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68. ČESKO-SLOVENSKÉ FARMAKOLOGICKÉ DNY V HRADCI KRÁLOVÉ

5. – 7. 9. 2018

SBORNÍK ABSTRAKT

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1 POŘÁDAJÍCÍ ORGANIZACE

Česká společnost pro experimentální a klinickou farmakologii a toxikologii (ČSEKFT) ČLS JEP

Slovenská farmakologická spoločnosť (SFaS) SLS Slovenská toxikologická spoločnosť (SETOX)

Lékařská fakulta, Univerzita Karlova, Hradec Králové Farmaceutická fakulta, Univerzita Karlova, Hradec Králové

VĚDECKÝ VÝBOR KONFERENCE Prof. MUDr. Stanislav Mičuda, Ph.D.

(předseda)

Prof. RNDr. Pavel Anzenbacher, DrSc.

Prof. PharmDr. Petr Pávek, Ph.D.

Doc. Ing. Jaroslav Chládek, Ph.D.

Doc. PharmDr. Jan Juřica, Ph.D.

Prof. MUDr. Jiří Kassa, CSc.

Doc. RNDr. Eva Kmoníčková, CSc.

Prof. PharmDr. Milan Nobilis, CSc.

Prof. MUDr. Ondřej Slanař, Ph.D.

Prof. MUDr. Jan Švihovec, Dr.Sc.

Prof. PharmDr. František Štaud, Ph.D.

Doc. PharmDr. Tomáš Šimůnek, Ph.D.

Prof. RNDr. Soňa Fraňová, Ph.D.

RNDr. Michal Dubovický, Ph.D.

ORGANIZAČNÍ VÝBOR KONFERENCE Prof. MUDr. Stanislav Mičuda, PhD.

Doc. PharmDr. Martin Štěrba, PhD.

MUDr. Jolana Cermanová, PhD.

Doc. Ing. Jaroslav Chládek, Ph.D.

Prof. PharmDr. Petr Pávek, Ph.D.

Prof. PharmDr. František Štaud, PhD.

PharmDr. Olga Lenčová, PhD.

Hana Kalhousová

Vydavatel:

Ústav farmakologie LF HK

Šimkova 870, Hradec Králové, 500 03 ISBN: 978-80-906595-6-8

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Seznam abstrakt

CHARACTERISTICS OF NICOTINE TAKING AND NICOTINE SEEKING IN A RAT MODEL OF DEPRESSION ... 9

PETRA AMCHOVA,ZUZANA BABINSKA,JANA RUDA-KUCEROVA ... 9

RISK OF INSULIN RESISTANCE IN VISCERAL ADIPOSE TISSUE AFTER PROLONGED SUPRAPHYSIOLOGICAL TESTOSTERONE ADMINISTRATION IN MALE RATS ... 11

EMIL BABIAK,GABRIEL DÓKA,JÁN KLIMAS ... 11

PUPILLOMETRY AS AN INDICATOR OF L-DOPA DOSAGES IN PARKINSON´S DISEASE PATIENTS ... 12

BARTOŠOVÁ O1.,BONNET C2.,ULMANOVÁ O2.,ŠÍMA M1.,PERLÍK F1.,RŮŽIČKA E2.,SLANAŘ O1. ... 12

USE OF HERBAL MEDICINES AND THE CO-USE OF CONVENTIONAL PHARMACOTHERAPY WITH HERBAL PRODUCTS IN SELECTED POPULATION GROUPS IN WEST BOHEMIA ... 14

MONIKA BLUDOVSKÁ,HALINA SKYRCHUK,JAKUB KOČIŠ,EVA BUCHALOVÁ,EVA KMONÍČKOVÁ ... 14

STEREOISOMERS OF 1-METHYLTRYPTOPHAN EFFECT RENAL FIBROSIS FOLLOWING ISCHEMIA-REPERFUSION INJURY. ... 15

ČEPCOVÁ D.,MIŠÚTH S.,VAVRINEC P.,VAVRINCOVÁ-YAGHI D. ... 15

IN VITRO SYNERGISTIC EFFECT OF ANTIMYCOTICS AND ESSENTIAL OILS AGAINST CANDIDA ALBICANS ISOLATES ... 17

EVA ČONKOVÁ,MARTINA VIŠŇOVSKÁ,PETER VÁCZI,EMA BÖHMOVÁ,ZUZANA SIHELSKÁ,MICHAELA HARČÁROVÁ ... 17

PREDICTING LONG-TERM COSTS AND HEALTH OUTCOMES FOR POLICY DECISION MAKING ... 19

TOMÁŠ DOLEŽAL ... 19

RESVERATROL MODIFIES BILIARY SECRETION OF CHOLEPHILIC COMPOUNDS IN SHAM-OPERATED AND CHOLESTATIC RATS ... 20

EVA DOLEŽELOVÁ1,ALENA PRAŠNICKÁ2,JOLANA CERMANOVÁ2,ALEJANDRO CARAZO3,LUCIE HYRŠOVÁ3,MILOS HROCH4, JAROSLAV MOKRÝ5,MICHAELA ADAMCOVÁ6,ALENA MRKVICOVÁ4,PETR PAVEK3,STANISLAV MIČUDA2 ... 20

EXPRESSION OF APOPTOSIS-RELATED PROTEINS BAX, BCL2 IN END-STAGE OF EXPLANTED HEART. ... 22

MARTINA DOLNÁ1,ADRIANA SAMÁKOVÁ2,MARTIN PINČEK2,NIKOLA SABOVÁ2,SIMONA VALAŠKOVÁ2,ANDREA GAŽOVÁ3, MICHAL HULMAN4,JÁN KYSELOVIČ1 ... 22

