PubMed Health⌕ Search

Biomedical subjects

J Bajgar

Publications and source records attributed to J Bajgar.

At least 19 recordsLinked to original sources
PubMed2005

Changes of acetylcholinesterase activity after long-term exposure to sarin vapors in rats.

In our study, rats were exposed to sarin vapors for 240 min at four different concentrations (0.30, 0.43, 0.58 and 0.82 microg/L) in a whole-body inhalation chamber. The acetylcholinesterase activity (AChE, EC 3.1.1.7) was measured in the whole blood, frontal cortex (FC), pontomedullar area (PM) and basal ganglia (BG). Convulsions and hypersalivation were observed in only one animal of the group exposed to the highest sarin concentration. The decrease in blood AChE activity was significant in all animals exposed to sarin vapors. The highest inhibition of AChE activity (61%) was determined in animals exposed to sarin vapors at a concentration of 0.82 microg/L. In the PM, AChE activity was decreased in all experimental groups, significantly only in the group exposed to sarin vapors at a concentration of 0.58 microg/L. Our results show that in long-term exposure to low concentrations of sarin, the significant decrease in AChE activity in the blood is followed by significant changes of AChE activity in the PM only. This part of the brain seems to be more sensitive than the FC or BG.

Acetylcholinesterase↗
PubMed2005

[A comparison of the efficacy of the reactivators of acetylcholinesterase inhibited with tabun].

The nerve agent tabun inhibits acetylcholinesterase (AChE; EC 3.1.1.7) by the formation of a covalent bond with the enzyme. Afterwards, AChE is not able to fulfil its role in the organism and subsequently cholinergic crisis occurs. AChE reactivators (pralidoxime, obidoxime and HI-6) as causal antidotes are used for the cleavage of the bond between the enzyme and nerve agent. Unfortunately, their potency for reactivation of tabun-inhibited AChE is poor. The aim of the study was to choose the most potent reactivator of tabun-inhibited AChE. We have tested eight AChE reactivators--pralidoxime, obidoxime, trimedoxime, HI-6, methoxime, Hlö-7 and our newly synthesized oximes K027 and K048. All reactivators were tested using our standard in vitro reactivation test (pH 8, 25 degrees C, time of inhibition by the nerve agent 30 minutes, time of reactivation by AChE reactivator 10 minutes). According to our results, only trimedoxime was able to achieve 50% reactivation potency. However, this relatively high potency was achieved at high oxime concentration (10(-2) M). At a lower concentration of 10(-4) M (the probably attainable concentration in vivo), four AChE reactivators (trimedoxime, obidoxime, K027, and K048) were able to reactivate AChE inhibited by tabun reaching from 10 to 18%.

Acetylcholinesterase↗
PubMed2004

Biochemical effects of low level exposure to soman vapour.

The aim of this study was to demonstrate changes in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities, tyrosine aminotransferase activity (TAT) and plasma corticosterone level, neuroexcitability and behavior following 24 hours and 4 weeks of soman sublethal inhalation exposure at low level. AChE activity in erythrocytes and BuChE activity in plasma was decreased (dependent on the concentration of soman) 24 h and 4 weeks after the exposure. Similar decrease in AChE activity in different brain parts was observed. One of stressogenic parameters (TAT) was changed after 24 h exposure only. 4 weeks after the exposure, these parameters (corticosterone and TAT) were in the range of normal values. Behaviour of experimental animals was changed 24 h after the exposure persisting 4 weeks after the exposure as well as neuroexcitability.

Acetylcholinesterase↗
PubMed2004

Relationship between plasmatic levels of sarin and cholinesterase inhibition in rats exposed to sarin vapors.

