Folia Pharmaceutica Universitatis Carolinae: LI
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Abstracts from the 10th Postgraduate and Postdoc Conference of the Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, 22–23 January 2020.
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UNIVERSITAS CAROLINA PRAGENSIS FOLIA PHARMACEUTICA UNIVERSITATIS CAROLINAE ISSN 1210-9495 FOLIA PHARMACEUTICA UNIVERSITATIS CAROLINAE LI LI folia_LI_obálka_hrb 11 mm.indd 1folia_LI_obálka_hrb 11 mm.indd 1 01.02.2024 9:4301.02.2024 9:43
Folia Pharmaceutica Universitatis Carolinae LI Arranged by Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Technical assistance by Tomáš Vojtíšek Lectured: Assoc. Prof. RNDr. Věra Klimešová, CSc., Assoc. Prof. PharmDr. Jakub Chlebek, Ph.D. Editorial Advisory Board: Assoc. Prof. RNDr. Pavel Doležal, CSc., Prof. PharmDr. Martin Doležal, Ph.D., Prof. MUDr. Jaroslav Dršata, CSc., Prof. MUDr. Radomír Hrdina, CSc., Prof. RNDr. Lubomír Opletal, CSc., Assoc. Prof. RNDr. Veronika Opletalová, Ph.D., Assoc. Prof. RNDr. Miroslav Polášek, CSc., Prof. RNDr. Jiří Vlček, CSc., Assoc. Prof. RNDr. Pavla Žáčková, CSc., Assoc. prof. RNDr. Veronika Opletalová, Ph.D. (editor) Published by Charles University Karolinum Press Prague 2024 Typeset by Karolinum Press © Charles University, 2024 ISSN 1210-9495 ISBN 978-80-246-5628-1 ISBN 978-80-246-5666-3 (pdf) https://doi.org/10.14712/9788024656663
Charles University Karolinum Press www.karolinum.cz [email protected]
CONTENTS Abstracts 10th Postgraduate and Postdoc Conference of the Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, 22–23 january 2020 . . . . . . . . . . 7 Bioorganic and Pharmaceutical Chemistry Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Pharmacognosy and Toxicology of Natural Products Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Pharmaceutical Technology Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Pharmaceutical Analysis and Bioanalytical Chemistry Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Biochemistry, Pharmacology and Toxicology Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Clinical and Social Pharmacy Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 Bibliography Publications of the Faculty of Pharmacy in Hradec Králové, Charles University in the Year 2017 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 Original Papers and Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 Articles in Journals without Impact Factor and Proceedings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 Monographies and Textbooks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Degrees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Publications of the Faculty of Pharmacy in Hradec Králové, Charles University in the Year 2018 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Original Papers and Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Articles in Journals without Impact Factor and Proceedings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Monographies and Textbooks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 Certified Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Degrees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Publications of the Faculty of Pharmacy in Hradec Králové, Charles University in the Year 2019 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Original Papers and Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Articles in Journals without Impact Factor and Proceedings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Monographies and Textbooks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 Utility Model and Certified Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 Degrees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Publications of the Faculty of Pharmacy in Hradec Králové, Charles University in the Year 2020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 Original Papers And Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 Articles in Journals without Impact Factor and Proceedings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 Monographies and Textbooks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 Degrees . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 Social Happenings 50th Anniversary of the Faculty of Pharmacy in Hradec Králové . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 Instructions for Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
7 2023 Folia Pharm . Univ . Carol . LI Pag . 7–101 ABSTRACTS 10th POSTGRADUATE AND POSTDOC CONFERENCE OF THE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ, CHARLES UNIVERSITY, HRADEC KRÁLOVÉ, 22–23 JANUARY 2020 BIOORGANIC AND PHARMACEUTICAL CHEMISTRY SECTION HOW TO NOT KILL MOSQUITO: CYSTEINE-TARGETED INSECTICIDES GÓRECKI, L .,1 ANDRÝS, R .,2 SCHMIDT, M .,1,2 KUČERA, T.,3 PSOTKA, M .,1,2 SVOBODOVÁ, B .,1,3 HRABCOVÁ, V .,2,3 HEPNAROVÁ, V .,1,3 BZONEK, P .,2,3 JUN, D .,1,3 KUČA, K.,2 KORÁBEČNÝ, J.,1,3 MUSÍLEK, K .1,2 1 Biomedical Research Centre, University Hospital in Hradec Králové, Czech Republic 2 Department of Chemistry, Faculty of Science, University of Hradec Králové, Czech Republic 3 Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic e-mail: lukasgorecki@seznam .cz Acetylcholinesterase cysteine-targeted insecticides against malaria vector Anopheles gambiae and other mosquitos have already been introduced. We have applied the olefin metathesis for the preparation of cysteine-targeted insecticides in high yields . The prepared compounds with either a succinimide or maleimide moiety were evaluated on Anopheles gambiae and human acetylcholinesterase with relatively high irreversible inhibition of both enzymes but poor selectivity . The concept of cysteine binding was not proved by several methods, and poor stability was observed with the chosen most potent/selective compounds in a water/buffer environment. Thus, our findings do not support the proposed concept of cysteine-targeted selective insecticides for the prepared series of succinimide or maleimide compounds . The study was supported by Ministry of Health of the Czech Republic (Project No. NV16-34390A), University of Hradec Králové (Projects No. SV2115-2018, No. VT20192021 and postdoctoral job positions at UHK), and University of Defence (Faculty of Military Health Sciences, Long-term development plan and SV/FVZ2019/01).
8 CYCLIZATION REACTIONS MEDIATED BY TRANSITION METALS MATOUŠ, P., KADANÍK, M., MAŘÍKOVÁ, J., TIMORACKÝ, M., KUNEŠ, J ., POUR, M . Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: matousp1@faf .cuni .cz Synthesis of various types of heterocycles is possible from enyne precursors using cationic gold(I) species as catalysts . Our previous research on the cyclisation of propargyl vinyl ethers to dihydropyrans II1 as well as chemoselective cyclizations of β-propargylamino acrylic esters to dihydropyridines IV2 was extended to include nucleophile-assisted reactions . The optimized synthetic protocol was applied to the preparation of a library of substituted tetrahydropyridines V . Their further transformations via e.g. cycloadditions gave highly substituted isoquinoline derivatives VI . Scheme 1. Gold(I)-Catalyzed Synthesis of Piperidine Aminals The study was supported by the Grant Agency of Charles University (Project No. 1590119), from the project of Specific Academic Research (SVV 260 401/2019) and by the Czech Science Foundation (Project No. 18-17868S). References 1. MATOUŠOVÁ, E., RŮŽIČKA, A., KUNEŠ, J. et al.: Chem . Commun ., 47, 2011, 6164–6199 . 2. MIKUŠEK, J ., MATOUŠ, P ., MATOUŠOVÁ, E . et al.: Adv . Synth . Catal ., 358, 2016, 2912–2922 . 3. SAITO, A ., KONISHI, T ., HANZAWA, Y .: Org . Lett ., 12, 2010, 372–374 .
9 SYNTHESIS AND REACTIVITY OF ELECTRONICALLY TUNED [3]DENDRALENES ANTAL, R., BRŮŽA, Z., KRATOCHVÍL, O., POUR, M. Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: antalr@faf .cuni .cz Dendralenes are acyclic cross-conjugated polyenes with an interesting, as yet unexamined reactivity and high potential for further synthesis .1 We have focused on the synthesis of variously substituted electron poor [3]dendralenes containing electron withdrawing groups (e.g. carboxylic group), or a combination of electron withdrawing and donating groups . Synthesis is based on readily available Z-metallodienes 1, which are subjected to Migita-Stille coupling2 yielding the intended final products 3 (Scheme 1) . Syntheses and possible applications of new compounds in domino Diels-Alder sequences (Scheme 2) will be discussed . Scheme 1. Migita-Stille coupling Scheme 2. Diels-Alder reactions The study was supported from the project of Specific Academic Research (SVV 260 401/2019), by the Grant Agency of Charles University (Project. No. 1348119) and by the Czech Science Foundation (Project No. 18-17868S). References 1. HENNING, H ., SHERBURN, M .: Angew . Chem . Int . Ed ., 51, 2012, 2298–2338 . 2. KRATOCHVÍL, J ., NOVÁK, Z ., GHAVRE, M . et al .: Org. Lett., 17, 2015, 520‒523.
16 DESIGN AND SYNTHESIS OF CASEIN KINASE II (CK2)/ HISTONE DEACETYLASES (HDAC) DUAL INHIBITIORS BOUZ, G .,1 ORTIN REMON, I .,2 De PASCUAL-TERESA, B .,2 RAMOS, A .2 1 Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Departamento de Quíımica y Bioquíımica, Facultad de Farmacia, Universidad CEU San Pablo, Madrid, Spain . e-mail: bouzg@faf .cuni .cz The aim of this study is to design and synthesize dual inhibitors combining the pharmacophores of the protein kinase CK2 and histone deacetylase (HDAC), see Fig . 1 below . CK2 is a ubiquitous serine/threonine protein kinase, whose upregulation is linked to tumor progression .1 On the other hand, HDACs are a class of epigenetic enzymes responsible for gene silencing . Altered expression and mutations of genes that encode HDACs is linked to tumor development .2 Synthetic procedures to obtain final compounds will be discussed in detail during the presentation . Fig. 1. Rational design of title compounds The study was supported from the project of Specific Academic Research (SVV 260 401/2019). References 1. KHAN, D . H ., HE, S ., YU, J . et al .: J . Biol . Chem ., 288, 2013, 16518–16528 . 2. WITT, O ., DEUBZER, H . E ., MILDE, T .et al .: Cancer Lett ., 277, 2009, 8–21 .
17 DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF POSITIONAL DERIVATIVES OF A SERIES OF N-(PYRAZIN-2-YL)CARBOXAMIDES NAWROT, D., BOUZ, G., ZITKO, J., DOLEŽAL, M. Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: nawrotd@faf .cuni .cz Among infectious diseases, tuberculosis caused by Mycobacterium tuberculosis, is a leading cause of death worldwide1 and major threat to public health . Tuberculosis can effectively be treated with first-line anti-TB drugs, however due to rising antimicrobial resistance new approaches to eradicate the disease are needed . A series of new N-(pyrazin2-yl)carboxamides as potential antimycobacterial and antibacterial agent is presented . Derivatives to be presented are compounds based on positional isomers of picolinic acid linked to pyrazine derivatives (pyrazin-2-amine, 6-chloropyrazin-2-amine, propyl 5-aminopyrazine-2-carboxylate), 4-amino-2-hydroxybenzoic acid or 4-aminobenzoic acid by amidic bond . Compounds were tested for biological activity against selected strains of Mycobacterium (M. tuberculosis H37Rv, M. tuberculosis H37Ra, M. kansasii, M. avium, M. smegmatis, M. aurum) . The minimum inhibitory concentration (MIC) for tested mycobacterial strains was determined for all tested compounds beside isoniazid, ciprofloxacin and rifampicin as a reference standard drug . Results of the biological testing and structure activity relationships are discussed in the presentation . The study was supported from the project of Specific Academic Research (SVV 260 401/2019) and by the Grant Agency of Charles University (Project No. C-C3/1572317). References 1. World Health Organization: Global Tuberculosis Report 2019 . https://www .who .int/publications/i/ item/9789241565714 . SYNTHESIS OF FREE OMEGA-HYDROXY CERAMIDES AND THEIR BEHAVIOUR IN THE STRATUM CORNEUM MODEL LIPID MEMBRANES SOMMEROVÁ, V ., OPÁLKA, L ., SVATOŠOVÁ, L ., VÁVROVÁ, K . Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: sommerov@faf .cuni .cz Omega hydroxy ceramides (O-Cer) belong to a subclass of Cer with ultralong ω-hydroxylated N-acyl chains . In extracellular spaces of human stratum corneum (SC), they are present in the free form or linked to the surface of corneocytes via their free hydroxy group and form the corneocyte lipid envelope (CLE) . The main aim of this project
18 was to prepare 3 subclasses of O-Cer (Cer OS, OP and OdS) using an improved synthetic strategy and study their behaviour after their addition into model lipid membranes . Complete synthesis of O-Cer has not yet been reported. We modified previously published procedure, where we focused on possible improvements of the synthesis of 32-hydroxydotriacontanoic acid, the backbone of O-Cer . The previously used Wittig reaction was changed for other olefinations, e.g . Julia and Julia-Kocienski reactions, which led to a significant improvement in the reaction yield. Synthesized O-Cer were added into model lipid membranes consisting of a mixture of Cer, free fatty acids, cholesterol and cholesteryl sulfate mimicking the composition of SC . Membrane organization showed that the addition of O-Cer does not change the arrangement in the long periodicity phase (~12 .3 nm), essential for the proper barrier function . Complete replacement of acylCer with O-Cer led to a formation of a new phase with shorter repeat distance (~10 .7 nm) . Permeability of the model membranes did not change significantly after the addition of O-Cer, however the complete replacement of acylCer with O-Cer increased permeability . In conclusion, the addition of O-Cer to the membrane did not improve the barrier properties and after a complete replacement of acylCer with O-Cer, the barrier was even more perturbed . The study was supported by the Czech Science Foundation (Project No. 19-09135J), by the Grant Agency of Charles University (Project No. 1194119), and from the project of Specific Academic Research (SVV 260 401/2019). SYNTHESIS OF NOVEL 2,3-DISUBSTITUTED PYRAZINES AS POTENTIAL ANTIMICROBIALS PALLABOTHULA, V . S . K ., ZITKO, J . Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: pallabov@faf .cuni .cz This research project is focused on synthesis of novel 3-substituted derivatives of pyrazinamide . The synthesis involves acylation of amino group of 3-aminopyrazine-2-carboxylate with acyl chlorides (benzoyl chlorides or phenylacetyl chlorides), followed by ammonolysis by ammonia in dry ethanol (Scheme 1) . Scheme 1. Synthesis of final compounds
19 The compounds will be assessed for in vitro antimicrobial activity against several mycobacterial strains (Mycobacterium tuberculosis H37Ra and H37Rv, M. avium, M. kansasii, M. smegmatis, M. aurum) and bacterial and fungal strains of clinical importance . As an off-spin to this project, the compounds will also be studied as potential inhibitors of (human) prolyl-tRNA synthetase . This is rationalized by their structural similarity to confirmed inhibitors reported in literature.1 The study was supported from the project of Specific Academic Research (SVV 260 401/ 2019) and by CELSA, Project title: Structure-based design of new antitubercular medicines, KU Leuven (Arthur Van Aerschot) – Charles University in Prague (Martin Doležal). References 1. ADACHI, R ., OKADA, K ., SKENE, R . et al.: Biochem . Biophys . Res . Commun ., 488, 2017, 393–399 . N-PYRAZINOYL SUBSTITUTED AMINO ACIDS AS POTENTIAL ANTIMYCOBACTERIAL AGENTS – SYNTHESIS AND BIOLOGICAL EVALUATION OF ENANTIOMERS JUHÁS, M., KUČEROVÁ, L., DOLEŽAL, M. Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: juhasm@faf .cuni .cz Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), causing millions of deaths each year . We present synthesis and biological evaluation of new potential antimycobacterial compounds containing fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids (Fig . 1) . The antimicrobial activity was evaluated on a variety of mycobacterial strains including Mycobacterium tuberculosis (Mtb) H37Ra and bacterial and fungal strains of clinical importance e.g. Staphylococcus aureus or Aspergillus flavus . Emphasis was made on comparison of activities of individual enantiomers . Fig. 1. General structure of the synthesized compounds Overall, high activity against Mtb was seen in derivatives containing more lipophilic l-amino acids . The most potent derivative contained phenylglycine moiety (MIC < 1 .98 µg ml−1, < 7 .3 µM) . Compounds possessed low cytotoxicity in HepG2 cell line
20 (IC50 > 500 µM) and good selectivity towards Mtb (SI > 40). No significant activity was detected against tested bacterial and fungal strains. To our best knowledge, this is the first study comparing the activities of D and L-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds . The study was supported from the project of Specific Academic Research (SVV 260 401/2019). SYNTHESIS OF SILICON COMPLEXES OF TETRAPYRAZINOPORPHYRAZINES KOLÁŘOVÁ, M., MILETÍN, M. Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: kolarova .michaela@faf .cuni .cz Azaphthalocyanines such as tetrapyrazinoporphyrazines are widely examined compounds . Due to their large system of conjugated double bonds, they exhibit interesting photophysical and photochemical properties. They find use in many medicinal fields as photodynamic therapy, monitoring RT-PCR or diagnostic imaging . As their structure is planar, strong π-π interactions between macrocycles cause aggregation of molecules.1 This is an undesirable property of all azaphthalocyanine derivatives because they lose their photoactivity in this state . One approach to suppress aggregation consist in the introduction of suitable metal cation into the macrocyclic core . Silicon cation has been used for this purpose mainly in phthalocyanine chemistry .2 Its binding capacity exceeds coordinating bonds in the macrocycle core and provides spear axial bonds, which can bear bulky substituents creating sufficient inhibition of the aggregation process. In this project we focus on different ways of silicon tetrapyrazinoporphyrazine synthesis . The study was supported from the project of Specific Academic Research (SVV 260 401/2019).
21 References 1. MILETÍN, M., ZIMČÍK, P., NOVÁKOVÁ, V.: Photochem. Photobiol. Sci, 17, 2018, 1749–1766. 2. MAREE, M . D ., KUZNETSOVA, N ., NYOKONG, T .: J . Photochem . Photobiol . A: Chemistry, 140, 2001, 117–125 . (E)-2-(2-ISONICOTINOYLHYDRAZINYLIDENE)PROPANOIC ACID DERIVATIVES AS PROMISING ANTIMYCOBACTERIAL SUBSTANCES PFLÉGR, V .,1 KRÁTKÝ, M .,1 STOLAŘÍKOVÁ, J.,2 VINŠOVÁ, J .1 1 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Laboratory for Mycobacterial Diagnostics and Tuberculosis, Institute for Public Health in Ostrava, Czech Republic e-mail: [email protected] (E)-2-(2-Isonicotinoylhydrazinylidene)propanoic acid has been presented and tested as an antimycobacterial agent by Kryukova et al .1 in the Soviet Union in the 1970s . A basic set of antibacterial tests has been described . Since then, derivatives of this compound have been presented only randomly . We are introducing a new comprehensive series in which we have been working on adjusting this structural motif (Fig . 1) . We are focused primarily on modifications of free carboxyl group by various amines or phenols to yield functional derivatives (amides and esters) via EDC coupling catalysed by 1-hydroxybenzotriazole or 4-(dimethylamino)pyridine . The prepared compounds were tested against Mycobacterium tuberculosis and some atypical strains of mycobacteria (M. avium, M. kansasii) with significantly lower MIC values (sometimes up to 64 times lower) compared to the parent drug isoniazid (INH) used as a synthetic precursor . The derivatives don’t show cytotoxicity to mammalian cells (assays were performed on HepG2 and MonoMac6 cells) and exhibit much greater ability to inhibit growth of the mycobacterial cells in comparison to the INH . Fig. 1. (E)-2-(2-Isonicotinoylhydrazinylidene)propanoic acid The study was supported by the Czech Science Foundation (Project No. 17-27514Y) and from the project of Specific Academic Research (SVV 260 401/2019). References 1. KRYUKOVA, L . M ., ZELENIN, K . N ., ÉRTEVTSIAN, L . N . et al .: Pharm . Chem . J ., 11, 1977, 26–29 .
22 N-METHYLHYDRAZINE-1-CARBOXAMIDES AS POTENTIAL CHOLINESTERASES INHIBITORS HOUNGBEDJI, N .-H .,1 ŠTĚPÁNKOVÁ, Š.,2 KRÁTKÝ, M .,1 VINŠOVÁ, J .1 1 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Czech Republic e-mail: houngben@faf .cuni .cz Due to the increasing number of cases, Alzheimer’s disease is a neurodegenerative disease that represents a serious threat to mankind . The impairment that this disease causes to one’s health, urge for the research of new potential drugs for the treatment of this illness . Nowadays, the therapy of Alzheimer’s disease is focused primarily on the use of acetylcholinesterase (AChE) inhibitors and dual AChE-butyrylcholinesterase (BuChE) inhibitors .1 Based on this fact, derivatives of N-methyl-hydrazine-1-carboxamide (Fig . 1) have been designed within this goal . The ability of the different derivatives to inhibit both AChE and BuChE was evaluated using modified Ellman’s method.2 AChE was inhibited with IC50 values within the range of 44–73 μM, whereas BuChE was inhibited with IC50 within the range of 170–514 μM. The most potent compound for AChE inhibition was 2-(4-chlorobenzoyl)-N-methylhydrazine-1-carboxamide (IC50 = 44.08 μM). More derivatives will be tested in order to determine the structure-activity relationship . O N H H N O H N R O N H H N O H N Cl the most potent AChE inhibitor R = H, Me, t-Bu, OMe, Cl, Br, F, I, OH, Me2N, NO2, CF3 2-(4-substitutedbenzoyl)-N-methylhydrazine-1-carboxamides Fig. 1 Structures of the studied compounds The study was supported by the Czech Science Foundation (Projects No. 17-27514Y and 2019638Y) and from the project of Specific Academic Research (SVV 260 401/2019). References 1. KRÁTKÝ, M., ŠTĚPÁNKOVÁ, Š., VORČÁKOVÁ, K. et al .: Molecules, 21, 2016, art . 191 . 2. KOVÁŘOVÁ, M., KOMERS, K., ŠTĚPÁNKOVÁ, Š. et al .: Z . Naturforsch . C – J . Biosci . 68, 2013, 133–138 .
23 PHARMACOGNOSY AND TOXICOLOGY OF NATURAL PRODUCTS SECTION ANALYSIS OF COPPER-CHELATING ACTIVITY OF ISORHAMNETIN AND TAMARIXETIN LOMOZOVÁ, Z .,1 MACÁKOVÁ, K .,1 KARLÍČKOVÁ, J.,1 CATAPANO, M . C .,2 MLADĚNKA, P.2 1 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: lomozovz@faf .cuni .cz Isorhamnetin and tamarixetin are the main O-methylated metabolites of the flavonoid quercetin . Flavonoids represent a large group of polyphenolic compounds which belong to plant secondary metabolites and have been suggested to have a positive impact on human health . They are a common component of the human diet . Chelation of transient metal ions is one of their proposed mechanisms of action . Copper is an essential trace element necessary for many physiological processes . However, free copper ions can cause damage to various biomolecules and lead to tissue impairment .1 Disorder of copper homeostasis can be treated with copper chelators . Due to the limited array of the currently used copper chelators, research of such compounds continues to be of clinical interest .2 In this in vitro study, tamarixetin and isorhamnetin were tested for their interactions with copper at four (patho) physiologically relevant pH conditions ranging from 4 .5 to 7 .5 by competitive and noncompetitive methods . Competitive studies showed that both compounds were active copper chelators and non-competitive studies showed that the preferred stoichiometries were mainly 3:2 and 2:1 (flavonoid:metal). Analysis of cupric ion reduction has also been performed. In conclusion, both compounds showed good ability to chelate and reduce copper ions . The study was supported by the Grant Agency of Charles University (Project No. 1080217 C) and from the project of Specific Academic Research (SVV 260 412/2019). References 1. ŘÍHA, M., KARLÍČKOVÁ, J., FILIPSKÝ, T. et al .: RSC Advances, 4, 2014, 32628–32638 . 2. CATAPANO, M. C., KARLÍČKOVÁ, J., TVRDÝ, V. et al .: J . Trace Elem . Med . Biol ., 46, 2017, 88–95 . SCREENING OF ANTIPLATELET ACTIVITY OF ISOQUINOLINE ALKALOIDS PARVIN, M . S .,1 MACÁKOVÁ, K .2 1 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: parvins@faf .cuni .cz
24 Alkaloids are nitrogen containing secondary metabolites mostly found in plants and other organisms . They have been used for the treatment of many ailments such as cancer, malaria, diabetes and cardiovascular diseases (CVDs) .1 Platelet cells perform a significant role in haemostasis and uncontrolled regulation of platelets can lead to CVDs progression. However, antiplatelet therapy has its limits, so current research seeks to find active substances with different mechanisms of action . In this study, we have measured antiplatelet activity of selected 14 isoquinoline alkaloids isolated from plants . Multiple Electrode Aggregometry has been used where multiple measurement is possible in one time . The screening was performed with the use of whole human blood . Arachidonic acid was used as aggregation inducer and acetylsalicylic acid (ASA) as the standard drug . Percentage of aggregation has been measured from correlation of base line and linear portion of the aggregation curve . The most potent compounds were papaverine, scoulerine and bulbocapnine. The first two substances exhibited similar inhibitory activity as ASA at the concentration of 40 µM while were significantly less potent at lower concentrations. Initial screening revealed the most potent substances that would need a series of experiments to determine the mechanism of their action . The compounds have already been tested for antagonism at thromboxane receptors using the stable thromboxane analogue U46619 . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1. AIN, Q . U ., KHAN, H ., MUBARAK, M . S . et.al.: Front . Pharmacol ., 7, 2016, art . 292 . PHYTOCHEMICAL ANALYSIS AND BIOLOGICAL ACTIVITY OF AZORELLA COMPACTA ŠTŮSKOVÁ, M., TŮMOVÁ, L. Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: stuskovm@faf .cuni .cz Azorella compacta Phil. (syn . yareta, Apiaceae) is a compact evergreen cushion shrub growing at altitudes between 3000 and 5000 metres in the South American Andes . The plant is frequently used in traditional medicine in the form of infusions and decoctions to treat various diseases (cold, pain, asthma, diabetes etc .) and relieve altitude sickness .1 The major secondary metabolites that have been described in azorella plant are diterpenoids . A few of the potential medical effects were observed, such as antihyperglycemic effect and in vivo inhibition of Plasmodium berghei growth in mice .2 An antimicrobial activity and an anti-Trypanosoma cruzi activity were further confirmed.3 Polyphenols are other metabolites found in the azorella plant . Previous experiments with aqueous extracts proved their antioxidant and immunomodulatory activity, however, it is not known which particular substances are responsible for the effects . The main aim of the study is to prove selected biological activities of aqueous and ethanolic extracts of the whole plant Azorella
25 compacta. Isolation and finding the specific substances responsible for biological effect is another goal of the study . Due to the current problems of widespread diseases and the lack or insufficient clarification of some findings on the effects of azorella plant, anti-aggregation, anti-tyrosinase, anti-allergic and anti-parasitic activities were selected for testing . On account of the early stage of research, this study has not provided any valid data yet . The presentation will be focused on the introduction of the plant and planed methods . The study was supported from the project of Specific Academic Research (SVV 260 416/ 2019). References 1. WICKENS, G . E .: Econ . Bot ., 49, 1995, 207–212 . 2. FUENTES, N . L ., SAGUA, H ., MORALES G . et al: Phytother . Res ., 19, 2005, 713–716 . 3. NÚÑEZ, S ., SAN-MARTÍN, A ., CORSINI, G .: J . Chil . Chem . Soc ., 63, 2018, 4200–4204 . CYTOTOXIC EVALUATION OF ASTAXANTHIN MONOESTERS FROM MICROALGAE HAEMATOCOCCUS PLUVIALIS FÁBRYOVÁ, T .,1,2 Da SILVA, D . C .,3 ANDRADE, P . B .,3 VALENTÃO, P .,3 PEREIRA, D . M .,3 KOPECKÝ, J .,2 CHEEL, J .,2 TŮMOVÁ, L.1 1 Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Laboratory of Algal Biotechnology-Centre ALGATECH, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic 3 REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Portugal e-mail: fabryovt@faf .cuni .cz Reddish ketocarotenoid astaxanthin (AXT) has more powerful antioxidant capacity than β-carotene, vitamin E, zeaxanthin, lutein or canthaxanthin .1 The ability of this compound to cope with various diseases and protect human body has been also examined . Nowadays, this pigment attracts more and more interest from various industries, such as nutraceutical and cosmetic, due to its different bio-functional properties that can have a huge impact on human health or its nutrition . The major natural source of AXT is the freshwater microalgae Haematococcus pluvialis, in which this compound is present mainly in the esterified form. AXT is esterified with different fatty acids that are well-known for having various biological properties . It is believed that they may bestow these properties to AXT esters . From H. pluvialis biomass, five AXT monoesters have been isolated in our laboratory by high performance countercurrent chromatography (HPCCC) and their identity was confirmed using the high-performance liquid chromatography–atmospheric pressure chemical ionization–high resolution tandem mass spectrometry (HPLC–APCI– HRMS/MS) . The fraction of astaxanthin monoesters showed a cytotoxic activity against the human gastric cancer cells (AGS cell line) using the MTT (3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide) reduction assay . Later, the cytotoxic effect of AXT esterified with linolenic acid (1), linoleic acid (2), palmitic acid (3), oleic acid (4) and stea-
32 ISOLATION OF AMARYLLIDACEAE ALKALOIDS FROM HIPPEASTRUM CULTIVAR FERRARI AND EVALUATION FOR THEIR BIOLOGICAL ACTIVITIES ALSHAMMARI, L .,1 KUNEŠ, J .,2 HAVELEK, R .,3 CAHLÍKOVÁ, L .1 1 ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 3 Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Czech Republic e-mail: alshamml@faf .cuni .cz Hippeastrum is a well-known ornamental Amaryllidaceae genus native to South America and comprises approximately 60 species, about 30 of which are found in Brazil; the majority are endemic and poorly studied .1 This genus has been traditionally used to cure piles, tumors and various inflammatory disorders such as asthma. Physiological activities reported for plants of this genus include psychopharmacological effects, inhibitory activity against Trichomonas vaginalis and cytotoxicity .2 The summary ethanolic extract was prepared from fresh bulbs of Hippeastrum cv. Ferrari and divided by column chromatography . More than three hundred fractions were collected and pooled together based on TLC into fifteen subfractions. So far, fourteen alkaloids belonging to different structural types have been isolated in pure form . The isolated compounds were identified by comparison of obtained analytical data (MS, NMR, optical rotatory) with the literature data . All isolated alkaloids were assayed for their biological activities, e.g. inhibition of HuAChE and HuBuChE, POP (prolyloligopeptidase), GSK-3β (glycogen synthase kinase-3β), anticancer potential (cytotoxicity against panel of cancerous and noncancerous cell lines) and others . Within isolated alkaloids montanine displayed strong cytotoxicity against all tested cancer cells with IC50 values between 1.04–1.99 μM. The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1 . DEEPA, C . P ., KURIAKOSE, B . B .: Int . J . Pharmacogn . Phytochem . Res . 6, 2014, 399–404 . 2 . SILVA, A . F . S ., De ANDRADE, J . P ., MACHADO, K . R . B . et al.: Phytomedicine, 15, 2008, 882–885 . ALIPHATIC AND AROMATIC DERIVATIVES OF MONTANINE-TYPE ALKALOIDS AND THEIR CYTOTOXIC ACTIVITY MAAFI, N .,1 CAHLÍKOVÁ, L .,1 KUNEŠ, J .2 1 ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: negarm@faf .cuni .cz
33 The Amaryllidaceae plant family is known as a fruitful source of particular alkaloids which possess different range of bioactivities, such as antitumor, antimalarial, antibacterial and cytotoxic ones . Among these compounds, montanine-type alkaloids are characterized by 5,11-methanomorphanthridine ring system and known for their potential cytotoxic activity . Montaine and coccinine isolated from Haemanthus humilis Jacq ., have been shown to have in vitro IC50 value between 1.9 and 23.3 μM against 6 different cancerous cell lines .1 In another study manthine and 3-O-methylpancracine were synthesized through rearrangement of haemantamine and showed growth inhibitory GI50 values between 3 to 31 μM on 6 cancerous cell lines.2 These facts introduce montanine-type structure as a potential cytotoxic framework to be investigated . This project is focused on different chemical group replacement on montanine type alkaloids in order to improve the cytotoxic activity and also to figure out the possible SAR of these compounds . Since these alkaloids are rare in natural sources, based on previous publications, they were synthesized using haemantamine intermolecular nucleophilic rearrangement2, and various chemical groups were tried in position 3 . In this presentation we will report the procedure of preparation of about 20 aliphatic and aromatic esters and ethers and results from their cytotoxic activity . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1. MASI, M ., GUNAWARDANA, S ., Van RENSBURG, M . J . et al.: S. Afr. J. Bot., 126, 2019, 277–281. 2. GOVINDARAJU, K ., INGELS, A ., HASAN, M . N . et al .: Bioorg . Med . Chem ., 28, 2018, 589–593 . DERIVATIVES OF AMARYLLIDACEAE ALKALOID AMBELLINE AS POTENTIAL DRUGS RITOMSKÁ, A .,2 HULCOVÁ, D .,2 MAŘÍKOVÁ, J.,1 CAHLÍKOVÁ, L .2 1 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: ritomska@faf .cuni .cz Twenty-one derivatives of crinane-type alkaloid ambelline were developed . All of them were inspected for their potential inhibitory activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) . Esters of ambelline seem to be promising selective inhibitors of BuChE, which plays a significant role in later stages of AD when levels of BuChE rapidly increase. The benefits of BuChE inhibition are predicted based on its symptomaticrelief mode of action, but also on suggestion an involvement of this enzyme in regulating disease progression . Seven aromatic derivatives with different substitutions on the attached aromatic ring were endowed with remarkable inhibitory potency against hBuChE (IC50 < 5 µM), highlighting three top-ranked compounds as follows: 11-O-(1-naphtoyl)ambel-
34 line, 11-O-(2-methybenzoyl)ambelline, and 11-O-(2-methoxybenzoyl)ambelline with IC50 values of 0 .10 ± 0 .01 µM, 0 .28 ± 0 .02 µM, and 0 .43 ± 0 .04 µM . Notably, four derivatives displayed selective hBuChE inhibition profile with selectivity index higher 100. In vitro investigation was supported by computational studies predicting compound’s plausible binding modes in the active sites of hBuChE . To predict CNS availability logBB was calculated and the data correlated well with those obtained from PAMPA assay . Based on the obtained data all compounds should be able to permeate blood-brain barrier . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1. GREIG, N . H ., UTSUKI, T ., YU, Q . et al.: Curr . Med . Res . Opin ., 17, 2001, 159–165 . ALKALOIDS AS POTENTIAL DRUGS IN THE TREATMENT OF ALZHEIMER’S DISEASE HULCOVÁ, D .,1 ŠAFRATOVÁ, M .,1 HOŠŤÁLKOVÁ, A.,2 CHLEBEK, J .,2 OPLETAL, L .,2 CAHLÍKOVÁ, L .2 1 Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: hulcovd@faf .cuni .cz Alkaloids are very important group of secondary metabolites with a number of interesting biological effects (anticancer, analgesic, anticholinesterase, antimalarial, …) . Among the best known and most important substances are for example ergot alkaloids used in the therapy of diseases of the circulatory system, Vinca alkaloids such as vincristine and vinblastine with anticancer activity or Amaryllidaceae alkaloid galanthamine which is used in the therapy of Alzheimer’s disease (AD) .1 AD is one of the most frequent causes of dementia in the world . AD consists of many cognitive and neuropsychiatric manifestations as is damage of memory, speech, orientation and others . During AD multiple pathological changes occur in the brain and some enzyme systems are damaged that results in loss of neurotransmitter acetylcholine (ACh) and formation of amyloid plaques and neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments, with the main component being hyperphosphorylated τ-protein. Phosphorylation of τ-proteins is primarily dependent on glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase 5 .2 Alkaloids of different structural types have been screened for their potency to inhibit GSK-3β at the concentration of 50 µM. Promising results have been demonstrated by two alkaloids 5/205 from Vinca minor (IC50 = 4 .08 ± 0 .14 µM) and GV 8-3b from Geissospermum vellosii Alemao (IC50 = 7 .18 ± 1 .12 µM) . The study was supported by project EFSA CDN, reg. č. CZ.02.1.01/0.0/0.0/16_019/000 0841 and from the project of Specific Academic Research (SVV 260 412/2019).