DIFFERENT EFFECTS OF ENDOCANNABINOID OLEAMIDE ON HUMAN AND RAT CYTOCHROME P450 ENZYMES ... 24

GABRIELA DOVRTĚLOVÁ1,ONDŘEJ ZENDULKA1,KRISTÝNA NOSKOVÁ1,JAN JUŘICA1,ONDŘEJ P2,JAN DUŠEK3,ALEJANDRO CARAZO3,IVETA ZAPLETALOVÁ4,NATAŠA HLAVÁČOVÁ5 AND PETR PÁVEK3 ... 24

THE EFFECT OF COMORBIDITIES ON GENE EXPRESSION OF THE PROTEINS ASSOCIATED WITH STORE- OPERATED CALCIUM ENTRY IN HUMAN FAILING HEARTS. ... 26

DRAGÚN M.1,MÁŤUŠ M.1,GAŽOVÁ A.2,HUDEC V.3,HULMAN M.3,KYSELOVIČ J.1 ... 26

SUB-CHRONIC INHALATION OF LEAD OXIDE NANOPARTICLES REVEALED THEIR BROAD DISTRIBUTION AND TISSUE-SPECIFIC SUBCELLULAR LOCALIZATION IN TARGET ORGANS ... 27

JANA DUMKOVÁ1,TEREZA SMUTNÁ2,LUCIE VRLÍKOVÁ2,PHILIPPE LE COUSTUMER3,4,5,ZBYNĚK VEČEŘA6,BOHUMIL DOČEKAL6, PAVEL MIKUŠKA6,LUKÁŠ ČAPKA6,PETR FICTUM7,ALEŠ HAMPL1,MARCELA BUCHTOVÁ2,8 ... 27

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TERIFLUNOMIDE IS AN INDIRECT HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR (CAR) ACTIVATOR

INTERACTING WITH EPIDERMAL GROWTH FACTOR (EGF) SIGNALING ... 29

1JAN DUSEK,1ALEJANDRO CARAZO,2ONDREJ HOLAS,1JOSEF SKODA,1TOMAS SMUTNY,1PETR PÁVEK ... 29

STEVIOL, AN AGLYCONE OF STEVIOL GLYCOSIDE SWEETENERS, INTERACTS WITH THE PREGNANE X (PXR) AND ARYL HYDROCARBON (AHR) RECEPTORS IN DETOXIFICATION REGULATION ... 30

JAN DUŠEK1,ALEJANDRO CARAZO1,JAN SOKODA1,ALZBETA HORVÁTOVA1, FRANTISEK TREJTNAR1,LUCIE HYRSOVA1,ONDREJ HOLAS2,TOMAS SMUTNY1,STANISLAV MICUDA3,PETR PAVEK1 ... 30

INTEGRATION OF MODEL SITUATIONS INTO TEACHING GENERAL PHARMACOLOGY WITH IMPLEMENTATION THE ISTAN SIMULATOR – STATUS ASTHMATICS. ... 31

ANDREA GAŽOVÁ1,MONIKA LAŠŠÁNOVÁ1,JANA TISOŇOVÁ1,ANDREA RAGANOVÁ1,JÁN KYSELOVIČ2 ... 31

EXPRESSION OF HCN CHANNELS IN MODEL OF PHARMACOLOGICALLY-INDUCED TORSADES DE POINTES ... 32

KATARÍNA HADOVÁ ... 32

INFLUENCE OF OLANZAPINE ON SELECTED METABOLIC PARAMETERS DEPENDING ON THE DURATION OF ADMINISTRATION AND THE DIET TYPE IN LABORATORY MICE ... 33

TOMÁŠ HAMMER1,JIŘÍ PROCHÁZKA1,MICHAL KARPÍŠEK1,2,PAVLA KAREŠOVÁ2,3,HANA KOTOLOVÁ1 ... 33

ACADEMIC CLINICAL TRIALS IN CZECH REPUBLIC ... 35

LENKA HOŘAVOVÁ1,LENKA SOUČKOVÁ1,2,3,KATEŘINA NEBESKÁ1 ... 35

RADIOACTIVELY LABELED RAMUCIRUMAB: IN VITRO BINDING AND INTERNALIZATION STUDIES IN VEGFR2 POSITIVE CELLS ... 37

JANOUŠEK J.,1BÁRTA P.,2TREJTNAR F.1 ... 37

NABUMETONE ALTERS MRNA EXPRESSION OF CYTOCHROME P450 IN THE LIVER AND IN THE INTESTINE OF GERM-FREE MICE ... 39

LENKA JOUROVÁ1,PAVEL ANZENBACHER2,BARBORA LIŠKOVÁ3,PETRA HERMANOVÁ4,TOMÁŠ HUDCOVIC4,HANA KOZAKOVÁ4, EVA ANZENBACHEROVÁ1 ... 39