In our study we monitored plasmatic levels of sarin and changes in cholinesterase activities in rats after exposure to sarin vapors at low concentration. Rats were exposed to sarin in inhalation chamber at concentration 1.25 or 2.5 microg/l for 60 minutes. The acetylcholinesterase activity was measured in erythrocytes and in different brain regions (frontal cortex--FC, pontomedullar area--PM, basal ganglia--BG). Butyrylcholinesterase activity and sarin levels were measured in plasma. Acetylcholinesterase activity in erythrocytes as well as butyrylcholinesterase activity in plasma were significantly decreased in both groups of animals after intoxication with sarin. In brain, the significant decrease in acetylcholinesterase activity was measured in FC and PM for both groups. In group exposed to higher concentration of sarin vapors, the plasmatic level of sarin was nearly 2 x higher than in group exposed to sarin at concentration 1.25 microg/l. The linear dependence between plasmatic levels of sarin and AChE activity was assayed in FC region of brain and in erythrocytes, exponential relationship in PM region of brain and for BuChE activity in plasma.

Acetylcholinesterase↗
PubMed2001

Toxic effects of sarin in rats at three months following single or repeated low-level inhalation exposure.

Male albino Wistar rats were once or repeatedly exposed to three various low concentrations of sarin for 60 min. in the inhalation chamber. The clinical status of control as well as sarin-poisoned rats was tested 3 months after exposure to sarin using biochemical, haematological, neurophysiological, behavioural and immunotoxicological methods. While biochemical and haematological parameters, including the activities of cholinesterases in erythrocytes, plasma and various organs (brain, diaphragm), did not differ from the control values regardless of the sarin concentration used, few signs of sarin-induced neurotoxicity and immunotoxicity in sarin-poisoned rats were demonstrated. This was especially true when the single exposure of rats to non-convulsive symptomatic concentration and repeated exposure of rats to clinically asymptomatic concentration of sarin was used. In rats repeatedly poisoned with clinically asymptomatic concentrations of sarin, the alteration of the gait characterized by ataxia, the increase in the stereotyped behaviour, the increase in the excitability of the central nervous system following the administration of the convulsive drug pentamethylenetetrazol were observed. In rats poisoned with non-convulsive symptomatic concentration of sarin, the subtle supression of spontaneous, as well as lipopolysaccharides-stimulated, proliferation of spleen lymphocytes and the bactericidal activity of peritoneal macrophages was primarily observed besides the signs of neurotoxicity. Our findings confirm that both non-convulsive symptomatic and clinically asymptomatic concentrations of sarin can only cause very few, subtle long-term signs of neurotoxicity and immunotoxicity in sarin-poisoned rats when the rats were exposed to asymptomatic sarin concentrations repeatedly.

Administration, Inhalation↗
PubMed1999

[Comparison of the reactivating effect of BI-6, a new asymmetrical bispyridinium oxime, with oxime HI-6 and obidoxime on soman-inhibited acetylcholinesterase in the diaphragm and various parts of the brain in rats].

BACKGROUND: Acute poisoning with the highly toxic organophosphorus agent, soman, is not treated satisfactorily even by the most modern antidotes. METHODS AND RESULTS: In experiments on rats, the reactivating effect of a new asymmetric bispyridinium oxime BI-6 was compared with widely used oximes HI-6 and obidoxime by investigating the changes of soman-inhibited acetylcholinesterase activity in the diaphragm and various parts of the brain in rats up to three hours following soman challenge. Our findings confirm that the new oxime BI-6 is a more effective reactivator of soman-inhibited acetylcholinesterase than obidoxime but not as effective as the oxime HI-6 especially in the peripheral compartment. CONCLUSIONS: The new oxime BI-6 is not as effective as HI-6 which seems to have definite advantages over other oximes in the treatment of soman poisoning.

Acetylcholinesterase↗
PubMed1999

Effect of 7-methoxytacrine and L-carnitine on the activity of choline acetyltransferase.

Changes of choline acetyltransferase (ChAT) activity in the hippocampus and the basal ganglia were studied in rats treated i.p. with L-carnitine (CRT) and 7-methoxytacrine (7-MEOTA) (i.m.) separately or 3-days treated with L-carnitine and then with one administration of 7-MEOTA. Both compounds increased ChAT activity when administered separately. 3-day treatment of CRT followed by administration of 7-MEOTA normalized ChAT activity.