35 References 1. CAHLÍKOVÁ, L ., MACÁKOVÁ, K ., BENEŠOVÁ, N . et al .: Natural Compounds (Small Molecules) as Potential and Real Drugs of Alzheimer’s Disease: A Critical Review . In: Studies in Natural Products Chemistry, vol 42 ., Atta-ur Rahman (ed .), Oxford/Amsterdam, Elsevier, 2014, pp . 153–194 . 2. HULCOVÁ, D ., BREITEROVÁ, K ., SIATKA T . et al .: Molecules, 23, 2018, art . 719 . ALKALOIDS OF AMARYLLIDACEAE FAMILY AS POTENTIAL DRUGS IN THERAPY OF DISEASES OF AFFLUENCE BREITEROVÁ, K .,1 MAŘÍKOVÁ, J.,2 KOUTOVÁ, D .,3 CAHLÍKOVÁ, L .1 1 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 3 Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové, Czech Republic e-mail: breiterk@faf .cuni .cz 51% of all drugs and 65% of small-molecule drugs approved between 1981–2014 are in certain connection with natural compounds .1 This proves that natural compounds and their derivatives are still an important source where new potential drugs can be sought . One of interesting groups of bioactive compounds are alkaloids . Amaryllidaceae family belongs among the twenty most important alkaloidal families with almost 600 of various Amaryllidaceae alkaloids isolated and structurally described so far . 34 .3 kg of fresh bulbs of Narcissus cv . Professor Einstein were processed to obtain 31 .7 g of summary alkaloidal extract . This extract was subjected to separation by different chromatographic methods. At the end, twenty-five alkaloids were isolated and identified by GCMS, ESI-MS, NMR, X-ray, optical rotation and literature . One compound was identified as a new unpublished alkaloid of lycorine structure type – 7-oxonorpluviine. All compounds isolated in sufficient amount have undergone series of bioassays associated with Alzheimer’s disease, cytotoxicity and activity against the liver stage malaria in vitro . The most promising was cytotoxic activity of pancracine – hence it went through study of the cell cycle and apoptosis induction interference . The study was supported by Pre-application research into innovative medicines and medical technologies INOMED (Project No. CZ.02.1.01/0.0/0.0/18_069/0010046) and from the project of Specific Academic Research (SVV 260 412/2019). References 1 . NEWMAN, D . J ., CRAGG, G . M .: J . Nat . Prod ., 79, 2016, 629–661 .
36 SEMISYNTHETIC DERIVATIVES OF AMARYLLIDACEAE ALKALOID HAEMANTHAMINE AS POTENTIAL DRUGS IN THE TREATMENT OF ALZHEIMER’S DISEASE PEŘINOVÁ, R.,1 KOHELOVÁ, E .,1 ŠPULÁK, M .,2 MAŘÍKOVÁ, J.,2 HULCOVÁ, D .,1 CAHLÍKOVÁ, L .1 1 ADINACO Research Group, Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic e-mail: perinovr@faf .cuni .cz Plants of Amaryllidaceae family include approximately 85 genera and 1100 species which have a wide distribution through both tropical and sub-tropical regions worldwide . Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide with complex etiology and multifaceted pathophysiology and data indicate an exponential rise in the number of cases of this disease . The well-known Amaryllidaceae alkaloid (AA) galanthamine is a marketed drug for AD therapy under the commercial name Reminyl© (galanthamine hydrobromide) .1 Studies also pointed out various pharmacological properties of semisynthetic derivatives of some AA . One of the most interesting AA alkaloids is alkaloid haemanthamine (HMT), which is widely distributed through Amaryllidaceae plants . Based on our previous results,1,2 where we reported promising activity of pilot series of HMT derivatives, we decided to continue in preparation of further semisynthetic derivatives . Several new aromatic and aliphatic esters and pilot ethers have been synthesized for structure-activity relationship (SAR). New compounds were identified by 1D and 2D NMR, GC/MS and ESI-MS methods . All newly developed compounds were screened for different biological activities connected with potential treatment of AD . Active compounds are studied in more detail (e.g. type of inhibition, docking studies, logBB etc .) . This project was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1. KOHELOVÁ, E., PEŘINOVÁ, R., MAAFI, N. et al .: Molecules, 24, 2019, art . 1307 . 2. HULCOVÁ, D ., BREITEROVÁ, K ., SIATKA, T . et al .: Molecules, 23, 2018, art . 719 . SEPARATION OF STEREOISOMERS OF HAEMANTHIDINE FROM ZEPHYRANTHES CITRINA KOHELOVÁ E .,1 JENČO J.,1 CAHLÍKOVÁ, L .,1 MAŘÍKOVÁ, J.2 1 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: kohelove@faf .cuni .cz
37 Zephyranthes is a genus of bulbous perennial plants belonging to Amaryllidaceae family that consists of about 90 various species . Phytochemical screening of their biologically active constituents revealed diverse group of compounds, especially Amaryllidaceae alkaloids having various pharmacological activities including anticancer, anticholinesterase, antiviral, antifungal and anti-inflammatory activity. To date, ten alkaloids of various structural types have been reported in Zephyranthes citrina .1 So far, 26 alkaloids from 30 kg fresh bulbs of Zephyranthes citrina have been isolated by liquid-liquid extraction and commonly used chromatographic methods . All compounds were identified by MS and NMR techniques. Several alkaloids were obtained in the mixture of isomers . Haemanthidine, an alkaloid of β-crinane structure type, has been isolated in our lab in the form of mixture of 4 isomers . Within previous studies this alkaloid showed promising cytotoxic activity against various cancer cell lines . The aim of this study was separation of individual isomers and study of their biological activity as the biological activity of individual isomers is unknown . Direct resolution of haemanthidine into its enantiomers was achieved by normal-phase TLC on silica gel plates impregnated with optically pure l-tartaric acid and l-histidine as chiral selectors . The mobile phase that enabled the best resolution was combination of cyclohexane-ethyl acetate-isopropanol-diethylamine (45 : 45 : 5 : 5), the spots were detected with Dragendorff’s reagent and under UV light . The studies of biological activities of each isomer are underway . The study was supported by the Charles University Grant Agency (Project No. 178518) and from the project of Specific Academic Research (SVV 260 412/2019). References 1. SINGH, B ., KATOCH, D .: Med . Aromat . Plants, 4, 2015, art . 212 . BIOLOGICAL EVALUATION OF ALKALOIDS ISOLATED FROM NARCISSUS CV . CARLTON AND ANTIPROLIFERATIVE POTENTIAL OF THEIR SEMISYNTHETIC DERIVATIVES AL MAMUN, A .,1 CAHLÍKOVÁ, L .,1 MAŘÍKOVÁ, J.2 1 Department of Pharmaceutical Botany, Faculty of Pharmacy, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Czech Republic e-mail: almamuna@faf .cuni .cz Plants of genus Narcissus L ., the most common genus of Amaryllidaceae family, have been used in traditional medicine worldwide . Most of the species can hybridize and some hybrid cultivars have been reported as potential sources of galanthamine and other Amaryllidaceae alkaloids (AA) .1 Narcissus pseudonarcissus cv. Carlton is an abundant species of Narcissus L . genus, often used for commercial extraction of galanthamine which is the most active AA used in the clinical management of mild to moderate stages of Alzheimer’s disease (AD) . So far, thirteen known AA have been isolated from Narcissus pseudonarcissus cv . Carlton . One undescribed isomer of hippeastrine and three new compounds
38 belonging to belladine structure types have been isolated. Compounds isolated in sufficient amounts were screened for acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), prolyloligopeptidase (POP), glycogen synthase kinase-3 beta (GSK-3β) and beta-secretase1 (BACE1) inhibition activity . Hippeastrine isomer and new compounds named carltonine A, carltonine B, and carltonine C demonstrate BuChE inhibition activity in µM and nM concentrations (10 .07 µM, 91 nM, 3 nM and 14 .84 µM, respectively) .2 The next part of the current study was the preparation of semisynthetic derivatives of galanthamine and screening their biological activities connected with AD and oncological diseases . The project was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1. JIN, Z .: Nat . Prod . Rep ., 33, 2016, 1318–1343 . 2. AL MAMUN, A., MAŘÍKOVÁ, J., HULCOVÁ, D. et. al.: Biomolecules 10, 2020, art . 800 . NEUROPROTECTIVE ACTIVITY OF NUPHAR LUTEA L . ALKALOID WIJAYA, V .,1 OPLETAL, L .,1 HULCOVÁ, D .,1 KUNEŠ, J .,2 MAŘÍKOVÁ, J.,2 CHLEBEK, J .1 1 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: wijayav@faf .cuni .cz During the screening of potential plant inhibitors against human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) at our department, a Nuphar lutea alkaloidal extract demonstrated potent and selective hBChE inhibitory activity (IC50 value of 11 .73 ± 1 .05 µg ml−1); against hAchE it was inactive (IC50 value > 100 µg ml−1) . From a dried plant material of N. lutea (12 .25 kg; leaves and rhizomes) a summary ethanol extract (37 .7 g) was prepared . It was subsequently fractionated with diethyl ether (Et2O-A; 1 .7 g and Et2O-B; 34 .4 g), chloroform (CHCl3-B; 0 .34 g), and ethyl acetate (EtOAc-B; 0 .95 g) by liquid-liquid extraction . The Et2O-B was separated by column chromatography on neutral alumina with step elution using petroleum ether, chloroform, and ethanol to collect 266 fractions that were monitored by TLC and 22 joined fractions were obtained . Subsequently, 5 fractions were separated by using different chromatographic techniques (flash chromatography and preparative TLC) to isolate five pure alkaloids (thiobinupharidine, neothiobinupharidine, two unpublished diastereomers of thiobinupharidine, and one unpublished diastereomer of deoxynupharidine) . Their structures were elucidated by mass spectrometry (EI, ESI), NMR, and optical rotation . hAChE and hBChE inhibitory activity of pure alkaloids was determined using a modified Ellman’s method.1 The diastereomer of deoxynupharidine showed moderate activity against hBChE with the IC50 value 69 .30 ± 5 .00 µM, other compounds were considered inactive (IC50 values > 100 µM) .
39 The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019). References 1. ELLMAN, G . L ., COURTNEY, K . D ., ANDRES, V . et al .: Biochem . Pharmacol . 7, 1961, 88–95 . PHARMACEUTICAL TECHNOLOGY SECTION IMPROVING THE DISSOLUTION RATE OF POORLY SOLUBLE MELOXICAM BY CO-MILLING BROKEŠOVÁ, J .,1 TRPĚLKOVÁ, Ž.,1 KOKTAN, J .,2 ŠKLUBALOVÁ, Z .1 1 Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Research and Development, Zentiva, k . s ., Czech Republic e-mail: brokesoj@faf .cuni .cz The aim of this work was to study the possibility of increasing the dissolution rate of the model drug meloxicam (MLX, BCS class II, solubility in water is 4 .4 µg ml−1 at 25 °C)1 using solventless co-milling with a hydrophilic drug carrier chitosan (CHIT) of 85% deacetylation degree . Firstly, the properties of both substances were estimated . MLX particles are very fine with a mean particle size x50 = 3 .7 µm and a relatively narrow distribution (span = 1 .94) . On the other hand, CHIT has platelet particles with a mean size x50 = 59 .3 µm and a wider distribution (span = 2 .30) . The melting point Tm = 262 .4 °C was detected for MLX (crystalline substance) . CHIT shows glass transition temperature Tg at 122 .5 °C (amorphous substance) . Subsequently, the binary powder mixtures were prepared at 1 : 1 and 1 : 8 ratios in a planetary ball mill . The effects of ball size, rpm and milling time on properties of co-milled mixtures were investigated . The changes in the particle size and particle size distribution were monitored by laser diffraction using a dry cell . Flow-through cell type of dissolution (USP 4, phosphate buffer pH 6 .8) with open loop was used to evaluate the dissolution rate of the drug in the co-milled powder mixtures . The detected dissolution rate r (mg dm−3 s−1) of MLX in the MLX:CHIT mixture co-milled in 1 : 8 ratio for 15 minutes was approximately four times higher than the dissolution rate of MLX within the first ten minutes. The reason is presumably an increase in specific surface area of the micronized drug particles together with deagglomeration during the co-milling/ mixing with the hydrophilic carrier with larger particles . The study was supported by the Grant Agency of Charles University (Project No. 1286218/2018, from the project of Specific Academic Research (SVV 260 401/2019) and Zentiva, k. s. References 1 . AMBRUS, R ., KOCBEK, P ., KRISTL, J . et al .: Int . J . Pharm ., 381, 2009, 153–159 .
40 AVALANCHE TESTING AND ITS RELATIONSHIP TO COHESION OF POWDERS TRPĚLKOVÁ, Ž., ŠKLUBALOVÁ, Z. Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: trpelkoz@faf .cuni .cz Powders and granular materials are two-phase systems where individual solid particles touch each other and are diffused in gaseous surroundings; the interparticle contacts influence the behaviour of the powder bed. Powder properties depend on many parameters such as particle size, shape, density, cohesive forces as well as on the air humidity and temperature .1 More cohesive materials can cause flow difficulties during pharmaceutical processes . Therefore, shear testing and new methods of avalanche measurements studying dynamic powder behaviour are used to describe these materials . It has been observed previously that some portion of powder microcrystalline cellulose (MCC) in mixtures with pellets made of microcrystalline cellulose (C100) improved compressibility of mixtures into tablets. In this work, the influence of MCC on the interparticle cohesion and flow properties were studied using the automated shear cell (ShearScan) and dynamic flow measurements (Revolution Powder Analyser). The more MCC in the mixture the higher cohesion was observed with worsening in avalanche behaviour from slumping (C100 and M90) through cascading (M80–M60) to cataracting when 50% or more of MCC was added . The relationship between the cohesion and avalanche angle was described with the linear regression with the coefficient of regression R = 0.9242. The results show the importance of careful choice of mixture composition to achieve the optimum composition for both good compression and flowability. The study was supported by the Grant Agency of Charles University (Project. No. 1286218/2018) and from the project of Specific Academic Research (SVV 260 401/2019). References 1. PRESCOTT, J . K ., BARNUM, R . A .: Pharm . Technol ., 24, 2000, 60–84 . CHARACTERIZATION OF RHEOLOGICAL PROPERTIES OF POLYMERS FOR FORMULATION OF LIQUISOLID SYSTEMS TARGETED TO THE COLON OGADAH, C ., VRANÍKOVÁ, B ., ŠKLUBALOVÁ, Z . Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: ogadahc@faf .cuni .cz Targeting drugs directly to the colon is beneficial for the local treatment of inflammatory bowel diseases and other colonic pathologies . Drug delivery systems which can control or sustain drug release in the colon are needed in order to achieve satisfactory drug levels for a longer duration, thereby minimizing dosing frequency and adverse effects .
41 A possible approach to control drug release is by the formulation of liquisolid systems by incorporating hydrophilic polymers as matrices . Such polymers become hydrated in aqueous medium to form a gel layer which controls the drug release . The ability of the polymer to control drug release is partly influenced by viscosity of the hydrated gel layer. Therefore, this study aims to characterize a range of polymer candidates (guar gum, sodium alginate, sodium carboxymethyl cellulose and various grades of hydroxypropyl methylcellulose) by rheological measurements . Biorelevant media Fasted State Simulated Gastric Fluid (FaSSGF) and Fasted State Intestinal Fluid (FaSSIF) of pH 1 .6 and 6 .5, resp ., were used to prepare polymer dispersions simulating the gel layer formed at the surface of hydrated matrices in the gastrointestinal tract . Flow rheology measurements were carried out on a rheometer . Flow curves were obtained, using a shear rate ramp at shear rate 0 .01–100 s−1 . Ostwald-de Waele (power law) model was applied to describe the rheological flow behaviour . The apparent viscosities of the polymers at shear rates of practical importance were reported. Although other formulation parameters will influence the drug release, viscosity data from the rheological studies will serve as a useful basis for further studies with regards to the formulation of liquisolid systems for colon-targeted drug delivery . The study was supported by the Grant Agency of Charles University (Project No. 70119/2019) and from the project of Specific Academic Research (SVV 260 401/2019). IN VITRO MODELS OF SKIN LIPID BARRIER SAGRAFENA, I .,1 PARASKEVOPOULOS, G .,1 VÁVROVÁ, K .2 1 Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: sagrafei@faf .cuni .cz First-line protection of the human body is carried out by the outermost skin layer, the stratum corneum (SC), which is composed of corneocytes embedded in a lipid matrix of ceramides, cholesterol and fatty acids .1 Skin diseases are associated with modified skin barrier functions which result from alterations in the skin barrier composition . In this regard, the use of model lipid membranes is a very useful tool to mimic healthy or diseased skin states .2 The aim of this study is to create model lipid membranes and investigate the polymorphic nature of the lipids at different annealing conditions . Initially, skin isolated lipids were annealed at different temperatures (from room temperature to 90 °C) in the presence or absence of water . Preliminary results did not show major differences for the lengths of long periodicity phase or cholesterol phase between the different annealing conditions, while short periodicity phase starts to be visible when annealing temperature is 70 °C in presence of water . Moreover, even if annealing of lipids was considered an essential step for the creation of model lipid membranes, our results indicate that lipids are also able to spontaneously arrange .
48 as an early stage biomarker for detection of kidney failure but no clinically useful chromatographic method for simultaneously determination of urinary retinol and creatinine as a urine dilution factor is currently available .1 Therefore, we developed new UHPLC-UVMS/MS method using column packed with fluorinated core-shell stationary phase, and acetonitrile with ammonium formate buffer solution as the mobile phase for separation of these two analytes that differ significantly in their physicochemical properties. The method involves very fast and simple sample preparation requiring small amount of sample matrix and solvents. Deuterium labeled internal standard was used for the more precise quantification .2 The method was tested with real-life samples using urine collected from patients suffering from colorectal or peritoneal cancer, and malignant neoplasm of kidney . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019), by Ministry of Health of the Czech Republic – conceptual development of research organization (UHHK, 00179906), by Ministry of Health of the Czech Republic (Project. No. NV18-03-00130) and from the project STARSS (Reg. No. CZ.02.1.01/0.0/0.0/15_003 /0000465) co-funded by ERDF. References 1. KUČEROVÁ, K., KUJOVSKÁ KRČMOVÁ, L., MATYSOVÁ, L. et al .: Trends Anal . Chem ., 95, 2017, 57–61 . 2. KUČEROVÁ, K., KUJOVSKÁ KRČMOVÁ, L., MIKANOVÁ, Z. et al.: J . Chromatogr . A, 1607, 2019, art . 460390 . MITOCHONDRIAL ANALYSIS OF HUMAN PLATELETS: COMPARISON OF DIFFERENTIAL CENTRIFUGATION AND CONTINUOUS FLOW APHERESIS VERNEROVÁ, A .,1,2 GARCIA-SOUZA, L . F .,3 GNAIGER, E .,3 KUJOVSKÁ KRČMOVÁ, L.,1,2 SOBOTKA, O .4,5 1 Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Clinical Biochemistry and Diagnostics, University Hospital in Hradec Králové, Czech Republic 3 Medical University of Innsbruck, Innsbruck, Austria and Oroboros Instruments, Innsbruck, Austria 4 3rd Department of Internal Medicine, University Hospital in Hradec Králové, Czech Republic 5 Department of Physiology, Faculty of Medicine in Hradec Králové, Charles University, Czech Republic e-mail: verneran@faf .cuni .cz Using modern high-resolution respirometers (HRR) the analysis of mitochondrial functions and the metabolic profile of platelets (PLT) from a small sample of human blood was made accessible . A standardized isolation procedure for human PLT was developed in the frame of international COST action MitoEAGLE and PLT prepared by this differential centrifugation (DC) secured a high inter-laboratory reproducibility of respirometry results .1 Continuous flow apheresis (CFA) is a clinical method for PLT isolation aiming at
49 the treatment of bleeding diathesis in severe thrombocytopenia with years of good clinical outcomes . The aim of this project was to introduce a new method of HRR at University Hospital Hradec Králové and compare mitochondrial respiration of PLT obtained by two different techniques: DC and CFA . HRR was assessed by Oroboros Oxygraph-2k FluoRespirometer (Oroboros Instruments, Austria) . According to our preliminary results, the isolation method did not affect maximal respiratory capacity of PLT in this study . PLT isolated by CFA had 30% decrease in succinate oxidation in comparison to DC . Moreover, CFA affected PLT viability . These differences were reversed after washing the PLT by phosphate buffer saline, suggesting possible influence of isolation medium on our results. We conclude that HRR is a highly sensitive and suitable method to describe the metabolic profile of human PLT. The application of HRR is promising in PLT research in patients with thrombocytopenia, sepsis and metabolic disorders as well as in diagnostics . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019), by Ministry of Health of the Czech Republic – conceptual development of research organization (UHHK, 00179906) and from European Union Framework Programme Horizon 2020 COST Action CA15203 MitoEAGLE. The loan of oxygraphs was kindly provided by Oroboros Instruments. References 1. SUMBALOVA, Z ., DROESCHER, S ., HILLER, E . et al .: Mitochondr . Physiol . Network 21 .17 (03), 2018, 1–16 . THE METHOD DEVELOPMENT FOR THE DETERMINATION OF CISPLATIN IN HUMAN PLASMA TUROŇOVÁ, D.,1,2 KUJOVSKÁ KRČMOVÁ, L.1,2 1 Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Clinical Biochemistry and Diagnostics, University Hospital in Hradec Králové, Czech Republic e-mail: turonovd@faf .cuni .cz Cisplatin is well known for its antitumor activity but it is also associated with side effects, relevancy of which depends on its exposure . Extended exposition can cause nephrotoxicity and other health problems .1,2 Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is a procedure combining maximal surgical removal of the tumor with intra-operative administration of a chemotherapeutic drug that is heated up . The aim of the whole process is to increase the anticancer effect and minimalize the systemic side effects of the chemotherapy in comparison with systemic chemotherapy .3 For the purpose of clinical research, a HPLC method with diode-array detection for the determination of cisplatin in human plasma with simple sample pretreatment has been developed and current results will be discussed . The separation was carried out in 8 minutes
50 using C18 core-shell column with mobile phase consisting of methanol, acetonitrile, and water . As internal standard palladium chloride was used . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019), by Ministry of Health of the Czech Republic – conceptual development of research organization (UHHK, 00179906) and by Ministry of Health of Czech Republic (Project No. NV18-03-00130). References 1. SHAIK, A . N ., ALTOMARE, D . A ., LESKO, L . J . et al .: J . Chromatogr . B ., 1046, 2017, 243–249 . 2. Handbook of LC-MS Bioanalysis: Best Practices, Experimental Protocols, and Regulations . Li, W ., Zhang, J ., Tse, F . L . S . (eds .), Hoboken, Wiley, 2013 . 3. WITKAMP, A . J ., De BREE, E ., Van GOETHEM, A . R . et al .: Cancer Treat . Rev ., 27, 2001, 365–374 . DEVELOPMENT AND VALIDATION OF UHPLC METHOD FOR THE MONITORING OF TARGET ACTIVE SUBSTANCES AND THEIR RELEASING FROM SOLID DISPERSIONS ARNOLTOVÁ, K .,1,2 KUJOVSKÁ KRČMOVÁ, L.,1,2 MATYSOVÁ, L .1 1 Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Clinical Biochemistry and Diagnostics, University Hospital in Hradec Králové, Czech Republic e-mail: arnoltok@faf .cuni .cz This work is part of a project, that is focused on the development, optimization, and validation of UHPLC methods and their subsequent application on the evaluation of new modern drug forms based on solid dispersions . The research is based on the development of modern drug forms, which use branched polymers as a carrier of active substances with the effort to influence the release of the target drugs and increase their bioavailability. The determination of drug-releasing from the new carrier is crucial for the research . Newly developed chromatographic methods will serve as the main tool for testing various materials used as a carrier of active substances, for the determination of drug content and detection of possible impurities . In the presented UHPLC method, miconazole, econazole and their main impurities were chosen as the target analytes . An UHPLC method, using diode-array detection, has been created. A KinetexTM C18 column, 1.7 μm particle size, 50 × 2.1 mm was used for the separation in combination with the acetate buffer, methanol, and acetonitrile as the mobile phase . Butylparaben was chosen as the internal standard . All substances were detected at the wavelength of 225 nm . The total analysis time was 9 minutes . The new method will be validated and used for testing various branched polymers as suitable carriers . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019).
51 References 1. ŠNEJDROVÁ, E ., DITTRICH, M ., DRASTÍK, M .: Int . J . Pharm ., 458, 2013, 282–286 . IDENTIFICATIONS OF ARTIFICAL MODIFICATIONS INDUCED IN THE COURSE OF LC-MS ANALYSES OF PEPTIDES LENČO, J. Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: lenco@faf .cuni .cz Column temperature is one of the key parameters that remarkably increases efficiency in bottom-up LC-MS proteomic analyses . We noticed, however, that at some point the benefit of elevated temperature to the peak shape is redeemed by lower number of identified peptides . We hypothesized that an on-column peptide degradation might occur when the peptides are separated at an elevated temperature using acidic mobile phases . To this end, we scrutinized the effect of temperature on the stability of model proteins trapped in a reversed phase column. We confirmed that temperature as high as 45 °C in combination with 0 .1% formic acid may already induce on-column peptide bonds cleavage . We subsequently carried out data-dependent LC-MS analyses of tryptic peptides at various column temperatures . We found out that besides on-column peptide bonds cleavage, peptides trapped in a stationary reversed phase may undergo various artificial chemical modifications in the presence of 0.1% formic acid in mobile phases. Additionally, the risk of artificial peptides formylation due to inappropriate sample handling was discovered within the study . The study was supported by the STARSS project (Reg. No. CZ.02.1.01/0.0/0.0/15_003/ 0000465) co-funded by ERDF and from the project of Specific Academic Research (SVV 260 412/2019). AUTOMATION OF ON-LINE SAMPLE PREPARATION FOR THE PEPTIDE MAPPING ANALYSIS OF BIOPHARMACEUTICALS KHALIKOVA, M., LENČO, J., FAISTAUEROVÁ, K., ŠVEC, F. Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: khalikom@faf .cuni .cz Peptide mapping is critical methodology in routine biopharmaceutical analysis used to confirm identity, characterize primary structure, monitor degradative events, and meet quality assurance .1 Peptide mapping is the gold standard method for the in-depth study of post-translational modifications (PTMs) of monoclonal antibodies (mAb). PTMs are critical quality attributes defining therapeutic efficacy and safety.2 Both PTMs and chemical
52 modifications may arise during production, processing, and storage of proteins.1 Thus, the identification and quantification of PTMs is essential in development and analysis of therapeutic biomolecules . Sample preparation for peptide mapping requires enzymatic digestion of protein that is typically a time-consuming and labor intensive process . It includes several steps prone to operator error that can induce an increase in artificial modifications such as asparagine deamidation .3 The multidimensional LC system was used for automation of the digestion procedure of trastuzumab to optimize the sample preparation of this mAb prior to peptide mapping . We will describe ongoing project focused on the setup of automated digestion process as a part of multiattribute analysis of mAb . Our study concerns effects of method conditions on the quality of digests of trastuzumab including type and pH of digestion buffer, incubation time, and temperature . This work was supported by the STARSS project (Reg. No. CZ.02.1.01/0.0/0.0/15_003/ 0000465) co-funded by ERDF and from the project of Specific Academic Research (SVV 260 412/2019). References 1. MOUCHAHOIR, T ., SCHIEL, J . E .: Anal . Bioanal . Chem ., 410, 2018, 2111–2126 . 2. JENKINS, N ., MURPHY, L ., TYTHER, R .: Mol . Biotechnol . 39, 2008, 113–118 . 3. HAO, P ., REN, Y ., DATTA, A . et al .: J . Proteome Res ., 14, 2015, 1308–1314 . ELECTROCHEMICAL STUDY OF OLIGONUCLEOTIDE PROBES LABELED BY QUANTUM DOTS FOR THE DETECTION OF BACTERIAL AND VIRAL PATHOGENS BANÁŠ, D .,1,2,6 AKSU, D . A .,1,3,4 NOGUERA, M . V .,1,3,5 PAY, M .,1,3,4 HOSNEDLOVÁ, B .,6 KIZEK, R .,1,3,6 1 Department of Research and Development, Prevention Medicals s . r . o ., Studénka-Butovice Czech Republic 2 Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic 3 Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic 4 Bezmialem Foundation University, Istanbul, Turkey 5 Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain 6 Veterinary Research Institute, Brno, Czech Republic e-mail: dominik .banass@gmail .com African swine fever virus (ASFV) is a virus with high morbidity and mortality, which is infectious for domestic and wild pigs and causes serious socioeconomic impact .1 Because of the non-existence of a suitable vaccine, it is necessary to determine the presence of the virus directly in the focus of infection . Thus, the cornerstone of design of a biosensor for rapid analysis of ASFV was suggested . This work is focused on the electrochemical study of oligonucleotides (ODNs) KING R and KING F which are specifically complementary to ASFV DNA, and quantum dots (CdTe QDs) as a label for these ODNs . The adsorptive
53 transfer technique was used for the accumulation of ODNs to a working electrode . In the first phase, the dependences of the current on concentration and time of accumulation of ODNs were measured. The calibration ranges from 0.4 to 1.7 μg mL−1 for KING F and 0.1 to 0.6 μg mL−1 for KING R were measured and the LODs, LOQs and CVs were calculated . CdTe QDs interacted with ODNs . CA (cytosine and adenine) signals of ODNs were 33 .9 ± 8 .7 nA and 22 .0 ± 3 .3 nA for KING F and KING R, respectively . For interaction CA signals were detected as follows: KING F/QDs 15 .8 ± 8 .6 nA, KING R/QDs 16 .1 ± 5 .1 nA and cadmium signals were detected as follows: KING F/QDs 61 .8 ± 15 .7 nA and KING R/QDs 89 .3 ± 18 .2 nA . This study brought pilot results for the creation of biosensor for detecting bacterial and viral pathogens, which can be useful for the suggestion of suitable pharmaceutical therapy . The study was supported by the EU programme for education, training, youth and sport ERASMUS+ and project AMOR QK1920113. References 1. GALINDO, I ., ALONSO, C .: Viruses, 9, 2017, art . 103 . LC-MS/MS STUDY OF THE FIRST PHASE OF IN VITRO BIOTRANSFORMATION OF NEW PROMISING TACRINE DERIVATIVES NOVÁK, M .,1,2 KUČERA, R.,1 DOLEŽAL, R.,2 PRCHAL, L .2 1 Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Biomedical Research Center, University Hospital in Hradec Králové, Czech Republic e-mail: novakm61@faf .cuni .cz Alzheimer’s disease is a neurodegenerative disorder causing decline in cognitive functions, gradual loss of self-control, development of disorientation, and afterwards motoric failure . Current symptomatic pharmacotherapy is primarily focused on acetylcholinesterase inhibitors and NMDA (N-methyl-d-aspartate) receptor blocking .1 Tacrine molecule, which is one of the acetylcholinesterase inhibitors, was withdrawn from the market due to the hepatotoxicity of its metabolite 7-hydroxytacrine in 2013 . The substitution of tacrine molecule may potentially block the formation of toxic metabolites . The introduction of methoxy group to position of 7 of 1,2,3,4-tetrahydroacridine led to 7-methoxytacrine .2 The aim of our work was to determine the metabolites of tacrine and 7-methoxytacrine and to evaluate the effects of biotransformation in a in vitro study . Human liver microsomes (HLM) were used as first phase in vitro biotransformation model and HPLC coupled with Q Exactive Plus mass spectrometer was used for the characterization of metabolites . The new HPLC-MS method for the separation and identification of tacrine and 7-methoxytacrine metabolites was created and structures of metabolites were experimentally designed from Full-MS and MS/MS spectra and confirmed by MassFrontier (MetWorks). The results of the study show that the main way of biotransformation of both compounds is their monohydroxylation and dihydroxylation . Moreover, several novel in vitro
54 metabolites of tacrine and 7-methoxytacrine which have not been reported in the literature so far were found and the relative proportion of individual metabolites was calculated . The work was supported from the project of Specific Academic Research (SVV 260 401/ 2019). References 1. JOUANNE, M ., RAULT, S ., VOISIN-CHIRET, A .-S .: Eur . J . Med . Chem ., 139, 2017, 153–167 . 2. PATOČKA, J., JUN, D., KUČA, K.: Curr. Drug Metab., 9, 2008, 332–335. ANALYSIS OF ECCRINE SWEAT PRCHAL, L . Biomedical Research Centre, University Hospital in Hradec Králové, Czech Republic e-mail: lukas .prchal@fnhk .cz Sweating is usually found unpleasant and annoying . It is, however, very important mechanism that provides our bodies with effective temperature control in different situations. Also its composition can be influenced by various substances or state of health. There are two main types of human sweat . Apocrine sweat consists predominantly of lipophilic substances while eccrine sweat, which could be described as hydrophilic, consists mainly from water and various ions and small amount of other substances .1 Our research focuses on eccrine sweat and these substances . Sweat is collected by patches worn for one week . Then the patch is collected and extracted and extracts are lyophilised . The samples are then analysed by HPLC coupled with mass spectrometry . As the majority of metabolites are hydrophilic, HILIC column was used to separate them at least partially . The analysis was performed in both positive and negative modes . In this initial state we have processed only a small amount of patches, which are considered healthy controls for future research . The study was supported by Ministry of Health of the Czech Republic – conceptual development of research organization (UHHK, 00179906). References 1. WILKE, K ., MARTIN, A ., TERSTEGEN, L . et al .: Int . J . Cosmet . Sci ., 29, 2007, 169–179 . ION MOBILITY SPECTROMETRY IN DOPING ANALYSIS PLACHKÁ, K .,1 PEZZATTI, J .,2 NICOLI, R .,3 VEUTHEY, J .-L .,2 GUILLARME, D .,2 NOVÁKOVÁ, L .1 1 Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, Switzerland 3 Swiss Laboratory for Doping Analysis, Centre Universitaire Romand de Médecine Légale, Switzerland e-mail: plachkka@faf .cuni .cz
55 This project aimed at examining the effects of using ion mobility spectrometry-mass spectrometry in doping control analysis using 194 compounds from World Anti-Doping Agency prohibited list, including stimulants and narcotics (Class I) and anabolic steroids, glucocorticoids, and hormones (Class II) . MSe data independent acquisition scan type with high-resolution mass spectrometry was used for the experiments . The analyses were carried out using q-TOF (quadrupole-time of flight) with and without activation of the ion mobility spectrometry dimension . The ultra-high-performance liquid chromatographymass spectrometry method was developed using standard mixtures to tune the settings of mass spectrometer and to optimize the data processing method . Subsequently, the method was used with urine samples prepared by dilute and shoot approach for Class I and by supported liquid-liquid extraction (SLE) for Class II . Prior to the analysis, SLE procedure was optimized to ensure sufficient sensitivity with final pre-concentration by factor of 10. Finally, the analyses of standard doping agents and urine samples were compared with and without ion mobility function, including the comparison of collision cross section (CCS) values, fragmentation, and quality of spectra . The robustness of the method was proved by intraday, interday, and interweek repeatability of retention times and CCS values, providing RSD values always lower than 2% . The effect of matrix on CCS values was examined as well as matrix effects and fulfillment of minimum required performance limits. The effect of ion mobility on the quality of spectra, elimination of interferences, and method sensitivity was evaluated with the aim to improve screening capabilities, especially to prevent false positive and false negative results . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019) and by the STARSS project (Reg. No. CZ.02.1.01/0.0/0.0/15_003/0000465) co-funded by ERDF. STUDY OF INCREASING SENSITIVITY IN ESI− BY ANION ATTACHMENT LHOTSKÁ, I., KOČOVÁ VLČKOVÁ, H., NOVÁKOVÁ, L. Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: lhotski@faf .cuni .cz Increasing detection sensitivity is crucial task in LC-MS method development . Apart from the instrument limits, ionization efficiency is the key to good sensitivity. In case of poorly ionized analytes, alternative LC-MS mobile phase additive can be considered . Besides conventional volatile acids and buffers enhancing deprotonation of analytes in ESI– and increasing conductivity, the ionization can be achieved by adduct formation or through gas phase proton-transfer reactions . For this study, ammonium fluoride was selected as anion attachment additive for its strong gas-phase proton affinity. Generally, signal improvement of less polar molecules can be provided by an anion attaching to electropositive region of analyte molecule forming an adduct . Fluoride anion, due to higher gas-phase basicity than most of other anions and
56 deprotonated molecules, is able to abstract the shared proton from the analyte and separate as HF. Finally, ionization efficiency is enhanced by production of [M-H]− in gas phase .1 Mobile phase containing ammonium fluoride (0.1–1.0 mM) was compared to conventional additive 0 .1% formic acid and its positive effect on signal intensity was assessed for broad spectrum of compounds varying in molecular weight, polarity, lipophilicity, and structures . Fluoride anion attachment potential as a solution for increasing sensitivity in ESI− will be discussed . The study was supported by the STARSS project (Reg. No. CZ.02.1.01/0.0/0.0/15_003/ 0000465) co-funded by ERDF and from the project of Specific Academic Research (SVV 260 412/2019). References 1. WANG, G ., COLE, R . B .: Anal . Chem ., 81, 2009, 8826–8838 . MODIFICATION OF CAPILLARY WALL BY GRAPHENE FOR SEPARATION IN CAPILLARY ELECTROPHORESIS LOCHMAN, L .,1 FELIX, O .,2 DECHER, G .,2 KUČERA, R.1 1 Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Institute Charles Sadron, National Centre for Scientific Research (CNRS), Strasbourg, France e-mail: lochmanl@faf .cuni .cz Graphene (G) is two-dimensional sp2 single-atom-thick carbon sheet with hexagonal structure. High specific area (theoretical value 2630 m2 g−1) together with the affinity to carbon ring structures via π-π stacking interactions make G and graphene oxide (GO) promising candidates for application in analytical chemistry .1,2 Our work aims at the modification of inner surface of bare silica capillary by Layerby-Layer method (LbL) .3 LbL is very simple self-assembly procedure which controls through electrostatic interactions adsorption of negatively charged GO onto wall covered by positively charged polyelectrolyte. Modification of capillary wall by GO is believed to substantially improve the separation properties for analysis of charged/neutral analytes due to the combination of the high CE efficiency and additional interactions with the modified surface. As it is difficult to characterize and optimize a nanoscale coating, the deposition was firstly done on the flat surface (silicon wafer or quartz slide) and different techniques (ellipsometry, UV-VIS spectroscopy, AFM) were employed . Different combinations of polyelectrolyte/GO were tested . Based on these results, the coating process was transferred into the capillary and the separation of the model analyte mixture was compared with unmodified capillary. The study was supported by Research programme Development and Study of Drugs (Progres Q42) and from the project of Specific Academic Research (SVV 260 401/2019).