URSODEOXYCHOLIC ACID IN ONCOLOGY PATIENTS – CLINICAL EXPERIENCE ... 41

JUŘICA J.1,2,DÚHOVÁ J.1,KÝR M.3 ... 41

EXPRESSION AND FUNCTION OF TRANSPORTERS/ENZYMES INVOLVED IN PLACENTAL METABOLISM OF TRYPTOPHAN ... 43

KARAHODA R.1,ČERVENÝ L.1,KASTNER P.2,KUČERA R.2,ŠTAUD F.1 ... 43

DOSE DEPENDENT PROPHYLACTIC EFFICACY OF 6-CHLOROTACRINE IN SOMAN-POISONED MICE ... 45

JIŘÍ KASSA,JAN KORÁBEČNÝ ... 45

NOVEL DERIVATIVES OF SALICYLAMIDES AND THEIR ANTIPROLIFERATIVE AND TOXIC EFFECTS IN VITRO AND IN VIVO ... 46

TEREZA KAUEROVÁ 1,TOMÁŠ GONĚC 2,JOSEF JAMPÍLEK 3,SUSANNE HAFNER 4,TATIANA SYROVETS 4,MARTA CHALUPOVÁ 1, JARMILA KLUSÁKOVÁ 1,PETER KOLLÁR 1 ... 46

TARGETED METABOLOMIC ANALYSIS OF 14-DAYS MODEL OF EOSINOPHILIC AIRWAYS INFLAMMATION IN GUINEA PIGS ... 48

MARTIN KERTYS1,2,MARIAN GRENDAR2,JURAJ MOKRY1,2 ... 48

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DRUG-INDUCED LONG QT SYNDROM – MOLECULAR MECHANISMS AND CLINICAL IMPLICATIONS... 50

KLIMAS JÁN ... 50

THE USE OF CLINICAL EVIDENCE AND REAL WORLD DATA IN HEALTH ECONOMIC ANALYSIS ... 51

JIŘÍ KLIMEŠ1,2 ... 51

THE IMPACT OF THE TREATMENT WITH INORGANIC NITRATES ON THE RIGHT VENTRICLE IN MONOCROTALINE-INDUCED PULMONARY HYPERTENSION ... 53

ZUZANA KMECOVÁ,KRISTINA LABJAKOVÁ,DANA KOPCOVÁ,JANA VETEŠKOVÁ,MICHAL RADIK,EVA MALÍKOVÁ,GABRIEL DÓKA, PETER KŘENEK,JÁN KLIMAS... 53

ROLE OF ETHICAL COMMITTEE IN THE DRUG EVALUATION PROCESS ... 55

MILAN KRIŠKA,JANA TISOŇOVÁ,MONIKA LAŠŠÁNOVÁ,MIRIAM PETROVÁ,RÓBERT VOJTKO,VIERA KRISTOVÁ ... 55

MONITORING OF MDD BIOMARKERS AND ITS IMPORTANCE ... 56

MICHAELA KRIVOŠOVÁ1,PATRIK KUŠNÍR1,ANNA URBANOVÁ1,2,MARTIN KERTYS1,MICHAL MEŠŤANÍK2,3,INGRID TONHAJZEROVÁ3,2,JURAJ MOKRÝ1,2 ... 56

CHANGES OF 35 RAT HEMODYNAMIC PARAMETERS INFLUENCED BY NOREPINEPHRINE AND ACETYLCHOLINE ... 58

LUCIA KURAKOVA1,KAROL ONDRIAS2,ELENA ONDRIASOVA1,FRANTISEK KRISTEK3 ... 58

MONITORING OF PLASMATIC CONCENTRATIONS OF ANTITUBERCULOTICS ... 60

KUŠNÍR P1,KRIVOŠOVÁ M1,KERTYS M1,PORVAZNÍK P2,MOKRÝ J1 ... 60

EXPERIMENTAL PIGS: RELATIONS BETWEEN ELECTROGASTROGRAPHIC ACTIVITY AND PLASMA LEVELS AFTER INTRAGASTRIC ADMINISTRATION OF A MODEL DRUG (NABUMETONE) ... 62

JAROSLAV KVĚTINA1,ILJA TACHECÍ1,MILAN NOBILIS2,VĚRA RADOCHOVÁ3,EVA PETEROVÁ1,4,ONDŘEJ HORÁČEK2,JAN BUREŠ1 62 MODEL SITUATIONS IN GENERAL PHARMACOLOGY WITH IMPLEMENTATION THE ISTAN SIMULATOR – CLINICAL CASE SITUATION - MALIGNANT HYPERTHERMIA ... 64

JÁN KYSELOVIČ1,MONIKA LAŠŠÁNOVÁ2,JANA TISOŇOVÁ2,ANDREA RAGANOVÁ2,ANDREA GAŽOVÁ2 ... 64

CA2+-DEPENDENT CL- CHANNELS BLOCKADE IN NOREPINEPHRINE-INDUCED CONTRACTION OF ADULT AND AGED RAT FEMORAL ARTERY ... 66

LISKOVA S.1,PETROVA M.1,KRISTOVA V.1,KUNES J.2,ZICHA J.2... 66

COGNITIVE SCREENING IN PATIENTS WITH METABOLIC SYNDROME IN SLOVAKIA – KOGNIMET - SK ... 67

ZUZANA MAČEKOVÁ 1,2),MIROSLAVA SNOPKOVÁ 3),TATIANA GEROČOVÁ 4),JÁN KLIMAS2) ... 67

IN VITRO EVALUATION OF ZINC EFFECTS USING VARIOUS CYTOTOXIC TESTS ... 69

DANA MARCINČÁKOVÁ1,PETRA SCHUSTEROVÁ2,MARCEL FALIS1,JAROSLAV LEGÁTH1 ... 69

EFFECT OF MICROBIOTA ON THE METABOLISM OF QUERCETIN IN HUMAN INTESTINE ... 70

ZUZANA MATUŠKOVÁ1,EVA ANZENBACHEROVÁ2,BARBORA PAPOUŠKOVÁ3,MILAN KOLÁŘ4,PAVEL ANZENBACHER1 ... 70

EFFECT OF RUTIN AND ATORVASTATIN TREATMENT ON DYSFUNCTIONS INDUCED BY METABOLIC SYNDROME-LIKE CONDITIONS ... 72

MICHÁLIKOVÁ D.1,2,TYUKOS KAPRINAY B.1,2,LIPTÁK B.1,2,STARÁ V.3,ŠVÍK K.1,SLOVÁK L.1,2,KOPRDOVÁ R.1,SOTNÍKOVÁ R.1, KNEZL V.1, BEZEK Š.1,MACH M.1,GÁSPÁROVÁ Z.1 ... 72

