Pharmacological Research
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pharmacological research Editor Prof. Viktor BAUER, MD., DSc. Consulting Editors Michal DUBOVICKÝ, PhD. Assoc. Prof. Magda KOUŘILOVÁ, PhD. Mojmír MACH, PhD. Ja na NAVA ROVÁ, PhD. Prof. Radomír NOSÁĽ, MD., DSc. Ružena SOTNÍKOVÁ, PhD. entálnej f rim ar pe ma ex ko l v ó a g t i s e ú i n y s g t o i t l u o t c e a o m r f a e h x p p e l r a i t m n e BRATISLAVA 2008 Trends in Pharmacological Research ISBN 978–80–970003–7–0 Published by Institute of Experimental Pharmacology, SASc. Dúbravská cesta 9, SK-841 04 Bratislava, Slovak Republic fax: +421-2-59477 5928 • e-mail: [email protected] Printed in Slovak Republic Cover, Interior Design & Typesetting Mojmir Mach, PhD. Copyright © 2008 Institute of Experimental Pharmacology All rights reserved. No part may be reproduced, stored in a retrieval system, or trans- mitted in any form or by any means, electronic, mechanical, photocopying, recording, or ortherwise, without prior written permission from the Copyright owners. pharmacological research Table of Contents Editorial V. Bauer 7 Brief history of the Institute of Experimental Pharmacology R. Nosáľ 8 Trends in studies of drug metabolism and of related drug–drug interactions P. Anzenbacher, E. Anzenbacherová 11 Smooth muscle tissues as models for study of drug action V. Bauer, R. Sotníková, V. Nosáľová, J. Navarová, Š. Mátyás, V. Pucovský, V. Rekalov, K. Szőcs, J. Nedelčevová, Z. Kyseľová, V. Dytrichová, J. Fatyková, M. Kollárová, L. Máleková, M. Srnová, Z. Stojkovičová, G. Tóthová 15 New ways of supplementary and combinatory therapy of rheumatoid arthritis (RA) by synthetic and natural substances with antioxidant properties: New perspectives for routinely administered drugs in RA K. Bauerová, S. Poništ, K. Valachová, D. Mihalová, L. Šoltés, D. Komendová, V. Tomeková, M. Štrosová, P. Gemeiner, G. Poli 25 Effect of cytochrome P450 induction on drug disposition in isolated rat liver preparation Š. Bezek, M. Kukan, T. Trnovec 33 Reflection on animal modeling of human cardiac diseases in preclinical pharmacology: From measurements of coronary blood flow and cardiac function to sophisticated approaches of protease-catalyzed soluble cardiac protein expression with experimental myocardial infarction J. Dřímal, V. Knezl, A. Babulová, L. Bacharová, F. Borovičová, M. Dravecká, P. Gibala, J. Gvozdjak, A. Gvozdjaková, J. Jakubovský, M. Kittová, D. Magna, A. Rybár, F.V. Selecký, R. Sotníková, S. Štolc, K. Strížová, J. Tokárová, R. Nosáľ, A. Sauberer, E. Nikšová, S. Markovič, J. Toroková, A. Puškárová, T. Kollár 41 pharmacological research New computational approach to mathematical modeling in pharmacological research M. Ďurišová, L. Dedík, M. Tvrdoňová 48 Breeding and testing facility Dobrá Voda A. Gajdošík, A. Gajdošíková, E. Ujházy, D. Golhová, B. Kopecká, V. Krchnárová 58 From comparative interspecies and ontogenetic pharmacokinetics up to the usage of microcamera-techniques for drug bioavailability studies (Historicizing comments on three decades of the existence of an experimental biopharmaceutical research in Hradec Králové, Czech Republic) J. Květina 66 The use of electrochemical measurement for real-time monitoring of nitric oxide generation by macrophages in vitro A. Lojek, M. Pekarová, R. Nosáľ, J. Hrbáč 77 H1-antihistamine Dithiaden® suppressed platelet aggregation and oxidative burst of neutrophils in vitro R. Nosáľ, K. Drábiková, V. Jančinová, T. Mačičková, J. Pečivová, M. Petríková, Z. Straková 82 Research focuses of the pharmacology in Martin G. Nosáľová, S. Fraňová, A. Strapková, J. Mokrý, M. Šutovská, V. Sadloňová 88 Trends in pharmacological research – contribution from studies of the membrane transport and cell signaling K. Ondriaš 96 Vasoactive effects of Provinols™ in experimental hypertension O. Pecháňová, I. Bernátová 102 Substituted pyridoindoles as antioxidants and aldose reductase inhibitors in prevention of diabetic complications: A preclinical study in vitro and in an animal model of experimental diabetes in vivo M. Štefek, P.O. Djoubissie, A. Gajdošík, A. Gajdošíková, M. Jusková, Ľ. Križanová, Z. Kyseľová, M. Májeková, L. Račková, V. Šnirc 109 pharmacological research New pyridoindoles with antioxidant and neuroprotective actions S. Štolc, V. Šnirc, A. Gajdošíková, A. Gajdošík, Z. Gáspárová, O. Ondrejičková, R. Sotníková, Á. Viola, P. Rapta, P. Jariabka, I. Syneková, M. Vajdová, S. Zacharová, V. Nemček, V. Krchnárová 118 Trends of research in pharmacology M. Tichý, P. Urban 137 Trends in developmental toxicology: Protection of the developing organism – an ever topical issue E. Ujházy, M. Mach, J. Navarová, A. Gajdošíková, A. Gajdošík, J. Janšák, V. Dytrichová, M. Dubovický 140 Angiogenesis A perspective target in cancer therapy