57 References 1. Graphene: Synthesis, Properties, and Phenomena . Rao, C . N . R ., Sood, A . K . (eds .), Weinheim, Wiley-VCH, 2012 . 2. WANG, X ., LIU, B ., LU, Q . et al.: J. Chrom. A, 1362, 2014, 1‒15. 3. DECHER, G.: Nature, 277, 1997, 1232‒1237. ANALYTICAL STUDY OF THE INFLUENCE OF EXPERIMENTAL CONDITIONS ON THE CHIRAL SEPARATION OF BORON CLUSTER COMPOUNDS HORÁČEK, O., KUČERA, R. Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: horaceko@faf .cuni .cz Boron clusters are artificial compounds which create 3D-cage structure and exhibit unique physicochemical properties . Carboranes are prepared by substituting BH units for CH units . They are studied as stereoselective catalysts, monomers for thermostable polymers and in medicine as compounds which enhance the effectivity of boron neutron capture therapy . Steric similarity with rotating phenyl ring enables extensive research of carboranes as new pharmacophores .1 Chirality of boron clusters is caused by introducing endo-/exoskeletal substituents, which impair the symmetry of the cage . Due to the chiral character of these compounds, it is vital to evaluate the influence of experimental conditions on chiral separations with respect to their potential use . Even though zwitterionic carboranes were successfully separated on native beta-cyclodextrin based chromatographic columns, attempts to separate anionic carboranes were unsuccessful .2 On the other hand, native beta-cyclodextrins were able to resolve some anionic carboranes in capillary zone electrophoresis .3 To clarify this contradiction, chromatographic behavior of anionic carboranes was tested on the native beta-cyclodextrin column (ChiraDex, Merck) . Our work aims to elucidate the discrepancy between chiral separations of anionic carboranes by high performance liquid chromatography and capillary zone electrophoresis . The study was supported from the project of Specific Academic Research (SVV 260 401/ 2019) . References 1. ISSA, F ., KASSIOU, M ., RENDINA, L . M .: Chem . Rev ., 111, 2011, 5701–5722 . 2. HORÁKOVÁ, H ., GRUNER, B ., VESPALEC, R .: Chirality, 23, 2011, 307–319 . 3. HORÁKOVÁ, H ., VESPALEC, R .: J . Chromatogr . A, 1143, 2007, 143–152 .
64 Organic polymer monoliths are excellent supports for the chromatographic separation of large molecules . Monolithic columns feature high permeability and low back pressure . However, they suffer from a rather small surface area needed for the separation of small molecules . On the other hand, porous metal-organic framework (MOF) crystals are highly porous with widely tunable properties . Unfortunately, their packing in separation columns is challenging due to their small particle size and non-spherical shape . Therefore, we designed a new generation of separation media combining advantages of organic polymer monoliths and MOF while reducing their drawbacks . We prepared polydivinylbenzene monolith containing ZnO nanoparticles as the MOF metallic precursor . ZnO nanoparticles were then converted to zeolitic imidazolate framework ZIF-8 via biomimetic crystallization using 2-methylimidazole as the organic linker with addition of a bioactive molecule – an amino acid – that enabled further modulation of MOF size and increased its selectivity . l-histidine, l-valine, phenylalanine, and glutamic acid were selected for our experiment and their effects on crystal morphology and adsorption selectivity were demonstrated . In situ polymerization time and MOF crystals growth were optimized to create open tubular capillary columns for enantioselective solid phase microextraction . Chiral selectivity and extraction capacity of the material were studied with batch extraction of propranolol enantiomers . The project was supported from the project of Specific Academic Research (SVV 260 412/ 2019), the STARSS project (Reg. No. CZ.02.1.01/0.0/0.0/15_003/0000465) co-funded by ERDF, CASSS Frantisek Svec Fellowship 2019, and The Mobility Fund of Charles University. COMBINING LAB-IN-SYRINGE WITH BEAD-INJECTION FOR PRECONCENTRATION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS IN SURFACE WATERS COUPLED ONLINE TO HIGH PERFORMANCE LIQUID CHROMATOGRAPHY GEMUH, C ., HORSTKOTTE, B ., SOLICH, P . Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: gemuhc@faf .cuni .cz The modern flow techniques Lab-In-Syringe (LIS) and Lab-On-Valve (LOV) were combined and hyphenated to high-performance liquid chromatography for online micro-solid phase extraction of 5 nonsteroidal anti-inflammatory drugs (NSAIDs), namely ketoprofen, naproxen, flurbiprofen, diclofenac, and ibuprofen. The combined system ensured adequate mixing of large volume of sample with buffer inside the syringe enabling higher enrichment than typically achieved by simple LOV . SPE on a micro-SPE, packed automatically and in-system following the Bead Injection principle, was carried out in the LOV conduit using 4 .4 mg of Oasis HLB® sorbent of particle size 30 μm for each sample analysis . Parameters such as injection volume, volume of sorbent suspension, ionic strength of buffer and the elution and loading flow rates were optimized. After washing the
65 micro-SPE column with water to remove any unretained matrix components, the retained analytes were eluted with acetonitrile/water (50 : 50, V/V) and 350 μL of the eluate loaded into the HPLC injection loop . Separation of 5 NSAID was done on Symmetry C18 column (4.6 × 150 mm, 5 μm) and C18 OPTI-GUARD® 1 mm guard column using a mobile phase of 30% (V/V) acetonitrile and 30% (V/V) methanol in 25 mmol L−1 ammonium formate buffer, pH 3 .5, in isocratic regime . The method developed was reproducible with RSD values of 1% to 7% on 20 μg L−1 level with linear range of 10 μg L−1 to 200 μg L−1 and LOD less than 5 μg L−1 . Recovery factors between 91 to 109 were obtained for surface water samples at 20 μg L−1 level . The study was supported from the project of Specific Academic Research (SVV 260 412/ 2019). POLYSULFONE MEMBRANE ENRICHED IN BIOACTIVE COMPOUNDS TO REDUCE OXIDATIVE STRESS AND INFLAMMATION IN DIALYSIS PATIENTS KOHLOVÁ, M .,1,3 ROCHA, S .,2,3 AMORIM, C . G .,3 SANTOS-SILVA, A .,2 SOLICH, P .,1 MONTENEGRO, C .3 1 Department . of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 UCIBIO\REQUIMTE Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Portugal 3 LAQV\REQUIMTE Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal e-mail: kohlm5aa@faf .cuni .cz Oxidative stress (OS) and chronic inflammation are commonly present in dialysis patients, due to frequent contact of patients’ blood with artificial membrane. To reduce oxidative stress, vitamin E-coated membranes are used to scavenge the reactive oxygen species formed during the hemodialysis . Although the use of this type of membrane showed diminishment in some inflammatory and OS markers,1 the overall beneficial effect on mortality is still uncertain . The aim of our work was to evaluate, if the enriched polysulfone (PSf) membranes with other bioactive substances, such as antioxidant lipoic acid or synthetic inhibitors of neutrophil elastase, could have preferable impact on OS and/or inflammation than vitamin E. Lipoic acid was incorporated in PSf membranes alone or together with vitamin E, while synthetic elastase inhibitors were immobilized on the membranes surface through adsorption. The biological activity and biocompatibility of the modified membranes were studied in vitro . Both types of bioactive compounds immobilized on PSf membrane showed promising effect on diminishment of OS/inflammation and therefore could be considered for future treatment . The study was supported by the Charles University Grant Agency (Project No. 860216), from the project of Specific Academic Research (SVV 260 412/2019), by EFSA-CDN (CZ.02.1.01/0.0/0.0/16_019/0000841) co-funded by ERDF, by the North Portugal Region-
66 al Operational Programme NORTE 2020 (Project. No. 01/0145/FEDER/000024), and from the project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI/01/0145/FEDER/031322). References 1. D’ARRIGO, G ., BAGGETTA, R ., TRIPEPI G . et al .: Blood Purif ., 43, 2017, 101–122 . LIQUID-PHASE MICROEXTRACTION OF ORGANOPHOSPHORUS PESTICIDES USING SUPRAMOLECULAR SOLVENT AS A CARRIER FOR FERROFLUID HASHEMI, B .,1 ZOHRABI, P .,2 SHAMSIPUR, M .,1 HASHEMI, M .1,2 1 Department of Analytical Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran 2 Department of Analytical Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran e-mail: hashemib@faf .cuni .cz Supramolecular solvents (SUPRASs) are water immiscible nano-structured solvents composed of 3D amphiphilic aggregates, which have been used in microextraction procedures . The most important feature of supramolecular solvents is their high solvation potential for a wide range of target analytes (both polar and non-polar ones) . As collecting of extracting solvent is of great importance in the liquid-phase microextraction, ferrofluids – suspended magnetic nanoparticles in a carrier liquid – can overcome the drawbacks such as centrifugation and refrigeration . In this study, we used supramolecular solvent as a carrier for ferrofluid and extracted three organophosphorus pesticides (OPPs) in water and fruit juice samples . To this end, oleic acid coated magnetic nanoparticles were prepared to omit the centrifugation step and they were used in combination with SUPRAS in the extraction process. The influence of main variables on the extraction efficiency was investigated using response surface methodology (RSM) based on central composite design (CCD) . Under the optimum experimental conditions, the resulting calibration curves were linear in the concentration range of 0.5–400 μg L−1 . The intra-day and inter-day precisions were evaluated to be in the range of 2 .0%–5 .3% and 2 .6%–5 .7%, respectively . The obtained limits of detection (LODs) also ranged from 0.1 to 0.35 μg L−1 . The study was supported by the Research Council of Razi University, (Faculty of Chemistry, Razi University, Kermanshah, Iran).
67 BIOCHEMISTRY, PHARMACOLOGY AND TOXICOLOGY SECTION IN VITRO SCREENING OF STRUCTURALLY DIFFERENT TOPOISOMERASE II INHIBITORS FOR PREVENTION OF ANTHRACYCLINE CARDIOTOXICITY KUBEŠ, J .,1 JANSOVÁ, H .,1 KARABANOVICH, G .,2 MELNIKOVÁ, I .,2 JIRKOVSKÁ, A .,1 SKALICKÁ, V .,1 JIRKOVSKÝ, E .,1 ROH, J .,2 ŠIMŮNEK, T.1 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: kubesja1@faf .cuni .cz Anthracyclines (ANTs) retain the prominent role in many cancer treatments due to their high efficacy. However, the use of all of the ANTs is associated with a risk of severe cardiotoxicity . To date, dexrazoxane (DEX) has been the only cardioprotective agent approved for clinical use; therefore, it represents the main lead in the search for effective cardioprotection . The focus regarding its cardioprotective mechanism has recently shifted from metal chelation to its effect on topoisomerase II (TOP2) . This inspired us to examine various structural types of compounds described as TOP2 inhibitors for potential cardioprotective effect. In the first stage, we screened a series of commercially available compounds reported to inhibit TOP2 for their protective properties on primary cultures of neonatal rat cardiomyocytes . We also examined the effects of studied compounds on proliferation of HL-60, cell line derived from acute promyelocytic leukemia, and their effect on antiproliferative activity of daunorubicin . Because mitigation of adverse effect loses meaning if it diminishes the main effect . From the series of inhibitors evaluated so far, three compounds show promising cardioprotection . Therefore, in the next stage, effect of the selected compounds on activity and depletion of TOP2 will be ascertained, to gain better mechanistical insight; and also, analogues of the perspective compounds are being prepared and studied . This study was supported from the project of Specific Academic Research (SVV 246 216/ 2019) and by InoMed (Project No. CZ.02.1.01/0.0/0.0/18_069/0010046) co-funded by the European Union. EVALUATION OF DAUNORUBICIN ANTIPROLIFERATIVE EFFECT ON TOPOISOMERASE 2Β DEPLETED HL-60 GENERATED WITH CRISPR-CAS9 SKALICKÁ, V .,1 KHAZEEM, M . M .,2 JAŠČEVSKÁ, N.,1 AUSTIN, C . A .,2 JIRKOVSKÁ, A .1 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Centre for Haemato-Oncology, Faculty of Medical Sciences, Newcastle University, United Kingdom e-mail: skalicv1@faf .cuni .cz
68 Topoisomerase II β (TOP2B) inhibition was identified as one of possible mechanisms of dexrazoxane protection of cardiomyocytes from anthracycline (ANT) cardiotoxicity . In 2012, Zhang et al. outlined, that mice with heart specific depletion of TOP2B were prevented from ANT-induced cardiac damage .1 Unlike heart cells, human leukemic cell line HL-60 contain both TOP2A and TOP2B isoforms . TOP2A enables cell division while the precise function of TOP2B has not been fully understood yet . Dexrazoxane (DEX) as the only approved cardioprotective agent acts as catalytic inhibitor of both TOP2 isoforms, and due to its TOP2 inhibition effect it is suspected of compromising the cytotoxicity effect of anthracyclines in cancer cells . The TOP2B was also implicated in the resistance of tumor cells and the increase of secondary malignances . We aimed at depleting TOP2B with CRISPR-Cas9 technology and evaluate the effects of daunorubicin (DAU) on these mutants regarding their sensitivity to DAU. HL-60 were transfected with specific CRISPR-Cas9 plasmid targeting TOP2B . Forty-eight hours after transfection the cells were sorted with GFP as a selection marker to 96-well plates . After approximately 6 weeks of cell growth individual clones were tested for TOP2B occurrence by immunofluorescence and western blotting. TOP2B deficient clones were spotted and genotyped to characterize individual clonal mutations . Based on these acquired data several homozygous and heterozygous TOP2B deficient mutants were identified. Antiproliferative effect of DAU was evaluated in both homozygous and heterozygous mutants using MTT . The study was supported from the project of Specific Academic Research (SVV 260 416/ 2019). References 1 . ZHANG, S ., LIU, X ., BAWA-KHALFE, T . et al: Nat . Med . 18, 2012, 1639–1642 . TYROSINE KINASE INHIBITORS AS MULTITASKING SOLDIERS AGAINST CANCER DRUG RESISTANCE: THE EXEMPLARY CASE OF MIDOSTAURIN MORELL, A ., NOVOTNÁ, E ., WSÓL, V . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: morellga@faf .cuni .cz Tyrosine kinase inhibitors (TKIs) are proven active antileukemic agents that suppress aberrant tyrosine kinase signaling involved in cell proliferation . TKIs have shown additional targeting of proteins involved in cancer multidrug resistance, like membrane transporters and detoxifying enzymes . Midostaurin is a selective inhibitor of FMS-like tyrosine kinase-3 (FLT3) approved for the treatment of acute myeloid leukemia (AML), in combination with anthracycline daunorubicin (DAU) . Midostaurin-based combination chemotherapy has demonstrated significant clinical benefits and safety, but the molecular mechanisms involved are still poorly understood . It has been reported how carbonyl reducing enzymes (CREs) expressed in leukemic cells contribute to resistance towards
69 daunorubicin . In this context, we evaluated the effect of midostaurin on DAU reduction by several recombinant CREs, observing a tight-binding inhibition of Aldo-keto reductase 1C3 (AKR1C3) . Likewise, midostaurin decreased DAU metabolism in an HCT116 cell model overexpressing AKR1C3 . Furthermore, acute myeloid leukemia cell line KG1a naturally expresses CREs that correlates to its inherent resistance to anthracyclines . Midostaurin performs a dual effect on KG1a cells, by inducing DAU accumulation but significantly reducing DAU metabolism. Confocal microscopy and flow cytometry showed that the combination with midostaurin increases the nuclear localization of daunorubicin in KG1a cells, probably due to the higher availability of the non-reduced form of DAU . Our findings revealed that midostaurin improves DAU cytotoxicity by the simultaneous inhibition of different proteins that are critical in cancer multidrug resistance . The study was supported by EFSA-CDN (CZ.02.1.01/0.0/0.0/16_019/0000841) cofunded by ERDF and from the project of Specific Academic Research (SVV 260 416/2019). EMD1214063 REVERSES MULTIDRUG RESISTANCE BY INHIBITING THE EFFLUX FUNCTION OF ABCB1 AND ABCG2 TRANSPORTERS VAGIANNIS, D .,1 ZHANG, Y .,1 BUDAGAGA, Y .,1 SKARKA, A .,2 ŠTAUD, F .,1 HOFMAN, J .1 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Chemistry, Faculty of Science, University of Hradec Králové, Czech Republic e-mail: vagiannd@faf .cuni .cz ABC (ATP-binding cassette) drug efflux transporters play an important role in pharmacokinetic drug-drug interactions as well as in the phenomenon of multidrug resistance (MDR) in cancer cells . EMD1214063 (EMD) is a novel c-MET tyrosine kinase inhibitor that has been developed for several types of cancer, including non-small cell lung cancer . In this study, we aimed at evaluating the inhibitory activity of EMD towards human ABC transporters and its role in the MDR . In accumulation studies in MDCKII cell lines overexpressing particular ABC transporters we showed that EMD is an inhibitor of ABCB1 and ABCG2. Furthermore, we demonstrated that EMD1214063 significantly reverses ABCB1and ABCG2-mediated daunorubicin and mitoxantrone MDR, respectively . For reversal experiments, MTT proliferation assay in MDCKII, A431 and HL60 cells overexpressing ABCB1 and ABCG2 transporters, was used . Additionally, EMD was found to be a substrate of ABCB1 but not of ABCG2 or ABCC1, in MDCKII monolayer transport assays followed by UHPLC/MS analysis. No significant induction effects of EMD on ABCB1, ABCG2 or ABCC1 mRNA levels were found in physiological cells as well as non-small cell lung cancer cellular models using qRT-PCR analysis . Overall, we conclude that EMD could participate in the pharmacokinetic drug-drug interactions and overcome the pharmacokinetic MDR phenomenon in cancer cells . Future in vivo confirmation of our results might potentially open the way for the establishment of safe and effective combination pharmacotherapy for many oncological patients .
70 The study was supported by the Czech Science Foundation (Project No. 20-20414Y), Grant Agency of Charles University (Project No. 1568218/C) and from the project of Specific Academic Research (SVV 260 414/2019). MIDOSTAURIN AS A NOVEL MODULATOR OF ABC TRANSPORTERS IN ACUTE MYELOID LEUKEMIA SUCHÁ, S .,1 ŠORF, A .,1 VÍŠEK, B .,2 ČEČKOVÁ, M.1 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 4th Department of Internal Medicine – Hematology, University Hospital in Hradec Králové, Czech Republic e-mail: suchas@faf .cuni .cz Midostaurin is a multi-kinase inhibitor recently approved for the treatment of patients diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome, who carry the FMS-like tyrosine kinase 3 (FLT3) mutation accountable for a poor prognosis . One of the most common mechanisms responsible for a failure of anticancer therapy is multidrug resistance (MDR) with ABC efflux transporters being one of important causative factors. Specifically ABCB1 and ABCG2 are confirmed to be related to resistant CD34+ leukemic blast cells . In this study we aimed to evaluate interaction of midostaurin with ABC transporters using resistant HL60 cell lines and ex vivo isolated peripheral blood monocyte cells (PBMC) from patients de novo diagnosed with AML . Gene expression of ABC transporters was established in AML patients’ PBMC employing droplet digital PCR . Our results showed that ABCB1 and ABCG2 were highly expressed in CD34+ cells while differences between FLT3+ and FLT3– patients fell short of statistical significance. Accumulation assays in resistant HL60-ABCB1 and HL60-ABCG2 cells revealed midostaurin as inhibitor of both transporters . When applied to PBMC of CD34+ patients, midostaurin significantly increased the intracellular levels of mitoxantrone, a conventional anticancer drug that is recognized as a substrate of ABC transporters . Since a noticeable correlation of ABCB1 and ABCG2 expression with the effect of midostaurin on accumulation of mitoxantrone in PBMC was found, we can assume that the expression of ABC transporters might affect therapeutic outcomes of combination therapy in AML . In conclusion, we show here the potential of midostaurin to contribute to overcoming the pharmacokinetic MDR in AML patients and thereby prevent the pharmacotherapy failure . The study was supported from the project of Specific Academic Research (SVV 260 414/ 2019) and PRIMUS 20/MED/010.
71 OVERCOMING DAUNORUBICIN RESISTANCE MEDIATED BY ALDO-KETO REDUCTASE 1B10 BUKUM, N ., MORELL, A ., NOVOTNÁ, E ., WSÓL, V . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: bukumn@faf .cuni .cz Tyrosine kinase inhibitors (TKi) have been found to have effective antitumor activity and have been approved or are under clinical trials .1 Recent studies show that some TKis are able to enhance the cytotoxicity of anthracyclines .2 Dasatinib is an orally administered, small-molecule inhibitor of multiple tyrosine kinases that blocks the function of the Bcr-Abl protein that signals cancer cells to multiply . Targeted therapy of dasatinib is used to treat most cases of chronic myeloid leukemia and acute lymphoblastic leukemia in patients .3 AKR1B10 has recently been found to be overexpressed in certain types of cancers, including hepatocellular carcinoma and lung cancer associated with tobacco smoking .4 Our combination strategy of the daunorubicin together with dasatinib may, therefore, minimize the adverse effects of each individual drug, enhance the effectiveness of the treatment and allow its prolonged continuity. Dasatinib exhibited a significant inhibitory effect on recombinant AKR1B10, with a half-maximal inhibitory concentration of 0.8 μM. Its inhibition constant Ki was found to be 0.4 μM, and the inhibition data best fitted a mixed-type mode with α = 1.7. In conclusion, based on our results, dasatinib may affect the therapeutic efficacy of anthracyclines by preventing anthracycline resistance and reducing their adverse effects . The study was supported by the Grant Agency of Charles University (Project No. 1006218) and from the project of Specific Academic Research (SVV 260 416/2019). References 1. ARORA, A ., SCHOLAR, E . M .: J . Pharmacol . Exp . Ther ., 315, 2015, 971–979 . 2. ZHAI, B ., SUN . X .: World J . Hepatol ., 5, 2013, 345–352 . 3. CONCHON, M ., FREITAS, C ., REGO, M . et al .: Rev . Bras . Hematol . Hemoter ., 33, 2011, 131–139 . 4. LIU, J ., WEN, G ., CAO, D .: Recent Pat . Anticancer Drug Discov ., 4, 2016, 246–253 . INHIBITION OF HUMAN ALDO KETO REDUCTASE (AKR1C3) BY OLAPARIB – A POSSIBLE REMEDY FOR DAUNORUBICIN RESISTANCE TAVARES, T . S .,1 HOFMAN, J .,2 MORELL, A . G .,1 WSÓL, V .1 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: silvatat@faf .cuni .cz
72 The chemotherapeutic application of daunorubicin has significant drawbacks due to drug resistance and related cardiotoxicity . Several members of aldo-keto reductase and short-chain dehydrogenases/reductases superfamilies are responsible for reductive metabolism of parent drug to its less potent metabolite daunorubicinol and belong thus to the most important daunorubicin resistance drivers . Olaparib is a poly (ADP-ribose) polymerase inhibitor used in the treatment of patients with ovarian cancer . In this work, we have aimed at describing possible interactions of olaparib with selected daunorubicin reductases and evaluate their possible utilization for overcoming daunorubicin resistance . Results of incubation experiments with recombinant carbonyl reductases (AKR1C3, AKR1B10, AKR1B1, AKR1A1, and CBR1) showed significant inhibition of AKR1C3, the most potent anthracycline reductase . High inhibitory potency (IC50 = 5 .913 µM) was subsequently confirmed in intact HCT116 cells overexpressing AKR1C3. Using proliferation XTT assay in the same cellular model we demonstrated the ability of olaparib to reverse enzyme-mediated daunorubicin resistance in a synergistic fashion . Currently, additional experiments focusing on the description of olaparib’s effect on expression of AKR1C3 gene in leukemic KG1α and hepatic HepG2 cells are being conducted. In conclusion, our results present olaparib as a potent AKR1C3 inhibitor able to effectively attenuate daunorubicin resistance at clinically relevant concentrations . Future in vivo studies would be helpful to support the rationality of our conclusions and possibly offer new therapeutic option for oncological patients . The study was supported by InoMed (Project No. CZ.02.1.01/0.0/0.0/18_069/0010046) co-funded by the European Union and from the project of Specific Academic Research (SVV 246 216/2019). NOVEL PHOTODYNAMICALLY ACTIVE HYDROPHILIC AND AMPHIPHILIC ANIONIC (AZA)PHTHALOCYANINE DERIVATIVES FOR TREATMENT OF TUMOROUS DISEASES HALAŠKOVÁ, M .,1 KOLLÁR, J .,2 ZIMČÍK, P.,2 MACHÁČEK, M.1 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: halaskma@faf .cuni .cz Photodynamic therapy is a clinically approved non-invasive treatment and subject of intense research for the eradication of solid tumors . Phthalocyanines (Pcs) proved to be very promising photosensitizers (PS) . Aim of this work is to evaluate the photodynamic activity of newly synthesized anionic water-soluble zinc(II) Pcs with sulfonyl or carboxyl substituents in in vitro conditions . Cytotoxicity experiments were performed mainly on human cervix carcinoma cell line HeLa using neutral red uptake assay . Localization of the compounds within the cell, uptake profiles of PSs to the cells and morphological changes after irradiation were also studied . The results of individual experiments have shown
73 high photodynamic activity after irradiation (phototoxicity; EC50) and exceptionally low inherent toxicity (toxicity in the absence of activating light; TC50) of all studied compounds . Phototoxicity was further evaluated on two other human tumor cell lines: MCF-7 (breast carcinoma) and HCT116 (colorectal carcinoma) . The most suitable properties were achieved with P44 (EC50 = 0.33 μM, TC50 ˃ 1000 μM) in the serum-containing medium. For all studied compounds, photodynamic effect resulted in significant morphological changes indicating ongoing cell death . It is worth noting that photodynamic activity of all studied compounds is negatively affected by the presence of serum (serum-free conditions resulted in up to 95-time increase in photoxicity) . Based on obtained results, selected compounds will be included in subsequent studies on 3D spheroid cultures as well as in the in vivo evaluation of their photodynamic efficiency on mouse tumor model. The study was supported by the Grant Agency of Charles University (Project No. 1620219), by the Czech Science Foundation (Project No. 19-14758Y) and from the project of Specific Academic Research (SVV 260 416/2019). PRECISION-CUT INTESTINAL SLICES FROM HUMAN TISSUE AS AN EX VIVO MODEL FOR ABCB1 TRANSPORTER INDUCTION MARTINEC, O .,1 BIEL, C .,2 ČERVENÝ, L.,1 VOKŘÁL, I.,1 De GRAAF, I . A . M .,3 OLINGA, P .2 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands 3 Department of Pharmacokinetics, Toxicology and Targeting, Groningen Research Institute of Pharmacy University of Groningen, Groningen, The Netherlands e-mail: martinon@faf .cuni .cz P-glycoprotein (ABCB1), an ATP-binding-cassette efflux transporter, limits intestinal absorption of its substrates and is a common site of drug-drug interactions (DDIs) . The drugs causing DDIs on this transporter can act as substrates, inhibitors and/or inductors . Therefore, the absorption of the compounds may be changed and can lead to inappropriate drug plasma levels . Current options for investigating the induction process are limited . For this purpose, we decided to evaluate and optimize human precision-cut intestinal slices (PCIS) to be suitable for long term induction studies . Three types of media were evaluated: 1) Williams’ Medium E (WME) as a standard medium used for PCIS; 2) two different organoid media (ORG and Vacy) with cooperation of Applied University of Utrecht . Incubations were performed with and without rifampicin, known inducer of the ABCB1, to validate the model for induction studies . During the evaluation, we collected samples after 24, 48, 72 hours . ATP/protein measurement was used as a viability marker, RT-PCR and immunohistochemical methods were used to study ABCB1 levels . Rhodamine 123 accumulation assay was used as a functional control of ABCB1 expression. In WME after 24 h rifampicin induced the efflux activity of the ABCB1 and increased level of the ABCB1 mRNA . With increasing incubation time,
80 2 Metal Metabolism Group, Department of Biochemistry, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, Great Britain The human zinc transporter ZnT8 is important for assembly of insulin hexamers of β-cells with zinc and for its storage. Its structure and function were modelled on the basis of the 3D structure of the E.coli zinc exporter YiiP .1 However, there are important differences in function as the YiiP protein exports an excess of zinc from cells, whereas ZnT8 exports zinc into subcellular vesicles when there is no apparent excess of zinc . There are two variants, one with tryptophan (W) and the other one with arginine (R) at position 325 . These variants have generated considerable interest as the R-variant is associated with a higher risk of developing type 2 diabetes .2 Since these mutations are at the apex of the C-terminal domain (CTD) towards the cytoplasm, it is not clear how they would affect zinc transport . We expressed the CTD of both variants of human ZnT8 and have begun structural and functional studies . In particular, we found that (i) the metal binding site of the human protein is different from that of E.coli protein, (ii) the human protein has a C-terminal extension with three cysteine residues that also bind zinc, (iii) there are small differences in stability between the two variants, and (iiii) nickel ions bind to the cytoplasmic domain of the zinc transporter ZnT8 . The study was supported by European Union ERASMUS+ Programme and the London Metallomics Facility (Project No. 202902/Z/16/Z) funded by Welcome Trust and from the project of Specific Academic Research (SVV 260 414/2019). References 1. LU, M ., FU, D .: Science, 317, 2007, 1746–1748 . 2. DAVIDSON, H . W ., WENZLAU, J . M ., O’BRIEN, R . M .: Trends Endocrinol . Metab ., 25, 2014, 415–424 . ISOLATED SILYMARIN FLAVONOLIGNANS AND THEIR ABILITY TO INTERACT WITH TRANSITION METALS AND PLATELETS TVRDÝ, V .,1 APPLOVÁ, L .,2 KARLÍČKOVÁ, J.,3 MACÁKOVÁ, K .,4 HRUBŠA, M .,1 VALENTOVÁ, K .,5 MLADĚNKA, P.1 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 3 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 4 Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 5 Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic e-mail: tvrdyvac@faf .cuni .cz Silymarin, a complex of flavonolignans extracted from fruits of Silybum marianum (L .) Gaertn ., is approved in the EU as a drug . It is also frequently used as a food supplement . Flavonolignans have a polyhydroxylated structure and are poorly absorbed . In addition,
81 if absorbed, they are rapidly conjugated. For this reason, parent flavonolignans rather remain in the gastrointestinal tract while their conjugates are the dominant forms in the systemic circulation . This study was focused on testing 1) the ability of optically pure flavonolignans to interact with transition metals and 2) if their sulphates can block platelet aggregation . Only 2,3-dehydrosilybin (racemate as well as both enantiomers – A and B) has shown moderate ability to chelate iron and copper . Silybin A, silybin B and silychristin were less potent or inactive chelators . Silychristin was found to be the most potent iron and copper reductant. This study also discovered a low potential of sulphates of flavonolignans to block aggregation in whole human blood. Parent flavonolignans were tested for comparison, but their potential was low as well, since it was observed only at concentrations ≥ 120 µM. Mechanistic study showed that their mild activity was likely mediated by antagonism at thromboxane receptors. Although some silymarin flavonolignans blocked recombinant cyclooxygenase 1, their effect on this platelet enzyme in whole human blood was negligible . In conclusion, it is highly improbable that this activity would be manifested in vivo due to relatively high concentrations needed to evoke this effect . On the contrary, oral administration of silymarin may influence the kinetics of copper and iron in the GIT. The study was supported from the project of Specific Academic Research (SVV 260 414/ 2019) and by the Czech Science Foundation (Project No. 18-00121S). PLATELET AGGREGATION IN HEALTHY POPULATION: PRELIMINARY DATA ON AGE-DEPENDENT DIFFERENCES HRUBŠA, M .,1 MACÁKOVÁ, K .,2 KARLÍČKOVÁ, J.,3 CARAZO, A .,1 PARVIN, S .,3 MLADĚNKA, P.1 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmacognosy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 3 Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: hrubsam@faf .cuni .cz Primary haemostasis is a process which contributes to preserving the integrity of the cardiovascular system . It is enabled by platelets, anucleate cells circulating in the bloodstream which aggregate in response to certain stimuli . Altered platelet aggregation can severely affect circulation and lead to many cardiovascular diseases . Dysregulation of this process can result in life-threatening events, such as stroke and acute myocardial infarction, which are the most prevalent causes of mortality in developed countries .1 An important factor influencing platelet aggregation is the age. There is, however, little data concerning the significance of this factor in experiments using whole blood. Therefore, we have performed a screening of 11 healthy individuals aged 21–58 of both sexes using Multiplate analyzer which utilizes whole blood and allows examination of various aggregation inducers . A response to several aggregation inducers and standard drugs affecting these inducers were evaluated . We have observed a fairly high interindividual variance with all
82 inducers and used drugs . Preliminary data showed a decrease in response to adenosine diphosphate (ADP) with increasing age . Younger individuals also appeared to be more responsive to acetylsalicylic acid (ASA) . Authors are aware that these are initial data and a higher sample size is required to reach more solid conclusion . The study was supported by Research programme Development and Study of Drugs (Progres Q42) and from the project of Specific Academic Research (SVV 260 414/2019). References 1. ALBERS, G . W ., AMARENCO, P ., EASTON, J . D . et al .: Chest 133, 2008, 630S–669S . SOLUBLE ENDOGLIN DOES NOT AFFECT CHOLESTEROL AND BILE ACIDS METABOLISM IN NASH MOUSE MODEL IGREJA SÁ, I . C .,1 PRAŠNICKÁ, A .,1 LAŠTŮVKOVÁ, H.,2 HROCH, M .,3 HYŠPLER, R .,4 DOLEŽELOVÁ, E.,1 MIČUDA, S.,2 NACHTIGAL, P .1 1 Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Pharmacology, Faculty of Medicine in Hradec Králové, Charles University, Czech Republic 3 Department of Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Czech Republic 4 Department of Research and Development, University Hospital in Hradec Králové, Czech Republic e-mail: igrejasi@faf .cuni .cz Plasma concentrations of soluble endoglin (sEng) are increased in cardiovascular and metabolic diseases associated with hypercholesterolemia, which affect liver functions . Previously, we showed that high sEng plasma levels affect cholesterol and bile acids (BA) homeostasis based on complex liver and intestinal effects . Therefore, the aim of the present study was to investigate effects of high levels of sEng on cholesterol and BA metabolism in liver upon induction of non-alcoholic steatohepatitis (NASH) . Three-months-old wild-type and transgenic male mice overexpressing human sEng were fed for 6 months with high fat diet (HFD) enriched with cholesterol and fructose or chow diet and underwent in vivo study with plasma and bile collection . Plasma biochemical analysis, LC/MS of plasma BA and histology were performed . Expression of enzymes and transporters in liver were assessed by qRT-PCR and Western blot. HFD significantly increased body and liver weight, and analysis of liver tissue confirmed NASH by presence of steatosis, fibrosis, oxidative stress, increased activity of ALP and ALT, and hypercholesterolemia in both HFD groups . However, high sEng levels did not significantly modulate development of diet-induced NASH and associated changes in cholesterol and BA metabolism in mice . The study was supported by the Ministry of Health of the Czech Republic (Project. No. 150/52/75201), by the Grant Agency of Charles University (Project No. 1166119) and from the project of Specific Academic Research (SVV 260 414/2019).