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ALTERATION OF BILE ACID HOMEOSTASIS BY IRON OVERLOAD IN RATS ... 74

STANISLAV MICUDA1,HANA LASTUVKOVA1,JOLANA CERMANOVA1,JITKA HÁJKOVÁ1,MILOS HROCH2,JAROSLAV MOKRY3,EVA DOLEZELOVAD,FATEMEH ALAEI FARADONBEH1,PETR PAVEK5,MARTIN LENICEK6,LIBOR VITEK6,PETR NACHTIGAL4,ALENA PRASNICKA1,4 ... 74

ISOFLAVONOIDS HAVE A DIRECT EFFECT ON CORONARY SMOOTH MUSCLES ... 75

THOMAS MIGKOS1,JANA POUROVÁ1,MARIE VOPRŠALOVÁ1,CYRIL AUGER2,VALERIE SCHINI-KERTH2,PŘEMYSL MLADĚNKA1.... 75

INHIBITION OF O-(6)-METHYLGUANINE DNA METHYLTRANSFERASE WITH O-(6)-BENZYLGUANINE INDUCES CELL SENESCENCE INDEPENDENTLY OF MAPK KINASE IN VASCULAR SMOOTH MUSCLE CELLS. ... 76

MIŠÚTH S.,ČEPCOVÁ D.,VAVRINCOVÁ-YAGHI D.,VAVRINEC P. ... 76

FLAVONOIDS, THEIR METABOLITES AND PLATELETS ... 78

PŘEMYSL MLADĚNKA1,LENKA APPLOVÁ1,JANA KARLÍČKOVÁ2,KATEŘINA MACÁKOVÁ2 ... 78

MODULATION OF ALLERGIC AIRWAY INFLAMMATION BY PHOSPHODIESTERASE INHIBITORS ... 79

JURAJ MOKRÝ ... 79

DESIGN AND BIOAVAILABILITY OF ABAD (17ß-HSD10) INHIBITORS FOR TREATMENT OF ALZHEIMER´S DISEASE OR OTHER MITOCHONDRIA RELATED DISEASES ... 81

KAMIL MUSILEK1-2*,ONDREJ BENEK1-2,LUCIE VINKLAROVA1-2,MONIKA SCHMIDT1-2,ADAM SKARKA2,JANA HATLAPATKOVA1,3, JAN MISIK1,3,KAMIL KUCA1-2,FRANK GUNN-MOORE4 ... 81

SOLUBLE ENDOGLIN AS INDUCER OF ENDOTHELIAL/VASCULAR DYSFUNCTION ... 83

PETR NACHTIGAL1,BARBORA VITVEROVA1,MATEJ VICEN1,IVETA NAJMANOVA1,EVA DOLEZELOVA1,CARMELO BERNABEU2, MIGUEL PERICACHO3 ... 83

SUNITINIB IN THE PAEDIATRIC ONCOLOGY – CURRENT CLINICAL RESEARCH ... 85

KATEŘINA NEBESKÁ1,JANA MERHAUTOVÁ1,LENKA SOUČKOVÁ1,2,3,REGINA DEMLOVÁ1,JAROSLAV ŠTĚRBA2 ... 85

ANALYSING CHANGES OF SELECTED BIOMARKERS OF APOPTOSIS (BAX, BCL-2) DURING THERAPY PATIENTS WITH ATRIAL FIBRILLATION. ... 87

MARTIN PINČEK1,ADRIANA SAMÁKOVÁ1,NIKOLA SABOVÁ1,SIMONA VALÁŠKOVÁ1,MARTINA DOLNÁ2,JÁN KYSELOVIČ2,ANDREA GAŽOVÁ3,MICHAL HULMAN4 ... 87

THE CONNECT4CHILDREN PROJECT (C4C): COLLABORATION IN PEDIATRIC CLINICAL PHARMACOLOGY ... 89

PAVLA POKORNÁ1,2,3,ONDŘEJ SLANAŘ1... 89

EFFECT OF FENOFIBRATE AND SILYMARIN ON P-GLYCOPROTEIN IN RATS ... 90

MARTIN PORUBA1,ZUZANA MATUŠKOVÁ1,MARTINA HÜTTL2,LUDMILA KAZDOVÁ2,ROSTISLAV VEČEŘA1 ... 90

TWO FLAVONOID METABOLITES, 3,4-DIHYDROXYPHENYLACETIC ACID AND 4-METHYLCATECHOL, RELAX RAT ARTERIES EX VIVO ... 92

JANA POUROVÁ1,IVETA NAJMANOVÁ2,MARIE VOPRŠALOVÁ1,THOMAS MIGKOS1,PŘEMYSL MLADĚNKA1 ... 92

ARYL HYDROCARBON RECEPTOR IN METABOLISM, CARCINOGENESIS AND DEVELOPMENT ... 93

JIŘINA PROCHÁZKOVÁ,MIROSLAV MACHALA ... 93

NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY – AN OVERVIEW ... 95

MICHAL REGEŠ1,2,DOMINIKA LUPTÁKOVÁ1,3,SONAM KAPOOR1,LADISLAV BAČIAK1,4,IVO JURÁNEK1 ... 95

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OLFACTORY BULBECTOMY MODEL OF DEPRESSION IN RATS EXHIBITS ALTERED VULNERABILITY TOWARDS

