently reactivated cholinesterase activity in blood as well as acetylcholinesterase activity in brain and diaphragm following GF intoxication, and practically eliminated stressogenic effects of GF (an increase in plasma corticosterone level and liver tyrosine aminotransferase activity). 3. Obidoxime had practically no effect on enzyme activity or stressogenic effects of GF agent. 4. These findings confirm that HI-6 has definite advantages over obidoxime in the treatment of intoxication with GF.

Acetylcholinesterase↗

PubMed1995

Changes of some biochemical and hematological parameters following administration of daunorubicin in rabbits.

The effects of the repeated i.v. administration of daunorubicin (50 mg/m2, once weekly, max. 9 weeks) were investigated in rabbits in vivo to analyze biochemical and hematological changes. Noninvasive polygraphic records were used to evaluate the function of the heart. The administration of daunorubicin induced changes especially in levels of protein (decrease in total protein and albumin) and of some ions (decrease in calcium, magnesium and phosphorus) as well as in hematological parameters (decrease in erythrocytes, leukocytes and thrombocytes). The results obtained correlate with data on mechanisms of daunorubicin toxicity.

Animals↗

PubMed1995

Changes in microvascularization of some rat organs following soman poisoning.

Vascularization of some organs of rat following soman (O-pinacolyl methylphosphonofluoridate) intoxication was studied using scanning electron microscopy. Corrosion casts were prepared with commercially available methyl metacrylate monomer which was partly polymerized, supplemented with catalyst and accelerator and injected into the prewashed and fixed vascular bed. The obtained corrosion casts were sectioned and trimmed using a stereoscopic light microscope. Microvascular casts of normal organs', bed pattern were studied under scanning electron microscope and compared with vascularization patterns after soman poisoning. Changes in the vascular bed architecture of kidneys, brain, adrenal glands and thymus were described.

Adrenal Glands↗

PubMed1994

Changes of cholinesterases in the blood and some tissues following administration of tacrin and its two derivatives to rats.

Tacrin, its 7-methoxy-(MEOTA) and 7-hydroxy-(HYOTA) derivatives were i.m. administered to rats in a dose of 1.2 x LD50 and acetylcholinesterase (blood, hippocampus, frontal cortex, basal ganglia, septum and diaphragm) or butyrylcholinesterase (liver) activities were detected. The inhibitory effect of the examined substances in vivo decreased in the following order: tacrin HYOTA > MEOTA. The marked inhibition of the enzymes studied following administration of all three compounds in the frontal cortex could suggest importance of this structure for action of these drugs.

Acetylcholinesterase↗

PubMed1994

Treatment of the stressogenic effect of dichlorvos.

1. Changes of corticosterone level in the plasma and tyrosine aminotransferase (TAT) in the liver following treated and untreated dichlorvos poisoning in rats were studied. 2. Corticosterone level during untreated poisoning was increased only. During treated dichlorvos poisoning and following antidotal treatment without poisoning, no significant changes of corticosterone level were observed. 3. Expressive increase of TAT activity in the third and 24th hour of untreated poisoning was demonstrated. Following treatment of dichlorvos poisoning with atropine, obidoxime and diazepam, the delayed and lower increase of TAT activity was observed. Following antidotal treatment without poisoning, no significant changes of TAT activity except its decrease in the third hour were demonstrated. 4. The treatment of dichlorvos poisoning practically eliminate stressogenic effects of dichlorvos. Moreover, the markers could be used for evaluating the effects of antidotes against organophosphate poisoning.

Animals↗

PubMed1994

Treatment of intoxication with GV compound in laboratory rats.

Changes of some physiological functions in rats were studied following intoxication with new type of highly toxic organophosphate GV [2-dimethylaminoethyl-(dimethylamido)-fluorophosphate] in doses of 2x and 4x LD50 i.m. The intoxication has begun with increasing motoric activity followed by increased salivation, rumination and bristling. Tachypnoe and fasciculations followed by convulsions and death were observed later. Therapy of intoxication with GV compound (in dose of 2x LD50) in rats demonstrated the best antidotal effect of combination of benactyzine, atropine and HI-6. In GV intoxication in higher doses (4x LD50), therapeutic efficacy (survival of experimental animals) was limited for 24 hours. HI-6 can be therefore considered as potentially universal reactivator for the treatment of nerve agents intoxication.

Animals↗

PubMed1994

[Comparison of the effect of selected anticholinergic agents on cholinergic and noncholinergic effects of GV substances during acute poisoning in rats].

In experiments on male rats, the effect of selected cholinolytic agents (atropine, benactyzine, G 3063) in combination with the reactivator of cholinesterases HI-6 on the cholinergic and non-cholinergic effects of GV substance in the course of acute sublethal intoxication was compared. The cholinergic affects of GV substance were examined by means of the changes in the activity of cholinesterases in whole blood, the CNS, diaphragm and liver, the noncholinergic stressogenic effects by means of the changes in the level of corticosterone in plasma and the activity of tyrosine amino transferase in the liver. It follows from the changes in the activity of cholinesterases that the cholinergic effects of GV substance are least influenced by atropine, whereas benactyzine and G 3063 exert an approximately similar effect. The difference in the effect is evident especially in the 24th hour of intoxication. Similarly stressogenic effects of GV substance are least influenced by an antidotal combination of atropine and HI-6. It means that the centrally acting cholinolytic agents benactyzine and G 3063 are more advantageous for the therapy of GV substance poisonings than the peripherally acting atropine.