L. Varinská, L. Mirossay, J. Mojžiš 151 Cytokine-stimulatory effects of acyclic nucleotide analogues: extrapolation of immunopharmacological data from animal to human cells Z. Zídek, E. Kmoníčková, A. Holý 158 AUTHORS INDEX 166 We would like to express our appreciation and thanks to our financial supporters ECOMED Dlhá 95 P.O. BOX 7 010 09 ŽILINA www.ecomed.sk FISHER Slovakia, spol. s r.o. Mäsiarska 13 054 01 Levoča www.fisherww.sk IMMUNOTECH a.s. A Beckman Coulter Company Radiová 1, 10227 Praha 10| www.immunotech.cz MEDIMPRAX spol. s r.o. Predaj zdravotníckej a laboratórnej techniky Líščie údolie 57 841 04 Bratislava www.medimprax.sk SCHOELLER Slovakia, s.r.o. Šustekova 12 851 04 Bratislava www.schoeller.sk SHIMADZU Slovakia, o. z. ul. Dr. V. Clementisa 10 821 02 Bratislava www.shimadzu.sk SIGMA-ALDRICH spol. s r.o. Sokolovská 100/94 CZ-186 00 Praha 8 www.sigma-aldrich.com ZLATÁ STUDŇA s.r.o. 082 37 Široké 631 www.zlatastudna.sk Editorial Pharmacology is different from most other biological sciences because it does not ask how nature works, but rather how can we change nature? Answering this ques- tion requires the integrated effort of multiple techniques (molecular, biochemical, cellular and systems-based) to come to a total understanding of the action of a drug. K. Brune, Trends in Pharmacological Sciences 22(6), 323–324, 2001. Pharmacological investigation has existed for as long as people have been taking drugs (natural and synthetic compounds). In its simplest sense, pharmacology means what drugs do to the body and vice versa. One of the most exciting aspects of pharmacology lies in the unique way it encourages interaction between different scientific approaches. This book is published on the occasion of the 60th anniversary of the Institute of Experimental Pharmacology of the Slovak Academy of Sciences. It embraces articles in experimental pharmacology and toxicology from the viewpoint of the basic scientists, the pharmacolo- gist or the toxicologist. Our intention was to direct the attention of the medical community on pharmacological and toxicological aspects of drugs. Moreover, we are presenting recent developments in studies of drug action which were, are, and are intended to be involved in the scope of interests of pharmacological institutions in the Slovak and Czech Republic. In both countries, diverse goals were achieved during the last decades in basic pharmaco- logical research (covering a range of sub-groups, such as neuro-, cardiovascular, gastrointes- tinal, respiratory, etc. pharmacology), pharmacokinetics, toxicology (drug toxicology, ad- verse and side effects, environmental toxicology, food toxicology), and clinical pharmacology. To characterize effects of biologically active compounds, besides classical and clinical pharmacology, drug metabolism, pharmacokinetics and analytical and clinical toxicology, different experimental approaches of various biomedical disciplines, like electrophysiol- ogy, biochemistry, molecular biology, pharmacogenetics, immunology, molecular toxicol- ogy, drug epidemiology, pharmacy and clinical pharmacy, among others, were employed on living matter such as cells, tissues or organs, both in animals and humans. Since some of the experimentators may not see the whole animal just sense details, and thus instead of grasping the whole, they dissect it to end up with just a foot, an ear or a piece of the tail (in other words, perhaps a few G proteins, kinases, lipases or phosphatases, etc.), their results call upon certain reservation in interpretation. Nevertheless, they opened up new perspectives and opportunities in drug design and development with or without direct relevance to therapeutics. Biomedical research in experimental and clinical pharmacology, targeting drug therapy and toxicology by exploiting the present knowledge on drug mechanisms of action, fate and toxicity is a rapidly progressing area. Our aim was to evidence that in our institutions not only carefully integrated hypotheses are generated but we also wish to stress the importance of maintaining a critical balance between the molecular understanding of drug targets, action and safety with their effects and toxicity in the whole animal in health and sickness. Viktor Bauer pharmacological research Brief history of the Institute of Experimental Pharmacology Radomír NOSÁĽ Director of the Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 Bratilsava, Slovak Republic The Institute of Experimental Pharmacology, Slovak Academy of Sciences, represents the most advanced research institution in basic and applied pharmacology in Slovakia. The Institute has played an important role in the development of the scientific fields “pharmacology” and “toxicology”. An integral part of the Institute is the Department of Toxicology and Animal Breeding