DRUG ADDICTION IN MODELS OF VOLUNTARY DRUG INTAKE ... 96

JANA RUDA-KUCEROVA,ZUZANA BABINSKA,PETRA AMCHOVA ... 96

TWO INSULIN-SENSITIZING ESTOLIDE COMPOUNDS DID NOT MODULATE BIOENERGETIC PROPERTIES OF MURINE LIVER AFTER SHORT-TERM GASTRIC ADMINISTRATION ... 98

DAVID RYCHTRMOC,PAVLA STAŇKOVÁ,OTTO KUČERA,ZUZANA ČERVINKOVÁ ... 98

THE EFFECT OF PHARMACOLOGICAL INTERVENTION ON FIBROBLAST CELL EXPRESSION OF VEGF-A PROTEIN. ... 100

NIKOLA SABOVÁ1,ADRIANA SAMÁKOVÁ1,MARTIN PINČEK1,SIMONA VALÁŠKOVÁ1,ONDREJ SPRUŠANSKÝ1,ANDREA GAŽOVÁ2, MARTINA DOLNÁ3,JÁN KYSELOVIČ3 ... 100

ANTIDEPRESSANTS AND MYOCARDIAL ISCHEMIA-REPERFUSION INJURY ... 102

SALVARAS L.SASVÁRIOVÁ M.,GULAČ P.,STANKOVIČOVÁ T. ... 102

CHARACTERISTICS OF BONE MARROW CELLS IN CHRONIC ISCHEMIC HEART DISEASE AND CRITICAL LIMB ISCHEMIA ... 104

ADRIANA SAMÁKOVÁ1,SIMONA VALAŠKOVÁ1,NIKOLA SABOVÁ1,MARTIN PINČEK1,ONDREJ SPRUŠANSKÝ1,ANDREA GAŽOVÁ2, JURAJ MAĎARIČ3,MICHAL HULMAN3,JÁN KYSELOVIČ4 ... 104

DOES MATERNAL DEPRESSION AND PRENATAL ADMINISTRATION OF VENLAFAXINE AFFECT THE MYOCARDIAL ACTIVITY OF OFFSPRING? ... 106

SASVÁRIOVÁ M.1,SALVARAS L.1,BELOVIČOVÁ K.2,BÖGI E.2,KNEZL V.2,STANKOVIČOVÁ T.1,DUBOVICKÝ M.2 ... 106

BASIC HEALTH-ECONOMIC PRINCIPLES IN THE CONTEXT OF CZECH HEALTH TECHNOLOGY ASSESSMENT .... 109

JANA SKOUPÁ1,2 ... 109

A FEASIBILITY STUDY OF THE TOXIC RESPONSES OF HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED HEPATOCYTES TO PHYTOCHEMICALS. ... 110

TOMÁŠ SMUTNÝ 1,2,RIINA HARJUMÄKI 2,LIISA KANNINEN 2,MARJO YLIPERTTULA 2,3,PETR PÁVEK 1,YAN-RU LOU 2... 110

MIRNA CONTROLS PREGNANE X RECEPTOR (PXR) EXPRESSION: REGULATION OF THE METABOLISM REGULATOR ... 112

TOMÁŠ SMUTNÝ1,SABINE GERBAL-CHALOIN2,STANISLAV MIČUDA3,PETR PÁVEK1 ... 112

PLACENTA – THE CENTRAL UNIT OF FETAL GROWTH AND PROGRAMMING ... 114

FRANTIŠEK ŠTAUD ... 114

PHARMACOKINETICS OF PROPHYLACTIC ANTIBIOTICS DURING CARDIAC SURGERY USING CPB ... 115

FLT3 INHIBITORS - MIDOSTAURIN, GILTERITINIB AND FLX925 AND THEIR ROLE IN ABCB1 AND ABCG2 MEDIATED MULTIDRUG RESISTANCE ... 116

MARTIN SVOREŇ1,ALEŠ ŠORF1,DIMITRIOS VAGIANNIS1,FRANTIŠEK ŠTAUD1,JAKUB HOFMAN1,MARTINA ČEČKOVÁ1 ... 116

ESTIMATION OF CONTINUOUS VANCOMYCIN MAINTENANCE DOSE IN CRITICALLY ILL ADULT ... 117

MARTIN ŠÍMA,ONDŘEJ SLANAŘ ... 117

ADHERENCE WITH PERINDOPRIL THERAPY – A PILOT STUDY USING TDM OF PERINDOPRILAT PLUS EVALUATION OF PERINDOPRILAT CLEARANCE ESTIMATION ... 118

MARTIN ŠÍMA1,MARTIN VODIČKA2,VĚRA MAREŠOVÁ3,TOMÁŠ ŠÁLEK4,RADOMÍR ČABALA3,ONDŘEJ SLANAŘ1 ... 118

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MODULATION OF DAUNORUBICIN PHARMACOKINETIC RESISTANCE BY CYCLIN-DEPENDENT KINASE