83 ENDOGLIN MODULATES ADHESION AND TRANSMIGRATION OF MONOCYTES IN OXYSTEROL INDUCED ENDOTHELIAL DYSFUNCTION VICEN, M .,1 HAVELEK, R .,2 MACHÁČEK, M.,3 TRIPSKÁ, K .,1 VITVEROVÁ, B .,1 NACHTIGAL, P .1 1 Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Czech Republic 3 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: vicenm@faf .cuni .cz Endoglin (CD105, TGF-βRIII receptor) is essential for proper function of endothelium, but participates also in inflammatory infiltration of monocytes. We hypothesized that endoglin play crucial role in monocyte adhesion and transmigration via endothelial cells when exposed to oxysterol simulating oxidized LDL effects in atherogenesis . HAECs were exposed to 7K (5, 10 ug/mL) for 12 hours . Gene expression (endoglin, KLF6, RELA (NF-κB p65), NR1H3 (LXR), ICAM-1) was evaluated using qRT-PCR. Protein levels of endoglin, ICAM-1 and P/E-selectins were evaluated by flow cytometry analysis. Protein levels and localization of RELA, eNOS, p-eNOS was evaluated using confocal fluorescent microscopy . Gene expression and protein levels of endoglin, eNOS, p-eNOS and cell adhesion molecules (ICAM-1, E/P-selectin) as well as transcription genes regulating endoglin expression were significantly increased after premedication with 7K compared to non-treated cells . Inhibition of transcription factors (KLF6, RELA, NR1H3 resulted in inhibition of 7K induced increase of endoglin expression . 7K was able to increase adhesion and transmigration of THP-1 monocytes, through endothelial cells monolayer . Silencing of endoglin in HAECs inhibited adhesion and transmigration of THP-1 monocytes . In this study, we demonstrated that 7K is able to induce inflammation and increase endoglin expression in endothelial cells via activation of KLF6, RELA and NR1H3 transcription genes . Moreover, we showed that 7K induced adhesion and transmigration of monocytes through endothelial monolayer depends on the expression of endoglin suggesting that endoglin might play crucial role in cholesterol (oxysterol) induced endothelial dysfunction . This study was supported by project EFSA-CDN (No. CZ.02.1.01/0.0/0.0/16_019 /0000841) co-funded by ERDF, by the Grant agency of Charles University (Project. No. 1216217), by the Czech health research council (Project No. 17-31754A), and from the project of Specific Academic Research (SVV 260 414/2019). ENDOGLIN EXPRESSION, SIGNALIZATION AND FUNCTION IN IFLAMMATION INDUCED ENDOTHELIAL DYSFUNCTION TRIPSKÁ, K .,1 VICEN, M .,1 HAVELEK, R .,2 NACHTIGAL, P .1 1 Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic
84 2 Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Czech Republic e-mail: tripskak@faf .cuni .cz Endoglin (Eng) expression is linked to regulation of endothelial nitric oxide synthase (eNOS) in endothelial cells resulting in proper function of endothelium . On the other hand, it was proposed that Eng also participates in inflammatory infiltration of leukocytes through endothelium and thus plays negative role in endothelial dysfunction . We aimed at evaluating Eng expression, signalization and function related to endothelial dysfunction induced by proinflammatory tumour necrosis factor alpha (TNF-α) in human aortic endothelial cells (HAECs). HAECs were treated with 10 ng mL− TNF-α for 12 h. The mRNA expression of Eng, eNOS, adhesion molecules (ICAM-1, VCAM-1) and transcription factors (KLF6, NF-κB, p65 and LXR-α) was measured with qRT-PCR. Protein levels of membrane Eng, ICAM-1, VCAM1, P/E-selectin and MMP-14 were measured by flow cytometry and soluble endoglin (sEng) levels by ELISA . Transmigration assay was performed using Nunc cell culture inserts. TNF-α treatment decreased mRNA expression and protein levels of Eng and eNOS . The mRNA expression and protein levels of cell adhesion molecules and MMP-14 were significantly increased as well as sEng levels. Interestingly, meanwhile mRNA expression of KLF6 and NF-κB were increased; mRNA expression of LXR-α was decreased. TNF-α induced inflammation led to increased adhesion but not transmigration of monocytes through endothelial cells. We demonstrated that inflammation decreases endoglin expression, increases adhesion but does not affect transmigration of monocytes through aortic endothelial cells . Reduced expression of Eng and increased levels of sEng (that inhibits effects of membrane endoglin) might be responsible for no change in transmigration of monocytes under inflammatory conditions. We propose that Eng participates on the regulation of endothelial dysfunction during inflammation, but to which extent must be further investigated . The study was supported by EFSA-CDN (No. CZ.02.1.01/0.0/0.0/16_019/0000841) cofunded by ERDF, by the Grant Agency of Charles University (Project. No. 1216217) and from the project of Specific Academic Research (SVV 260 414/2019). THE TOXICITY OF ALANTOLACTONE AND GERMACRONE TOWARDS DIFFERENTIATED HepaRG CELLS AND THEIR INFLUENCE ON CHOLESTEROL METABOLISM ZÁRYBNICKÝ, T ., MATOUŠKOVÁ, P ., BOUŠOVÁ, I . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: zarybnto@faf .cuni .cz Sesquiterpenes alantolactone (ALA) and germacrone (GER) are naturally occurring molecules that are studied as potential anti-cancer agents . ALA is one of the major sesquiterpene lactone compounds isolated from the roots of Inula helenium (Asteraceae) . GER
85 is a main bioactive constituent found in Zedoary oil extracted from Curcuma zedoaria Roscoe (Zingiberaceae) . Both of these plants were used in traditional medicine historically . Using the differentiated HepaRG (dHepaRG) cells, a human hepatocyte-like model, we wanted to compare the toxicity towards dHepaRG cells in comparison with results published on highly proliferative cancer cell lines after ALA and GER treatment . Furthermore, a bioinformatic tool BATMAN-TCM1 was searched for new molecular targets of tested sesquiterpenes . Analysis of their common targets led us to studying their effects on cholesterol metabolism and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a major regulatory enzyme in mevalonate pathway . HMGCR protein and mRNA expression were studied at multiple time points, concentrations, as well as single and multiple dose . HMGCR protein expression has shown inhibition after ALA and GER treatment, but mostly at the highest concentrations tested, equal to respective half-maximal inhibitory concentration of cell viability . The mRNA changes were much more variable and time and concentration dependent . The cholesterol level in dHepaRG cells was measured by Amplex Red Cholesterol Assay Kit in a multiple dose experiment in comparison to the model inhibitor lovastatin . The study was supported by the Czech Science Foundation (Project No. 18-09946S) and from the project of Specific Academic Research (SVV 260 416/2019). References 1. Liu, Z ., Guo, F ., Wang, Y . et al.: Sci . Rep . 2016, 6, art . 21146 . THE UDP-GLYCOSYLTRANSFERASES IN HAEMONCHUS CONTORTUS AND THE METABOLISM OF ANTHELMINTICS DIMUNOVÁ, D ., RAISOVÁ STUCHLÍKOVÁ, L ., MATOUŠKOVÁ, P . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: dimunovd@faf .cuni .cz UDP-glycosyltransferases (UGTs) are important enzymes in the metabolism of xenobiotics and eobiotics . Glycosylation is often the most important conjugation reaction catalyzed by these enzymes in drug metabolism . This reaction results in enhanced elimination of the drug from the organism . Increased expression of UGTs can cause reduction of pharmacotherapy efficiency and development of resistance to drugs. Our model organism is Haemonchus contortus, a gastrointestinal parasite of small ruminants that have a great ability to develop resistance to anthelmintic drugs . Our previous metabolism study showed that albendazole, ricobendazole and flubendazole underwent several glycosylation steps. Differences of glycosides quantities between resistant and sensitive strains confirmed the connection between anthelmintics metabolism and resistance .1 In addition, some enzymes from the UGT superfamily, e.g. UGT368B2, are significantly more expressed in adult H. contortus of resistant strains than sensitive strains .2 For functional characterization, the UGT368B2 was expressed in baculovirus-infected insect cells . However, the preliminary
86 results show that UGT368B2 cannot metabolize benzimidazole anthelmintics but steroids . This particular UGT has different role in the organism than biotransformation of xenobiotics (e.g . benzimidazoles) . Revealing the features of UGTs from H. contortus (e.g. affinity to hexose or to different substrate) could contribute to a more detailed understanding of the reaction’s mechanism catalyzed by these enzymes and their role in helminths . This study was supported by the Czech Science Foundation (Project No. 17-11954Y), by Charles University (PRIMUS/17/SCI/04) and from the project of Specific Academic Research (SVV 260 416/2019). References 1. STUCHLÍKOVÁ, L. R., MATOUŠKOVÁ, P., VOKŘÁL, I. et al .: Int . J . Parasitol . Drugs Drug Resist ., 8, 2018, 50–58 . 2. MATOUŠKOVÁ, P ., LECOVÁ, L ., LAING, R . et al .: Int . J . Parasitol . Drugs Drug Resist . 8, 2018, 420–429 . PROFILING MicroRNA EXPRESSION IN SUSCEPTIBLE AND RESISTANT STRAINS OF HAEMONCHUS CONTORTUS USING SMALL RNA SEQUENCING NGUYEN, L . T ., MATOUŠKOVÁ, P ., SKÁLOVÁ, L . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: nguyenli@faf .cuni .cz The widespread development of anthelmintic resistance (AR) in Haemonchus contortus compromises treatment of helminthosis caused by this economically important parasite of small ruminants . The molecular mechanisms of AR are not fully elucidated . In our study, we focus on microRNAs (miRNAs) which are a class of small non-coding RNAs . MiRNAs play important role in post-transcriptional regulation of gene expression and their dysregulation has been linked to a range of different pathologies . A comprehensive understanding of the functions of miRNAs in AR might help us to develop better strategies to the sustainable parasite control . For this reason, we undertook the small RNA sequencing of H. contortus isolates with various level of resistance to anthelmintics, namely the susceptible strain, the benzimidazole resistant strain and the multi-drug resistant strain . Differential expression analysis revealed significantly upor downregulated miRNAs in adults of resistant strains in comparison to sensitive ones . Since cytochromes P450, UDPglycosyltransferases and P-glycoproteins were reported to play role in drug resistance,1 we investigated them as the putative targets of differentially expressed miRNAs using RNAhybrid software. Moreover, from the sequencing data, 207 sequences were defined as potential novel miRNAs using miRDeep2 program . The study was supported by Charles University (PRIMUS/17/SCI0/4) and from the project of Specific Academic Research (SVV 260 416/2019).
87 References 1. MATOUŠKOVÁ, P., VOKŘÁL, I., LAMKA, J. et al .: Trends Parasitol ., 32, 2016, 481–491 . METABOLIC PATHWAYS OF NEW POTENTIAL ANTHELMINTICS IN HAEMONCHUS CONTORTUS AND ITS HOST ZAJÍČKOVÁ, M.,1 NAVRÁTILOVÁ, M .,1 NGUYEN, L . T .,1 PRCHAL, L .,2 STUCHLÍKOVÁ, R . L .,1 KELLEROVÁ, P .,1 SKÁLOVÁ, L .1 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Biomedical Research Centre, University Hospital in Hradec Králové, Czech Republic e-mail: zajickm@faf .cuni .cz Haemonchus contortus is one of the most important parasitic nematodes of small ruminants with worldwide distribution causing significant loses to many farmers. Anthelmintic drugs still represent the main strategy to control burdens of H. contortus . Unfortunately, widespread resistance to available anthelmintics makes treatment difficult. Therefore, there is a global need for new and effective anthelmintic drugs . Two newly synthetized compounds HBK4 and BLK127 as well as already registered antidepressant drug sertraline are promising candidates for new anthelmintics . It is known that drug resistance is associated with accelerated drug metabolism and for this reason we would like to compare biotransformation of HBK4, BLK127 and sertraline in drug-resistant and drug-sensitive strains of H. contortus. In addition, we will also monitor biotransformation and hepatotoxicity of these compounds in ovine liver . The study was supported by the Charles University Grant Agency (Project No. 1568519) and from the project of Specific Academic Research (SVV 260 416/2019). CIRCULATION OF ANTHELMINTICS IN THE ENVIRONMENT NAVRÁTILOVÁ, M ., STUCHLÍKOVÁ RAISOVÁ, L ., SKÁLOVÁ, L . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: navratimart@faf .cuni .cz Several ways can cause drug resistance in sheep breeding . Our project monitors the intake of a residual amount of the albendazole (ABZ) and its transformation products (TPs) during grazing of sheep . Our preceding studies showed the ability of plants to uptake and metabolize anthelmintics such as benzimidazole, macrocyclic lactones and amino-acetonitrile derivatives in six plant species . Plant derived metabolites can be considered as deactivation products, but some of them show even higher anthelmintic effectiveness than the parent compound . Moreover, a lot of anthelmintics metabolites (especially glycosides) can be converted back
88 to parent compound through enzymatic or acidic hydrolysis in the gastrointestinal tract of grazing animals . In the case of infected animals, nematodes thus might be exposed to very low doses of anthelmintics and this phenomenon could help to increase the anthelmintic resistance . This project simulates such a situation and monitors the occurrence of residues of ABZ and TPs in biological samples collected from ten domestic sheep (Ovis aries) . In the pilot study naive sheep (without nematodes) were used . Two species of meadow plants Medicago sativa and Trifolium pratense, common plants on pastures, were chosen . An experimental field area with these plants was fertilized by excrements from ABZ treated sheep (different flock of sheep) in spring 2019. ABZ and TPs have been found in the fertilized plants and in related soil too, after two months from fertilization . Furthermore, these plants were administered to the sheep for ten days and during that time samples of abomasum content, faeces, and plasma were collected in different time intervals . ABZ and the main TPs, ABZ-sulfone, and ABZ-sulfoxide, were detected in all samples . UHPLC-MS/MS was used for qualitative and quantitative analyses . The study was supported by the Czech Science Foundation (Project No. 18-07724S), and from the projects of Specific Academic Research (SVV 260 416/2019 and 260 412/2019). EFFECT OF ANTHELMINTIC RESIDUES ON TRANSCRIPTION LEVEL OF BIOTRANSFORMATION ENZYMES KELLEROVÁ, P., MATOUŠKOVÁ, P., NAVRÁTILOVÁ, M., ŠTĚRBOVÁ, K., STUCHLÍKOVÁ RAISOVÁ, L ., SKÁLOVÁ, L . Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: voborilp@faf .cuni .cz Anthelmintics, the only effective treatment of devastating infection diseases of animals caused by parasitic helminths, have been widely and heavily distributed all over the world . In the agriculture, the most used classes of anthelmintics are benzimidazoles, macrocyclic lactones, imidazothiazoles and amino-acetonitrile derivatives . Parasitic helminths, especially nematodes, have developed resistance to all of them . In front of all parasites stands Haemonchus contortus, as the quickest nematode in resistance development . This hematophagous parasite living in sheep abomasum and causing enormous losses in animals’ production, is well studied for mechanisms of resistance development . H. contortus prosper with very effective detoxification system via biotransformation enzymes and can relatively quickly react to constant usage of anthelmintic drugs . In our current studies we observed that even very low – sublethal concentrations of anthelmintics, that may be preserved in environment, can cause up and down regulation of biotransformation enzymes on transcription levels . Furthermore, the analysis of albendazole metabolites showed enhanced biotransformation after preincubation in sublethal concentrations of albendazole .
89 The study was supported by the Czech Science Foundation (Project No. 18-07724S), by Charles University projects (PRIMUS/17/SCI/04 and UNCE/18/SCI/012) and from the project of Specific Academic Research (SVV 260 416/2019). PRELIMINARY RESULTS OF ANTI-INFLAMMATORY ACTIVITY IN SELECTED FERN SPECIES PAVIČIĆ, A.,1,2 SZOTÁKOVÁ, B .,1 LANGHANSOVÁ, L .2 1 Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Institute of Experimental Botany, Czech Academy of Sciences, Prague, Czech Republic e-mail: pavicia@faf .cuni .cz Ferns are a potential source of bioactive phytochemicals and based on our previous research, we tested selected species for the anti-inflammatory activity. The crude methanol extracts were screened at a concentration of 10 µg mL−1 for inhibitory activity against pro-inflammatory enzymes cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) . The COX-1 inhibitors have been reported as effective in the prevention of neuroinflammatory or cardiovascular diseases1 and several tumours .2 COX-2 is considered as a key pro-inflammatory enzyme, over-expressed in most sites of inflammation and responsible for the characteristic inflammatory symptoms (redness, pain, edema, fever and loss of functions) .2 5-LOX inhibitors have been reported to play a role in the prevention of tumours, allergic disorders and asthma .2 Our results revealed that the most fern species have potential in selective COX-1 inhibitory activity. Significant inhibition of COX-1 was measured in Dryopteris cambrensis (92 .46%) and Athyrium distentifolium (91 .18%) . Only a few fern species revealed moderate inhibition to COX-2 (Dryopteris expansa and Dryopteris aemula). Significant 5-LOX inhibitory activity was measured in Onoclea sensibilis (71 .06%) and Dryopteris caucasica (68 .32%) . Our results reveal several European ferns as a potential source of anti-inflammatory compounds. The study was supported from the project of Specific Academic Research (SVV 260 416/ 2019). References 1. PERRONE, M . G ., SCILIMATI, A ., SIMONE, L . et al.: Curr . Med . Chem ., 17, 2010, 3769–3805 . 2. CHARLIER, C ., MICHAUX, C .: Eur . J . Med . Chem ., 38, 2003 ., 645–659 . DETERMINATION OF TOXICITY OF BRAF INHIBITORS IN VITRO MAIXNEROVÁ, J ., HYRŠOVÁ, L ., TREJTNAR, F . Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic e-mail: maixj6a1@faf .cuni .cz
96 POTENTIALLY INAPPROPRIATE PRESCRIBING IN OLDER ADULTS IN CENTRAL AND EASTERN EUROPE AND ASSOCIATED RISK FACTORS – PRELIMINARY RESULTS OF TWO SYSTEMATIC LITERATURE REVIEWS BRKIĆ, J.,1 KUMMER I .,1 POULÍKOVÁ K .,1 FIALOVÁ, D .1,2 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Geriatrics and Gerontology, 1st Faculty of Medicine, Charles University, Czech Republic e-mail: jovanabrkic37@gmail .com Potentially inappropriate prescribing (PIP) in older adults is highly prevalent in Europe and risk factors (RFs) of PIP have been described by several studies .1,2,3,4 The aim of our study was to conduct two systematic literature reviews determining 1) the prevalence of PIP in Central and Eastern European Countries (CEECs) participating in the Horizon 2020 EUROAGEISM FIP7 project (Albania, Bulgaria, Croatia (HR), Czech Republic (CZ), Estonia, Lithuania, Serbia and Slovakia) and 2) to document social, economic and healthcare-provision related RFs of PIP . We searched in SCOPUS and MEDLINE databases (papers published by 2019) and included only primary studies published in English as full-texts . Of 146 and 2740 studies in primary literature search, 14 and 69 were selected using pre-defined criteria, respectively. The prevalence of PIP ranged from 15 .7% (CZ) to 68 .8% (HR) . In total, 72 RFs were analyzed . Among economic and social RFs “patients’ low income” reached the highest odds ratio (OR = 2 .48 (1 .82–3 .39), p < 0 .001) and “not having a partner” (OR = 1 .50 (1 .10–2 .10), p < 0 .05) . Among care-related RFs these were ”residency in long-term care institutions” and “admission to acute care” (OR = 2 .29 (2 .25–2 .33), p < 0 .001) and (OR = 3 .35 (2 .43–4 .62), p < 0 .05), respectively), as well as “care provided by nongeriatricians” (OR = 5 .54 (1 .62–18 .89), p = 0 .01) or “by more prescribers” (OR = 1 .40 (1 .29–1 .51), p < 0 .001) . The results create an important base for the started EUROAGEISM Horizon 2020 FIP7 project, assessing PIP in older adults in 10 European and other countries . This project supports the development of geriatric clinical pharmacy in different settings of care . The study was supported by the EUROAGEISM H2020 project, FIP7 program (ITNMSCF No764632), INOMED (Project No. CZ.02.1.01/0.0/0.0/ 18069/0010046) and from the project of Specific Academic Research (SVV 260 417/2019) and Research programme Development and Study of Drugs (Progres Q42) at the Department of Social and Clinical Pharmacy, Charles University – Scientific group “Ageing and Changes in the Therapeutic Value of Drugs in the AgeD” chaired by Assoc. Prof. Daniela Fialová, PharmDr., Ph.D. References 1. MORIN, L ., LAROCHE, M ., TEXIER, G . et al: J . Am . Med . Dir . Assoc ., 17, 2016, 862 .e1–862 .e9 . 2. TOMMELEIN, E., MEHUYS, E., PETROVIĆ, M. et al .: Eur. J. Clin. Pharmacol., 71, 2015, 1415‒1427. 3. SANTOS, A ., SILVA, D ., ALVES-CONCEICAO, V . et al.: J. Clin. Pharm. Ther., 40, 2015, 167‒176. 4. FIALOVÁ, D., LAFFON, B., MARINKOVIĆ, V. et al.: Eur. J. Clin. Pharmacol., 75, 2019, 451‒466.
97 INITIAL EXPERIMENT WITH THE LEFT ATRIAL APPENDAGE OCCLUSION WITH THE AMPLATZER AMULETTM KOBLIŠKOVÁ, Z., HARAMIOVÁ, Z., TESAŘ, T. Department of Organization and Management of Pharmacy, Faculty of Pharmacy in Bratislava, Comenius University, Slovak Republic e-mail: kobliskova@fpharm .uniba .sk Atrial fibrillation is the most common rhythm disorder in clinical practice. Stroke is one of the most severe thromboembolic disorders associated with atrial fibrillation.1 The CHA2DS2VASc scoring system assess the risk of stroke in patients with atrial fibrillation.2 Oral anticoagulation is recommended in atrial fibrillation patients at moderate to high risk of stroke and thromboembolism .3 The HAS-BLED scoring system evaluates the risk of bleeding in patients receiving anticoagulation therapy .4 Percutaneous left atrial appendage occlusion provides a treatment alternative for patients with atrial fibrillation at high risk of stroke in whom anticoagulation therapy is associated with high bleeding risk .5 Goals of our observational, retrospective, multi-centre, case-series study were: 1) describe the initial experience with the Amplatzer AmuletTM left atrium appendage occlusion in Slovakia; 2) evaluate the effectiveness and safety of the procedure in stroke prevention in patients with atrial fibrillation. We analyzed 93 patients with atrial fibrillation at high risk of stroke undergoing left atrial appendage occlusion from June 2015 to October 2018 . The mean patient age was 70 .9 ± 8 .6 years . The mean CHA2DS2VASc and HAS-BLED score was 4 .4 ± 4 .4 and 3 .5 ± 0 .9, respectively . The left atrial appendage was successfully closed in 98 .9% (92) of patients . The mean total procedural time was 110 .4 ± 54 .5 min . Periprocedural complications were observed in 5 .4% (5) of patients . Three months after the procedure, small postprocedural leaks up to 3 mm were observed in 89 .2% (83) of patients . In this initial experience study, left atrial appendage occlusion was shown to be an effective and safe alternative to anticoagulation therapy in patients with atrial fibrillation at high risk of stroke for whom anticoagulation therapy is associated with high bleeding risk . The study was supported by Faculty of Pharmacy, Comenius University, Bratislava. References 1. KIRCHOF, P ., BENUSSI, S ., AHLSSON, A . et al.: Eur . Heart J ., 37, 2013, 2893–2962 . 2. OLESEN, J . B ., LIP, G . Y . H ., HANSEN, P . R . et al.: BMJ, 342, 2011, d124 . 3. PISTERS, R ., LANE, D . A ., NIEUWLAAT, C . B . et al.: Chest .,138, 2010, 1193–1100 . 4. APOSTOLAKIS, S ., GUO, Y ., BULLER, H . et al.: J. Am. Coll. Cardiology, 60, 2012, 861‒870. 5. KIRCHOF, P ., BENUSSI, S ., AHLSSON, A . et al.: Eur . Heart J ., 37, 2013, 2897–2899 .
98 IMPACT OF A COMPUTERIZED PROTOCOL ON THROMBOPROPHYLAXIS USE IN GENERAL SURGERY: STUDY DESIGN GAMBACORTA, J .,1,2 HORÁK, P .,3,4 VLČEK, J.1,5 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 University Hospital in Motol, Prague, Czech Republic 3 First Faculty of Medicine, Prague, Charles University, Czech Republic 4 Hospital Na Bulovce, Prague, Czech Republic 5 University Hospital in Hradec Králové, Czech Republic e-mail: gambacorta@faf .cuni .cz A large proportion of hospitalized patients are at risk for venous thromboembolism (VTE), but there is a low rate of appropriate prophylaxis in clinical practice .1 According to the American College of Chest Physicians (ACCP) guidelines, all hospitalized patients admitted in a surgical ward should be assessed for the risk of VTE .2 Various strategies to improve the use of thromboprophylaxis have been recommended including the computerized systems .3 To our knowledge, there is no protocol standardization or any other active strategy leading to the appropriate thromboprophylaxis in surgical patients described in the Czech literature . In the past, there was also a lack of standardization in prescribing thromboprophylaxis to the surgical patients in our hospital . Therefore we decided to create and implement the VTE prophylaxis computerized protocol (VTEP-CP) as a decision support tool for physicians . After the protocol has been routinely used by physicians for several years, we decided to analyze the rate of compliance with the guidelines on VTE prophylaxis and to determine the incidence of VTE and major bleeding before and after implementation of VTEP-CP . The list of patients admitted in the surgical ward that underwent elective general surgery was provided through the hospital information system for a period of eleven months in 2012 (group A = before VTEP-CP implementation) and eleven months in 2014 (group B = before VTEP-CP implementation) . We were able to obtain some of the required data of the patients in electronic form directly from the hospital information system and thus create a baseline database that we must now complete with the data from the patient medical records . Patients in group A are scored by the VTEP-CP using the data from the hospital admission form . For group B, the data from the VTEP-CP are used and also medical records are reviewed . The risk score, the dose and type of LMWH recommended by the VTEP-CP, the dose and type of LMWH administered to the patient and usage of mechanical prophylaxis is registered for both groups . We also review the documentation of patients for the diagnosis of VTE and signs or diagnosis of major bleeding . In the presentation, we will discuss the study design, its limitations, and the possible benefit of the research in the field of clinical pharmacy. The study was supported by Research programme Development and Study of Drugs (Progres Q42) and from the project of Specific Academic Research (SVV 260 417/2019) .
99 References 1. COHEN, A . T ., TAPSON, V . F ., BERGMANN, J . F . et al .: Lancet, 371, 2008, 387‒394. 2. GOULD, M . K ., GARCIA, D . A ., WREN, S . M . et al .: Chest, 141, 2012, e227S‒e277S. 3. KUCHER, N ., KOO, S ., QUIROZ, R . et al.: N. Engl. J. Med., 74, 2005, 969‒977. NEUTROPHIL-TO-LYMPHOCYTE RATIO AND PROGNOSTIC INFLAMMATORY AND NUTRITIONAL INDEX AS THE PREDICTORS OF POSTOPERATIVE INFECTION AFTER KNEE OR HIP ARTHROPLASTY DOMECKÝ, P .,1 PÁTKOVÁ, A .,1 KUČERA, T.,2 PATEROVÁ, P .,3 ŠPONER, P .,2 MALÝ, J .1 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Orthopaedics, University Hospital in Hradec Králové, Czech Republic 3 Department of Clinical Microbiology, University Hospital in Hradec Králové, Czech Republic e-mail: domeckyp@faf .cuni .cz Surgical site infection (SSI) is a potential complication of all surgical procedures and also the second most common type of nosocomial infection . The very presence of SSI leads to an increase in mortality . In patients with developed infection who underwent a surgical procedure, there is double mortality compared to non-infected patients . SSI prevalence may be reduced by various preoperative and postoperative measures . One of the ways in which SSI is affected is antibiotic prophylaxis (AP) . It is desirable to adjust AP length for arthroplasty, according to individual SSI risk estimated by appropriate processes . The aim of this study is to stratify patients based on the risk of postoperative infection and to verify the findings in clinical practice on the basis of examinations focusing mainly on laboratory tests, especially neutrophil-to-lymphocyte ratio (NLR) and prognostic inflammatory and nutritional index (PINI). NLR is an easily verifiable, easy, broadly robust, and appropriate laboratory test . Neutrophil levels in the blood are increased due to cytokines, while lymphocyte counts are reduced by surgical trauma . The increase occurs within 2 days after surgery and the return to physiological values takes place in a matter of days . It depends on the nutritional status of the patient, therefore its use in combination with PINI seems appropriate . These properties have been demonstrated in the diagnosis of cardiovascular diseases . In 2020, we plan to perform a prospective interventional study with an approximate number of 300 patients . In addition to the systematic literature review, we will collect patient and surgical procedure data before, during and after surgery . The usability of NLR and PINI will be evaluated with the postoperative complication analysis . Complications will be monitored 28–35 days after the surgery . Regarding these results, the interventions will be arranged to optimize and individualize the use of AP . The study was supported from the project of Specific Academic Research (SVV 260 417/ 2019).
100 AVAILABILITY OF INFORMATION ON LOWER GERIATRIC DOSING OF POTENTIALLY INAPPROPRIATE MEDICATIONS (PIMS) IN NATIONAL DRUG FORMULARIES AND SUMMARY OF PRODUCT CHARACTERISTICS (SPCS) APOSTOLI, P .,1 MANFREDI, R .,2 GREŠÁKOVÁ, S .,1 BRKIĆ, J.,1 FIALOVÁ, D .1,3 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Faculty of Pharmacy in Bologna, Alma Mater Studiorum University of Bologna, Italy 3 Department of Geriatrics and Gerontology, First Faculty of Medicine in Prague, Charles University, Czech Republic e-mail: apostolpr@faf .cuni .cz One of the main public health concerns nowadays is the appropriate prescribing for older patients .1 The concept of potentially inappropriate medications in the aged (so called PIMs ‒medications having higher risks than benefits in older adults or potentially ineffective in the aged) was defined to better ensure the medication safety in older adults.2 The aim of our study was to clarify for how many PIMs (potentially inappropriate medications) geriatric dosing is stated in official drug information sources. Information on recommended single and daily geriatric dose for all PIMs (364) identified by expert panels in different explicit criteria was searched between March and May 2019 using AIFA website (Agenzia Italiana del Farmaco), BNF (British National Formulary) and US PDR (US Prescriber’s Drug Reference) . The same single dose for middle age and geriatric population was found in all SPCs for 234 (64.3%) PIMs, lower single dose for geriatric patients was clarified for 61 (16 .8%) PIMs in all SPCs and for 19 (5 .2%) in some SPCs . For daily geriatric dosing, 3 above stated results were 212 (58 .2%), 69 (19 .0%) and 33 (9 .1%), respectively . For 50 (13.7%) PIMs no information was found about specific approaches in geriatrics and for 6 .9% PIMs only ‘‘general warnings to be more cautious in older adults’’ were available . Recommendation of geriatric dosing was stated in less than 30% of SPCs of PIMs . In the majority of SPCs, the geriatric dose was not clarified. Therefore, new evidence on appropriate geriatric dosing from clinical and/or observational studies is needed to clarify specific aspects of the use of PIMs (indications, single and daily dosing) in order to better ensure higher safety of medications in geriatric patients . The study was supported by INOMED (Project No. CZ.02.1.01/0.0/0.0/ 18069/0010046), EU COST Action IS1402, EUROAGEISM H2020 project (ITN-MSCFNo764632), from the project of Specific Academic Research (SVV 260 417) and Research programme Development and Study of Drugs (Progres Q42) at the Department of Social and Clinical Pharmacy, Charles University – Scientific group “Ageing and Changes in the Therapeutic Value of Drugs in the AgeD” chaired by Assoc. Prof. Daniela Fialová, PharmDr., Ph.D. References 1. REMON-GUITERAS, A ., MEYER, G ., THÜRMANN, P . A .: Eur . J . Clin . Pharmacol ., 71, 2015, 861–875 . 2. FIALOVÁ, D., LAFFON, B., MARIANKOVIĆ, V. et al.: Eur . J . Clin . Pharmacol ., 75, 2019, 451–466 .
