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Biomedical subjects

J Machácková

Publications and source records attributed to J Machácková.

At least 19 recordsLinked to original sources
PubMed2002

Cardiac troponin T following repeated administration of pyridoxal isonicotinoyl hydrazone in rabbits.

Pyridoxal isonicotinoyl hydrazone (PIH) is a new tridentate Fe-chelating agent that should be very promising in many pathological states resulting from both an iron-overload and formation of free radicals. The aim of our study was to investigate the effect of PIH on the cardiovascular system focusing to the regulatory protein -- cardiac troponin T (cTnT). The study was carried out in two groups of Chinchilla male rabbits: 1) PIH (50 mg/kg dissolved in 10 % Cremophor i.p., once a week, 10 administrations, n=8) and 2) Cremophor (2 ml/kg i.p. in the same schedule, n=7). Plasma concentrations of cTnT (as a marker of myocardial damage) were measured using a commercial kit (Roche). cTnT was within the physiological range (i.e. < 0.1 microg/l) during the whole experiment in the Cremophor group. In the PIH group, the cTnT levels were not significantly increased when compared with the control group or with the initial values (except with those before the 5th administration). Furthermore, we analyzed the cytosolic and myofibrillar fraction of cTnT in the left ventricular myocardium. Using SDS-PAGE and Western blot we resolved three isoforms. The profiling of TnT did not differ significantly between the PIH-treated group and the Cremophor-treated group. Our data concerning cTnT support the opinion that the possible cardiotoxicity of PIH is very low.

Animals↗
PubMed2001

[Plasma levels of troponin T in rabbits after administration of new antineoplastic agents (Oracin and Dimefluron) and daunorubicin].

Recently, cardiac troponin T (cTnT) has been shown to be a sensitive marker of anthracycline-induced cardiomyopathy. In our study, the cardiotoxicity of repeated i.v. administration (once a week, 10 administrations) of daunorubicin combined with new antineoplastic drugs (with mild side-effects) were followed in two groups of rabbits: 1) Dimefluron (3,9-dimethoxybenfluron hydrochloride-12 mg/kg) + daunorubicin (3 mg/kg), 2) Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride--10 mg/kg) + daunorubicin (3 mg/kg) and compared with the control group (saline--1 ml/kg) and the group with experimentally induced cardiomyopathy (daunorubicin--3 mg/kg). The concentration of cTnT in heparinized plasma samples was measured using commercial kit (Roche). In the control group, plasma levels of cTnT were always within the physiological range (i.e. lower than 0.1 microgram/l) during the experiment. During the development of daunorubicin-induced cardiomyopathy, after the eighth administration of drug, cTnT was significantly higher (0.31 +/- 0.11 microgram/l) in animals with premature deaths compared with the rest of the group (0.04 +/- 0.03 microgram/l). The animals with pathological values of cTnT were at higher risk of premature deaths (P = 0.0006). The combination of daunorubicin either with Oracin or with Dimefluron caused neither significant changes of cTnT levels nor significant deterioration of other followed-up parameters (especially, functional and toxicological parameters). Similarly to the daunorubicin group, the animals with pathological levels of cTnT after the eighth administration of antineoplastic drugs were at higher risk of premature death (P = 0.025). Our results show that the plasma concentration of cardiac troponin T could be a suitable predictive marker of cardiotoxicity of antineoplastic drugs.

Animals↗
PubMed2000

Anthracycline-induced cardiotoxicity.