INHIBITORS ... 120

ALEŠ ŠORF1,EVA NOVOTNÁ2,JAKUB HOFMAN1,VLADIMÍR WSÓL2,FRANTIŠEK ŠTAUD1,MARTINA ČEČKOVÁ1 ... 120

NEW POTENTIAL ANTICANCER DRUGS AND THEIR EFFECT ON HUMAN LIVER MICROSOMAL CYTOCHROMES P450 ... 121

ALENA ŠPIČÁKOVÁ1,PETR KRAUS3,PAVEL ANZENBACHER1,2,MIROSLAV STRNAD3 ... 121

NEW INSIGHTS INTO PHARMACOLOGICAL CARDIOPROTECTION IN ANTHRACYCLINE CARDIOTOXICITY SETTINGS ... 122

MARTIN ŠTĚRBA1,PETRA BRÁZDOVÁ1,EDUARD JIRKOVSKÝ1,2,ANNA JIRKOVSKÁ3,ZUZANA POKORNÁ1,GALINA KARABANOVICH4, JAROSLAV ROH4,HANA PISKÁČKOVÁ5,PETRA ŠTĚRBOVÁ5,TOMÁŠ ŠIMŮNEK3 ... 122

THE INFLUENCE OF ION CHANNELS ACTIVITY MODULATORS ON EXPERIMENTALLY-INDUCED ALLERGIC ASTHMA PATHOGENESIS AND SYMPTOMATOLOGY... 124

MARTINA ŠUTOVSKÁ1,MARTA JOŠKOVÁ1,MICHAELA KOCMÁLOVÁ2,IVANA KAZIMIEROVÁ2,JANA BARBORÍKOVÁ1,MIROSLAVA MOLITORISOVÁ1,SOŇA FRAŇOVÁ1. ... 124

CONTROVERSY AROUND VANCOMYCIN TARGET TO ACHIEVE OPTIMAL THERAPEUTIC EFFECT: TROUGH ONLY OR BOTH PEAK AND TROUGH LEVELS, AUC/MIC RATIO VERSUS CMAX/MIC RATIO: WHERE IS THE EVIDENCE BASED PRACTICE? ... 126

TESFAYE H... 126

DRUG-DRUG INTERACTIONS OF LAMIVUDINE WITH DRUG OCT2 SUBSTRATES IN THE PERFUSED RAT KIDNEY ... 127

FRANTIŠEK TREJTNAR,EVA TEICHMANOVÁ ... 127

INTERPLAY OF ABC AND SLC TRANSPORTERS IN THE TRANSPLACENTAL TRANSFER OF MARAVIROC ... 128

LENKA TUPOVA1,BIRGIT HIRSCHMUGL2,VERONIKA PILAROVA3,VIRAG SZEKELY4,CSILLA LACZKA4,LUCIENOVAKOVA3,CHRISTIAN WADSACK2,FRANTISEK STAUD1,MARTINA CECKOVA1 ... 128

EFFECTIVENESS OF ANTISEPTICS AGAINST CANDIDA ALBICANS ISOLATES ... 130

PETER VÁCZI,EVA ČONKOVÁ ... 130

PROTEIN KINASE INHIBITOR ALISERTIB INHIBITS ABCC1 DRUG EFFLUX TRANSPORTER AS WELL AS VARIOUS CYP450 ISOFORMS AND MODULATES PHARMACOKINETIC MULTIDRUG RESISTANCE ... 132

DIMITRIOS VAGIANNIS,MARTIN SVOREN,FRANTISEK STAUD,MARTINA CECKOVA,JAKUB HOFMAN ... 132

MOLECULAR HYDROGEN ACTING AS ANTIOXIDANT: VALIDATION OF RADIATION-INDUCED HEART DISEASE AND SCAVENGING IN SITU GENERATED HYDROXYL RADICALS ... 134

KATARÍNA VALACHOVÁ1,BRANISLAV KURA2,JÁN SLEZÁK2,LADISLAV ŠOLTÉS1 ... 134

CLINICAL STUDY OF EFFECTIVENESS AND SAFETY OF CUCURBITA PEPO SEED EXTRACT ON STRESS URINARY INCONTINENCE IN WOMEN ... 135

SIMONA VALÁŠKOVÁ1,ANDREA GAŽOVÁ2,ADRIANA SAMÁKOVÁ1,NIKOLA SABOVÁ1,MARTIN PINČEK1,JÁN KYSELOVIČ3 ... 135

HPLC METHOD FOR DETERMINATION OF CEFAZOLIN IN HUMAN PLASMA ... 137

VANDUCHOVA A.1,2,STROJIL J.1 ... 137

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SILYMARIN POSITIVELY INFLUENCED THE EXPRESSION OF NRF2 IN RAT SUFFERING FROM METABOLIC SYNDROME. ... 138

ROSTISLAV VEČEŘA1,MARTIN PORUBA1,ZUZANA MATUŠKOVÁ1,MARTINA HÜTTL2,LUDMILA KAZDOVÁ2. ... 138 PHARMACOLOGICAL INHIBITION OF VASOPRESSIN-INDUCED EXPRESSION OF ENDOTHELIN-1 IN SMOOTH MUSCLE CELL CULTURE ... 140

JANA VETEŠKOVÁ,GABRIEL DÓKA,PETER VAVRINEC,DIANA YAGHI-VAVRINCOVÁ,JÁN KLIMAS,PETER KŘENEK ... 140 ENDOGLIN PLAYS IMPORTANT ROLE IN 7-KETOCHOLESTEROL INDUCED ENDOTHELIAL DYSFUNCTION IN HUMAN AORTIC ENDOTHELIAL CELLS... 142

MATEJ VICEN1,RADIM HAVELEK2,EVA DOLEZELOVA1,ALENA PRAŠNICKÁ.1,IVETA NAJMANOVÁ1,PETR NACHTIGAL1 ... 142 MODERN APPROACH TO REFINE CALCULATIONS OF DIABETIC VASCULAR REACTIVITY DISORDERS AND THEIR CAPTOPRIL-INDUCED ALLEVIATIONS ... 144