101 SPECIFICITY OF THE EU(7)-PIM LIST OF POTENTIALLY INAPPROPRIATE MEDICATIONS FOR THE EVALUATION OF RATIONALITY OF DRUG PRESCRIBING IN OLDER ADULTS IN EUROPEAN COUNTRIES GREŠÁKOVÁ, S .,1 BRKIĆ, J.,1 APOSTOLI, P .,1 REISSIGOVÁ, J .,2 FIALOVÁ, D .1,3 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic 2 Department of Statistical Modelling, Czech Academy of Sciences, Prague, Czech Republic 3 Department of Geriatrics and Gerontology, First Faculty of Medicine in Prague, Charles University, Czech Republic e-mail: gresakova .silvia@faf .cuni .cz The EU(7)-PIM (potentially inappropriate medication) list presents nowadays the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe .1,2 The aim of our study was to determine the specificity of EU(7)-PIM list in ten European countries. Research teams from Czech Republic, Croatia, Estonia, Hungary, Poland, Serbia, Slovak Republic, Spain, Portugal, and Turkey participated in this study conducted by WG1b group of the EU COST Action IS1402 initiative . Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug regulatory authorities in the period October 2015 – November 2018 . The EU(7)PIM list was applied in this study as a research tool . Approval rates for EU(7)-PIMs ranged from 39 .0% in Estonia to 71 .4% in Spain . Higher percentages of approved PIMs were documented in Spain (71 .4%), Turkey (67 .5%), Portugal (67 .1%), and Poland (60 .6%), lower in Hungary (55 .5%), Czech Republic (51 .1%), Slovak Republic (47 .9%), Serbia (42 .8%), Croatia (41 .5%) and Estonia (39 .0%) . The majority of approved PIMs were also currently marketed in all countries except in Turkey (19 .8–21 .7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46 .4–48 .1%) . Applicability of the EU(7)-PIM list is limited in some countries . The EU project EUROAGEISM H2020 (2017–2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits . The study was supported by the EU COST Action IS1402, EUROAGEISM H2020 project (ITN-MSCF No764632), INOMED (Project No. CZ.02.1.01/0.0/0.0/ 18069/0010046), from the project of Specific Academic Research (SVV 260 417/2019) and Research programme Development and Study of Drugs (Progres Q42) at the Department of Social and Clinical Pharmacy, Charles University – Scientific group “Ageing and Changes in the Therapeutic Value of Drugs in the AgeD” chaired by Assoc. Prof. Daniela Fialová, PharmDr., Ph.D. References 1 . RENOM-GUITERAS, A ., MEYER, G ., THÜRMANN, P . A .: Eur . J . Clin . Pharmacol ., 71, 2015, 861–875 . 2. FIALOVÁ, D., BRKIĆ, J., LAFFON, B. et al.: Ther . Adv . Drug Saf ., 10, 2019, art . 2042098619854014 .
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105 ČERMÁK, P., OLŠOVSKÁ, J., MIKYŠKA, A., DUŠEK, M., KADLEČKOVÁ, Z., VANÍČEK, J., NYČ, O., SIGLER, K ., BOŠTÍKOVÁ, V ., BOŠTÍK, P .: Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L .) on gut anaerobic bacteria . APMIS, 125 (11), 2017, 1033–1038 . ČERVINKOVÁ, B., KUJOVSKÁ KRČMOVÁ, L., KLABAČKOVÁ, S., SOLICHOVÁ, D., SOLICH, P.: Rapid determination of lipophilic vitamins in human serum by ultra-high performance liquid chromatography using a fluorinated column and high-throughput miniaturized liquid-liquid extraction. Journal of Separation Science, 40 (17), 2017, 3375–3382 . ČERVINKOVÁ, B., KUJOVSKÁ KRČMOVÁ, L., ŠESTÁKOVÁ, V., SOLICHOVÁ, D., SOLICH, P.: A fully validated bioanalytical method using an UHPLC-MS/MS system for quantification of DNA and RNA oxidative stress biomarkers . Analytical and Bioanalytical Chemistry, 409 (14), 2017, 3611–3621 . ČUŘÍKOVÁ, B. A., PROCHÁZKOVÁ, K., FILKOVÁ, B., DIBLÍKOVÁ, P., SVOBODA, J., KOVÁČIK, A., VÁVROVÁ, K ., ZBYTOVSKÁ, J .: Simplified stratum corneum model membranes for studying the effects of permeation enhancers . International Journal of Pharmaceutics, 534 (1–2), 2017, 287–296 . DAVLETBAEVA, P ., CHOCHOLOUŠ, P ., BULATOV, A ., ŠATÍNSKÝ, D ., SOLICH, P .: Sub–1 min separation in sequential injection chromatography for determination of synthetic water-soluble dyes in pharmaceutical formulation . Journal of Pharmaceutical and Biomedical Analysis, 143, 2017, 123–129 . DOLEŽELOVÁ, E., PRAŠNICKÁ, A., CERMANOVÁ, J., CARAZO FERNÁNDEZ, A. J., HYRŠOVÁ, L., HROCH, M., MOKRÝ, J., ADAMCOVÁ, M., MRKVICOVÁ, A., PÁVEK, P., MIČUDA, S.: Resveratrol modifies biliary secretion of cholephilic compounds in sham-operated and cholestatic rats. World Journal of Gastroenterology, 23 (43), 2017, 7678–7692 . DOLEŽELOVÁ, E., STEIN, E., DEROSA, G., MAFFIOLI, P., NACHTIGAL, P., SAHEBKAR, A.: Effect of ezetimibe on plasma adipokines: A systematic review and meta-analysis . British Journal of Clinical Pharmacology, 83 (7), 2017, 1380–1396 . DONG, L., KOVÁŘOVÁ, J., BAJZÍKOVÁ, M., BEZAWORK-GELETA, A., ŠVEC, D., ENDAYA, B., SACHAPHIBULKIJ, K., COELHO, A., ŠEBKOVÁ, N., RŮŽIČKOVÁ, A., TAN, A., KLUČKOVÁ, K., JUDASOVÁ, K., ZÁMEČNÍKOVÁ, K., RYCHTARČÍKOVÁ, Z., GOPALAN, V., ANDĚRA, L., SOBOL, M., YAN, B., PATTNAIK, B., BHATRAJU, N., TRUKSA, J., STOPKA, P., HOZÁK, P., LAM, A., SEDLÁČEK, R., OLIVEIRA, P., KUBISTA, M., AGRAWAL, A., DVOŘÁKOVÁ-HORTOVÁ, K., ROHLENA, J., BERRIDGE, M. V., NEUŽIL, J.: Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. eLife, 6, 2017, art. e22187. DREIER, D ., LATKOLIK, S ., RYCEK, L ., SCHNUERCH, M ., DYMÁKOVÁ, A ., ATANASOV, A ., LADURNER, A ., HEISS, E ., STUPPNER, H ., SCHUSTER, D ., MIHOVILOVIC, M ., DIRSCH, V .: Linked magnolol dimer as a selective PPAR gamma agonist – structure-based rational design, synthesis, and bioactivity evaluation. Scientific Reports, 7, 2017, art. 13002. DU, K ., DUINTJER TEBBENS, E . J ., MEURANT, G .: Any admissible harmonic Ritz value set is possible for GMRES . Electronic Transactions on Numerical Analysis, 47, 2017, 37–56 . DUŠEK, J ., CARAZO FERNÁNDEZ, A . J ., TREJTNAR, F ., HYRŠOVÁ, L ., HOLAS, O ., SMUTNÝ, T ., MI - ČUDA, S., PÁVEK, P.: Steviol, an aglycone of steviol glycoside sweeteners, interacts with the pregnane X (PXR) and aryl hydrocarbon (AHR) receptors in detoxification regulation. Food and Chemical Toxicology, 109, 2017, 130–142 . FERNÁNDEZ-RAMOS, C ., BALLESTEROS, O ., ZAFRA-GÓMEZ, A ., ŠATÍNSKÝ, D ., SOLICH, P ., NAVALÓN, A ., VERGE, C ., De FERRER, J ., PEREZ-PASCUAL, M ., VÍLCHEZ, J . L .: Seasonal variations in the behavior of alcohol sulfates in agricultural soils: A field study. Water, Air & Soil Pollution, 228 (3), 2017, art . 104 . FIBIGR, J ., ŠATÍNSKÝ, D ., SOLICH, P .: A new approach to the rapid separation of isomeric compounds in a Silybum marianum extract using UHPLC core-shell column with F5 stationary phase . Journal of Pharmaceutical and Biomedical Analysis, 134, 2017, 203–213 . FIBIGR, J ., ŠATÍNSKÝ, D ., SOLICH, P .: A UHPLC method for the rapid separation and quantification of anthocyanins in acai berry and dry blueberry extracts . Journal of Pharmaceutical and Biomedical Analysis, 143, 2017, 204–213 . FIBIGR, J ., ŠATÍNSKÝ, D ., SOLICH, P .: A UHPLC method for the rapid separation and quantification of phytosterols using tandem UV/Charged aerosol detection – A comparison of both detection techniques . Journal of Pharmaceutical and Biomedical Analysis, 140, 2017, 274–280 .
112 ŠKOLOVÁ, B., KOVÁČIK, A., TESAŘ, O., OPÁLKA, L., VÁVROVÁ, K.: Phytosphingosine, sphingosine and dihydrosphingosine ceramides in model skin lipid membranes: Permeability and biophysics . Biochimica et Biophysica Acta – Biomembranes, 1859 (5), 2017, 824–834 . ŠMÍDOVÁ, B ., ŠATÍNSKÝ, D ., DOSTÁLOVÁ, K ., SOLICH, P .: The pentafluorophenyl stationary phase shows a unique separation efficiency for performing fast chromatography determination of highbush blueberry anthocyanins . Talanta, 166, 2017, 249–254 . ŠPAČEK, J., KESTŘÁNEK, J., JÍLEK, P., LEŠKO, D., PLUCNAROVÁ, S., BUCHTA, V.: Comparison of two long-term gestagen regimens in the management of recurrent vulvovaginal candidiasis: A pilot study . Mycoses, 60 (4), 2017, 260–265 . ŠPIČÁKOVÁ, A., SZOTÁKOVÁ, B., DIMUNOVÁ, D., MYSLIVEČKOVÁ, Z., KUBÍČEK, V., AMBROŽ, M., LNĚNIČKOVÁ, K., KRASULOVÁ, K., ANZENBACHER, P., SKÁLOVÁ, L.: Nerolidol and farnesol inhibit some cytochrome P450 activities but did not affect other xenobiotic-metabolizing enzymes in rat and human hepatic subcellular fractions . Molecules, 22 (4), 2017, art . 509 . ŠPULÁK, M ., GHAVRE, M ., POUR, M .: Recent advances in the transition-metal catalyzed synthesis of multisubstituted pentenolides and related pyranones . Tetrahedron Letters, 58 (4), 2017, 263–270 . ŠVEC, F .: Monolithic columns: A historical overview . Electrophoresis, 38 (22–23), 2017, 2810–2820 . TSHEPELEVITSH, S., HERNITS, K., JENČO, J., HAWKINS, J. M., MUTEKI, K., SOLICH, P., LEITO, I.: Systematic optimization of liquid-liquid extraction for isolation of unidentified components. ACS Omega, 2 (11), 2017, 7772–7776 . TŮMOVÁ, L., DOLEČKOVÁ, I., HENDRYCHOVÁ, H., KAŠPAROVÁ, M.: Arbutin content and tyrosinase activity of Bergenia extracts . Natural Product Communications, 12 (4), 2017, 549–552 . TŮMOVÁ, L., DUČAIOVÁ, Z., CHEEL, J., VOKŘÁL, I., SEPÚLVEDA, B., VOKURKOVÁ, D.: Azorella compacta infusion activates human immune cells and scavenges free radicals in vitro . Pharmacognosy Magazine, 13 (50), 2017, 260–264 . VAŘEJČKOVÁ, M., GALLARDO-VARA, E., VICEN, M., VITVEROVÁ, B., FIKROVÁ, P., DOLEŽELOVÁ, E., RATHOUSKÁ, J., PRAŠNICKÁ, A., BLAŽÍČKOVÁ, K., MIČUDA, S., BERNABÉU, C., NĚ MEČKOVÁ, I., NACHTIGAL, P.: Soluble endoglin modulates the pro-inflammatory mediators NF-kappa B and IL-6 in cultured human endothelial cells . Life Sciences, 175, 2017, 52–60 . VITÁSKOVÁ, D ., MELICHAR, B ., BARTOUŠKOVÁ, M ., VLACHOVÁ, Z ., VRÁNA, D ., JANKOVÁ, J ., ADAM, T., JURÁŇOVÁ, J., ZLÁMALOVÁ, N., KUJOVSKÁ KRČMOVÁ, L., JAVORSKÁ, L., KLOS, D., ŠTUDENTOVÁ, H .: Neoadjuvant combination therapy with trastuzumab in a breast cancer patient with synchronous rectal carcinoma: A case report and biomarker study . Pteridines, 28 (3–4), 2017, 233–241 . VLČKOVÁ, H., PILAŘOVÁ, V., NOVÁK, O., SOLICH, P., NOVÁKOVÁ, L.: Micro-SPE in pipette tips as a tool for analysis of small-molecule drugs in serum . Bioanalysis, 9 (11), 2017, 887–901 . VRANÍKOVÁ, B ., PAVLOKOVÁ, S ., GAJDZIOK, J .: Experimental design for determination of effects of superdisintegrant combinations on liquisolid system properties . Journal of Pharmaceutical Sciences, 106 (3), 2017, 817–825 . VYTŘÍSALOVÁ, M., TOUŠKOVÁ, T., FUKSA, L., KARAŠČÁK, R., PALIČKA, V., BÝMA, S., ŠTĚPÁN, J.: How general practitioners and their patients adhere to osteoporosis management: A follow-up survey among Czech general practitioners . Frontiers in Pharmacology, 8, 2017, art . 258 . WALLMEYER, L ., DIETERT, K ., SOCHOROVÁ, M ., GRUBER, A ., KLEUSER, B ., VÁVROVÁ, K ., HEDTRICH, S .: TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents. Scientific Reports, 7, 2017, art . 774 . ZELENÁ, L., ŘEZNÍČEK, J., ČEČKOVÁ, M., SKLENÁŘOVÁ, H.: Universal efavirenz determination in transport study, rat placenta perfusion and placenta lysate by HPLC-UV . Journal of Pharmaceutical and Biomedical Analysis, 137, 2017, 70–77 . ZEMANOVÁ, L ., KIRUBAKARAN, P ., HERNANDO PATO, I ., ŠTAMBERGOVÁ, H ., VONDRÁŠEK, J .: The identification of new substrates of human DHRS7 by molecular modeling and in vitro testing . International Journal of Biological Macromolecules, 105, 2017, 171–182 . ZIMČÍK, P., MÁLKOVÁ, A., HRUBÁ, L., MILETÍN, M., NOVÁKOVÁ, V.: Bulky 2,6-diphenylphenylsulfanyl substituents efficiently inhibit aggregation in phthalocyanines and tetrapyrazinoporphyrazines and control their photophysical and electrochemical properties . Dyes and Pigments, 136, 2017, 715–723 .
113 ZIMČÍKOVÁ, E., ŠIMKO, J., KAREŠOVÁ, I., KREMLÁČEK, J., MALÁKOVÁ, J.: Behavioral effects of antiepileptic drugs in rats: Are the effects on mood and behavior detectable in open-field test? Seizure, 52, 2017, 35–40 . ARTICLES IN JOURNALS WITHOUT IMPACT FACTOR AND PROCEEDINGS ARNdT, T., DOHNAL, F.: Osudy židovských farmaceutů z českých zemí během holocaustu (The fate of Jewish pharmacists from the Czech Lands during the holocaust). Česká a slovenská farmacie, 66 (1), 2017, 35–45. ARNdT, T., DOHNAL, F.: Příběh jednoho zmizelého světa. Lékárna U bílého jednorožce v Praze, její osud a osud jejích majitelů (nejen) ve dvacátém století (The story of a vanished world. The White Unicorn Pharmacy in Prague, its destiny and the destiny of its owners (not only) into the twentieth century) . Dvacáté století / The Twentieth Century, 9 (1), 2017, 120–141 . ARNdT, T., DOHNAL, F.: Významné osobnosti z řad židovských farmaceutů z českých zemí od 18. do 20. století (Significant persons from the Jewish pharmacists of the Czech Lands from 18th to 20th century). In: Medicína, farmacie a veterinární lékařství: Kapitoly k dějinám a vybraným tématům. Brno, Technické muzeum, 2017, 71–77 . ISBN 978-80-87896-43-3 . BABICA, J., VALÁŠKOVÁ, L., SVATOŠ, L.: České farmaceutické muzeum a jeho nová expozice Z apatyky do fabriky (Czech Pharmaceutical Museum and its new exhibition called From Pharmacy to Factory) . In: Medicína, farmacie a veterinární lékařství: Kapitoly k dějinám a vybraným tématům. Brno, Technické muzeum, 2017, 7–17 . ISBN 978-80-87896-43-3 . dOHNAl, F.: Několik poznámek k historii oboru válečná chirurgie v českých zemích do roku 1939 (Several notes on the history of the branch of military surgery in the Czech lands until 1939) . In: Medicína, farmacie a veterinární lékařství: Kapitoly k dějinám a vybraným tématům. Brno, Technické muzeum, 2017, 40–45. ISBN 978-80-87896-43-3 . ČÁŇOVÁ, K., ROZKYDALOVÁ, L., RUDOLF, E.: Anthelmintic flubendazole and its potential use in anticancer therapy . Acta Medica (Hradec Králové), 60 (1), 2017, 5–11 . DVOŘÁČKOVÁ, S., LÁDOVÁ, K., MALÝ, J., KOLÁŘ, J., PENKA, M.: Adherence k léčbě non-vitamin K perorálními antikoagulancii u nevalvulární fibrilace síní: Přehled literatury (Medication adherence to nonvitamin K antagonist oral anticoagulants at non-valvular atrial fibrillation: The literature review). Vnitřní lékařství, 63 (10), 2017, 633–639. ENCARNACAO, J ., BÁRTA, P ., FORNSTEDT, T ., ANDERSSON, K .: Impact of assay temperature on antibody binding characteristics in living cells: A case study . Biomedical Reports, 7 (5), 2017, 400–406 . KESTŘÁNEK, J., LEŠKO, D., BUCHTA, V., JÍLEK, P., ŠPAČEK, J.: Aktuální pohled na možnosti diferenciální diagnostiky a léčby vulvovaginálního diskomfortu (Current view on diagnostics and treatment possibilities of vulvovaginal discomfort) . Gynekologie a porodnictví, 1 (5), 2017, 310–318 . LÁDOVÁ, K., MALÝ, J., VEGERBAUER, M., THOMSON, P.: Použití neregistrovaných léčiv na příkladech v pediatrii (Unlicensed drug use in examples from pediatric practice) . Pediatrie pro praxi, 18 (1), 2017, 22–26 . LEŠKO, D., BUCHTA, V., SALAVEC, M., JÍLEK, P., KESTŘÁNEK, J., DRBOHLAVOVÁ, A., ŠPAČEK, J.: Současné využití technik v diagnostice recidivujícího vulvovaginálního dyskomfortu (Current use of techniques in the diagnosis of recurrent vulvovaginal discomfort). Česká gynekologie, 82 (2), 2017, 152–157. MAlÝ, J ., MALÁ, K .: XIX . sympozium klinické farmacie René Macha (XIX . Symposium on Clinical Pharmacy René Mach) . Hradec Králové, Farmaceutická fakulta UK, 2017, 81 pp . ISBN 978-80-906644-1-8 . MElICHAR, B., SPISAROVÁ, M., BARTOUŠKOVÁ, M., KUJOVSKÁ KRČMOVÁ, L., JAVORSKÁ, L., ŠTUDENTOVÁ, H .: Neopterin as a biomarker of immune response in cancer patients . Annals of Translational Medicine, 5 (13), 2017, art . 280 . NACHTIGAl, P., ŠIMŮNEK, T., ATKINSON, J.: Pharmacy Practice and Education in the Czech Republic. Pharmacy, 5 (4), 2017, art . 54 . PETRŽELOVÁ, M., HORÁK, P., HORDĚJČUKOVÁ, A., MATYSOVÁ, L.: Omeprazolová suspenze 2 mg/ml – Nová léková forma pro pediatrii (Omeprazole suspension 2 mg/ml – A new dosage form for pediatric use) . Praktické lékárenství, 13 (1), 2017, 18–20 . VAŇKOVÁ, B., MALÝ, J., MALÁ, K., DUSILOVÁ SULKOVÁ, S.: Analýza lékových problémů u pacientů po transplantaci ledvin – kazuistiky (Analysis of drug-related problems in patients after kidney transplantation – Case reports) . Aktuality v nefrologii, 23 (4), 2017, 191–201 .
114 VÁVROVÁ, K., KOVÁČIK, A., OPÁLKA, L.: Ceramides in the skin barrier. European Pharmaceutical Journal, 64 (2), 2017, 28–35 . VOSÁTKA, J., DVOŘÁČKOVÁ, S., MALÝ, J., KOLÁŘ, J.: Revize farmakoterapie u polymorbidního geriatrického pacienta se zaměřením na rizika pádu a jejich řešení (The pharmacotherapy review in the polymorbid geriatric patient with focus on the risk of falls and its management) . Praktické lékárenství, 13 (2e), 2017, e16–e24 . MONOGRAPHIES AND TEXTBOOKS KOLDA, J.: Kukusbaad – uzdrowisko jako wyraz świadomości człowieka baroku (Kukusbaad – Spa as a reflection of Baroque man’s thinking) . In Elitarny model europejskiego uzdrowiska – ewolucja koncepcji i jej funkcjonowanie w praktyce. Wrocław, Arboretum, 2017, 35–52. ISBN 978-83-62563-57-9. HAVLÍČKOVÁ, I., DOSTÁLOVÁ, Š., KATEROVÁ, Z.: English for Pharmacy and Medical Bioanalytics, 2nd ed ., Prague, Karolinum Press, 2017 . ISBN 978-80-246-2797-7 . MATOUŠKOVÁ, P .: MicroRNAs and reference gene methodology . In Handbook of Nutrition, Diet, and Epigenetics . Cham, Springer, 2017, 1–17 . ISBN 978-3-319-31143-2 . NOVÁKOVÁ, L ., PLACHKÁ, K .: Pharmaceutical applications . In Supercritical Fluid Chromatography . Amsterdam, Elsevier, 2017, 461–494 . ISBN 978-0-12-809207-1 . NOVÁKOVÁ, L., PLACHKÁ, K., JAKUBEC, P.: Ultra-high performance supercritical fluid chromatographymass spectrometry . In Handbook of Advanced Chromatography/Mass Spectrometry Techniques . London, AOCS Press, 2017, 445–487 . ISBN 978-0-12-811732-3 . NOVÁKOVÁ, L ., SVOBODA, P ., PAVLÍK, J .: Ultra-high performance liquid chromatography . In Liquid Chromatography: Fundamentals and Instrumentation . Amsterdam, Elsevier, 2017, 719–769 . ISBN 978-0-12805393-5 . SKÁLOVÁ, L ., BOUŠOVÁ, I ., MACHALA, M ., MATOUŠKOVÁ, P ., PÁVEK, P ., PODLIPNÁ, R ., SOUČEK, P., SVOBODOVÁ, H., SZOTÁKOVÁ, B., TREJTNAR, F., VONDRÁČEK, J., WSÓL, V.: Metabolismus léčiv a jiných xenobiotik (Metabolism of drugs and other xenobiotics), 2nd modified and extended ed., Prague, Karolinum Press, 2017 . ISBN 978-80-246-3733-4 . DEGREES Lectures for the Professorship Appointments, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2017 doc . RNDr . PETER MIKUŠ, Ph .D .: Associate Professor, Head of the Department of Pharmaceutical Analysis and Nuclear Pharmacy, Comenius University, Faculty of Pharmacy, Bratislava (SK) Discipline: Analytical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 6 . 11 . 2015 Continuation: 8 . 12 . 2015 Title of Lecture: Pokročilé metódy kapilarnej elektroforézy vo farmaceutickej a biomedicinskej analyze (Advanced methods of capillary electrophoresis in pharmaceutical and biomedical analysis), 8 . 3 . 2016 Appointment: 19 . 6 . 2017 doc . PharmDr . KATEŘINA VÁVROVÁ, Ph .D .: Associate Professor, Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Hradec Králové . Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 22 . 9 . 2016 Continuation: 11 . 10 . 2016 Title of Lecture: Role ceramidů ve zdravé i nemocné kožní bariéře (The role of ceramides in healthy and sick skin barrier), 13 . 12 . 2016 Appointment: 19 . 6 . 2017
115 doc . PharmDr . TOMÁŠ ŠIMŮNEK, Ph .D .: Associate Professor, Department of Biochemical Sciences, Dean of the Faculty, Faculty of Pharmacy, Hradec Králové . Discipline: Biochemistry, MŠMT 24 295/2007-30/1 Inauguration: 21 . 11 . 2016 Continuation: 13 . 12 . 2016 Title of Lecture: Perspektivy výzkumu toxických a protektivních účinků léčiv na kardiovaskulární systém (Perspectives of the research of toxic and protective effects of drugs on cardiovascular system), 14 . 3 . 2017 Appointment: 13 . 12 . 2017 Habilitation Theses and Lectures for Associated Professor Appointments, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2017 RNDr . LENKA KUJOVSKÁ KRČMOVÁ, Ph .D .: Senior Lecturer, Department of Analytical Chemistry, Faculty of Pharmacy, Hradec Králové . Discipline: Analytical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 6 . 9 . 2016 Continuation: 11 . 10 . 2016 Habilitation Thesis: Vývoj chromatografických metod pro klinický výzkum (Development of chromatographic methods for clinical research), defended 13 . 12 . 2016 Title of Lecture: Moderní trendy ve zpracování biologického materiálu v klinickém výzkumu (Modern trends in processing of biological material in clinical research), 13 . 12 . 2016 Appointment: 1 . 2 . 2017 Mgr . JARMILA ZBYTOVSKÁ, Dr . rer . nat .: Senior Lecturer, Department of Pharmaceutical Technology, Faculty of Pharmacy, Hradec Králové . Discipline: Pharmaceutical Technology, MŠMT 29 593/2011-M3 Inauguration: 20 . 2 . 2017 Continuation: 14 . 3 . 2017 Habilitation Thesis: Kožní bariéra a možnosti jejího ovlivnění z farmaceutického pohledu (Skin barrier and possibilities of influencing it from the pharmaceutical point of view), defended 13. 6. 2017 Title of Lecture: Nanonosiče pro dermální a transdermální podání léčiv (Nanocarriers for dermal and transdermal administration of drugs), 13 . 6 . 2017 Appointment: 1 . 10 . 2017 PharmDr. MARTINA ČEČKOVÁ, Ph.D.: Senior Lecturer, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hradec Králové . Discipline: Human and Veterinary Pharmacology, MŠMT 24 295/2007-30/1 Inauguration: 18 . 5 . 2017 Continuation: 13 . 6 . 2017 Habilitation Thesis: Role membránových transportérů ve farmakokinetice a mnohočetné lékové rezistenci (Role of membrane transporters in multi-drug resistence), defended 10 . 10 . 2017 Title of Lecture: Farmakokinetické lékové interakce zprostředkované transportéry (Pharmacokinetic drug interactions mediated by transporters), 10 . 10 . 2017 Appointment: 1 . 12 . 2017 Doctoral Dissertation Theses to obtain the Ph.D. Degree, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2017 Mgr. AMBROŽ, MARTIN: Seskviterpeny v protinádorové terapii (Sesquiterpenes in cancer therapy), 30. 11. 2017, Ph .D . PharmDr. ARNDT, TOMÁŠ: Československá a česká farmacie – projevy, dopady a důsledky genocidy Židů a dalších forem rasového pronásledování (Czechoslovak and Czech pharmacy – expressions, impacts and consequences of the genocide of Jews and other forms of racial persecution), 7 . 12 . 2017, Ph .D .
116 MSc . BELKINA, TATIANA: Non-prescribed antibiotic use in some developing countries and its association with drug resistance, 2 . 5 . 2017, Ph .D . PharmDr. BENEŠ, MICHAL: Technologické aspekty formulování pevných roztoků (Technological aspects of solid solution formulations), 20 . 6 . 2017, Ph .D . Mgr . CARAZO FERNÁNDEZ, ALEJANDRO JOSÉ: Nuclear receptors – new ligands study and importance of the genetic variability, 29 . 6 . 2017, Ph .D . Mgr. CIDLINA, ANTONÍN: Vliv strukturních aspektů na fotofyzikální vlastnosti ftalocyaninů (Influence of structural aspects on photophysical properties at phthalocyanines), 14 . 9 . 2017, Ph .D . Mgr. ČERVINKOVÁ, BARBORA: Uplatnění moderních separačních technik v analýze biologického materiálu (Application of modern separation techniques in the analysis of biological material), 18 . 9 . 2017, Ph .D . Mgr . HROCH, LUKÁŠ: Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer’s disease, 14 . 9 . 2017, Ph .D . Mgr. KADOVÁ, ZUZANA: Vliv modulace zánětu na exkreční mechanismy během intrahepatální cholestázy (Influence of inflammation modulation on excretory mechanisms during intrahepatic cholestasis), 29. 6. 2017, Ph .D . Mgr. KASALOVÁ, EVA: Moderní separační techniky pro analýzu biologického materiálu v klinickém výzkumu (Modern separation techniques for the analysis of biological material in clinical research), 28 . 11 . 2017, Ph .D . PharmDr. KLOVRZOVÁ, SYLVA: Formulace tekutých pediatrických přípravků v podmínkách nemocniční lékárny (Formulation of extemporaneous paediatric liquid preparations in the hospital pharmacy), 15 . 2 . 2017, Ph .D . Mgr. KOVÁČIK, ANDREJ: Studium vlivu hydroxylace ceramidů na permeabilitu a mikrostrukturu modelových lipidových membrán (Study of effect of ceramide hydroxylation on permeability and microstructure of model lipid membranes), 8 . 12 . 2017, Ph .D . Mgr. LNĚNIČKOVÁ, KATEŘINA: Modulace biotransformačních a antioxidačních enzymů vybranými přírodními látkami (Modulation of biotransformation and antioxidant enzymes by selected natural compounds), 30 . 11 . 2017, Ph .D . Mgr . NAJMANOVÁ, IVETA: Vliv polyfenolických látek na hladký cevní sval (The effect of polyphenolic substances on vascular smooth muscle), 24 . 3 . 2017, Ph .D . Mgr. PILAŘOVÁ, VERONIKA: Vývoj a optimalizace kroku úpravy vzorku pro rychlé chromatografické analýzy (Development and optimization of sample preparation step for fast chromatographic analysis), 28 . 2 . 2017, Ph .D . Mgr . PRCHAL, LUKÁŠ: Anthelmintic and other xenobiotic biotransformation in helminths and its contribution to resistance development, 30 . 11 . 2017, Ph .D . Mgr. SEMELKOVÁ, LUCIA: Příprava derivátů pyrazinu jako potenciálních antituberkulotik: Studium vztahů mezi chemickou strukturou a biologickou aktivitou (Preparation of pyrazinamide derivatives as potential antituberculotics: Study of structure activity relationships), 14 . 9 . 2017, Ph .D . Mgr . SMUTNÝ, TOMÁŠ: Novel approaches for development of in vitro liver cell models, 24 . 3 . 2017, Ph .D . Mgr. SVOBODA, PAVEL: Matricové efekty v LC-MS analýze: vznik, hodnocení a jejich odstranění (Matrix effects in LC-MS analysis: occurrence, evaluation, and their elimination), 25 . 9 . 2017, Ph .D . Mgr. ŠESTÁK, VÍT: Analytické a bioanalytické hodnocení nových protinádorových léčiv (Analytical and bioanalytical assessment of novel anticancer drugs), 18 . 9 . 2017, Ph .D . Mgr . TOUŠKOVÁ, TEREZA: Kvalitativní a kvantitativní aspekty adherence v léčbě osteoporózy (Qualitative and quantitative aspects of adherence to osteoporosis treatment), 3 . 11 . 2017, Ph .D . Mgr. VÁCHOVÁ, LENKA: Syntéza a studium fotofyzikálních a fotochemických vlastností ftalocyaninů a azaftalocyaninů (Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines), 14 . 9 . 2017, Ph .D . Mgr. VAŘEJČKOVÁ, MICHALA: Sledování vlivu statinů a solubilního endoglinu na markery endotelové dysfunkce u vybraných buněčných linií a kultur (Monitoring the effect of statins and soluble endoglin on markers of endothelial dysfunction in selected cell line and culture), 21 . 9 . 2017, Ph .D . Mgr . ZAHÁLKA, LUKÁŠ: Stability studies of oral liquid preparations using HPLC, 25 . 9 . 2017, Ph .D .
