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Biomedical subjects

M Mráz

Publications and source records attributed to M Mráz.

At least 19 recordsLinked to original sources
PubMed1999

Therapeutic effect of heat shock on T-cell lymphoma in inbred Sprague-Dawley rat.

Anticancer effect of heat shock, either alone or in combination with the drug PMEDAP, and cold water immersion stress were studied in an in vivo model of s.c. transplanted rat T-cell lymphomas in an inbred Sprague-Dawley rat line (SD/cub). Significant anticancer effect was induced by repeated sessions of heat shock; decrease of s.c. lymphoma weight and prolongation of survival time of treated rats was found to be dependent on the number of HS sessions. Much stronger therapeutic effect was observed after repeated heat shock in combination with PMEDAP administration. Light and electron microscopy studies were performed to characterize the alterations within the lymphomas. Morphologically, cellular alterations corresponding with apoptosis were observed in lymphoma cells after repeated heat shock. Indirect immunoperoxidase technique was used to detect HSP 72/73 protein(s), p53 and Bcl2 proteins in lymphomas heated directly or indirectly. The induction of HSP 72/73 protein(s) was found in the lymphoma tissues from autopsied animals exposed to heat shock; the intensity of its expression was dependent on the experimental design. The expression of p53 and BcL2 proteins was not changed in lymphoma cells of HS treated animals as compared to that of untreated lymphoma bearing controls; the Bcl2 protein was present in both treated and untreated lymphomas, and the p53 protein remained undetectable in all samples. Contrary to the heat shock, the cold stress did not suppress growth of lymphomas and, furthermore, accelerated the infiltration of parenchymatous organs with lymphoma cells.

Adenine↗
PubMed1998

Bacteremia due to methicillin-resistant staphylococci occurs more frequently in neutropenic patients who received antimicrobial prophylaxis and is associated with higher mortality in comparison to methicillin-sensitive bacteriemia.

Bacteriemia due to coagulase-negative staphylococci (CNS) resistant to methicillin and sensitive only to glycopeptides in 220 cancer patients was prospectively analyzed for risk factors and outcome. A group of 33 cases of bacteriemia with CNS-sensitive only to glycopeptides was compared with a group of 187 cases with CNS sensitive to methicillin. All cases appeared in two affiliated major cancer institutes in Bratislava with the same antibiotic policy. Univariate analysis showed differences in recorded risk factors: acute leukemia (48 vs. 33%, P < 0.05), neutropenia (57 vs. 32%, P < 0.045), previous prophylaxis with quinolones (30 vs. 11%, P < 0.01) and penicillin-V (15 vs. 3%, P < 0.02) and previous colonisation with CNS (27 vs. 3%, P < 0.01) were more frequently associated with bacteriemia resistant to methicillin and sensitive only to glycopeptides. Attributable mortality was also higher in this subgroup in comparison to bacteriemias with CNS sensitive to methicillin (12 vs. 3%, P < 0.05) however, overall mortality was similar. Bacteriemias due to CNS caused by sensitivity only to glycopeptides occurred more frequently in neutropenic patients (1), with acute leukemia (2), receiving quinolone and penicillin prophylaxis (3), and previously colonized (4), patients and had worse prognosis in comparison to those with methicillin-sensitive staphylococcal bacteriemias.

Antibiotic Prophylaxis↗
PubMed1998

Phase I and phase II xenobiotic biotransformation in different inbred strains of rats: study in immobilized perfused hepatocytes.

The present study was designed to compare phase I and phase II biotransformation reactions in immobilized perfused hepatocytes as a cellular system obtained from inbred rat strains which represent models for some cardiovascular diseases, namely, spontaneously hypertensive rats (SHR), rats sensitive and resistant to isoprenaline-induced myocardial lesions (IS and IR, respectively) as compared to Wistar rats (W). The biotransformation kinetics for hexobarbital (HX), 7-ethoxycoumarin (7-EC), 1-chloro-2,4-dinitrobenzene (CDNB) and 4-nitrophenol (4-NP) were followed up in the hepatocyte perfusate. W and SHR rat hepatocytes have metabolized HX at a higher rate than those of the IR and IS strains. Hepatocytes from the W strain exhibited a higher rate of 7-EC deethylation activity compared to hepatocytes obtained from the IR or IS strains. Hepatocytes obtained from SHR and IR rats showed the highest glutathione-S-transferase (GST) activity towards CDNB compared to the IS or W strain. 4-NP disappearance was higher in the perfusion medium of hepatocytes obtained from the W and IS strains compared to the IR strain. These significant differences in drug biotransformation between various studied strains, which may be genetically determined, can be well demonstrated by using an efficient drug metabolizing model of the immobilized perfused hepatocytes. The importance of these differences should be considered during the study of the experimental therapy of the relevant disease as obtained from the specific experimental strain, where it may be expected that the pharmacokinetic profile of a drug in vivo and consequently its pharmacodynamic or toxic effects will be strain dependent.