Animals↗
PubMed1999

Cholinesterases in dexrazoxane-treated daunorubicin cardiomyopathy in rabbits.

Changes in cholinesterases activities in daunorubicin cardiomyopathy and in dexrazoxane (DRZX)-treated daunorubicin cardiomyopathy were investigated in rabbits. Acetyl- and butyrylcholinesterase (AChE and BuChE) were determined using Ellman's method. In the serum, a significant decrease of BuChE was observed in the daunorubicin group (9.05 at the beginning and 7.15 microcat/l at the end of the experiment). After DRZX, no significant changes were found and a significant increase in BuChE was observed in the control group (10.26-12.38 microcat/l). AChE activity in the left and right cardiac ventricles was not significantly different between the groups while in the septum there was a significantly lower AChE activity found in the daunorubicin group only. BuChE activity was significantly decreased in the left (15.64 ncat/g) and right (19.27 ncat/g) heart ventricles, in the septum and in the liver in the daunorubicin group. A significant decrease in serum total protein and albumin was demonstrated only in the daunorubicin group. Our results support the hypothesis about the influence of daunorubicin on protein (and enzyme) synthesis in the liver and heart. A protective effect of DRZX on cholinesterases activity was observed. The changes in cholinesterase activities may thus reflect their possible role in cardiomyopathy.

Acetylcholinesterase↗
PubMed1998

Changes of acetylcholinesterase activity in various parts of brain following nontreated and treated soman poisoning in rats.

Changes of acetylcholinesterase (AChE) activity in various parts of the brain (frontal cortex, medulla oblongata, pons Varoli, cerebellum, hypothalamus, and hippocampus), following im sublethal non-treated and treated soman poisoning were studied. As a treatment, two antidotal mixtures containing atropine and either obidoxime or oxime HI-6 were used. This antidotal treatment was administered im for 30 s following soman intoxication. The AChE activities in the various brain tissues were evaluated at 1 and 3 h following soman administration. As expected, the highly toxic organophosphorus compound, soman, markedly inhibited AChE activity in all the brain sections at both time intervals. Both oximes had little influence on soman-induced AChE inhibition, but only the HI-6 mixture was able to reactivate soman-inhibited AChE significantly in some of the brain parts (frontal cortex, pons Varoli, hypothalamus). In the brain, the effect of HI-6 against soman-induced AChE inhibition is higher in comparison with obidoxime, but not quite satisfactory. Despite its limited effectiveness in the brain, HI-6 seems to be the most effective oxime yet found against soman poisoning because of its high reactivating effect in the peripheral compartment and other beneficial effects.

Acetylcholinesterase↗
PubMed1998

Myocardial elements content and cardiac function after repeated i.v. administration of DMPS in rabbits.

1. A dithiol chelating agent--2,3-dimercapto-1-propanesulphonate (DMPS)--may be administered in acute or chronic intoxication with certain heavy metals (e.g. cadmium, cobalt, lead) that may cause cardiotoxicity. 2. DMPS can act as a depleter of physiologically important elements (e.g. potassium, magnesium, calcium) in various tissues including cardiac one. The possibility of subsequent alteration in cardiac function cannot be excluded. 3. Changes in the myocardial concentration of the above mentioned elements at the end of the experiment and cardiac function were studied during repeated i.v. administration of DMPS as single doses of 50 mg/kg/ week for 10 weeks in rabbits. Biochemical, haematological and histological examinations were also performed. 4. Most of the measured parameters were not affected by the repeated administration of DMPS. A significant decrease in magnesium and a near significant decrease in calcium in cardiac muscle was not accompanied by functional or morphological changes. It is still suggested, however, that care should be taken in using DMPS for treating patients with cardiotoxicity as a result of poisoning with heavy metals.