Anthracycline antibiotics are among the most effective and widely used antineoplastic drugs. Their usefulness is limited by a cumulative dose-related cardiotoxicity, whose precise mechanisms are not clear as yet. The principal role is possibly exerted by free oxygen radicals generated by "redox-cycling" of anthracycline molecule and/or by the formation of anthracycline-ferric ion complexes. The iron catalyzes the hydroxyl radical production via Haber-Weiss reaction. The selective toxicity of ANT against cardiomyocytes results from high accumulation of ANT in cardiac tissue, appreciable production of oxygen radicals by mitochondria and relatively poor antioxidant defense systems. Other additional mechanisms of the anthracycline cardiotoxicity have been proposed--calcium overload, histamine release and impairment in autonomic regulation of heart function. The currently used methods for an early identification of anthracycline cardiotoxicity comprise ECG measurement, biochemical markers, functional measurement and morphologic examination. Among a plenty of studied cardioprotective agents only dexrazoxane (ICRF-187) has been approved for clinical use. Its protective effect likely consists in intracellular chelating of iron. However, in high doses dexrazoxane itself may cause myelotoxicity. This fact encourages investigation of new cardioprotectants with lower toxicity. Orally active iron chelators and flavonoids attract more attention. Modification of dosage schedule and synthesis of new anthracycline analogues may represent alternative approaches to mitigate anthracycline cardiotoxicity while preserving antitumour activity.

Animals↗
PubMed2000

[Effects of new antineoplastic agents (dimethoxybenflurone and Oracin) on the cardiovascular system and other parameters in the rabbit in vivo].

Anthracycline derivatives belong among the most effective antineoplastic drugs but their therapeutic use is limited by their side effects--a dose-related cardiotoxicity. The influence of repeated i.v. administration (once weekly, max. 10 weeks) of new antineoplastic agents--dimethoxybenfluron (DMB) (3,9-dimethoxybenfluron hydrochloride, C23H24O4NCl, M.w. 413.9, Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, Hradec Králové, Czech Republic; 12 or 24 mg base/kg) and Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride), C20H19N2O3Cl, M.w. 370.84, Research Institute for Pharmacy and Biochemistry, Prague, Czech Republic; 5 or 10 mg/kg) on cardiovascular, biochemical, haematological and histological parameters were studied in rabbits in vivo. Data obtained in these groups were compared with the group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2 i.v.) and with the control group (saline 1 ml/kg). Only mild and mostly no significant changes of the cardiovascular parameters (DMB 12 group: PEP:LVET ratio--0.408-0.502, LV dP/dtmax.--1337.0 kPa/s; DMB 24 group: PEP:LVET ratio--0.407-0.433, LV dP/dtmax.--1438.2 kPa/s), biochemical parameters (decrease in natrium, ALP and increase in glucose, GPX and GSH levels) and haematological parameters (increase in erythrocytes and decrease in leukocytes after the larger dose of the drug) were found in the dimethoxybenfluron groups. Repeated administration of the lower dose of Oracin induced only mild and mostly no significant changes of parameters (PEP:LVET ratio--0.393-0.475, LV dP/dtmax.--1092.4 kPa/s) in comparison with the control group. Though significant in some intervals, only a mild oscillation of the PEP:LVET ratio (0.368-0.446), decrease in LV dP/dtmax. (991.2 kPa/s) and--in comparison with control group--significantly higher blood pressure and lower heart rate were found after the higher dose of Oracin. In the most of haematological and biochemical parameters (with the exception of chlorides, protein and albumin levels) no significant changes were present. Histological examination of the heart revealed normal structure of the myocardium including minute changes of myocardium following administration of antineoplastic agents in all groups. Administration of new antineoplastic agents induced mostly mild changes of the followed-up parameters (PEP:LVET ratio, LV dP/dtmax., heart rate, levels of cardiac troponin T, survival of animals, haematological and biochemical parameters); the values of parameters were mostly significantly different from those in rabbits with daunorubicin-induced cardiomyopathy. On the basis of our results it is possible to conclude that the administration of dimethoxybenflurone and Oracin did not induce signs of cardiotoxicity in rabbits in vivo. This observation is considered to be important from the viewpoint of possible further clinical use of these new antineoplastic agents.

Animals↗
PubMed1999

IGF-I in experimental daunorubicin-induced cardiomyopathy in rabbits.