117 Rigorous Theses to obtain the degree PharmDr. (Doctor of Pharmacy, graduates of the study programme Pharmacy) or RNDr. (Doctor of Natural Sciences, graduates of study programme Bioanalytical Laboratory Diagnostics in Medicine), Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2017 Mgr. ADAMCOVÁ, MARKÉTA: Studium biologické aktivity alkaloidů izolovaných z Argemone grandiflora (Papaveraceae) I . (Study of biological activity of isolated alkaloids from Argemone grandiflora (Papaveraceae) I .), 21 . 9 . 2017, PharmDr . Mgr. ANDRÝS, RUDOLF, Ph.D.: Vývoj a aplikace afinitního nosiče pro izolaci lidských karbonyl-redukujících enzymů (Development and applications of affinity carrier for isolation of human carbonyl-reducing enzymes), 10 . 2 . 2017, PharmDr . Mgr. BARVÍNKOVÁ, ZUZANA: Stanovení fluoridů ve vzorcích zubních past pomocí SIA systému (Determination of fluoride in toothpaste using SIA system), 24. 2. 2017, PharmDr. Mgr. BAVLOVIČ, JAN: Charakterizace multirezistentních izolátů Klebsiella pneumoniae a Enterococcus faecium spektroskopickými a genotypickými metodami (Characterisation of multidrug resistant Klebsiella pneumoniae and Enterococcus faecium isolates by spectroscopic and genotypic method), 17 . 2 . 2017, PharmDr . Mgr. BENEK, ONDŘEJ, Ph.D.: Preparation and evaluation of potential drugs inhibiting mitochondrial enzymes, 06 . 3 . 2017, PharmDr . Mgr. BORKOVCOVÁ, RENÁTA: Vliv rychlosti lisování na parametry testu stresové relaxace (The influence of the tableting speed on the parameters of the stress relaxation test), 19 . 12 . 2017, PharmDr . Mgr. BURGETOVÁ, LENKA: Přípravek s terbinafinem aplikovatelný na mykózy (The application of terbinafine in the treatment of mycosis), 3 . 5 . 2017, PharmDr . Mgr. CIDLINA, ANTONÍN: Syntéza kationických ftalocyaninů (Synthesis of cationic phthalocyanines), 09. 11. 2017, PharmDr . Mgr. ČERVINKOVÁ, BARBORA, Ph.D.: Uplatnění moderních separačních technik v analýze biologického materiálu (Application of modern separation techniques in the analysis of biological material), 30 . 10 . 2017, RNDr . Mgr. DĚDKOVÁ, LUCIE: Sekvenční injekční chromatografie – testování moderních chromatografických kolon pro rychlé a efektivní separace (Sequential injection chromatography – testing of modern chromatographic columns for fast and effective separations), 24 . 10 . 2017, PharmDr . Mgr. DOLÁKOVÁ, ANDREA: Štúdium monovrstevných lipidových modelov ochorení kožnej bariéry (Study of monolayer lipid models of skin barrier diseases), 19 . 12 . 2017, PharmDr . Mgr. DRASTÍKOVÁ, MARKÉTA, Ph.D.: Využití separačních metod v klinickém výzkumu (Using of separation methods for clinical research), 30 . 10 . 2017, RNDr . Mgr. ĎURIŠOVÁ, MARKÉTA: Studium role nukleosidových transportéru v intestinální absorpci s využitím in vitro transportního modelu založeném na buněčné linii Caco-2 (Study of the role of nucleoside transporters in intestinal absorption with the use of in vitro transport method based on the Caco-2 cell line), 22 . 9 . 2017, PharmDr . Mgr . FARKAŠOVSKÝ, MAREK: Alkaloidy Narcissus pseudonarcissus L . cv . Dutch Master a ich cholinesterázová a prolyloligopeptidázová inhibičná aktivita (Alkaloids from Narcissus pseudonarcissus L . cv . Dutch Master and their cholinesterase and prolyl oligopeptidase inhibitory activity), 21 . 9 . 2017, PharmDr . Mgr. FEKETE, SOŇA, Ph.D.: The effect on bone metabolism of selected substances affecting the central nervous system, 10 . 2 . 2017, RNDr . Mgr. FIŠEROVÁ, KATEŘINA: Vliv albendazolu na proliferaci buněk in vitro (Influence of albendazole on cell proliferation in vitro), 10 . 2 . 2017, RNDr . Mgr. HERBOLT, DANIEL: Vývoj nové spektrofotometrické metodiky pro screening chelatace iontů zinku (Development of a novel spectrophotometric method for zinc ions chelatation screening), 22 . 9 . 2017, PharmDr . Mgr. HESSLER, FILIP, Ph.D.: Využití couplingových reakcí k syntéze potenciálně biologicky aktivních látek (Use of coupling reactions in the synthesis of potentially biologically active compounds), 24 . 2 . 2017, PharmDr . Mgr. HOFMANOVÁ, TEREZA: Léková pochybení u psychiatricky nemocných pacientů (Dosage errors in psychiatrically diagnosed patients), 02 . 1 . 2017, PharmDr . Mgr. HOLZNEROVÁ, ANEŽKA: Testování a optimalizace on-line SPE HPLC podmínek pro stanovení mykotoxinu patulinu v jablečných nápojích (On-line SPE HPLC method optimization for determination of patulin mycotoxin in apple drinks), 30 . 10 . 2017, RNDr .
118 Mgr . HROCH, LUKÁŠ, Ph .D .: Inhibitors of mitochondrial enzymes as potential therapeutics for Alzheimer’s disease, 09 . 11 . 2017, PharmDr . Mgr. JAKUBÍKOVÁ, HANA: Liberace terbinafinu z polyesterů větvených kyselinou polyakrylovou (The release of terbinafine from polyesters branched with polyacrylic acid), 3. 5. 2017, PharmDr. Mgr. JANĎOUREK, ONDŘEJ, Ph.D.: Deriváty pyrazinu jako potenciální antituberkulotika – příprava a studium biologických vlastností (Derivatives of pyrazine as potential antituberculars – preparation and study of biological properties), 6 . 3 . 2017, PharmDr . Mgr. JANOUŠEK, MARTIN: Využití zlatného katalyzátoru při syntéze substituovaných pyridinů (The synthesis of substituted pyridines employing gold(I) catalyst), 24 . 2 . 2017, PharmDr . Mgr. JANSOVÁ, HANA, Ph.D.: Studium možností farmakologické ochrany srdečních buněk před oxidačním stresem a antracyklinovými cytostatiky (Study of potential pharmacological protection of cardiac cells against oxidative stress and antracycline anticancer drugs), 21 . 3 . 2017, PharmDr . Mgr. JEDLIČKOVÁ, ADÉLA: In vitro hodnocení fotodynamické aktivity derivátů tetrapyridoporphyrazinu pro léčbu solidních nádorů (In vitro evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of solid tumours), 10 . 2 . 2017, RNDr . Mgr. JEŘÁBEK, JAKUB: Design and synthesis of hybrid compounds based on tacrin/resveratrol derivatives, 09 . 11 . 2017, PharmDr . Mgr. JEŘÁBKOVÁ, JANA: Výzkum nových ligandů FXR receptoru (Study of novel FXR ligands), 22. 9. 2017, PharmDr . Mgr. KATRNOŠKOVÁ, SIMONA: Studium cytotoxicity potenciálních antituberkulotik s využitím vybraných metod na jaterní a ledvinné buněčné linii (Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line), 17 . 2 . 2017, PharmDr . Mgr. KOMRSKOVÁ, JITKA: Hledání a testování nových inhibitorů vybraného mykobakteriálního enzymu (Identification of new potent inhibitors of selected mycobacterial enzyme), 25. 9. 2017, RNDr. Mgr. KONDĚLKOVÁ, KATEŘINA, Ph.D.: Vliv Goeckermanovy terapie na vybrané parametry imunity u pacientů s psoriázou (The effect of Goeckerman therapy on selected immune markers in patients with psoriasis), 10 . 2 . 2017, RNDr . Mgr. KOŠŤÁKOVÁ, ŠÁRKA: Stanovení aktivity a exprese vybraných isoforem glutathion-S-transferasy v in vivo modelu glutamátem navozené obezity (Assessment of activity and expression of selected isoforms of glutathione S-transferase in the in vivo model of glutamate-induced obesity), 10 . 2 . 2017, RNDr . Mgr. KRATOCHVÍL, JIŘÍ, Ph.D.: Syntéza specificky substituovaných heterocyklů katalytickými reakcemi (Synthesis of specifically substituted heterocycles via catalytic reactions), 24. 2. 2017, PharmDr. Mgr. KŘÍŽOVÁ, KATEŘINA: Vývoj a validace HPLC metody pro stanovení antokyanů v kanadských borůvkách (HPLC method development and validation for analysis of anthocyanins in highbush blueberries), 24 . 2 . 2017, PharmDr . Mgr. KUBEŠ, JAN, Ph.D.: Transportní mechanismy sekundárních metabolitů přes membrány rostlinných buněk (Transport mechanisms of secondary metabolites across membranes of plant cells), 16 . 1 . 2017, PharmDr . Mgr. LOKVENCOVÁ, KATEŘINA: Farmakokinetika ivermektinu v trusu ovce domácí (The pharmacokinetics of ivermectin in the feces of Ovis ammon), 25 . 9 . 2017, PharmDr . Mgr. MARTAN, DAVID: Influence of TNF-α on hENaC subunits expression, 25. 9. 2017, PharmDr. Mgr. MIKUŠEK, JIŘÍ, Ph.D.: Syntéza a využití vybraných dusíkatých heterocyklů (Synthesis and utilization of selected nitrogen heterocycles), 24 . 2 . 2017, PharmDr . Mgr. MÍSAŘ, JAKUB: Interakce fenylpropionových kyselin se železem (Interaction of phenylpropionic acids with iron), 16 . 1 . 2017, PharmDr . Mgr. MOTLOVÁ, TEREZA: Studium vlivu kluzných látek na průběh lisování tabletoviny s mikrokrystalickou celulosou (The evaluation of the influence of lubricants on the compaction process of tableting mixtures with microcrystalline cellulose), 3 . 5 . 2017, PharmDr . Mgr. NOVÁKOVÁ, DANA: Studium plazmatické vazebnosti radiofarmak značených 18F z hlediska mezidruhového srovnání (Study of interspecies differences in plasma protein binding of 18F-labeled radiopharmaceuticals), 17 . 2 . 2017, PharmDr . Mgr . OPÁLKA, LUKÁŠ, Ph .D .: Syntéza lidských ω-O-acylceramidů a hodnocení jejich vlivu na bariérové vlastnosti kožních lipidových membrán (Synthesis of human ω-O-acylceramides and evaluation of their effects on barrier properties of skin lipid membranes), 24 . 2 . 2017, PharmDr .
119 Mgr. PAŠKOVÁ, BARBORA: Studium antimykotické aktivity nově syntetizovaných sloučenin (The study of antimycotic activity of newly synthetized substances), 17 . 02 . 2017, PharmDr . Mgr . PÁSZTÓ, LENKA: Biologická aktivita makromycet – D (Biological activity of macromycetes – D), 30 . 5 . 2017, PharmDr . Mgr . PAVLÍK, FRANTIŠEK: Metabolismus anthelmintik v rostlinách (Metabolism of anthelmintics in plants), 10 . 2 . 2017, PharmDr . Mgr . PECHOVÁ, MARTINA: Stanovení vybraných fenolických látek v ovoci (Determination of selected phenolic compounds in fruit), 30 . 10 . 2017, RNDr . Mgr. PETLÁNOVÁ, TEREZA: Studium interakce nově syntetizovaných sloučenin s bakteriálním agens (Study of the interaction of newly synthesized compounds with bacterial agents), 17 . 2 . 2017, PharmDr . Mgr. PILAŘOVÁ, VERONIKA, Ph.D.: Vývoj a optimalizace kroku úpravy vzorku pro rychlé chromatografické analýzy (Development and optimization of sample preparation step for fast chromatographic analysis), 9 . 10 . 2017, PharmDr . Mgr. PILKOVÁ, ALENA: Identifikace a analýza terapie užívané těhotnými ženami (Identification and analysis of therapy used by pregnant women), 7 4 . 2017, PharmDr . Mgr. PIMKOVÁ, KRISTÝNA, Ph.D.: Proteomická analýza vybraných onkohematologických onemocnění (Proteomic analysis of selected oncohematological diseases), 10 . 2 . 2017, RNDr . Mgr. PIPOTOVÁ, HELENA: Vliv průběhu těhotenství na vznik alergií u dětí – porovnání studií z let 2005 a 2011 (The influence of course of pregnancy on the risk of allergies in children – studies comparison from the year 2005 and from the year 2011), 22 . 9 . 2017, PharmDr . Mgr. POLÁKOVÁ, TEREZIE: Asociace utilizace nutričních substrátů a prediktorů morbidity a mortality u pacientů s CHOPN (Association of nutrition substrate utilization and predictors of morbidity and mortality in patients with COPD), 17 . 2 . 2017, PharmDr . Mgr. POLONIOVÁ, VERONIKA: Epilepsie v dětské populaci v okrese Bruntál – farmakoterapeutické postupy a zkušenosti v léčbě (Epilepsy in children in the Bruntál district – experience of pharmaceutical treatment), 22 . 9 . 2017, PharmDr . Mgr. POPOVSKÁ, LENKA: Optimalizace postupu izolace fosforylovaných peptidů ze směsi metodou afinitní chromatografie na oxidech kovů pro analýzu hmotnostní spektrometrií (Optimization of procedure for isolation of phosphorylated peptides from a peptide mixture by metal oxide affinity chromatography for mass spectrometry analysis), 30 . 10 . 2017, RNDr . Mgr. POSPĚCHOVÁ, LUCIE: Neuroprotective and antioxidant effects of a series of coumarinsin in vitro Alzheimer’s disease models, 22 . 9 . 2017, PharmDr . Mgr. RUDECKÁ, KATEŘINA: Formulace a (trans)dermální podání imiquimodu (Formulation and (trans)dermal application of imiquimod), 26 . 10 . 2017, PharmDr . Mgr. RŮŽIČKOVÁ, MICHAELA: Vyhledání referenčních genů pro relativní kvantifikaci mRNA z Haemonchus contortus (Reference gene selection for mRNA quantification in Haemonchus contortus), 10 . 2 . 2017, PharmDr . Mgr. SEMELKOVÁ, LUCIA, Ph.D.: Příprava derivátů pyrazinu jako potenciálních antituberkulotik: Studium vztahů mezi chemickou strukturou a biologickou aktivitou (Preparation of pyrazinamide derivatives as potential antituberculotics: Study of structure activity relationships), 9 . 11 . 2017, PharmDr . Mgr. SCHIMMEROVÁ, ANETA: Příprava nesymetrického azaftalocyaninu pro značení DNA sond zvyšujících citlivost molekulárně-biologických metod (Synthesis of low-symmetry azaphthalocyanine for the labeling of DNA probes increasing the susceptibility of the molecular-biological methods), 9 . 11 . 2017, PharmDr . Mgr. SLEZÁČKOVÁ, JANA: Vliv teploty sušení na vlastnosti sprejově sušené laktosy (The effect of the drying temperature on the properties of spray-dried lactose), 26 . 10 . 2017, PharmDr . Mgr. SKOŘEPOVÁ, ZUZANA: Hodnocení vlastností granulátů a tablet připravených ze škrobů (Evaluation of the properties of granules and tablets prepared from starch), 3 . 5 . 2017, PharmDr . Mgr . SMUTNÝ, TOMÁŠ, Ph .D .: Novel approaches for development of in vitro liver cell models (Nové přístupy ve vývoji in vitro jaterních buněčných modelů), 22. 9. 2017, PharmDr. Mgr. STACHOVÁ, HANA: Vývoj HPLC metody pro stanovení umělých barviv ve vzorcích zeleného piva (HPLC method development for artificial colorants determination in green beer samples), 30. 10. 2017, RNDr. Mgr. STUDENÁ, HANA: Problematika obsahu těžkých kovů v rostlinných drogách: Sambuci nigrae fructus (The problems of content of heavy metals in herbal drugs: Sambuci nigrae fructus), 30 . 10 . 2017, RNDr .
120 Mgr. ŠAFRATOVÁ, MARCELA, Ph.D.: Studium inhibičního (toxického) vlivu alkaloidů vybraných druhů rostlin z čeledi Amaryllidaceae na některé lidské enzymové systémy (in vitro studie) III (Study of inhibition (toxicity) activity of alkaloids from selected plant species of Amaryllidaceae family on human enzyme systems (in vitro study) III), 16 . 1 . 2017, PharmDr . Mgr . ŠEBL, RENÉ: Syntéza substituovaných pyrazino[2,3-b]pyrazinů jako prekurzorů azaftalocyaninů (Synthesis of pyrazino[2,3-b]pyrazines – azaphthalocyanine precursors), 6 . 3 . 2017, PharmDr . Mgr. ŠENITKOVÁ, IVA, Ph.D.: Strukturní a funkční analýza faktorů virulence mikroba Francisella tularensis (Structural and functional analysis of Francisella tularensis virulence factors), 16 . 6 . 2017, RNDr . Mgr. ŠESTÁK, VÍT, Ph.D.: Analytické a bioanalytické hodnocení nových protinádorových léčiv (Analytical and bioanalytical assessment of novel anticancer drugs), 9 . 10 . 2017, PharmDr . Mgr . ŠILAROVÁ, MICHAELA: Permeabilita a mikrostruktura modelových lipidových membrán stratum corneum: srovnání nehydroxylovaných a (R)- a (S)-α-hydroxylovaných ceramidů (The permeability and microstructure of model stratum corneum lipid membranes: comparison of non-hydroxylated and (R)- and (S)-α-hydroxylated ceramides), 31. 10. 2017, PharmDr. Mgr. ŠKOLOVÁ, BARBORA, Ph.D.: Syntéza a studium analogů ceramidů (Synthesis and study of ceramide analogues), 24 . 2 . 2017, PharmDr . Mgr. ŠTURCOVÁ, KLÁRA: Analýza farmakoterapie u pacientů ve zdravotnickém zařízení následné péče I (Analysis of the pharmacotherapy in patients in aftercare health facility I), 29 . 3 . 2017, PharmDr . Mgr. ŠTURMOVÁ, ZUZANA: Studium přímo lisovatelných tabletovin s granulovanou α-laktosou monohydrátem a mazadly (The study of directly compressible tableting materials with granulated α-lactose monohydrate and lubricants), 19 . 12 . 2017, PharmDr . Mgr. ŠUMPELOVÁ, KATEŘINA: Účinek kvercetinu a jeho vybraných metabolitů na izolovaných aortálních kroužcích potkana (The effect of quercetin and its selected metabolites on isolated aortal rings of rat), 22. 9. 2017, PharmDr . Mgr. ŠVIDRNOCHOVÁ, MICHAELA: Vliv derivátů benzoxazindionu na vybrané mykobakteriální enzymy (Influence of benzoxazinedione derivatives on selected mycobacterial enzymes), 10. 2. 2017, PharmDr. Mgr. TAMBOROVÁ, BARBORA: Assessment of chelation of cupric ions with flavones by use of hematoxylin method, 16 . 1 . 2017, PharmDr . Mgr. TRHLÍKOVÁ, ANNA: Hodnocení reologických a adhezivních vlastností polotuhých excipientů (Evaluation of rheological and adhesive properties of semisolid excipients), 3 . 5 . 2017, PharmDr . Mgr. UHLÍŘOVÁ, ŠTĚPÁNKA: Příprava fluorescenčních senzorů odvozených od azaftalocyaninů se zvýšenou selektivitou pro vybrané kationty kovů (Syntheses of azaphthalocyanine fluorescence sensors with the improved selectivity towards desired metal cations), 9 . 11 . 2017, PharmDr . Mgr. URBANOVÁ, MARTINA: Využití disperzní extrakce na tuhou fázi pro analýzu vybraných obsahových látek zázvorovníku lékařského (Dispersive solid-phase extraction for the analysis of chosen substances in Zingiber officinale), 24 . 2 . 2017, PharmDr . Mgr. VAŇÁSKOVÁ, BARBORA, Ph.D.: Deriváty pyrazinkarboxylové kyseliny jako potenciální antituberkulotika – příprava a studium biologických vlastností (Derivatives of pyrazinecarboxylic acid as potential antituberculotics – synthesis and biological evaluation), 6 . 3 . 2017, PharmDr . Mgr. VAVREČKOVÁ, MAGDA: Syntéza potenciálně fotodynamicky aktivních derivátů tetrapyridoporfyrazinů (Synthesis of tetrapyridoporphyrazines with potential photodynamic activity), 6 . 3 . 2017, PharmDr . Mgr. VEREŠOVÁ, ERIKA: Účinok vybraných seskviterpénov na antioxidačné enzýmy v diferencovanej bunkovej línii Caco-2 (The impact of selected sesquiterpenes on the activity of antioxidant enzymes in the differentiated Caco-2 cell line), 10 . 2 . 2017, PharmDr . Mgr. VYHLÍDALOVÁ, BARBORA: Studium přímo lisovatelných tabletovin s aglomerovanou α-laktosou monohydrátem a mazadly (The study of directly compressible tableting materials with agglomerated α-lactose monohydrate and lubricants), 26 . 10 . 2017, PharmDr . Mgr . ZAPPE, LUKÁŠ: Role of disulphide bonds in hA2A subtype adenosine receptor, 25 . 9 . 2017, PharmDr .
121 PUBLICATIONS OF THE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ, CHARLES UNIVERSITY IN THE YEAR 2018 ORIGINAL PAPERS AND REVIEWS ANDRŠ, M ., POSPÍŠILOVÁ, M ., SEIFRTOVÁ, M ., HAVELEK, R ., TICHÝ, A ., VEJRYCHOVÁ, K ., POLEDNÍKOVÁ, M., GÓRECKI, L., JUN, D., KORÁBEČNÝ, J., ŘEZÁČOVÁ, M.: Purin-6-one and pyrrolo[2,3-d] pyrimidin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity . Future Medicinal Chemistry, 10 (17), 2018, 2029–2038 . APPLOVÁ, L., VELJOVIĆ, E., MURATOVIĆ, S., KARLÍČKOVÁ, J., MACÁKOVÁ, K., ZAVRŠNIK, D., SASO, L., DURIĆ, K., MLADĚNKA, P.: 9-(4′-Dimethylaminophenyl)-2,6,7-trihydroxyxanthene-3-one is a potentially novel antiplatelet drug which antagonizes the effect of thromboxane A2 . Medicinal Chemistry, 14 (2), 2018, 200–209 . BALANSIN RIGON, R ., KAESSMEYER, S ., WOLFF, C ., HAUSMANN, C ., ZHANG, N ., SOCHOROVÁ, M ., KOVÁČIK, A., HAAG, R., VÁVROVÁ, K., ULRICH, M., SCHÄFER-KORTING, M., ZOSCHKE, C.: Ultrastructural and molecular analysis of ribose-induced glycated reconstructed human skin . International Journal of Molecular Sciences, 19 (11), 2018, art . 3521 . BAUDISCHOVÁ, L., STRÁŽNICKÁ, J., POKLADNÍKOVÁ, J., JAHODÁŘ, L.: The quality of information on the internet relating to top-selling dietary supplements in the Czech Republic . International Journal of Clinical Pharmacy, 40 (1), 2018, 183–189 . BERÁNEK, M., FIALA, Z., KREMLÁČEK, J., ANDRÝS, C., KREJSEK, J., HAMÁKOVÁ, K., PALIČKA, V., BORSKÁ, L .: Serum levels of aryl hydrocarbon receptor, cytochromes P450 1A1 and 1B1 in patients with exacerbated psoriasis vulgaris . Folia Biologica, 64 (3), 2018, 97–102 . BERLEC, A ., ŠKRLEC, K ., KOCJAN, J ., OLENIC, M ., ŠTRUKELJ, B .: Single plasmid systems for inducible dual protein expression and for CRISPR-Cas9/CRISPRi gene regulation in lactic acid bacterium Lactococcus lactis. Scientific Reports, 8 (January), 2018, art. 1009. BOHDÁLKOVÁ, L., BOHDÁLEK, P., BŘÍZOVÁ, E., PACHEROVÁ, P., KUBĚNA, A .: Atmospheric metal pollution records in the Kovářská Bog (Czech Republic) as an indicator of anthropogenic activities over the last three millennia . Science of the Total Environment, 633 2018, 857–874 . BORISOV, S ., POMMER, R ., ŠVEC, J ., PETERS, S ., NOVÁKOVÁ, V ., KLIMANT, I .: New red-emitting Schiff base chelates: Promising dyes for sensing and imaging of temperature and oxygen via phosphorescence decay time . Journal of Materials Chemistry C, 6 (33), 2018, 8999–9009 . BOUZ, G., AL HASAWI, N.: The zebrafish model of tuberculosis – No lungs needed. Critical Reviews in Microbiology, 44 (6), 2018, 779–792 . BRABCOVÁ, I., HAJDUCHOVÁ, H., TÓTHOVÁ, V., BÁRTLOVÁ, S., FILKA, J., DOSEDĚL, M., MALÝ, J., VLČEK, J.: Analysis of selected cases of falls of hospitalized patients. Journal of Nursing, Social Studies, Public Health and Rehabilitation, 9 (3–4), 2018, 121–128 . BRABCOVÁ, I., HAJDUCHOVÁ, H., TÓTHOVÁ, V., BÁRTLOVÁ, S., FILKA, J., DOSEDĚL, M., MALÝ, J., VLČEK, J.: Selected risk factors of falls in hospitalized patients: A case-control study. Neuroendocrinology Letters, 39 (7), 2018, 481–488 . BREITEROVÁ, K., LOČÁREK, M., KOHELOVÁ, E., TALÁCKOVÁ, M., HULCOVÁ, D., OPLETAL, L., CAHLÍKOVÁ, L .: Daffodils as potential crops of biologically-active compounds: Assessment of 40 ornamental taxa for their alkaloid profile and cholinesterases inhibition activity. Natural Product Communications, 13 (4), 2018, 419–422 . CARAZO FERNÁNDEZ, A . J ., DUŠEK, J ., HOLAS, O ., ŠKODA, J ., HYRŠOVÁ, L ., SMUTNÝ, T ., SOUKUP, T., DOSEDĚL, M., PÁVEK, P.: Teriflunomide is an indirect human constitutive androstane receptor (CAR) activator interacting with epidermal growth factor (EGF) signaling . Frontiers in Pharmacology, 9, 2018, art . 993 . CATAPANO, M. C., KARLÍČKOVÁ, J., TVRDÝ, V., SHARMA, S., PRASAD, A., SASO, L., CHHILLAR, A., KUNEŠ, J., POUR, M., PARMAR, V., MLADĚNKA, P.: Mono and dihydroxy coumarin derivatives: Copper chelation and reduction ability . Journal of Trace Elements in Medicine and Biology, 46, 2018, 88–95 .
128 differences and the identification of new metabolites. International Journal for Parasitology: Drugs and Drug Resistance, 8 (1), 2018, 50–58 . RAISOVÁ STUCHLÍKOVÁ, L., SKÁLOVÁ, L., SZOTÁKOVÁ, B., SYSLOVÁ, E., VOKŘÁL, I., VANĚK, T., PODLIPNÁ, R.: Biotransformation of flubendazole and fenbendazole and their effects in the ribwort plantain (Plantago lanceolata) . Ecotoxicology and Environmental Safety, 147, 2018, 681–687 . REId, J., PRYDDERCH, H., ŠPULÁK, M., SHIMIZU, S., WALKER, A., GATHERGOOD, N.: Green profiling of aprotic versus protic ionic liquids: Synthesis and microbial toxicity of analogous structures . Sustainable Chemistry and Pharmacy, 7, 2018, 17–26 . RIASOVÁ, P., DOUBKOVÁ, D., PINCOVÁ, L., JUNG, O., POLÁŠEK, M., JÁČ, P.: Development of micellar electrokinetic chromatography method for the determination of three defined impurities in indomethacin. Electrophoresis, 39 (20), 2018, 2550–2557 . SCHRÖTEROVÁ, L., JEŽKOVÁ, A., RUDOLF, E., CALTOVÁ, K., KRÁLOVÁ, V., HANUŠOVÁ, V.: Inositol hexaphosphate limits the migration and the invasiveness of colorectal carcinoma cells in vitro . International Journal of Oncology, 53 (4), 2018, 1625–1632 . SIATKA, T .: Production of anthocyanins in callus cultures of Angelica archangelica . Natural Product Communications, 13 (12), 2018, 1645–1648 . SKALICKÝ, M., KUBEŠ, J., HEJNÁK, V., TŮMOVÁ, L., MARTINKOVÁ, J., MARTIN, J., HNILIČKOVÁ, H.: Isoflavones production and possible mechanism of their exudation in Genista tinctoria L . suspension culture after treatment with vanadium compounds . Molecules, 23 (7), 2018, art . 1619 . SKARKOVÁ, V ., KRÁLOVÁ, V ., KRBAL, L ., MATOUŠKOVÁ, P ., SOUKUP, J ., RUDOLF, E .: Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells . Experimental Cell Research, 369 (2), 2018, 295–303 . SKLENÁŘOVÁ, H ., BÍLKOVÁ, A ., PECHOVÁ, M ., CHOCHOLOUŠ, P .: Determination of major phenolic compounds in apples: Part I – Optimization of high-performance liquid chromatography separation with diode array detection . Journal of Separation Science, 41 (15), 2018, 3042–3050 . SMUTNÝ, T., HARJUMÄKI, R., KANNINEN, L., YLIPERTTULA, M., PÁVEK, P., LOU, Y.: A feasibility study of the toxic responses of human induced pluripotent stem cell-derived hepatocytes to phytochemicals . Toxicology in Vitro, 52, 2018, 94–105 . SOUKUP, O., KORÁBEČNÝ, J., MALIŇÁK, D., NEPOVIMOVÁ, E., PHAM, N., MUSÍLEK, K., HRABINOVÁ, M., HEPNAROVÁ, V., DOLEŽAL, R., PÁVEK, P., JOŠT, P., KOBRLOVÁ, T., JANOČKOVÁ, J., GÓRECKI, L., PSOTKA, M., NGUYEN, T. D., BOX, K., OUTHWAITE, B., ČEČKOVÁ, M., ŠORF, A., JUN, D., KUČA, K.: In vitro and in silico evaluation of non-quaternary reactivators of AChE as antidotes of organophosphorus poisoning – A new hope or a blind alley? Medicinal Chemistry, 14 (3), 2018, 281–292 . SOUKUP, T., BARVÍK, I., NEKVINDOVÁ, J., VELETA, T., KUBĚNA, A., DUINTJER TEBBENS, E. J., PÁVEK, P., DOSEDĚL, M.: Are haplotypes in a single methotrexate pathway more predictive for response in rheumatoid arthritis than in different pathways? Pharmacogenomics, 19 (5), 2018, 379–381 . STOJKOVÁ, P., ŠPIDLOVÁ, P., LENČO, J., ŘEHULKOVÁ, H., KRÁTKÁ, L., STULÍK, J.: HU protein is involved in intracellular growth and full virulence of Francisella tularensis . Virulence, 9 (1), 2018, 754–770 . ŠAFRATOVÁ, M., HOŠŤÁLKOVÁ, A., HULCOVÁ, D., BREITEROVÁ, K., HRABCOVÁ, V., MACHADO, M ., FONTINHA, D ., PRUDENCIO, M ., KUNEŠ, J ., CHLEBEK, J ., JUN, D ., HRABINOVÁ, M ., NOVÁKOVÁ, L ., HAVELEK, R ., SEIFRTOVÁ, M ., OPLETAL, L ., CAHLÍKOVÁ, L .: Alkaloids from Narcissus poeticus cv . Pink Parasol of various structural types and their biological activity . Archives of Pharmacal Research, 41 (2), 2018, 208–218 . ŠIROKÁ, J., ČEČKOVÁ, M., URBÁNEK, L., KRYŠTOF, V., GUCKÝ, T., HOFMAN, J., STRNAD, M., ŠTAUD, F .: LC-MS/MS method for determination of cyclin-dependent kinase inhibitors, BP-14 and BP-20, and its application in pharmacokinetic study in rat . Journal of Chromatography B, 1089, 2018, 24–32 . ŠORF, A., HOFMAN, J., KUČERA, R., ŠTAUD, F., ČEČKOVÁ, M.: Ribociclib shows potential for pharmacokinetic drug-drug interactions being a substrate of ABCB1 and potent inhibitor of ABCB1, ABCG2 and CYP450 isoforms in vitro . Biochemical Pharmacology, 154, 2018, 10–17 . ŠTAUd, F ., KARAHODA, R .: Trophoblast: The central unit of fetal growth, protection and programming . International Journal of Biochemistry and Cell Biology, 105, 2018, 35–40 . TSACHAKI, M., MLADENOVIĆ, N., ŠTAMBERGOVÁ, H., BIRK, J., ODERMATT, A.: Hexose-6-phosphate dehydrogenase controls cancer cell proliferation and migration through pleiotropic effects on the unfoldedprotein response, calcium homeostasis, and redox balance . The FASEB Journal, 32 (5), 2018, 2690–2705 .