Acute Disease↗

PubMed1993

[Non-cholinergic effects of organophosphates].

The author summarizes contemporary knowledge on the action of organophosphates with emphasis on non-cholinergic mechanisms. Intoxication with these substances is characterized by four basic processes: absorption, transport, metabolism and the toxic effect proper. The latter involves cholinesterase inhibition at the cholinergic synapses with subsequent accumulation of acetylcholine. However, non-cholinergic processes are also involved such as the effect on levels of cyclic nucleotides, the peptidergic system, receptors, liver metabolism and the stressogenic action. From the review ensues that knowledge of non-cholinergic, mechanisms of action could reveal new approaches to treatment of intoxications with these substances.

Animals↗

PubMed1993

Action of nerve agents to cholinesterases.

Changes of acetylcholinesterase activity in the blood and different organs of the rat following intoxication with sarin, soman, VX and 2-dimethylamino-ethyl-(dimethylamido)phosphonofluoridate (GV) in doses of approximately 2 x LD50 (i.m.) were obtained from literature data and by experiment. The time course of acetylcholinesterase inhibition in the 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 summarized and compared. When blood enzyme activities were 70-100% normal, no signs were seen; at 60-70%, salivation occurred; at less than 30-55%, disturbed ventilation and fasciculations were seen while at 15-30%, convulsions occurred. Less than 10% was fatal. In experiments with narcotized dogs, the blood acetylcholinesterase activity and its reactivatability with trimedoxime were determined following intoxication (i.m.) with the above mentioned four compounds. It can be 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 nerve gas exposure. Moreover, determination of reactivatability of blood acetylcholinesterase indicates more information than simple enzyme activity determination.

Acetylcholinesterase↗

PubMed1993

Changes of rat blood and tissue cholinesterases following administration of tacrine derivatives in vivo.

Acetylcholinesterase (blood, hippocampus, frontal cortex, basal ganglia, septum and diaphragm) or butyrylcholinesterase (liver) activities following i.m. administration of tacrine (9-amino-1,2,3,4-tetrahydroacridine), its 7-methoxy- and 7-hydroxy derivatives to rats in dose of 1.2 x LD50 were detected. The most marked inhibition of the enzymes studied following tacrine administration was demonstrated in the frontal cortex, diaphragm, liver and blood. Inhibition of acetylcholinesterase in the frontal cortex and blood only was observed following administration of tacrine derivatives. The results indicate that inhibition of cholinesterases could be important but not unique part explaining the action of these drugs in general.

Animals↗

PubMed1993

Anticholinesterase action of organophosphates: importance of the liver.

Acetylcholinesterase activity in the blood, pontomedullar area, basal ganglia of the brain and diaphragm following sublethal soman (i.m., 31 micrograms/kg) and 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate (GV) poisoning (i.m., 6 micrograms/kg) was studied in groups of rats (n = 6) pretreated as follows: intact, hepatectomized, sham-operated and narcotized animals. Except hepatectomized rats, all animals in the groups survived; in hepatectomized rats, 2 animals died following soman poisoning. Acetylcholinesterase activity was decreased in each group. The highest and significant (p < 0.05-0.0001) decrease of this activity in the pontomedullar area and diaphragm following hepatectomy was demonstrated. The results indicate that undiminished liver functional capacity is an important factor influencing soman and GV anticholinesterase action.

Animals↗

PubMed1993

Validity of two different methods to detect liver injury.

Following single administration of carbon tetrachloride (p.o., 200 microliters/200 g) to female rats, activities of transaminases AST and ALT were determined from 1 hr to 7 days after the intoxication. At the same time intervals, aminopyrine breath test (ABT) was applied. The results indicate that marked decrease of ABT was observed within the first 3 hrs of exposition and lasted 24 hrs. On the other hand, statistically significant elevation of plasma enzymes was demonstrated from the 3rd hr of administration and lasted also 24 hrs. The results indicate that ABT reacts more rapidly to carbon tetrachloride administration than the changes of plasma transaminase.

Alanine Transaminase↗

PubMed1993

Methods for testing of compounds with non-lethal effect.

The effect of some toxic chemicals differing in their mechanism of action was studied by means of the method of the spontaneous motoric activity. Qualitative and quantitative changes in behaviour following administration of sublethal doses of these compounds were found. Depending on the doses administered, exploratory activity (both horizontal and vertical) following soman administration was decreased. Very low doses of VX decreased motoric activity of animals in dependence in time of its action. Anticholinergic substance QB significantly increased the frequency of motor activity. Noradrenergic neurotoxin DSP 4 decreased both horizontal and vertical activities depending on time of its exposition. The increase followed by decrease of spontaneous motor activity was observed following administration of yperite.

Animals↗