1. The occurrence of IGF-I was investigated in rabbits with experimentally daunorubicin-induced cardiomyopathy. IGF-I was measured in the heart, serum, liver and skeletal muscle. 2. A significant increase in the IGF-I was found in the left heart ventricle in daunorubicin cardiomyopathy (152.9 +/- 10.0 ng/g vs 95.1 +/- 4.2 ng/g in the control group). This site of increased IGF-I activity corresponded well with the maximum of morphological changes (dispersed cytolysis of cardiomyocytes mostly without developed subsequent interstitial myofibrosis). 3. The highest levels of IGF-I were present in right and left cardiac atrium (but without significant differences between the groups). Furthermore, in skeletal muscle, the levels of IGF-I in the daunorubicin group (839.0 +/- 142.1 ng/g) were significantly higher in comparison with the control group (482.5 +/- 83.1 ng/g). 4. The level of IGF-I in the left ventricle in the daunorubicin group (but not in the control group) was significantly higher than that in the liver. There were no correlations observed between the levels of IGF-I in the heart and in the serum. 5. The increase in IGF-I concentrations in the left heart ventricle after the administration of daunorubicin may thus reflect possible autocrine/paracrine role of IGF-I in cardiomyopathy.

Animals↗
PubMed1999

The influence of dimethoxybenfluron on biochemical and haematological parameters in rabbits.

The influence of repeated i.v. administration of dimethoxybenfluron (NO-1-B) (12 or 24 mg base/kg once weekly, 10 weeks) on biochemical and haematological parameters were studied in rabbits in vivo. No significant changes were mostly found in the serum ion levels between the dimethoxybenfluron and the control groups, as well as in most of other biochemical parameters (including total protein and albumin levels). Nevertheless, the lower dose of dimethoxybenfluron caused an increase in the glucose level. Furthermore, no significant changes were mostly present also in haematological parameters in the dimethoxybenfluron groups of rabbits (a mild decrease in thrombocytes and leucocytes). The results of our study support an assumption of good tolerance of dimethoxybenfluron from the viewpoint of its influence on biochemical and haematological parameters in rabbits and may be considered of importance for a possible therapeutic use of the derivatives.

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↗
PubMed1990

Lichen ruber and bullous pemphigoid.

The authors describe the case of a male patient, 20 years old, with a rapidly developing picture of disseminated lichen ruber planus together with the formation of vesicles and blisters. Immunofluorescent examination demonstrated lichen ruber associated with bullous pemphigoid. A good therapeutic effect was obtained with a combination of Triamcinolon and Tigason.

Adult↗
PubMed1988

The incidence of allergy to propolis in 605 consecutive patients patch tested in Prague.

605 consecutive patients were patch tested with the standard CDRG test series and with a 10% alcoholic solution of propolis. Positive allergic reactions to propolis were observed in 25 patients (4.2%); thirteen of them exhibited a simultaneous positive patch test to balsam of Peru. In view of the relatively high incidence of allergic reactions and the appearance of pseudo-cross-sensitivity to another common allergen, balsam of Peru, propolis should not be used in topical medicaments or as a component of cosmetic preparations.

Administration, Cutaneous↗
PubMed1981

Sacroiliac joints in chronic dermatoses.

In 34 patients with different chronic skin diseases (including eczemas, lichen ruber, erythrodermia, pyodermia, pemphigus erythematosus, vasculitis, parapsoriasis varioliformis, scleroderma adultorum Buschke, prophyria cutanea tarda, rosacea, dermatomyositis, erythematodes chronicus discoides and indurative tuberculosis), X-ray studies revealed sacroiliac-changes consistent with a low-grade inflammation. This oteoarthritis slightly differs from the patterns disclosed earlier by the same authors in psoriatic patients, lacking any clinical bone or joint symptoms. So far, it has not been possible to explain their nature, cause or development.

Adult↗