129 TŮMOVÁ, L ., HENDRYCHOVÁ, H ., VOKURKOVÁ, D .: Immunostimulant activity of Bergenia extracts . Pharmacognosy Magazine, 14 (56), 2018, 328–332 . TVRDÝ, V., CATAPANO, M. C., RAWLIK, T., KARLÍČKOVÁ, J., BIEDERMANN, D., KŘEN, V., MLADĚNKA, P., VALENTOVÁ, K.: Interaction of isolated silymarin flavonolignans with iron and copper. Journal of Inorganic Biochemistry, 189, 2018, 115–123 . VAŇKOVÁ, B., MALÁ, K., KUBĚNA, A., MALÝ, J., DUSILOVÁ SULKOVÁ, S.: Immunosuppressive therapy related adherence, beliefs and self-management in kidney transplant outpatients . Patient Preference and Adherence, 12, 2018, 2605–2613 . VITVEROVÁ, B., BLAŽÍČKOVÁ, K., NAJMANOVÁ, I., VICEN, M., HYŠPLER, R., DOLEŽELOVÁ, E., NĚMEČKOVÁ, I., DUINTJER TEBBENS, E. J., BERNABÉU, C., PERICACHO, M., NACHTIGAL, P.: Soluble endoglin and hypercholesterolemia aggravate endothelial and vessel wall dysfunction in mouse aorta . Atherosclerosis, 271, 2018, 15–25 . VODÁČKOVÁ, P., VRANÍKOVÁ, B., SVAČINOVÁ, P., FRANC, A., ELBL, J., MUSELÍK, J., KUBALÁK, R., SOLNÝ, T .: Evaluation and comparison of three types of spray dried coprocessed excipient Avicel® for direct compression . BioMed Research International, 18, 2018, art . 2739428 . VOSÁTKA, R., KRÁTKÝ, M., ŠVARCOVÁ, M., JANOUŠEK, J., STOLAŘÍKOVÁ, J., MADACKI, J., HUSZÁR, S ., MIKUŠOVÁ, K ., KORDULÁKOVÁ, J ., TREJTNAR, F ., VINŠOVÁ, J .: New lipophilic isoniazid derivatives and their 1,3,4-oxadiazole analogues: Synthesis, antimycobacterial activity and investigation of their mechanism of action . European Journal of Medicinal Chemistry, 151, 2018, 824–835 . VOSÁTKA, R ., KRÁTKÝ, M ., VINŠOVÁ, J .: Triclosan and its derivatives as antimycobacterial active agents . European Journal of Pharmaceutical Sciences, 114, 2018, 318–331 . ZAHÁLKA, L ., KLOVRZOVÁ, S ., MATYSOVÁ, L ., ŠKLUBALOVÁ, Z ., SOLICH, P .: Furosemide ethanolfree oral solutions for paediatric use: Formulation, HPLC method and stability study . European Journal of Hospital Pharmacy: Science and Practice, 25 (3), 2018, 144–149 . ZÁRYBNICKÝ, T., BOUŠOVÁ, I., AMBROŽ, M., SKÁLOVÁ, L.: Hepatotoxicity of monoterpenes and sesquiterpenes . Archives of Toxicology, 92 (1), 2018, 1–13 . ZÁRYBNICKÝ, T ., MATOUŠKOVÁ, P ., LANCOŠOVÁ, B ., ŠUBRT, Z ., SKÁLOVÁ, L ., BOUŠOVÁ, I .: Inter-individual variability in acute toxicity of R-pulegone and R-menthofuran in human liver slices and their influence on miRNA expression changes in comparison to acetaminophen. International Journal of Molecular Sciences, 19 (6), 2018, art . 1805 . ZITKO, J., DOLEŽAL, M.: Old drugs and new targets as an outlook for the treatment of tuberculosis. Current Medicinal Chemistry, 25 (38), 2018, 5142–5167 . ZITKO, J., JANĎOUREK, O., PATEROVÁ, P., NAVRÁTILOVÁ, L., KUNEŠ, J., VINŠOVÁ, J., DOLEŽAL, M.: Design, synthesis and antimycobacterial activity of hybrid molecules combining pyrazinamide with a 4-phenylthiazol-2-amine scaffold . MedChemComm, 9 (4), 2018, 685–696 . ZITKO, J., MINDLOVÁ, A., VALÁŠEK, O., JANĎOUREK, O., PATEROVÁ, P., JANOUŠEK, J., KONEČNÁ, K., DOLEŽAL, M.: Design, synthesis and evaluation of N-pyrazinylbenzamides as potential antimycobacterial agents . Molecules, 23 (9), 2018, art . 2390 . ARTICLES IN JOURNALS WITHOUT IMPACT FACTOR AND PROCEEDINGS ARNdT, T ., DOHNAL, F ., BABICA, J .: Lékárna, lékárníci a léky v ghettu Terezín . (Pharmacy, pharmacists and drugs in the Terezín ghetto). Česká a slovenská farmacie, 67 (3), 2018, 116–129. dOHNAl, F.: První kroky Československé republiky v oblasti vojenského zdravotnictví (The first steps of the Czechoslovak Republic in the field of military health care). In Medicína, farmácia a veterinárna medicína v období vzniku Československej republiky. Bratislava, Stimul, 2018, 122–127. ISBN 978-80-8127-218-9. dOHNAl, F., KLEIN, L.: Dvojí výročí Vojenského lékařského výzkumného a doškolovacího ústavu Jana Evangelisty Purkyně v Hradci Králové (The double anniversary of the J. E. Purkinje Military Medical Research and Training Institute in Hradec Králové) . Vojenské zdravotnické listy, 87 (4), 2018, 184–191 . DOSEDĚL, M., MALÝ, J., VOSÁTKA, J., MIKOLÁŠEK, P., BRABCOVÁ, I., HAJDUCHOVÁ, H., BÁRTLOVÁ, S., TÓTHOVÁ, V., VLČEK, J.: Zapojení klinického farmaceuta do managementu pádů u polymorbidního geriatrického pacienta s opakovanými pády v anamnéze (Clinical pharmacist involvement in fall
130 management in a polymorbid geriatric patient with a history of recurrent falls). Česká a slovenská farmacie, 67 (5–6), 2018, 205–211 . FIALOVÁ, D.: Specifické rysy racionální geriatrické farmakoterapie: Role klinických farmaceutů v individualizované léčbě ve stáří (Specific features of rational geriatric pharmacotherapy: The role of clinical pharmacists in individualized drug treatment in older age). Vnitřní lékařství, 64 (11), 2018, 1028–1037. KOLÁŘ, J., KOSTŘIBA, J., KOTLÁŘOVÁ, J., AMBRUS, T., SMEJKALOVÁ, L.: Wastage of medicines and its financial impact on the healthcare system in the Czech Republic. Česká a slovenská farmacie, 67 (5–6), 2018, 192–199 . KOLDA, J.: Zárodky zdravotnických knihoven českých milosrdných bratří v 18. století (The beginnings of health libraries of the Czech Brothers Hospitallers in the 18th century). Česká a slovenská farmacie, 67 (5–6), 2018, 216–220 . MALÝ, J ., MALÁ, K ., HORKÝ, P .: XX . sympozium klinické farmacie René Macha (XX . Symposium on Clinical Pharmacy René Mach) . Hradec Králové, Faculty of Pharmacy, 2018, 89 pp . ISBN 978-80-906644-2-5 . PAVLUŠOVÁ, M ., KLIMEŠ, J ., ŠPINAR, J ., ZEMAN, K ., JARKOVSKÝ, J ., BENEŠOVÁ, K ., MIKLÍK, R ., POHLUDKOVÁ, L ., FELŠÖCI, M ., VESELÁ, V ., BLAHOVCOVÁ, M ., DOSTÁL, F ., VONKA, R., PAŘENICA, J.: Chronické srdeční selhání – dopad onemocnění na pacienty a zdravotní systém v České republice: retrospektivní analýza typu cost-of-illness (Chronic heart failure – Impact of the condition on patients and the healthcare system in the Czech Republic: A retrospective cost-of-illness analysis) . Cor et Vasa, 60 (3), 2018, e224–e233 . VOSÁTKA, J., VAŇKOVÁ, B., DVOŘÁČKOVÁ, S., MALÝ, J.: Léčivé přípravky a doplňky stravy ovlivňující nežádoucí symptomy klimakteria (Medicinal products and dietary supplements affecting unfavorable symptoms of climacterium) . Praktické lékárenství, 14 (4), 2018, 162–169 . MONOGRAPHIES AND TEXTBOOKS FIALOVÁ, D., KUMMER, I., DRŽAIĆ, M., LEPPÉE, M.: Ageism in medication use in older patients. In Contemporary Perspectives on Ageism . Cham, Springer, 2018, pp . 213–240 . ISBN 978-3-319-73819-2 . GAJDZIOK, J., VRANÍKOVÁ, B., KOSTELANSKÁ, K., VETCHÝ, D., MUSELÍK, J., GONĚC, R.: Drug solubility and bioavailability improvement . Possible methods with emphasis on liquisolid systems formulation . München, GRIN Verlag, 2018, 176 pp . ISBN 978-3-668-81046-4 . HAVLÍČKOVÁ, I., DOSTÁLOVÁ, Š., KATEROVÁ, Z.: English for Pharmacy and Medical Bioanalytics, 2nd ed . (reprint), Prague, Karolinum Press, 2018, 296 pp . ISBN 978-80-246-2797-7 . JAHODÁŘ, L.: Rostliny způsobující otravy (Plants causing poisoning). Prague, Karolinum Press, 2018, 384 pp. ISBN 978-80-246-4050-1, ISBN 978-80-246-4190-4 (e-book, PDF) . KLEMERA, P .: Aplikovaná matematika (Applied mathematics), 3rd ed ., Prague, Karolinum Press, 2018, 94 pp . ISBN 978-80-246-3863-8 . KUNEŠOVÁ, K.: Latina pro farmaceuty. Učebnice pro posluchače oborů Farmacie a Zdravotnická bioanalytika (Latin for pharmacist . Textbook for students of pharmacy and medical bioanalytics), 4th ed . (2nd reprint), Prague, Karolinum Press, 2018, 196 pp . ISBN 978-80-246-2346-7 . SKÁLOVÁ, L ., BOUŠOVÁ, I ., MACHALA, M ., MATOUŠKOVÁ, P ., PÁVEK, P ., PODLIPNÁ, R ., SOUČEK, P., SVOBODOVÁ, H., SZOTÁKOVÁ, B., TREJTNAR, F., VONDRÁČEK, J., WSÓL, V.: Metabolismus léčiv a jiných xenobiotik (Metabolism of drugs and other xenobiotics), 2nd modified and extended ed., Prague, Karolinum Press, 2018, 172 pp . ISBN 978-80-246-3762-4 (e-book, PDF) . SVATOŠ, L .: Hospitalstiftung und Krankenhaus der Barmherzigen Brüder in Kukus 1696–1780 (The Hospital Foundation and Hospital of the Brothers Hospitallers of Saint John of God in Kuks 1696–1780) . In Germanische Provinz des Hospitalordens des Hl . Johannes von Gott bis 1780 . Cieszyn, Konwent Zakonu Bonifratrów, 2018, pp . 399–433 . ISBN 978-83-932300-5-1 . SVATOŠ, L .: Krankenprotokolle des Kukuser Krankenhauses des Ordens der Barmherzigen Brüder (1744–1780) (Medical Records of Patients of Hospital of the Brothers Hospitallers of Saint John of God in Kuks (1744–1780)) . In Germanische Provinz des Hospitalordens des Hl . Johannes von Gott bis 1780 . Cieszyn, Konwent Zakonu Bonifratrów, 2018, pp . 457–483 . ISBN 978-83-932300-5-1 . SVATOŠ, L ., RUSEK, V .: Apothekenkunde der Barmherzigen Brüder in der Frühen Neuzeit (The pharmacy practice of the Brothers Hospitallers of Saint John of God in the early modern period) . In Germanische Provinz
131 des Hospitalordens des Hl . Johannes von Gott bis 1780 . Cieszyn, Konwent Zakonu Bonifratrów, 2018, pp . 47–64 . ISBN 978-83-932300-5-1 . ŠKLUBALOVÁ, Z., VRANÍKOVÁ, B.: Oční přípravky (Ocularia, ophthalmica) (Ophthalmic preparations (ocularia, ophthalmica), Praha, Maxdorf, 2018, 120 pp . ISBN 978-80-7345-572-9 . ŠPAČEK, J., KALOUSEK, I., JÍLEK, P., BAVOR, J., BENDOVÁ, M., BOČKOVÁ, I., BOUDA, J., BUCHTA, V., HALADA, P., HOŘEJŠÍ, J., CHOVANEC, J., KALOUSEK, Š., KESTŘÁNEK, J., KOPECKÝ, P., KOŠŤÁL, M., KŘÍŽ, J., KUDELA, M., LACO, J., LIEBICHOVÁ, I., ONDROVÁ, D., OTČENÁŠEK, M., PETERA, J ., PILKA, R ., POSPÍŠILOVÁ, B ., ROB, L ., ROBOVÁ, H ., SALAVEC, M ., SEDLÁKOVÁ, I ., SIRÁK, I., SLÁMA, J., ŠTĚPÁN, J., TOŠNER, J., ŽEMLICKOVÁ, H.: Vybrané kapitoly z gynekologie (Selected chapters in gynecology), Praha, Mladá fronta, 2018, 676 pp . ISBN 978-80-204-4646-6 . CERTIFIED METHODOLOGY BÍLKOVÁ, A., VÁVRA, R., HOLLÁ, M., SKLENÁŘOVÁ, H., CHOCHOLOUŠ, P., DVOŘÁKOVÁ, R., HORNA, A., EICHLEROVÁ, E.: Metodika stanovení hlavních fenolických sloučenin v genotypech jabloní s ohledem na různé podmínky skladování. (Methodology of determination of main phenolic compounds in genotypes of apples with regard to various storage conditions), Holovousy, Výzkumný a šlechtitelský ústav ovocnářský, 2018, 43 pp. ISBN 978-80-87030-68-4. DEGREES Lectures for the Professorship Appointments, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2018 doc. PharmDr. PETR ZIMČÍK, Ph.D.: Associate Professor, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, Hradec Králové . Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 30 . 8 . 2017 Continuation: 10 . 10 . 2017 Title of Lecture: Fotodynamická terapie – Minulost, současnost, budoucnost (?) (Photodynamic therapy – Past, present, future (?)), 12 . 12 . 2017 Appointment: 05 . 12 . 2018 Habilitation Theses and Lectures for Associated Professor Appointments, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2018 PharmDr . JAROSLAV ROH, Ph .D .: Senior Lecturer, Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Hradec Králové . Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 7 . 9 . 2017 Continuation: 10 . 10 . 2017 Habilitation Thesis: Příprava a studium antituberkuloticky účinných látek ze skupiny dusíkatých heterocyklů (Preparation and study of antituberculous agents from the class of nitrogen heterocycles), defended 12 . 12 . 2017 Title of Lecture: Nové strukturní typy antituberkulotik v preklinické a klinické fázi vývoje (Novel structural types of antituberculous drugs in preclinical and clinical phases of development), 12 . 12 . 2017 Appointment: 1 . 3 . 2018
132 Doctoral Dissertation Theses to obtain the Ph.D. Degree, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2018 Mgr. BUREŠ, JAN: Analytické a bioanalytické hodnocení nových potencionálních léčiv ze skupiny chelátorů železa (Analytical and bioanalytical evaluation of novel potential drugs from the group of iron chelators), 11 . 5 . 2018, Ph .D . Mgr. HULCOVÁ, DANIELA: Biologická aktivita alkaloidů Narcissus pseudonarcissus L . cv . Dutch Master (Amaryllidaceae) (Biological activity of alkaloids from Narcissus pseudonarcissus L . cv . Dutch Master (Amaryllidaceae)), 25 . 10 . 2018, Ph .D . Ing. HURYCHOVÁ, HANA: Studium statických a dynamických sypných vlastností farmaceutických excipientů (Study of static and dynamic flow properties of pharmaceutical excipients), 13. 6. 2018, Ph.D. Mgr . HYRŠOVÁ, LUCIE: Nové aspekty funkce a regulace pregnanového X receptoru (New aspects of pregnane X receptor function and regulation), 6 . 12 . 2018, Ph .D . Mgr. LOCHMAN, LUKÁŠ: Studium rozpoznávacích částí senzorických azaftalocyaninů (Study of recognition moieties of sensoric azaphthalocyanines), 23 . 1 . 2018, Ph .D . Mgr. PATKOVÁ, ANNA: Aplikace nepřímé kalorimetrie u dvou různých inzulinorezistentních stavů – polytraumatu a gravidity (Indirect calorimetry application in two different insulin-resistant states – polytrauma and pregnancy), 26 . 9 . 2018, Ph .D . Mgr. ŘEZNÍČEK, JOSEF: Interakce antivirotik s lékovými transportéry; vliv na farmakokinetiku (Interactions of antiretrovirals with drug transporters; role in pharmacokinetics), 14 . 9 . 2018, Ph .D . Ing. STRÁNSKÁ, DENISA: Nanovlákenné membrány jako nosiče léčiv II (Nanofibrous membranes as drug delivery systems II), 20 . 9 . 2018, Ph .D . Mgr. VANĚČKOVÁ, NINA: Study of the inhibitory (toxic) effect of the alkaloids from chosen plants of Amaryllidaceae family on some human enzymatic systems (in vitro study) II, 25 . 10 . 2018, Ph .D . Mgr. ZEMČÍKOVÁ, LUCIE: Vliv přírodních látek na transport lékovými OATP transportéry (The effect of natural compounds on transport by OATP drug transporters), 16 . 11 . 2018, Ph .D . Rigorous Theses to obtain the degree PharmDr. (Doctor of Pharmacy, graduates of the study programme Pharmacy) or RNDr. (Doctor of Natural Sciences, graduates of study programme Bioanalytical Laboratory Diagnostics in Medicine), Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2018 Mgr. AMBROŽ, MARTIN, Ph.D. Seskviterpeny v protinádorové terapii (Sesquiterpenes in cancer therapy), 29 . 5 . 2018, PharmDr . Mgr . ANDRŠ, MARTIN, Ph .D .: Investigation of compouds affecting the neoplastic cell changes, 17 . 5 . 2018, PharmDr . Mgr. BABINSKÁ, AGÁTA: Využitie kapalinovej chromatografie vo farmaceutickej analýze III (Use of liquid chromatography in pharmaceutical analysis III), 22 . 11 . 2018 . PharmDr . Mgr. BAĎUROVÁ, KRISTÝNA: Hodnocení obsahu fenolických látek v ovoci (Evaluation of phenolic compounds content in fruits), 15 . 11 . 2018, RNDr . Mgr. BAKOVÁ, IZABELA: Izolace alkaloidů druhu Magnolia soulangeana Soul .-Bod . a studium jejich biologické aktivity (Isolation of alkaloids of the species Magnolia soulangeana Soul .-Bod . and study of their biological activity), 28 . 2 . 2018, PharmDr . Mgr. BEIL, KAMIL: Hodnocení oxidace nutričních substrátů a energetického výdeje u polytraumatizovaných pacientů na nutriční podpoře (Evaluation of the nutritional subtrates oxidation and energy expenditure in polytrauma patients on nutritional support), 15 . 2 . 2018, PharmDr . Mgr . BELKINA, TATIANA, Ph .D .: Non-prescribed antibiotic use in some developing countries and its association with drug resistance, 10 . 4 . 2018, PharmDr . Mgr. BÉREŠOVÁ, MICHAELA: Štúdium konsolidačného chovania laktosy a jej zmesí (Study of consolidation behaviour of lactose and its blends), 24 . 4 . 2018, PharmDr . Mgr. BLAŽÍČKOVÁ, KATEŘINA, Ph.D.: Vztah tkáňového a solubilního endoglinu k endotelové dysfunkci a možnosti jejich ovlivnění (Tissue and soluble endoglin relation to the endothelial dysfunction and possible treatment), 15 . 2 . 2018, PharmDr . Mgr. BLAŽKOVÁ, ANDREA: Modifikace kapilární stěny pro separační účely I (Modification of the capillary wall for the separation purpose I), 23 . 3 . 2018, PharmDr .
133 Mgr . BOUNTALIS, KONSTANTINOS SPYRIDON: Soluble endoglin effects on endothelial dysfunction markers in mice, 14 . 9 . 2018, PharmDr . Mgr. BROKEŠOVÁ, KATEŘINA: Deriváty aminobenzoových kyselin jako potenciální antimikrobní látky (Derivatives of aminobenzoic acids as potential antimicrobial agents), 9 . 11 . 2018, PharmDr . Mgr . BULVOVÁ, LEONTINA: Alkaloidy Papaver rhoeas L. (Papaveraceae) a jejich biologická aktivita vztažená k Alzheimerově chorobě I (Alkaloids of Papaver rhoeas L . (Papaveraceae) and their biological activity related to Alzheimerʼs disease I), 28. 2. 2018, PharmDr. Mgr. BUREŠ, JAN, Ph.D.: Analytické a bioanalytické hodnocení nových potencionálních léčiv ze skupiny chelátorů železa (Analytical and bioanalytical evaluation of novel potential drugs from the group of iron chelators), 15 . 11 . 2018, PharmDr . Mgr. BURKERTOVÁ, ALICE: Alkaloidy čeledi Amaryllidaceae: Isolace, strukturní identifikace, biologická aktivita. I (Alkaloids of Amaryllidaceae family: Isolation, structural identification, biological activity. I), 28 . 2 . 2018, PharmDr . Mgr. ČAKURDOVÁ, MARTA: Alkaloidy Papaver rhoeas L. (Papaveraceae) a jejich biologická aktivita vztažená k Alzheimerově chorobě II (Alkaloids of Papaver rhoeas L . (Papaveraceae) and their biological activity related to Alzheimerʼs disease II), 27. 6. 2018, PharmDr. Mgr. ČERMÁKOVÁ, MARTINA: Western blot analýza vybraných molekul oxidačního stresu v aortě apoE/LDLR deficientního myšího modelu (Western blot analysis of selected oxidative stress markers in aorta of apoE/LDLR deficient mice), 27. 6. 2018, RNDr. Mgr. DOSTÁLOVÁ, ELIŠKA: Studium sypných a konsolidačních vlastností velikostních frakcí bezvodé laktosy (Study of bulk and consolidation properties of size fractions of anhydrous lactose), 24 . 10 . 2018, PharmDr . Mgr . DOUBKOVÁ, DAGMAR: Vývoj kapilární elektroforetické metody pro stanovení vybraných lékopisných nečistot indometacinu (Development of capillary electrophoresis method for the determination of three pharmacopoeial impurities in indomethacin), 22 . 11 . 2018, PharmDr . Mgr. DYMÁKOVÁ, ANDREA: Effect of synthetic magnolol derivatives on activity of nuclear receptors PPARγ and RXRα, 06. 02. 2018, PharmDr. Mgr. DZÁMOVÁ, PAVLÍNA: Hodnocení sypných a konsolidačních vlastností magnesium aluminometasilikátu (Evaluation of flow and consolidation properties of magnesium aluminometasilicate), 29. 5. 2018, PharmDr. Mgr . EISNER, TOMÁŠ: Synthesis of novel cardioprotectants and metabolites of potent anticancer drug Bp4eT, 9 . 11 . 2018, PharmDr . Mgr. ERBENOVÁ, KATEŘINA: Studium interakce antiretrovirotika maraviroku s lékovými transportéry ABCB1 a ABCG2 (Study on interaction potential of maraviroc with drug transporters ABCB1 and ABCG2), 15 . 2 . 2018, PharmDr . Mgr. FOUSOVÁ, DOMINIKA: Studium přímo lisovatelných tabletovin a tablet s retetardační složkou obsahující polyvinyl-acetát a povidone (A study of directly compressible tableting materials and tablets with the retarding component containing polyvinyl acetate and povidone), 17 . 4 . 2018, PharmDr . Mgr . GAJDOŠOVÁ, VANESA: Analýza liekových problémov (“drug-related problems”) v zdravotníckom zariadení IV (Analysis of drug-related problems in a healthcare facility IV), 21 . 6 . 2018, PharmDr . Mgr. GORBUNOVOVÁ, EVA: Porovnání chelatace iontů mědi benzoovými kyselinami (Comparison of copper ion chelation by benzoic acids), 12 . 9 . 2018, PharmDr . Mgr. GOROVÁ, BARBORA: Železo-chelatační vlastnosti extraktů plodů z různých variet bezu černého (Ironchelating properties of fruit extracts of various elderberries), 14 . 9 . 2018, PharmDr . Mgr. GULÁŠ, ONDREJ: Testovanie separačného potenciálu stacionárnych fáz na báze porézneho grafitového uhlíku (Evaluation of separation potential of stationary phases based on porous graphitic carbon), 22 . 11 . 2018, PharmDr . Mgr . HADRAVSKÁ, PAVLÍNA: Metabolomic analysis of bile acids in various biological samples, 14 . 09 . 2018, PharmDr . Mgr. HALVOVÁ, PETRA, Ph.D.: Terapeutické monitorování léčiv v klinické praxi a výzkumu – Nové možnosti TDM cyklosporinu A a jeho metabolitů po transplantaci ledvin (Therapeutic drug monitoring in clinical practice and research – new possibilities of TDM of cyclosporine A and its metabolites after renal transplantation), 2 . 10 . 2018, PharmDr . Mgr. HARTINGER, JAN, Ph.D.: Molekulární podstata etiologie toxického působení fluoropyrimidinů se zaměřením na palmární-plantární erythrodysesthesii a použití potenciálních antidot (Molecular basis of fluo-
134 ropyrimidine toxic effect etiology with focus on palmar-plantar erythrodysesthesia and potential antidote use), 15 . 2 . 2018, PharmDr . Mgr . HIRŠOVÁ, PETRA, Ph .D .: Effect of epigallocatechin gallate on bile production, 15 . 2 . 2018, PharmDr . Mgr . HLADKÝ, PAVEL: Formulace a (trans)dermální podání imiquimodu (Formulation and (trans)dermal delivery of imiquimod), 24 . 10 . 2018, PharmDr . Mgr. HOMOLA, PAVEL: Studium vybraných chelátorů železa pro prevenci oxidačního stresu u buněčné linie PC12 (Study of selected iron chelators for oxidative stress prevention in PC12 cell line), 27 . 6 . 2018, PharmDr . Mgr. HRUŠKOVÁ, MAGDA: Alkaloidy dřeva druhu Liriodendron tulipifera L. a jejich aktivita vůči lidským cholinesterasam (Alkaloids from the wood of the species Liriodendron tulipifera L . and their activity against human cholinesterases), 8 . 6 . 2018, PharmDr . Mgr. JANČÁROVÁ, ALENA: Sulfonované azaftalocyaniny – syntéza a hodnocení jejich fotodynamické aktivity (Sulfonated azaphthalocyanines – synthesis and evaluation of their photodynamic activity), 8 . 11 . 2018, PharmDr . Mgr. JANETKOVÁ, MONIKA: Využití HPLC v chirálních separacích III (The employment of HPLC in the field of chiral separations III), 23 . 3 . 2018, PharmDr . Mgr. JANÍČEK, TOMÁŠ: Účinek vybraných seskviterpenů na antioxidační enzymy u buněčné linie Caco-2 (The effect of selected sesquiterpenes on antioxidant enzymes in Caco-2 cell line), 6 . 2 . 2018, PharmDr . Mgr. JELENKOVÁ, KLÁRA: Vliv monepantelu na expresi vybraných enzymů u vlasovky slezové (Effect of monepantel on the expression of selected enzymes in Haemonchus contortus), 6 . 2 . 2018, PharmDr . Mgr. JIŘIČKOVÁ, NINA: Nesilikagelové materiály v analýze léčiv III (Non-silica based materials in drug analysis III), 15 . 11 . 2018, PharmDr . Mgr. JON, VOJTĚCH: Syntéza a studium 1-O-acylceramidů (Synthesis and study of 1-O-acylceramides), 28 . 2 . 2018, PharmDr . Mgr. JUHÁS, MARTIN: Definition of the carbohydrate binding capacities of the novel enterotoxin LT-IIc, 8. 11. 2018, PharmDr . Mgr. KALÁBOVÁ, DIANA: Děkani farmaceutické fakulty UK v Hradci Králové (Deans of Charles University, Faculty of Pharmacy in Hradec Králové), 15 . 3 . 2018, PharmDr . Mgr. KASALOVÁ, EVA, Ph.D.: Moderní separační techniky pro analýzu biologického materiálu v klinickém výzkumu (Modern separation techniques for the analysis of biological material in clinical research), 28 . 6 . 2018, RNDr . Mgr . KERHARTOVÁ, MARKÉTA: Syntéza nových hybridních molekul M1 agonisty s inhibitory acetylcholinesterasy (Synthesis of novel hybrid molecules combining an M1 agonist and acetylcholinesterase inhibitors), 11 . 1 . 2018, PharmDr . Mgr. KLAUČOVÁ, MARTINA: Použitie Amesovho testu v štúdiu genotoxicity novo vyvíjaných látok (Ames test in the drug development), 12 . 9 . 2018, PharmDr . Mgr. KLÍMOVÁ, KAMILA: Alkaloidy rostlin čeledi Amaryllidaceae a jejich biologická aktivita 1 (Alkaloids of the family Amaryllidaceae and their biological activity 1), 27 . 6 . 2018, PharmDr . Mgr. KLINEROVÁ, JANA: Extrakce zinku z vodných roztoků pomocí extrakce na tuhou fázi v sekvenční injekční analýze (Extraction of zinc from water solutions using solid phase extraction in sequential injection analysis), 28 . 6 . 2018, RNDr . Mgr. KOLENIČ, MAREK: Studie transalkylace u aromatických tert-butylsulfidů (Study of transalkylation of tert-butylsulfides), 8. 11. 2018, PharmDr. Mgr . KOLLÁROVÁ, NIKOLA: Detection of Sap2 in the secretome of Candida albicans cell wall and secretory mutants, 15 . 2 . 2018, PharmDr . Mgr . KÖSZEGY, ERIK: Liberácia kyseliny listovej z mikrovlákien na báze kyseliny hyaluronovej (Liberation of folic acid from microfibers based on hyaluronic acid), 29. 5. 2018, PharmDr. Mgr. KOUKLÍKOVÁ, ETELA: Studium vlivu inhibitorů cyklin-dependentních kinas na expresi vybraných AKR a CBR enzymů v lidských buněčných liniích (Study of the effect of cyclin-dependent kinase inhibitors on the expression of selected AKR and CBR enzymes in human cell lines), 14 . 9 . 2018, RNDr . Mgr. KOVÁČIK, ANDREJ, Ph.D.: Studium vlivu hydroxylace ceramidů na permeabilitu a mikrostrukturu modelových lipidových membrán (Study of effect of ceramide hydroxylation on permeability and microstructure of model lipid membranes), 28 . 2 . 2018, PharmDr . Mgr. KOVÁŘOVÁ, BARBORA: Reporter gene studies for nanoparticle mediated DNA and siRNA delivery, 27 . 6 . 2018, PharmDr .
135 Mgr. KOVÁŘOVÁ, LENKA: Asociace fázového úhlu s parametry energetického metabolismu u pacientů s CHOPN (Association of phase angle with parameters of energy metabolism in patients with COPD), 14 . 9 . 2018, PharmDr . Mgr. KREJCAROVÁ, JANA: Western blot analýza vybraných molekul zánětu v aortě apoE/LDLR deficientního myšího modelu (Western blot analysis of selected inflammatory markers in aorta of apoE/LDLR deficient mice), 15 . 2 . 2018, PharmDr . Mgr. KRIVOŠOVÁ, MICHAELA: Hodnotenie potenciálne nevhodných liečiv a liekových postupov v starobe I (Evaluation of potentially inappropriate drugs and drug procedures in the old age I), 21 . 6 . 2018, PharmDr . Mgr. KROULÍKOVÁ, PAVLA: Testování inhibiční aktivity nových protinádorových léčiv vůči vybraným izoformám cytochromu P450 (Study of inhibition activity of new antitumor drugs against chosen isoforms of cytochromes P450), 15 . 2 . 2018, PharmDr . Mgr. KUNOVSKÁ, KLÁRA: Hodnocení antioxidační aktivity přírodních látek (Evaluation of antioxidant activity of natural compounds), 23 . 3 . 2018, PharmDr . Mgr. KVĚTOŇ, MARTIN: Screening systémových amyloidóz v materiálu endoskopických biopsií (Screening for systemic amyloidoses in endoscopic biopsy samples), 14 . 9 . 2018, RNDr . Mgr. LALINSKÁ, ANEŽKA: Studium interakcí antiretroviálního léčiva tenofoviru a jeho proléčiva tenofoviru disoproxil fumarátu s placentárními nukleosidovými transportéry (Study of interactions of antiviral drug tenofovir and its prodrug tenofovir disoproxil fumarate with placental nucleoside transporters), 14 . 9 . 2018, PharmDr . Mgr. LÁZNIČKA, LUKÁŠ: Hodnocení viskozity celulosových základů pro magistraliter přípravu (Evaluation of viscosity of the cellulosis bases for extemporaneous preparation), 29 . 5 . 2018, PharmDr . Mgr. LEHEČKOVÁ, ZDEŇKA: Effects of exotic plant extracts on proliferation and migration of normal human dermal fibroblasts, 12. 9. 2018, PharmDr. Mgr. LEŠKOVÁ, PATRÍCIA: Štúdium lisovateľnosti a vlastností tabliet zo zmesného suchého spojiva s mannitolom pre tablety dispergovateľné v ústach (A study of the compressibility and the properties of tablets from the coprocessed dry binder with mannitol for oral disintegrating tablets), 24 . 10 . 2018, PharmDr . Mgr. LNĚNIČKOVÁ, KATEŘINA, Ph.D.: Modulace biotransformačních a antioxidačních enzymů vybranými přírodními látkami (Modulation of biotransformation and antioxidant enzymes by selected natural compounds), 29 . 5 . 2018, PharmDr . Mgr. LOCHMAN, LUKÁŠ, Ph.D.: Studium rozpoznávacích částí senzorických azaftalocyaninů (Study of recognition moieties of sensoric azaphthalocyanines), 17 . 5 . 2018, PharmDr . Mgr. MACHÁČEK, MILOSLAV, Ph.D.: Studium nových fotosensitizérů ze skupiny ftalocyaninů a azaftalocyaninů pro fotodynamickou léčbu nádorových onemocnění (Study of novel phthalocyanine and azaphthalocyanine photosensitizers for the photodynamic therapy of cancer), 6 . 2 . 2018, RNDr . Mgr. MALINOVÁ, TEREZA: Využití kapalinové chromatografie ve farmaceutické analýze IV (Use of liquid chromatography in pharmaceutical analysis IV), 15 . 11 . 2018, PharmDr . Mgr. MATĚJKOVÁ, LENKA: Vliv nanočástic na proteom rostlin (Effect of nanoparticles on plant proteome), 6 . 2 . 2018, PharmDr . Mgr. MĚRKOVÁ, VERONIKA: Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages, 6 . 2 . 2018, PharmDr Mgr . MILTOVÁ, LUCIE: Synthesis of new organic compounds containing chalcogens, 17 . 5 . 2018, PharmDr . Mgr. MOCOVÁ, KLÁRA: Stanovení stechiometrie komplexů 7,8-dihydroxykumarinů s mědí (Determination of the stoichiometry of the copper complexes with 7,8-dihydroxycoumarins), 14 . 9 . 2018, PharmDr, Mgr. MORAVČÍK, ŠTEFAN: Využitie laktónov v syntéze acylceramidov (Use of lactones in acylceramide synthesis), 9 . 11 . 2018, PharmDr . Mgr . NAJMANOVÁ, IVETA, Ph .D .: Vliv polyfenolických látek na hladký cevní sval (The effect of polyphenolic substances on vascular smooth muscle), 15 . 2 . 2018, PharmDr . Mgr. NGUYEN THI, THU HA: Studium přímo lisovatelných tabletovin a tablet se směsným suchým pojivem obsahujícím laktosu, povidon a krospovidon (A study of directly compressible tableting materials and tablets with the coprocessed dry binder containing lactose, povidone and crospovidone), 17 . 4 . 2018, PharmDr . Mgr . NOVÁK, FILIP: HPLC-high resolution mass spectrometry analysis of in vitro and in vivo metabolism of scoparone, 14 . 9 . 2018, PharmDr . Mgr. NOVOTNÁ, MARTA: Semipreparativní separace biokonjugátů azaftalocyanínů (Semipreparative separation of bioconjugates of azaphtalocyanines), 23 . 3 . 2018, PharmDr .