Animals↗
PubMed1997

Effects of repeated administration of dithiol chelating agent--sodium 2,3-dimercapto-1-propanesulphonate (DMPS)--on biochemical and haematological parameters in rabbits.

The effects of weekly intravenously administered a dithiol chelating agent-sodium 2,3-dimercaptopropane-sulphonate (DMPS)-in a single dose of 50 mg/kg/week for 10 weeks on biochemical and haematological parameters were studied in rabbits. DMPS was well tolerated, an increase in body weight was similar in the DMPS-treated and control animals. DMPS caused significant decrease in plasma calcium and vitamin E concentrations at the end of the experiment. No significant differences in haematological parameters between the DMPS and control groups were observed. A significant decrease in magnesium content in myocardial tissue was observed in the DMPS-treated rabbits. The above-mentioned biochemical changes should be taken into account in studies of possible chelating and radical scavenging effects of DMPS in various pathological conditions.

Animals↗
PubMed1997

Changes of cholinesterase activity in the erythrocytes, plasma, diaphragm, liver and various parts of the brain in the rabbit following transfusion of erythrocytes with soman inhibited acetylcholinesterase.

1. The changes of cholinesterase activity in rabbit blood, peripheral tissues and the central nervous system following transfusion of erythrocytes with soman inhibited acetylcholinesterase we were demonstrated. 2. After incubation with soman for 0.5 or 24 h, erythrocytes without acetylcholinesterase activity were injected to intact rabbits and cholinesterase activity in the erythrocytes, plasma, diaphragm, liver and various parts of the brain were evaluated 24 h following blood-transfusion. 3. When erythrocytes were incubated with soman for 24 h, no changes of cholinesterase activity in the rabbit following blood-transfusion were observed with an exception of erythrocyte acetylcholinesterase. 4. When erythrocytes were incubated with soman for 0.5 h, a significant decrease in cholinesterase activity in the erythrocytes, plasma, diaphragm and liver following blood-transfusion was found. These data show that soman is able to release from erythrocytes and inhibit cholinesterase activities not only in vitro but also in vivo although the significant inhibition of cholinesterase activities by soman was only observed in the peripheral compartment.

Acetylcholinesterase↗
PubMed1997

Differential inhibition of the brain acetylcholinesterase molecular forms following sarin, soman and VX intoxication in laboratory rats.

The female Wistar rats were intoxicated (i.m.) with sarin, soman and VX in doses equal to 1xLD50 and pontomedullar areas of the brain were prepared, homogenized, centrifuged and in these samples, acetylcholinesterase (AChE, EC 3.1.1.7) activities were determined. In the same samples, AChE was separated using polyacrylamide gel electrophoresis and AChE molecular forms were detected and densitometrically evaluated. In control animals, AChE was separated into four forms differing in their electrophoretic mobility and their quantitative content in the sample. The form with lowest electrophoretic mobility represent the main part of AChE activity constituting the whole enzymatic activity. Following intoxication with the nerve agents mentioned, the whole AChE activity in the pontomedullar area of the brain was decreasing in intervals of ten minutes (soman and sarin) or one hour (VX). The AChE activity at the time of death (or terminal stage) was represented 5-30% of controls. Molecular forms of AChE were inhibited in different extent: the form with lowest electrophoretic mobility was diminished to zero level while the form with the highest mobility was practically unaffected, independently on the type of nerve agent. From quantitative expression of percentage content of the forms vs their activity we can imply that value of the total AChE activity represent the "mean" activity of the forms determined.

Acetylcholinesterase↗
PubMed1996

Lack of cardiotoxicity of a new antineoplastic agent, a synthetic derivative of indenoisochinoline: comparison with daunorubicin in rabbits.