Animals↗
PubMed1998

Differences in heart phospholipids in two inbred rat strains differing in sensitivity to the development of heart lesions.

The content of phospholipids and their fatty acid composition were followed in the hearts of two inbred strains of rats: IR, resistant against the development of isoprenaline-induced myocardial lesions and IS, sensitive to their development. In the hearts of rats of the resistant strain, a lower content of phosphatidylcholine and its plasmalogen fraction was found compared to IS rats. The total amount of phospholipids was only insignificantly lower in IR rats. Greater differences were found in individual fatty acids. The most important finding concerned lower arachidonic acid and higher linoleic acid content in heart phospholipids of IR rats. These differences were exactly opposite to changes reported in the literature in animals known to have a higher resistance against myocardial damage due to various interventions. Our results do not support the hypothesis claiming the importance of changes in phospholipids and their FA composition for the resistance of the heart against the development of necrotic lesions.

Animals↗
PubMed1995

[Differences in the behavior of organic lesions, immunologic and metabolic parameters in 2 inbred strains of rats].

Two inbred rat strains were obtained by selective breeding and inbreeding: IR (isoprenaline resistant) and IS (isoprenaline sensitive). In addition to known differences between the two strains (1) other differences were found. As compared to IS strain, IR rats were more aggressive and showed more comfort behaviour in open field test. IR rats developed larger stress-induced gastric lesions but smaller heart lesions. They had larger spleen and thymus and more severe arthritis after Freund adjuvans administration. The two strains might be useful in studying the effects of drugs on various pathological processes. Their hybrids are being used to study interrelations between different genetic factors.

Animals↗
PubMed1994

A preliminary evaluation of drug biotransformation in hepatocytes of genetically defined rat strains.

This study was directed to use the genetically developed isoprenaline-sensitive (S), isoprenaline-resistant (R) and spontaneous hypertensive rats (SHR) as standard diseased animal models for in vitro liver function evaluation of drug biotransformation. Hepatic hexobarbital hydroxylase and glutathione transferase (GST) were evaluated by using hexobarbital and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates, at concentrations of 0.21 mmol/l and 1 mmol/l, respectively. The assay was conducted by using isolated hepatocytes in suspension and hepatocytes in a bioreactor configuration. The data demonstrate that there are certain cellular pharmacokinetic differences in hexobarbital hydroxylase and GST activities in hepatocytes obtained from Wistar, SHR, R and S strains which can be better demonstrated, when using the model of perfused and immobilized hepatocytes.

Animals↗
PubMed1993

The changes in the myocardium under experimental conditions.

An effect of different interventions on the electron microscopic structure and morphometric parameters of the myocardium were studied. Application of cyclophosphamide and isoprenaline in the experimental animals allows the similar changes of mitochondrial partial volume like hypoxic periods of cardiac surgery by coronary bypass operation. Although the initial agents are different, the primary affected structures are sarcoplasm and mitochondria, whose proportions change promptly. The primary effect may be connected with alteration of membrane permeability caused by increased osmotic active ion transport on responsibility of the inhibited Na, K-ATP-ases (or F0 F1-ATP-ases irreversibly altered in mitochondria). The morphometric evaluation confirms not only statistically significant differences among the experimental groups treated by cyclophosphamide, isoprenaline and by cardioplegic ischaemic periods in the human myocardium but also by application of physiological saline in the control groups. Comparing the morphometric evaluation by manual processing with computer mediated image analysis we can conclude that the results correspond upon conditions of the specific defined raster for Weibel's intersection test only.

Adult↗
PubMed1992

[Salmonellosis and shigellosis in the differential diagnosis of acute abdomen].

There are only very few reports in our literature on problems and pitfalls of the differential diagnosis and present incidence of acute abdominal salmonellosis and shigellosis. Based on evaluated results of a three-year investigation from their department the authors draw attention to the relatively frequent concurrent incidence of acute abdomen and infectious diarrhoeal disease, the difficulty of differential diagnosis and indication of surgery even when the results of cultivation examinations are known due to the common interlinked symptomatology and coincidence. The symptoms imitating acute abdomen in infectious diarrhoeal diseases predispose by concentration of infectious patients in surgical departments the development of nosocomial infections and epidemics.

Abdomen, Acute↗
PubMed1987

Increase and regression of the protective effect of high altitude acclimatization on the isoprenaline-induced necrotic lesions in the rat myocardium.

