iê w OF THE FACULTY OF MEDICINE AND DENTISTRY OF PALACKÝ UNIVERSITY, OLOMOUC CZECH REPUBLIC VOLUME 157, SUPPLEMENT 1 PALACKÝ UNIVERSITY PRESS, OLOMOUC 2013 BIOMEDICAL PAPERS Volume 157, Supplement 1 Published quarterly MK ČR E 12793 Published and printed by Palacký University Press, Olomouc Křížkovského 8, 771 47 Olomouc, IČO 61989592 Olomouc 2013 ISSN 1213-8118 eISSN 1804-7521 63. Czech and Slovak Pharmacological Days September 11–13, 2013 Olomouc, Czech Republic Honorary Committee Miroslav Mašláň (Rector, Palacky University Olomouc) Ladislav Mirossay (Rector, Pavel Jozef Safarik University, Kosice) Milan Kolář (Dean, Faculty of Medicine and Dentistry, Palacky University Olomouc) Roman Havlík (Director, Faculty Hospital Olomouc) Pavel Anzenbacher (Chairman of the Scientifi c Committee) Scientifi c Committee Pavel Anzenbacher Michal Dubovický Soňa Franová Vladimír Geršl Peter Ondra Petr Pávek Ondřej Slanař Pavel Suchý Vilím Šimánek Jitka Ulrichová Organizing Committee Pavel Anzenbacher Eva Anzenbacherová Jitka Hybnerová Jana Novaková Jitka Ulrichová Karel Urbánek Rostislav Večeřa Guest Editor Biomedical Papers Karel Urbánek Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 Sep; 157 (Supplement 1) Dear participants, 63. Czech and Slovak Pharmacological Days are Development of experimental techniques has opened taking place again, after six years, in Olomouc, Czech possibilities to answer questions about which we only Republic. It is a honor for all enthusiasts who work in dreamed of in the past. Also, the borders between life the field of pharmacology and related sciences in this sciences seem to be more fuzzy than before which hope- city and a pleasure to invite colleagues from both our fully will contribute to application of approaches formerly sister countries, and enjoy the hospitality and friendship typical for each discipline. of Olomouc and Haná region. The organizers also hope that this Conference will be Pharmacology has evolved during last years into a sci- a good place for exchanging experience in science as well ence with many new applications, and, simultaneously, as in the education of pharmacology in general. with new challenges and tasks to be solved in the future. Thank you for coming to Olomouc. Pharmacology and pharmacogenetics is taken as an ex- ample of personalization of medicine in the 21st century. Pavel Anzenbacher v Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 Sep; 157 (Supplement 1) CONTENTS Abstracts, Oral presentations ......S1 Abstracts, Posters .......................S16 Communications ........................S50 vi Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 Sep; 157 (Supplement 1):S1–S88. O-1 O-2 Ethanol and its principle metabolite acetaldehyde Effect of methycobalamin application in patients affect inward rectifier potassium current IK1 in rat with autism ventricular myocytes Adela Corejovaa, Drahomira Rauovab, Daniela Janosikovac, Marketa Bebarovaa, Peter Matejovica, Michal Pasekb, Veronika Pospisilovad, Maria Mikovae, Juraj Repiskyc, Milena Simurdovaa, Jiri Simurdaa Silvia Lakatosovaf, Anna Hrabovskaa, Jan Kyselovica aDepartment of Physiology, Faculty of Medicine, Masaryk aDepartment of Pharmacology and Toxicology, Faculty of University, Brno, Czech Republic Pharmacy, Comenius University in Bratislava, Bratislava, Slovak bInstitute of Thermomechanics - branch Brno, Czech Academy of Republic Sciences, Brno, Czech Republic bDepartment of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic Alcohol intoxication may induce arrhythmias, most cFaculty of Philosophy and arts, Trnava University, Slovak frequently the atrial fibrillation (AF). Increase of inward Republic rectifier potassium currents including the voltage-gated dAutism center Andreas in Bratislava, Slovak Republic e current IK1 is known to play an important role in the Autism center FRANCESCO in Prešov, Slovak Republic pathogenesis of AF. Data describing effects of ethanol fInstitute of Physiology, Faculty of Medicine, Comenius University and its principle metabolite acetaldehyde on mamma- in Bratislava, Slovak Republic lian IK1 are rare and controversial. Hence, we aimed to analyse IK1-changes in the presence of ethanol and acet- Oxidative stress has been suggested to be one of the aldehyde in enzymatically isolated rat right ventricular key elements in the pathophysiology of autism. An inter- myocytes by the whole cell patch clamp technique at room vention targeted to the glutathion metabolic precursors temperature. Ethanol (0.2–200 mM) and acetaldehyde could improve plasma biomarkers of impaired methyla- (3–300 μM) were applied by the rapid perfusion system tion capacity and improve behavior in patients with au- (each concentration in 3–19 cells). A