Sborník vědeckých prací Lékařské fakulty Karlovy university v Hradci Králové 

About: Sborník vědeckých prací Lékařské fakulty Karlovy university v Hradci Králové is an academic journal. The journal publishes majorly in the area(s): Soman & Transplantation. It has an ISSN identifier of 0049-5514. Over the lifetime, 229 publications have been published receiving 723 citations.

The influence of inhibitors and other factors on cholinesterases.

Abstract: 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)

Noninvasive polygraphic cardiac changes in daunorubicin-induced cardiomyopathy in rabbits.

Abstract: The use of anthracycline antitumour agents (eg, adriamycin and daunorubicin) is limited by their dose-related cardiotoxicity The effects of the repeated iv administration of daunorubicin (50 mg/m2, once weekly, max 11 weeks)) were investigated in rabbits in vivo from the point of view of the occurrence of cardiotoxicity and compared with a control group of animals Noninvasive polygraphic records (in ketamine anaesthesia, 50 mg/kg im) were used for the measurement of systolic time intervals (especially the PEP:LVET ratio) to evaluate the function of the heart The administration of daunorubicin induced a significant, progressive increase in the PEP:LVET ratio (03775-09473) and in the PEP:LVETcorr ratio, as well as a lengthening of the preejection period PEP and a shortening of the left ventricular ejection time LVET without significant changes in the electromechanical systole Q-2 The values in the daunorubicin group were mostly significantly different from the control group of animals The results of polygraphic records reflect thus a presence of cardiac dysfunction on the basis of daunorubicin-induced cardiomyopathy It is thus possible to conclude that the results obtained in the study confirm the adequacy of the rabbit model of daunorubicin-induced cardiomyopathy and the methods used in the study