RÓBERT VOJTKO,MIRIAM PETROVÁ,LUKÁŠ DOBIAŠ,VIERA KRISTOVÁ ... 144 EFFECT OF QUINOA (CHENOPODIUM QUINOA) AND BUCKWHEAT (FAGOPYRUM) ON THE LEVEL OF

EXPRESSION OF CYTOCHROME P450 AND SELECTED TRANSPORTERS IN RAT LIVER ... 146 IVETA ZAPLETALOVÁ1,PAVEL ANZENBACHER1,ONDŘEJ ŠŤASTNÍK2,LEOŠ PAVLATA2,EVA MRKVICOVÁ2,EVA ANZENBACHEROVÁ3 ... 146

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Characteristics of nicotine taking and nicotine seeking in a rat model of depression Petra Amchova, Zuzana Babinska, Jana Ruda-Kucerova

Department of Pharmacology, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic

Introduction: Nicotine is a widely consumed drug which is legally available in most countries and lead to serious health consequences. Furthermore, cigarette smoking is highly associated with depression and depression seems to prime smoking. Development of an effective pharmacological approach designed for addicted patients with depression requires

translational animal models. The most commonly used model of dual disorder has become combination of bilateral olfactory bulbectomy (OBX) and operant drug self-administration, which has already provided solid evidence of differential reactivity towards amphetamines, ketamine and cannabimimetics. This study was designed to complete the current evidence by evaluation of nicotine use and seeking behaviour in this model.

Methods: Adult male Wistar rats were randomly divided into two groups; in one group the OBX was performed while the other group was sham operated. After three weeks of nicotine i.v. self-administration conducted under a fixed ratio 1 schedule of reinforcement rats

underwent two weeks of forced abstinence followed by a drug-free reinstatement session.

Forced swim test took place before the self-administration protocol and on the first day of abstinence.

Results: OBX induced characteristic hyperactive locomotor phenotype and increase of immobility scores in the forced swim test (FST). Maintenance of nicotine self-administration did not differ between OBX and sham operated rats. However, context-induced reinstatement of nicotine seeking was significantly higher in the OBX group and immobility assessed by FST after chronic nicotine intake was normalized.

Conclusion: These results are in line with previous studies showing OBX-induced

dissimilarities in drug seeking and drug taking and represent complementary information to previous studies using psychostimulants, cannabimimetic and ketamine. Furthermore, results of the forced swim test suggest alleviation of the OBX-induced phenotype by chronic nicotine intake.

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10 Acknowledgements

This study was performed at Masaryk University as part of the project „Behavioural psychopharmacology and pharmacokinetics in preclinical drug research“, number

MUNI/A/1132/2017, with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2018. This work was further funded by funds from the Faculty of Medicine MU to junior researcher Jana Ruda-Kucerova.

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Risk of insulin resistance in visceral adipose tissue after prolonged supraphysiological testosterone administration in male rats

Emil Babiak, Gabriel Dóka, Ján Klimas

Department of Pharmacology and Toxicology, Faculty of Pharmacy of the Comenius University in Bratislava, Ulica odbojárov 10, Bratislava, Slovakia

Long term changes in levels of hormones in human body often lead to pathological conditions and serious illnesses. Women with higher concentration of testosterone have higher

tendencies to suffer from insulin intolerance that transforms into diabetes mellitus. Even though regulation of testosterone in males is different, we expect that high doses of exogenous testosterone may cause similar effect of insulin resistance as in female population.

Testosterone has characteristic lipolytic effect on adipose tissue. 8-week testosterone administration (100 mg/kg s.c. depot once a week) in male Wistar rats led to significant lipolytic effect on perirenal and retroperitoneal fat pad. Gene expression of selected pro- inflammatory cytokines (TNF; Il1b; Il6; p > 0,05) and genes associated with insulin signaling (Insr; Glut1; Glut4; p > 0,05) in this adipose tissue did not suggested developed insulin resistance at the time, however we detected increased gene expression variability in most of the selected genes and fold-changes were in agreement with expected changes during insulin resistance. These observations after supraphysiological doses of exogenous testosterone may correspond with clinical findings of insulin intolerance and formation of diabetes mellitus in men with prolonged anabolic steroids abuse.

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Pupillometry as an indicator of l-dopa dosages in parkinson´s disease patients Bartošová O1., Bonnet C2., Ulmanová O2., Šíma M1., Perlík F1., Růžička E2., Slanař O1.

1Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

2Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

SUMMARY Introduction

Parkinson´s disease (PD) is the second-most common neurodegenerative disorder that affects 2 – 3 % of the population ≥ 65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, is the neuropathological hallmark of PD. L-DOPA is the gold standard in PD therapy, due to its ability to restore dopamine extracellular levels in the Parkinsonian brain. Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupill diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study was to evaluate the effect of L-DOPA dosage on pupillometric parameters in PD patients.

Subject and methods

Sixteen PD patients and fourteen healthy control subjects (CS) were studied. Pupillometry was performed after the participants had a full eight-hour sleep and in PD patients, one hour after the administration of their individual morning dose of L-DOPA. Pupillometry was performed by a single examiner using a monocular infrared pupillograph Compact Video Pupillometer NeuroLight (IDMed, Marseille, France).