dual effect of etha- tistic disorder. The aim of our project was to examine nol on IK1 was observed. At very low concentrations up to whether methylcobalamin application would affect the 0.8 mM (∼0.04‰), ethanol inhibited IK1, however, at con- gluthatione redox status and autistic disorder symptoms. centrations above 20 mM (∼0.92‰), ethanol conversely 37 patients with autistic disorder were enrolled. Exclusion stimulated IK1. The effect was voltage-independent. In ac- criteria for subject selection were: Asperger syndrome, cordance with these results, IK1-stimulation was preceded high-functioning autism, epilepsy, selected pharmacother- by a transient IK1-inhibition at the beginning of ethanol apy affecting CNS. Oral form of methylcobalamine was application. 2 and 8 mM ethanol (∼0.09 and 0.37‰, re- given daily at dose 500 μg. Venous blood was collected at spectively) caused inhibition of IK1 in some cells but its d0 and d100 and redox status of glutathione and levels of stimulation in others. Acetaldehyde inhibited IK1 with the homocystein, cystine and cobalamine were determined. concentration causing 50%-inhibition IC50 = 61.1±5.1 μM The psychological profile was defined at d0 and d100 by (the Hill coefficient nH = 1.51±0.18), i.e. IK1-inhibition psychologist using scale. Oral application of methylcobal- seems to be negligible in the clinically relevant plasma amine at the dose 500 μg per day influenced glutathione concentrations of acetaldehyde (in healthy humans usu- redox status. Social interaction was increased, including ally up to 3.7 μM). We conclude that ethanol exerts a dual social responsiveness and eye contact. Oral application of effect on the cardiac IK1. Inhibition of IK1 in some cells and methylcobalamine in patients with autism seems to poten- its stimulation in others might result in the heterogeneity tiate antioxidative mechanisms and leads to the changes of cardiac repolarization with possible arrhythmogenic in the psychological profile of the patients. consequences. It is unlikely that, in healthy humans, ac- etaldehyde significantly contributes to the arrhythmogen- esis observed after the alcohol consumption. O-3 Molecular forms of cholinesterases in heart a,b b a ACKNOWLEDGMENT Dominika Dingova , Eric Krejci , Anna Hrabovska aDepartment of Pharmacology and Toxicology, Faculty of This work was supported by the grant project Pharmacy, Comenius University in Bratislava, Slovak Republic NT14301-3/2013. bCentre d’Etude de la Sensori-Motricite, CNRS UMR 8194, Universite Paris Descartes, 45 rue des Saints Peres, 75006 Paris, France Cholinesterases are important enzymes that are tar- geted by various xenobiotics. In pharmacology, cholines- terase inhibitors are used in the diagnosis and treatment of skeletal muscle weakness and the therapy of memory S1 Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 Sep; 157 (Supplement 1):S1–S88. decline. Recently, importance of cholinesterases in heart mood disorders during pregnancy and the postpartum has been highlighted by multiple research groups. period. An abnormal stimulation of serotonin receptors as Moreover, a link between changed enzyme activities and a result of an increased synaptic availability of serotonin some cardiovascular diseases has been suggested. and impairment of the activity of serotonin transporters Aim of the present project was to characterize and during the brain development due to administration of localize molecular forms of cholinesterases in heart. these drugs can lead to functional alterations accom- Genetically modified mice lacking different mo- panied by postpartum neurobehavioral dysfunctions. lecular forms of cholinesterases were used in the proj- However, there are lack of knowledge on possible adverse ect. Cholinesterase activities were determined in heart effects of SSRI/SNRI drugs on the functional brain devel- compartments by Ellman’s method. Different molecular opment and behavior of the offspring. In our experimental forms were distinguished in biochemical method of su- study, we focused on adverse reactions of developmental crose gradient. Precise localization of different molecular exposure to venlafaxine (VENF) on early postnatal and forms of cholinesterases in heart was determined in light neurobehavioral development of rat offspring. Our experi- microscopy by modified Karnovsky and Roots staining. mental study with venlafaxine showed that it may interfere Specific monoclonal and polyclonal antibodies were used with brain development by gender-dependant way and af- to visualize cholinesterases by fluorescence microscopy. fect neurobehavioral adaptations of rat offspring in a new We confirmed the presence of multiple molecular environment. forms of acetyl- and