Cardiac resistance to the cardiotoxic effect of isoprenaline--ISO (single dose of 0.1 mg X kg-1) was studied in rats acclimatized to intermittent high altitude--IHA (barochamber, 8 h a day, 5 days a week, stepwise up to 7000 m). The extent of lesions was evaluated quantitatively by means of the increased accumulation of 203HgCl2. Five weeks' acclimatization was followed by a marked increase in the resistance of the myocardium to the necrogenic effect of ISO; this effect was more expressed in the left ventricle, so that the right to left difference generally observed under normoxic conditions disappeared. The increased resistance of the myocardium to ISO-induced damage persisted long after the animals had been returned to normoxic conditions; even six weeks after the last hypoxic exposure the sensitivity of the myocardium to damage had still not returned to the values of unacclimatized animals.

Acclimatization↗
PubMed1985

Physical activity of different intensities and the development of myocardial resistance to injury.

The conditions under which increased motor activity leads to raised resistance of the myocardium to injury were studied. Motor activity was raised by running on a treadmill; myocardial resistance was evaluated quantitatively from the extent of isoprenaline (ISO)-induced lesions. After 3 weeks of forced running (5 days a week), using an adequate daily dose, the cardiotoxic effect of ISO was reduced. Adequacy of the daily dose of exercise depended both on the distance run per day and on the rate at which the animals ran. If the training regimen was continued for further weeks, with the same daily dose of exercise, there was no significant increase in protection of the myocardium. In animals aged less than 3 months, myocardial resistance changed after higher daily doses of running than those needed in older animals. The cardioprotective effect of increased motor activity was not conditioned by increase in the weight of the myocardium.

Age Factors↗
PubMed1985

Mercapturates in the urine of persons exposed to N,N-dimethylformamide.

N,N-dimethylformamide, a nucleophilic aprotic dipolar solvent, has multipurpose uses, especially in the manufacture of plastics. Its acute toxicity for mammals is low; it is hepatotoxic. Vapors are absorbed by the lungs, in the liquid form it causes cutaneous maceration and is rapidly absorbed through the skin. In the organism it is primarily metabolized to N-monomethylformamide, to a lesser extent to formamide. Urine of individuals exposed to N,N-dimethylformamide was newly found to have higher levels of thioethers, most likely mercapturates, as yet of unknown chemical structure. The correlation between the urinary concentrations of mercapturates (y) and N-monomethylformamide (x) can be expressed by equation y = 4.93 + 0.58 x, with the coefficient of correlation r = 0.90. Part of N,N-dimethylformamide metabolites is likely to react with biopolymers, part of it is excreted as metabolic end products, i.e. carbon dioxide, water and urea. Breakdown to mercapturates may implicate N,N-dimethylformamide as being a potential carcinogen.

Acetylcysteine↗
PubMed1984

Urinary excretion of mandelic and phenylglyoxylic acids after human exposure to styrene vapour.

The kinetics of the urinary excretion of mandelic and phenylglyoxylic acids were studied in volunteers exposed to the known concentrations of styrene vapour. The level and the time of exposure were suitably changed to simulate situations in the industrial environment. The aim was to find out the reasons for the contradictory reports in the literature and to verify parameters characterizing the course of excretion of both metabolites. It was found that the course of mandelic acid excretion might be influenced by the length of styrene exposure. If exposure was longer than 4 hours the maximum of excretion was at the end of the exposure time; after short-term exposures (4 h or less) it was somewhat delayed. Maximum excretion of phenylglyoxylic acid was delayed both after short-term and 8-hour exposures. Excretion of the metabolites was diphasic (biexponential). The effective half-lives were found to be independent of the level of exposure. The apparent half-lives (determined in the post-exposure time of 0-16 hours) tended to become prolonged at daily repeated exposures. The ratio of mandelic to phenylglyoxylic acid changed considerably with the level of exposure. In biological monitoring it is advisable to determine both metabolites.

Female↗
PubMed1983

Influence of motor activity on the development of isoprenaline induced heart lesions.

The influence of spontaneous motor activity on the development of isoprenaline-induced heart lesions was studied in male rats of different ages. The extent of the lesions was evaluated quantitatively from raised accumulation of 203HgCl2 in the damaged tissue. Spontaneous activity in rotation cages rose with the animals, age and attained maximum values (6 562 m/d) at 3 months. The increase in motor activity in 10 months was very low and attained only 561 m/d. In all the experimental groups in which spontaneous activity was higher than this limit, a decrease in the cardiotoxic effect of isoprenaline was found after 2--3 weeks. The extent of the heart lesions in the individual animals was not proportional to the degree of their motor activity. The smallest myocardial damage was not found in animals which ran the most metres and vice versa. A marked decrease in the extent of the heart lesions occurred when the motor regimen was prolonged to 70 days. After a three days' break in the motor regimen, reduction of the cardiotoxic effect was still maintained. The extent of the heart lesions after 14 days' interruption corresponded to the values found in animals which were not allowed increased motor activity.

Aging↗