Results

The statistical analysis revealed statistically significant differences between the groups of CS and PD patients in the maximum pupil diameter (MAX) and minimum pupil diameter (MIN) , with higher values in PD, while the values of variation ((MAX - MIN)/MAX)*100, difference between MAX and MIN, maximum constriction velocity and latency for the onset of constriction did not differ between the two groups. Non-linear regression analysis of the relationships between the L-DOPA doses and pupillometric parameters in PD patients showed a significant dose-response relationship between the MAX values and both the morning L- DOPA dose and the total daily L-DOPA dose (78 % and 93 % respectively, of the observed variation can be explained by L-DOPA dosing).

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13 Conclusion

Pupillometry represents a sensitive tool for non-invasive evaluation of the peripheral effects of L-DOPA in PD, especially with daily doses below 400 mg L-DOPA.

Acknowledgements

This study has been supported by UNCE 204022 and Progres Q25.

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Use of herbal medicines and the co-use of conventional pharmacotherapy with herbal products in selected population groups in west bohemia

Monika Bludovská, Halina Skyrchuk, Jakub Kočiš, Eva Buchalová, Eva Kmoníčková Department of Pharmacology and Toxicology, Charles University, Faculty of Medicine in Plzeň, alej Svobody 76, 323 00 Plzeň, Czech Republic

The prevalence of use of herbal medicinal products is globally high and continues to increase.

Despite of indisputable benefit, and similarly to conventional pharmacotherapy, using herbal remedies can put patients at risk for a variety of adverse reactions and interactions with

prescription or over-the-counter drugs. The number of published studies concerning herb-drug interactions constantly increases. Herbal remedies are often perceived as being natural and therefore safe alternative to conventional pharmacotherapy. Many patients do not consider herbal preparations to be drugs and do not inform their physician about the use of herbs.

The survey is being conducted as a follow-up to the research carried out on the general population. In this survey we focused on the use of herbal medicines in selected population groups: children and elderly people (age ≥ 60 years). Mothers were also inquired about the use of herbal medicines during pregnancy and breastfeeding.

The aim of the survey is to collect and evaluate detailed data about the prevalence of use of herbal remedies and food supplements, communication with the physician, type and source of herbal products, concomitant use of conventional drugs, reasons for the use, the frequency and the length of the use. Data were collected via a questionnaire.

To date, we have collected data from 247 respondents, 136 parents and 111 elderly people.

69% of parents (45% of men and 75% of women) reported using herbal medicines for their children, 47% without consulting the physician. 51% of women who reported using herbal medicines for their children also reported the use of herbal products during pregnancy or lactation or both. 84% of elderly people reported the use of herbal remedies or herbal food supplements during the past 12 months. Most elderly patients do not communicate the use of herbal remedies with the physician without being asked. An alarming percentage of

physicians never ask about the use of herbal products.

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Stereoisomers of 1-methyltryptophan effect renal fibrosis following ischemia-reperfusion injury.

Čepcová D., Mišúth S., Vavrinec P., Vavrincová-Yaghi D.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, Bratislava, Slovakia; cepcova@fpharm.uniba.sk

Ischemia-reperfusion injury (IRI) during renal transplantation can result in reduction of renal function and subsequent fibrosis, and until now there is no antifibrotic treatment available.

One of tubulointerstitial fibrosis modulators is oxidative stress that plays a role in transforming growth factor-β (TGF-β) pathway and α smooth muscle actin (α-SMA) expression. Our previous research suggests that D and L stereoisomers of 1-methyl- tryptophan (1-M-T) have protective effect in rat renal IRI model (particularly on α-SMA expression), which is dependent on reperfusion length.

The aim of this study was therefore to investigate the effect of 1-M-T isomers on TGF-β signaling in both in vivo model of rat IRI and in vitro model using NIH/3T3 cells.

In rat IRI model 30 min. bilateral ischemia was induced followed by 24, 48 and 96 hrs reperfusion. Four groups of rats were used – sham-operated animals, IRI, IRI treated with D isomer (1-M-D-T) and IRI treated with L isomer (1-M-L-T). 1-M-D-T and 1-M-L-T were administrated orally in doses 200mg/kg 24 hrs and 1 hr before ischemia, and then individually in every reperfusion time set with 24-hr intervals until sacrifice. Four groups were used in fibroblast culture model: control group, TGF- β stimulated group (5ng/ml) and TGF- β stimulated and 1-M-D-T or 1-M-L-T (750 µmol/l) treated group. In the in vitro model same administration time pattern as in rat IRI model with 48hr reperfusion was used. Expression of proteins involved in TGF-β pathway (α-SMA, MEK, pERK, ERK, pJNK, JNK, pSMAD2, SMAD2/3) was in both models (in rat kidney/cell culture) assessed by western blot.

In animal model we observed significantly decreased α-SMA expression in group treated with 1-M-D-T after 24-hrs reperfusion and in group treated with 1-M-L-T after 96-hrs reperfusion compared to IRI group (p˂0,05). We did not find such changes in model with 48-hrs

reperfusion. In model with 96-hrs reperfusion the effect of treatment on α-SMA expression was associated with significantly decreased MEK expression and ERK

phosphorylation(p˂0,05). In cell culture model treatment with both 1-M-T isomers decreased α-SMA expression. On the contrary this change was associated with increased ERK

phosphorylation and JNK expression (p˂0,05).

In conclusion, our data show that both 1-M-T stereoisomers effect fibrosis in renal IRI variously and dependently on reperfusion length. Moreover, we show that they possibly interfere with TGF-β signaling pathway, which we confirmed in vitro. 1-M-T stereoisomers could be thus perspective tool in therapy of fibrosis following IRI

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Supported by the grant VEGA 1/0247/17 and Comenius University grant UK/314/2017.

Odkazy

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