The effect of repeated i.v. administration (once weekly, 12 administrations) of a new antineoplastic agent, Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5, 11-dioxo-5,6-dihydro-11 H-indeno [1,2-c]-isochinoline hydrochloride, 10 mg/kg) and daunorubicin (3 mg/kg) were investigated in rabbits in vivo. The criterion of occurrence of cardiotoxicity was compared with a control group of animals. Noninvasive polygraphic records were used to evaluate the function of the heart. The morphological changes of the heart were evaluated after the death of animals. There were no significant changes found in the ratio of the pre-ejection period/left ventricular ejection time (PEP: LVET ratio) after administration of Oracin (values between 0.3080 and 0.3310) or in the control group (values between 0.3425 and 0.3885). The administration of daunorubicin induced a significant, progressive increase in the PEP: LVET ratio (0.3775-0.9473), which was significantly different both from the Oracin-treated and the control group of animals. Histological examination of the hearts from the control group revealed normal structure of the myocardium including minute changes (dispersed cardiomyocytes with intensively eosinophilic cytoplasm, and several single cells with degenerated myofibrils) similar to the normal changes in muscle tissue. A very similar scenario was found in the Oracin group with the exception of one case where a slightly higher number of degenerated and necrotic cells was occurring. Administration of daunorubicin resulted in severe dispersed damage of the myocardium (myocytolysis with subsequent interstitial fibrosis), the changes being markedly different from those of the Oracin treatment and the control group. On the basis of our results it is possible to conclude that the administration of Oracin (10 mg/kg i.v.) did not induce signs of cardiotoxicity in rabbits in vivo.

Animals↗
PubMed1996

The influence of pharmacological pretreatment on efficacy of HI-6 oxime in combination with benactyzine in soman poisoning in rats.

1. The influence of pharmacological pretreatment (pyridostigmine, benactyzine and trihexyphenidyle), designated PANPAL, on soman-induced cholinergic and stressogenic effects as well as on the efficacy of antidotal treatment (HI-6 plus obidoxime) in rats was studied. 2. PANPAL prophylaxis significantly decreased soman-induced cholinesterase inhibition in blood, brain and diaphragm as well as stressogenic effects of soman (an increase in plasma corticosterone level and liver tyrosine aminotransferase activity). 3. PANPAL pretreatment did not improve the efficacy of HI-6 in combination with benactyzine on soman-induced anticholinesterase and stressogenic effects. 4. These findings confirm that PANPAL prophylaxis can improve prognosis of soman poisoning especially by protection of cholinesterases.

Animals↗
PubMed1996

Changes in cholinesterase activities after daunorubicin administration to rabbits.

1. Acetyl- and butyrylcholinesterase (AChE, BuChE) activities were studied in rabbits with experimentally induced daunorubicin cardiomyopathy. 2. A significant decrease of the plasma BuChE in the daunorubicin group was observed. 3. In the daunorubicin group, AChE activity in the heart was significantly decreased only in the interventricular septum. 4. BuChE activity was significantly decreased in the cardiac septum and ventricles and in the liver following daunorubicin treatment. 5. Changes in cholinesterase activities are probably caused by an effect of daunorubicin oon protein synthesis during the development of certain types of cardiomyopathy.

Acetylcholinesterase↗
PubMed1996

[Comparison of the therapeutic effectiveness of selected cholinesterase reactivators with atropine in acute fosdrine poisoning in mice].

In experiments on male mice, the effect of the cholinesterase reactivators obidoxime, methoxime and HI-6 in combination with atropine sulfate on the acute intoxication with the organophosphorous insecticide fosdrine was tested in dependence on the period of administration of drugs after intoxication and on the dose of oxime by influencing the LD50 value in 48-hour survival of experimental animals. It has been demonstrated that the rate of the therapeutic intervention is a much more important factor influencing the effect of oximes than the dose of oximes. A shortening of the period of drug administration from 2 minutes to 30 seconds substantially increases the effects of all three oximes. A comparison of the effects of all three reactivators has shown that the oxime HI-6 is significantly more effective than the remaining two reactivators in the case of therapy of intoxication 30 seconds after the application of the noxa. In the therapy of intoxication 2 minutes after the exposure of experimental animals to fosdrine, the effect of the antidotal therapy was relatively low regardless of the selected oxime.

Acute Disease↗