136 Mgr. NOVÝSEDLÁKOVÁ, ALENA: Účinky vybraných izoflavonoidov in vitro na izolovanej aorte potkana (The in vitro effects of selected isoflavonoids on isolated rat aorta), 15. 2. 2018, PharmDr. Mgr. OBERTOVÁ, NIKOLA: Inhalačné podanie liečiv v terapii obštrukčných chorob pľuc (Use of inhaled drugs in obstructive pulmonary diseases), 21 . 6 . 2018, PharmDr . Mgr . OBRDLÍK, DANIEL: Syntéza ceramidu NS pomocí Grubbsovy metateze (Synthesis of ceramide NS using Grubbs metathesis), 28 . 2 . 2018, PharmDr . Mgr. OHÁŇKOVÁ, ALENA: Hodnocení stability gestodenu s využitím HPLC (Evaluation of stability of gestodene using HPLC), 15 . 11 . 2018, PharmDr . Mgr. ONDRÁŠIKOVÁ, MICHAELA: Zdravý životný štýl záujemcov o zdravú výživu (Healthy lifestyle of people interested in healthy diet), 21 . 6 . 2018, PharmDr . Mgr . PAKÁNOVÁ, ALICA: Sekundární metabolity rostlinných kultur in vitro II (Secondary metabolites of plant cultures in vitro II), 27 . 6 . 2018, PharmDr . Mgr. PAĽOVÁ, ROMANA: Miniaturized and fast method for solubility and level of supersaturation determinations of drug nanocrystals, 24 . 4 . 2018, PharmDr . Mgr. PATARÁKOVÁ, PAULA: Vplyv prenylovaných flavonoidov na biotransformačné enzýmy in vitro (Effect of prenylated flavonoids on biotransformation enzymes in vitro), 6 . 2 . 2018, PharmDr . Mgr. PLŠKOVÁ, MARTINA: Systémová zánětlivá odpověď organismu na klostridiovou infekci (The systemic inflammatory response of the organism to Clostridium difficile infection), 6 . 2 . 2018, RNDr . Mgr . PODHORSKÁ, GABRIELA: Effects of simple sugar consumption on cognitive functions in female rats, 6 . 2 . 2018, PharmDr . Mgr. POLEDNÍKOVÁ, MICHAELA: Syntéza a biologické hodnocení purinových inhibitorů fosfatidylinositol3-kinas a příbuzných proteinkinas I (Synthesis and biological evaluation of purine inhibitors of phosphatidylinositol 3-kinases and related protein kinases I), 11 . 1 . 2018, PharmDr . Mgr. PRAŽIENKOVÁ, NIKOLA: Vliv domácího prostředí na vznik alergií u dětí (The effect of household characteristics on the allergies in children), 15 . 2 . 2018, PharmDr . Mgr . PRCHAL, LUKÁŠ, Ph .D .: Anthelmintic and other xenobiotic biotransformation in helminths and its contribution to resistance development, 29 . 5 . 2018, PharmDr . Mgr. PŘEDOTA, VÁCLAV: Analýza magistraliter receptů v lékárně nemocnice České Budějovice (The analysis of extemporaneously compounded prescriptions in the pharmacy of the Hospital České Budějovice), 21. 6. 2018, PharmDr . Mgr. PŮLKRÁBKOVÁ, MARTINA: Hodnocení fotodynamické aktivity derivátů tetrapyrido-porphyrazinu pro léčbu nádorových onemocnění (Evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of tumorous diseases), 27 . 6 . 2018, PharmDr . Mgr . PUZYREVSKÁ, JANA: Biologická aktivita obsahových látek rostlin XXXIV . Alkaloidy nati Glaucium flavum CRANTZ a jejich vliv na lidské cholinesterasy (Biological activity of plant metabolites XXXIV . Alkaloids from the herb of Glaucium flavum CRANTZ and their impact on human cholinesterases), 28 . 2 . 2018, PharmDr . Mgr. ŘEHOUNKOVÁ, MICHAELA: Genetické markery pro sledování posttransplantačního chimerismu (Genetic markers for monitoring post-transplant chimerism), 14 . 9 . 2018, RNDr . Mgr. REPEĽOVÁ, BEÁTA: Studium vlivu antiretrovirálních léčiv na transmembránový transport tenofoviru disoproxil fumarátu přes monovrstvu MDCKII-ABCB1 buněk (Study of effects of antiretroviral drugs on transmembrane transport of tenofofovir disoproxil fumarate across MDCKII-ABCB1 cell monolayer), 15 . 2 . 2018, PharmDr . Mgr. ŘEZNÍČEK, JOSEF, Ph.D.: Interakce antivirotik s lékovými transportéry; vliv na farmakokinetiku (Interactions of antiretrovirals with drug transporters; role in pharmacokinetics), 13 . 11 . 2018, PharmDr . Mgr. RÖSLEROVÁ, ELIŠKA: Analýza vzdělávání farmaceutů v České republice po dosažení odborné způsobilosti (Analysis of education of pharmacists in the Czech Republic after graduation), 21. 6. 2018, PharmDr . Mgr. RŮŽIČKA, ŠTĚPÁN: Vývoj HPLC metody pro stanovení vybraných karotenoidů v ovoci (HPLC method development for carotenoids determination in fruits), 04 . 05 . 2018, PharmDr . Mgr. RÝDLOVÁ, KATEŘINA: Alkaloidy Narcissus ‘Dutch Master’ (Amaryllidaceae) a jejich biologická aktivita III (Alkaloids of Narcissus ‘Dutch Master’ (Amaryllidaceae) and their biological activity III), 28 . 2 . 2018, PharmDr .
137 Mgr. SAGANDYKOVA, AIGUL: The effect of lipid signaling pathway interference on sorafenib cytotoxic efficacy and function of efflux transporters in mouse hepatocellular carcinoma cells, 14. 9. 2018, PharmDr. Mgr . ŠAMAJOVÁ, MARIANNA: Vstup baktérie Mycobacterium bovis BCG do B lymfocytov (Entry of bacteria Mycobacterium bovis BCG into B lymphocytes), 12 . 9 . 2018, PharmDr . Mgr . SEDLÁKOVÁ, JANA: Synthesis of phosphoramidate prodrugs “ProTides” as novel potential therapeutic agents for the treatment of congenital disorders of glycosylation and mitochondrial DNA depletion syndrome, 9 . 11 . 2018, PharmDr . Mgr . ŠIŠMOVÁ, PETRA: The impaired change in plasma long-chain acylcarnitine level as a marker of insulin resistence, 15 . 2 . 2018, PharmDr . Mgr. ŠOFRANKOVÁ, ALEXANDRA: Fraktálne aspekty sypného a konsolidačného chovania mikrokryštalickej celulosy (Fractal aspects of flow and consolidation behaviour of microcrystalline cellulose), 24. 4. 2018, PharmDr . Mgr. SOUKUPOVÁ, ANDREA: Hodnocení potenciálních léčiv Alzheimerovy choroby jakožto inhibitorů prolyloligopeptidasy (Evaluation of potential Alzheimer’s disease drugs as prolyloligopeptidase inhibitors), 14 . 9 . 2018, PharmDr . Mgr . ŠPATENKOVÁ, NIKOLA: Vplyv onkomarkeru CA 19-9 na prognózu pacientov s karcinómom pankreasu (Influence of oncomarker CA 19-9 in prognosis of patients with pancreatic cancer), 15. 2. 2018, PharmDr. Mgr. STEHLÍKOVÁ, TEREZA: Časné změny exprese eNOS a ICAM-1 v aortě myší po podávání vysokotukové diety (Early changes in eNOS and ICAM-1 expression in mice aorta after administration of high fat diet), 15 . 2 . 2018, PharmDr . Mgr. STRAKA, ONDŘEJ: Syntéza substituovaných arylguanidinů jako potenciálních léčiv XIII (Synthesis of substituted arylguanidines as potential drugs XIII), 9 . 11 . 2018, PharmDr . Mgr. STUPKOVÁ, EVA: Výrobní program lékárny U Černého orla na Malé Straně (Products of Black Eagle Pharmacy at Malá Strana district of Prague), 15 . 3 . 2018, PharmDr . Mgr. SVOBODA, PAVEL, Ph.D.: Matricové efekty v LC-MS analýze: Vznik, hodnocení a jejich odstranění (Matrix effects in LC-MS analysis: Occurrence, evaluation, and their elimination), 23 . 3 . 2018, PharmDr . Mgr . SVOBODOVÁ, MAGDALÉNA: Microglia control adenosine A2A-receptor mediated astrogliosis, 15 . 2 . 2018, PharmDr . Mgr. SWIERCZKOVÁ, IVA: Časné změny exprese tkáňového endoglinu a VCAM-1 v aortě myší po podávání vysokotukové diety (Early changes in tissue endoglin and VCAM-1 expression in mice aorta after administration of high fat diet), 6 . 2 . 2018, RNDr . Mgr. TEPLÁ, LENKA: HILIC separace acikloviru a jeho degradačního produktu II (HILIC separation of acyclovir and its degradation product II), 4 . 5 . 2018, PharmDr . Mgr. TIRALA, PETR: Formulace a (trans)dermální podání lipozómů s obsahem imiquimodu (Formulation and (trans)dermal delivery of liposomes containing imiquimod), 24 . 10 . 2018, PharmDr . Mgr. TOMANOVÁ, PAVLA: Fyzikálně chemické vlastnosti léčiv (Physico-chemical properties of drugs), 8. 11. 2018, PharmDr . Mgr. TOUŠKOVÁ, TEREZA, Ph.D.: Kvalitativní a kvantitativní aspekty adherence v léčbě osteoporózy (Qualitative and quantitative aspects of adherence to osteoporosis treatment), 10 . 4 . 2018, PharmDr . Mgr. TRNČÁKOVÁ, VERONIKA: Modulační účinek humulenu, karyofylenu a karyofylenoxidu na vybrané biotransformační enzymy v lidských jaterních buňkách (Modulatory effect of humulene, caryophyllene and caryophyllene oxide on selected biotransformation enzymes in human liver cells), 14 . 9 . 2018, RNDr . Mgr. TUČKOVÁ, TEREZA: Základní charakterizace lidských enzymů DHRS7B a DHRS7C (Basic characterization of human enzymes DHRS7B and DHRS7C), 27 . 6 . 2018, PharmDr . Mgr. TURŇOVÁ, IVANA: Stanovenie mastných kyselín v ľudských tkanivách (Determination of fatty acids in human tissues), 28 . 6 . 2018, RNDr . Mgr. UHER, MARTIN: Pulsní léčba glukokortikoidy a změny exprese mikroRNA u pacientů se systémovými autoimunitními onemocněními (MicroRNA expression in glucocorticoid-treated patients with systemic autoimmune diseases), 14 . 9 . 2018, RNDr . Mgr. VÁCHOVÁ, LENKA, Ph.D.: Syntéza a studium fotofyzikálních a fotochemických vlastností ftalocyaninů a azaftalocyaninů (Synthesis and study of photophysical and photochemical properties of phthalocyanines and azaphthalocyanines), 17 . 5 . 2018, PharmDr . Mgr. VALER, VOJTĚCH: Syntéza derivátů azaftalocyaninů s fenolickou skupinou jako fluorescenčních senzorů pro pH (Synthesis of phenol-substituted azaphthalocyanines as fluorescent pH sensors), 17. 5. 2018, PharmDr.
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147 Von GERICHTEN, J ., LAMPRECHT, D ., OPÁLKA, L ., SOULARD, D ., MARSCHING, C ., PILZ, R ., SENCIO, V ., HERZER, S ., GALY, B ., NORDSTRÖM, V ., HOPF, C ., GRÖNE, H ., TROTTEIN, F ., SANDHOFF, R .: Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: Dependency on diet and inflammation. Journal of Lipid Research, 60 (11), 2019, 1892–1904. VYTŘÍSALOVÁ, M., HENDRYCHOVÁ, T., TOUŠKOVÁ, T., ZIMČÍKOVÁ, E., VLČEK, J., NEVORÁNEK, L ., SVOBODA, M ., HEJDUK, K ., BRAT, K ., PLUTINSKÝ, M ., NOVOTNÁ, B ., MUSILOVÁ, P ., ČERNOHORSKÝ, M., KOBLÍŽEK, V.: Breathing out completely before inhalation: The most problematic step in application technique in patients with non-mild chronic obstructive pulmonary disease . Frontiers in Pharmacology, 10, 2019, art . 241 . ZÁRYBNICKÝ, T., MATOUŠKOVÁ, P., AMBROŽ, M., ŠUBRT, Z., SKÁLOVÁ, L., BOUŠOVÁ, I.: The selection and validation of reference genes for mRNA and microRNA expression studies in human liver slices using RT-qPCR . Genes, 10 (10), 2019, art . 763 . ZEMANOVÁ, L ., NAVRÁTILOVÁ, H ., ANDRÝS, R ., ŠPERKOVÁ, K ., ANDREJS, J ., KOZÁKOVÁ, K ., MEIER, M ., MÖLLER, G ., NOVOTNÁ, E ., ŠAFR, M ., ADAMSKI, J ., WSÓL, V .: Initial characterization of human DHRS1 (SDR19C1), a member of the short chain dehydrogenase/reductase superfamily . Journal of Steroid Biochemistry and Molecular Biology, 185, 2019, 80–89 . ARTICLES IN JOURNALS WITHOUT IMPACT FACTOR AND PROCEEDINGS HAJDUCHOVÁ, H., BRABCOVÁ, I., TÓTHOVÁ, V., BÁRTLOVÁ, S., DOSEDĚL, M., MALÝ, J., VLČEK, J .: Applying the intervention programme in clinical practice . Journal of Nursing, Social Studies, Public Health and Rehabilitation, 10 (1–2), 2019, 14–20 . HAJDUCHOVÁ, H., BRABCOVÁ, I., TÓTHOVÁ, V., BÁRTLOVÁ, S., DOSEDĚL, M., MALÝ, J., VLČEK, J .: Factors associated with falls in hospitals: Outcomes for nursing care . Kontakt, 21 (2), 2019, 114–120 . HOLICKÁ, L., DOČEKALOVÁ, Š., ŠTICHHAUER, R., ROZSÍVAL, P., EIMER, L., ROZSÍVALOVÁ, P.: Tragická záměna – Poleptání kyselinou mravenčí. (Formic acid burns – Two cases of terrible medication administration error) . Pediatrie pro praxi, 20 (2), 2019, 114–117 . KARLÍČKOVÁ, J.: Potenciální léčebné využití kanabidiolu (CBD) z konopí setého. (Potential therapeutic use of cannabidiol (CBD) from Cannabis sativa) . Praktické lékárenství, 15 (4), 2019, 227–230 . MACHÁČEK, M., KOLLÁR, J., HALAŠKOVÁ, M., STEKLÁ, M., MAKHSEED, S., ŠIMŮNEK, T., ZIMČÍK, P.: Influence of cationic, anionic or non-charged substituents on photodynamic activity of watersoluble zinc (aza)phthalocyanines . In 17th International Photodynamic Association World Congress . Bellingham: Society of Photo-Optical Instrumentation Engineers, 2019, art . 11070_9M . ISBN 978-1-5106-2833-5 . MALÁ, K., PATKOVÁ, A., ŠOLÍNOVÁ, J., Da COSTA, F. A.: Měření tepové frekvence v lékárnách jako nástroj pro zvyšování povědomí o fibrilaci síní v České republice – pilotní projekt. (Pulse check as a tool to raise awareness of atrial fibrillation in pharmacies in the Czech Republic – a pilot project). Česká a slovenská farmacie, 68 (5), 2019, 198–203 . MALÝ, J ., MALÁ, K ., HORKÝ, P ., DOMECKÝ, P .: XXI . sympozium klinické farmacie René Macha (XXI . Symposium on Clinical Pharmacy René Mach) . Hradec Králové, Farmaceutická fakulta UK, 2019, 85 pp . ISBN 978-80-906644-5-6 . MALÝ, J., VALKO, A., DOSEDĚL, M.: Farmakoterapie jako rizikový faktor pádu pohledem klinického farmaceuta . (Pharmacotherapy as a risk factor of fall from the clinical pharmacist’s perspective) . Geriatrie a gerontologie, 8 (4), 2019, 164–167 . SVATOŠ, L.: Století dějin farmacie v samostatném státu 1918–2018. (A century of history of pharmacy in the independent Czechoslovakia and Czech Republic 1918–2018). Dějiny věd a techniky (History of Science and Technology), 52 (1), 2019, 34–42 . ŠPAČEK, J., BUCHTA, V., LEŠKO, D., KESTŘÁNEK, J., JÍLEK, P.: Současné možnosti managementu vulvovaginálního dyskomfortu (Current opinion of management of vulvovaginal discomfort) . Acta Medicinae, 8 (5–7), 2019, 20–26 . VAŇKOVÁ, B., MALÁ, K., DUSILOVÁ SULKOVÁ, S., MALÝ, J.: Přehled poznatků o účinnosti intervencí na podporu adherence k léčbě u pacientů po orgánových transplantacích (Review analyzing the effectiveness of interventions to promote medication adherence in patients after solid organ transplantation) . Klinická farmakologie a farmacie, 33 (1), 2019, 4–11 .
148 VLČEK, J., BÁRTLOVÁ, S., BRABCOVÁ, I., DOSEDĚL, M., HAJDUCHOVÁ, H., KUBĚNA, A., MALÝ, J., TÓTHOVÁ, V., VOSÁTKA, J.: Minimalizace rizik a teorie tří pilířů u léčiv zvyšujících riziko pádů (Risk minimization and three pillar theory for drugs that increase the risk of falls]) . Klinická farmakologie a farmacie, 33 (4), 2019, 30–34 . VOSÁTKA, J., MALÝ, J., DOSEDĚL, M.: Riziko pádu u pacientů užívajících léčiva ovlivňující centrální nervový systém pohledem klinického farmaceuta (The risk of falls in patients using drugs affecting central nervous system from the perspective of a clinical pharmacist) . Praktické lékárenství, 15 (4), 2019, 218–222 . MONOGRAPHIES AND TEXTBOOKS DOHNAL, F., DUINTJER TEBBENS, E. J., ROH, J., CAHLÍKOVÁ, L., SKLENÁŘOVÁ, H., SOLICH, P., NACHTIGAL, P., BOUŠOVÁ, I., DRŠATA, J., HRDINA, R., LÁZNÍČEK, M., SIATKA, T., DOLEŽAL, M., ŠKLUBALOVÁ, Z., VLČEK, J., MALÝ, J., MALÁ, K., ROZSÍVALOVÁ, P., FIALOVÁ, D., BEZOUŠKA, J., KATEROVÁ, Z ., HANDLOVÁ, Š ., OPLETAL, L ., CHLEBKOVÁ, A ., VALÁŠKOVÁ, L ., RUDIŠAR, L .: Sborník k 50. výročí založení Farmaceutické fakulty Univerzity Karlovy v Hradci Králové. (The 50th Anniversary of the Faculty of Pharmacy of the Charles University in Hradec Králové) . Hradec Králové, Farmaceutická fakulta UK, 2019, 176 pp . ISBN 978-80-906644-3-2 . HARTL, J., DOLEŽAL, M., MILETÍN, M., OPLETALOVÁ, V., ZIMČÍK, P: Farmaceutická chemie IV (Pharmaceutical Chemistry IV), 3rd ed ., Prague, Karolinum Press, 2019, 166 pp . ISBN 978-80-246-4264-2 . MUŽÍKOVÁ, J., HOLAS, O., ONDREJČEK, P., SVAČINOVÁ, P., ŠNEJDROVÁ, E .: Speciální praktická cvičení z farmaceutické technologie (Special Practical Exercises from Pharmaceutical Technology), 1st ed., Prague, Karolinum Press, 2019 . ISBN 978-80-246-4275-8 (e-book, PDF) . SCRIBA, G. K. E., JÁČ, P.: Cyclodextrins as chiral selectors in capillary electrophoresis enantioseparations . In Chiral Separations: Methods and Protocols . New York, Humana, 2019, 339–356 . ISBN 978-1-4939-9437-3 . WAISSER, K., NOVOTNÁ, E.: Názvosloví organických sloučenin (Nomenclature of organic compounds), 2nd ed . (reprint), Prague, Karolinum Press, 2019, 160 pp ., ISBN 978-80-246-3418-0 . UTILITY MODEL AND CERTIFIED METHODOLOGY BÍLKOVÁ, A., ŠIŠKA, F., HOLLÁ, M., SKLENÁŘOVÁ, H.: Sušený jablečný produkt (Dried apple product). Praha: Úřad průmyslového vlastnictví, 2019, Utility model No. CZ33395(U1). HOLLÁ, M., SKLENÁŘOVÁ, H., CHOCHOLOUŠ, P., ADAMCOVÁ, A., KOŠKOVÁ, S., ŠMÍDOVÁ, B., BÍLKOVÁ, A ., NEKVINDOVÁ, V ., SURAN, P .: Metodika pro kvalitativní hodnocení ovoce a zpracovatelských produktů z hlediska obsahu látek prospěšných pro zdraví člověka (Methodology for the qualitative assessment of fruit and processing products in terms of the content of substances beneficial to human health). Hradec Králové: Farmaceutická fakulta UK, 2019, 55 pp . ISBN 978-80-906644-4-9 . DEGREES Lectures for the Professorship Appointments, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2019 doc . PharmDr . KAMIL MUSÍLEK, Ph .D .: Associate Professor, Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 9 . 11 . 2017 Continuation: 12 . 12 . 2018 Title of Lecture: Reaktivátory cholinesteras a perspektiva jejich využití při intoxikacích organofosforovými sloučeninami (Cholinesterase reactivators and the perspective of their use in intoxications with organophosphorus compounds), 12 . 6 . 2018 Appointment: 23 . 5 . 2019
149 doc . PharmDr . LUCIE NOVÁKOVÁ, Ph .D .: Associate Professor, Department of Analytical Chemistry, Faculty of Pharmacy, Hradec Králové Discipline: Analytical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 5 . 11 . 2018 Continuation: 11 . 12 . 2018 Title of Lecture: Moderní superkritická fluidní chromatografie (Modern supercritical fluid chromatography), 12. 3. 2019 Appointment: 28 . 11 . 2019 Habilitation Theses and Lectures for Associated Professor Appointments, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2019 PharmDr . LUCIE CHOCHOLOUŠOVÁ HAVLÍKOVÁ, Ph .D .: Senior Lecturer, Department of Analytical Chemistry, Faculty of Pharmacy, Hradec Králové Discipline: Analytical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 23 . 8 . 2018 Continuation: 9 . 10 . 2018 Habilitation Thesis: Stabilita léčivých látek z pohledu analytické chemie (Stability of drug substances from the perspective of analytical chemistry), defended 11 . 12 . 2018 Title of Lecture: Moderní přístupy v problematice sledování nečistot léčivých látek (Modern approaches in the field of monitoring impurities of active substances), 11. 12. 2018 Appointment: 1 . 3 . 2019 RNDr . LUCIE ZEMANOVÁ, Ph .D .: Senior Lecturer, Department of Chemistry, Faculty of Science, University of Hradec Králové, Hradec Králové Discipline: Biochemistry, MŠMT 24 295/2007-30/1 Inauguration: 6 . 9 . 2018 Continuation: 9 . 10 . 2018 Habilitation Thesis: Význam enzymů z nadrodin AKR a SDR u člověka (The importance of enzymes from the superfamilies AKR and SDR in humans), defended 11 . 12 . 2018 Title of Lecture: Lidské membránové enzymy a jejich role v organismu (Human membrane enzymes and their roles in the body), 11 . 12 . 2018 Appointment: 1 . 3 . 2019 Ing. PETRA MATOUŠKOVÁ, Ph.D.: Scientific/Academic Worker, Department of Biochemical Sciences, Faculty of Pharmacy, Hradec Králové Discipline: Biochemistry, MŠMT 24 295/2007-30/1 Inauguration: 7 . 9 . 2018 Continuation: 9 . 10 . 2018 Habilitation Thesis: Stanovení genové exprese (Determination of gene expression), defended 11 . 12 . 2018 Title of Lecture: Nekódující RNA – diagnostické markery budoucnosti? (Non-coding RNA – diagnostic markers of the future?), 11 . 12 . 2018 Appointment: 1 . 3 . 2019 PharmDr . MARTIN KRÁTKÝ, Ph .D .: Senior Lecturer, Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Hradec Králové Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 11 . 8 . 2018 Continuation: 12 . 11 . 2018 Habilitation Thesis: Vztahy mezi strukturou a aktivitou malých antimikrobně aktivních molekul a tuftsinových nosičů (Relationships between structure and activity of small antimicrobial active molecules and tuftsin carriers), defended 12 . 3 . 2019
150 Title of Lecture: Peptidové nosiče pro malé antimykobakteriální sloučeniny (Peptide carriers for small antimycobacterial compounds), 12 . 3 . 2019 Appointment: 1 . 7 . 2019 PharmDr. LUKÁŠ ČERVENÝ, Ph.D.: Senior Lecturer, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hradec Králové Discipline: Human and Veterinary Pharmacology, MŠMT 24 295/2007-30/1 Inauguration: 29 . 10 . 2018 Continuation: 11 . 12 . 2018 Habilitation Thesis: Role transportních mechanismů v materno-fetálním přestupu antiretrovirotik (The role of transport mechanisms in maternal-fetal transfer of antiretrovirotics), defended 12 . 3 . 2019 Title of Lecture: Farmakokinetické lékové interakce antiretrovirálních léčiv; mechanismy vzniku, rizika a výhody (Pharmacokinetic drug interactions of antiretroviral drugs; mechanisms of origin, risks and benefits), 12. 3. 2019 Appointment: 1 . 7 . 2019 PharmDr . DANIELA FIALOVÁ, Ph .D .: Senior Lecturer, Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Hradec Králové Discipline: Clinical and Social Pharmacy, MŠMT 29 593/2011-M3 Inauguration: 12 . 11 . 2018 Continuation: 11 . 12 . 2018 Habilitation Thesis: Hodnocení racionality geriatrické farmakoterapie v mezinárodním kontextu (Evaluation of the rationality of geriatric pharmacotherapy in an international context), defended 12 . 3 . 2019 Title of Lecture: Specifika geriatrické farmakoterapie a výhledy budoucího výzkumu v klinické farmacii v geriatrii (Specifics of geriatric pharmacotherapy and future research perspectives in clinical pharmacy in geriatrics), 12 . 3 . 2019 Appointment: 1 . 7 . 2019 Ing. PAVEL BOBÁĽ, CSc.: Senior Lecturer, Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 18 . 12 . 2018 Continuation: 12 . 3 . 2019 Habilitation Thesis: Syntetické přístupy k přípravě biologicky aktivních heterocyklů a jejich isosterů (Synthetic approaches to the preparation of biologically active heterocycles and their isosteres), defended 10 . 6 . 2019 Title of Lecture: Inhibitory histondeacetylas: molekulární architektura a protinádorová aktivita (Histone deacetylase inhibitors: Molecular architecture and antitumor activity), 10 . 6 . 2019 Appointment: 1 .10 . 2019 PharmDr . JOSEF MALÝ, Ph .D .: Senior Lecturer, Department of Social and Clinical Pharmacy, Faculty of Pharmacy, Hradec Králové Discipline: Clinical and Social Pharmacy, MŠMT 29 593/2011-M3 Inauguration: 15 . 1 . 2019 Continuation: 12 . 3 . 2019 Habilitation Thesis: Možnosti rozvoje kultury bezpečí ve farmakoterapii (Possibilities of developing a culture of safety in pharmacotherapy), defended 11 . 6 . 2019 Title of Lecture: Současný stav a perspektivy farmaceutické péče v České republice (Current status and perspectives of pharmaceutical care in the Czech Republic), 11 . 6 . 2019 Appointment: 1 . 10 . 2019 PharmDr . PETR CHOCHOLOUŠ, Ph .D .: Senior Lecturer, Department of Analytical Chemistry, Faculty of Pharmacy, Hradec Králové Discipline: Analytical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 25 . 1 . 2019
151 Continuation: 12 . 3 . 2019 Habilitation Thesis: Vývojové trendy v sekvenční injekční chromatografii (Trends in sequential injection analysis), defended 10 . 6 . 2019 Title of Lecture: Stacionární fáze pro separace v průtokových metodách (Stationary phases for separations in flow methods), 10 . 6 . 2019 Appointment: 1 . 10 . 2019 Ing. KATEŘINA MACÁKOVÁ, Ph.D.: Scientific/Academic Worker, Department of Pharmaceutical Botany, Faculty of Pharmacy, Hradec Králové Discipline: Pharmacognosy, NAU-518/2018-9 Inauguration: 7 . 2 . 2019 Continuation: 4 . 3 . 2019 Habilitation Thesis: Přírodní látky potenciálně využitelné v prevenci a léčbě některých chronických onemocnění (Natural substances potentially usable in the prevention and treatment of some chronic diseases), defended 11 . 6 . 2019 Title of Lecture: Biologické účinky flavonoidů a jejich potenciální využití v terapii (Biological effects of flavonoids and their potential use in therapy), 11 . 6 . 2019 Appointment: 1 . 10 . 2019 PharmDr . JAN ZITKO, Ph .D .: Senior Lecturer, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy, Hradec Králové Discipline: Pharmaceutical Chemistry, MŠMT 24 295/2007-30/1 Inauguration: 11 . 2 . 2019 Continuation: 12 . 3 . 2019 Habilitation Thesis: Návrh, příprava a hodnocení derivátů pyrazinamidu jako potenciálních antimykobakteriálních sloučenin (Design, preparation and evaluation of pyrazinamide derivatives as potential antimycobacterial compounds), defended 10 . 6 . 2019 Title of Lecture: Počítačem podporovaný návrh a vývoj léčiv – CADD (Computer Aided Drug Design and Development – CADD), 10 .06 .2019 Appointment: 1 . 10 . 2019 Doctoral Dissertation Theses to obtain the Ph.D. Degree, Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2019 Mgr. APPLOVÁ, LENKA: Ovlivnění aktivace krevních destiček polyfenolickými látkami a jejich metabolity (The influence of polyphenolic compounds and their metabolites on platelet activation), 20. 9. 2019, Ph.D. Mgr. BERKA, PAVEL: Biofarmaceutické aspekty makromolekulárních nosičů pro systémovou sublingvální aplikaci léčiv (Biopharmaceutical aspects of macromolecular carriers for systemic sublingual drug delivery), 30 . 9 . 2019, Ph .D . Mgr. BREITEROVÁ, KATEŘINA: Alkaloidy rostlin čeledi Amaryllidaceae jako potenciální léčiva v terapii civilizačních onemocnění (Alkaloids of the Amaryllidaceae family as potential drugs in therapy of diseases of affluence), 26. 6. 2019, Ph.D. Mgr. BRŮŽA, ZDENĚK: Syntéza a využití polysubstituovaných pyranonů (Synthesis and application of polysubstituted pyranones), 29 . 8 . 2019, Ph .D . Mgr. ČEPA, ADAM: Modifikace fragmentů protilátek, jejich značení nekonvenčními pozitronovými zářiči a biologické testování pro diagnostiku PET (Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics), 1 . 2 . 2019, Ph .D . Mgr . DUŠEK, JAN: Development of novel constitutive androstane receptor (CAR) ligands, 20 . 9 . 2019, Ph .D . Mgr. DVOŘÁČKOVÁ, ELIŠKA: Analýza lékových problémů na oddělení z pohledu farmaceuta (Analysis of drug problems at hospital department from the pharmacist’s point of view), 25 . 9 . 2019, Ph .D . Mgr. FIBIGR, JAKUB: Využití HPLC techniky v analýze doplňků stravy na bázi rostlinných extraktů (Application of HPLC technique in analysis of food supplements based on plant extracts), 19 . 2 . 2019, Ph .D .
152 Mgr. HORKÝ, PAVEL: Nové deriváty přírodních látek s biologickým účinkem (Synthesis and biological activity of novel natural product derivatives), 14 . 6 . 2019, Ph .D . Mgr. JANOUŠEK, JIŘÍ: Studium vlastností radioaktivně značených monoklonálních protilátek pro zobrazování v onkologii (The study of properties of radiolabelled monoclonal antibodies for imaging in oncology), 20 . 9 . 2019, Ph .D . Mgr. JAVORSKÁ LENKA: Vývoj bioanalytických metod pro stanovení diagnostických markerů a léčiv s využitím chromatografických technik (Development of bioanalytical methods for the determination of diagnostic markers and drugs using chromatographic techniques), 23 . 9 . 2019, Ph .D . Mgr. JOSKOVÁ, VĚRA: Klinická aplikace metody bioimpedanční spektroskopie u polytraumatizovaných pacientů a těhotných žen (The clinical application of bioimpedance spectroscopy in polytrauma patients and in pregnant women), 4 . 2 . 2019, Ph .D . Mgr. KOPEČNÁ, MONIKA: Syntéza a studium akcelerantů transdermální permeace léčiv (Synthesis and evaluation of transdermal drug permeation enhancers), 29 . 8 . 2019, Ph .D . Mgr. LHOTSKÁ, IVONA: Využití moderních chromatografických technik v analýze cizorodých a kontaminujících látek v potravinách (Modern chromatographic techniques in food contamination analysis), 19 . 2 . 2019, Ph .D . Mgr. TOMÁŠ NEJEDLÝ: Vývoj HPLC metod pro analytické hodnocení léčivých přípravků a modelové studie přírodní degradace reziduí léčiv (Development of HPLC methods for analytical evaluation of drug products and model studies of natural degradation of drug residues), 26 . 6 . 2019, Ph .D . Mgr. NĚMEČEK, JAN: Syntéza substituovaných dusíkatých heterocyklů jako potenciálních antituberkulotika (Synthesis of substituted nitrogen heterocycles as potential antitubercular agents), 14 . 6 . 2019, Ph .D . Mgr. NOVOSVĚTSKÁ, LUCIE: Sequential injection analysis capability in automation of analytical processes, 26 . 6 . 2019, Ph .D . Mgr. SOCHOROVÁ, MICHAELA: Studium bariérových lipidů v kůži a kožních modelech (Study of barrier lipids in the skin and skin models), 29 . 8 . 2019, Ph .D . Mgr. SYSLOVÁ, ELIŠKA: Anthelmintika v rostlinách – příjem, biotransformace a transkripční odpověď (Anthelmintics in plants – uptake, biotransformation and transcriptional response), 13 . 12 . 2019, Ph .D . Mgr. ŠORF, ALEŠ: Studium interakcí nových protinádorových léčiv s lékovými transportéry (A study of interactions of novel anticancer drugs with drug transporters), 12 . 12 . 2019, Ph .D . Mgr . VITVEROVÁ, BARBORA: Solubilní endoglin a jeho role v patogenezi endotelové dysfunkce (Soluble endoglin role in the pathogenesis of endothelial dysfunction), 18 . 10 . 2019, Ph .D . Mgr. VOSÁTKA, RUDOLF: Design a syntéza nových potenciálně antibakteriálně účinných sloučenin (Design and synthesis of new potentially antibacterial active compounds), 27 . 5 . 2019, Ph .D . Rigorous Theses to obtain the degree PharmDr. (Doctor of Pharmacy, graduates of the study programme Pharmacy) or RNDr. (Doctor of Natural Sciences, graduates of study programme Bioanalytical Laboratory Diagnostics in Medicine), Faculty of Pharmacy in Hradec Králové (CZ), Charles University (CZ), 2019 Mgr. APPLOVÁ, LENKA, Ph.D.: Ovlivnění aktivace krevních destiček polyfenolickými látkami a jejich metabolity (The influence of polyphenolic compounds and their metabolites on platelet activation), 19. 12. 2019, PharmDr . Mgr. BALCIAROVÁ, ANDREA: Formulácia a testovanie nanočastíc z vetvených polyesterov s rifampicínom (Formulation and testing of rifampicin-loaded branched polyesters nanoparticles), 28 . 3 . 2019, PharmDr . Mgr. BÄROVÁ, KAROLÍNA: GC analýza léčiv s využitím iontové kapaliny jako stacionární fáze I (GC analysis of drugs with utilization of ionic liquid as a stationary phase I), 5 . 6 . 2019, PharmDr . Mgr. BAUDISCHOVÁ, LENKA: Kvalita poskytovaných informací u nejprodávanějších doplňků stravy v České republice na internetu (The quality of information on top selling dietary supplements on the internet in the Czech Republic), 22 . 1 . 2019, PharmDr . Mgr. BAŽANTOVÁ, MICHAELA: Exercise as medicine. Growth hormone response to high-intensity interval training, 15 . 2 . 2019, PharmDr . Mgr. BERDYCH, MARTIN: Zavedení nového analytického systému do rutinní biochemické laboratoře (Implementation of new analytical system into a routine biochemical laboratory), 6 . 5 . 2019, RNDr .
153 Mgr. BIELESZOVÁ, DOMINIKA: Studium liberace terbinafinu z PLGA nanočástic (Terbinafine release from PLGA-based nanoparticles), 30 . 9 . 2019, PharmDr . Mgr. BÍMOVÁ, DANIELA: Studium směsného suchého pojiva s mannitolem, laktosou, dextrosou a krospovidonem pro tablety dispergovatelné v ústech (A study of the coprocessed dry binder with mannitol, lactose, dextrose and crospovidone for orally disintegrating tablets), 17 . 10 . 2019, PharmDr . Mgr. BLAŠKOVÁ, DOMINIKA: Postoje a znalosti o očkování proti HPV I (Attitudes and beliefs on HPV infection and vaccination), 5 . 6 . 2019, PharmDr . Mgr. BRADOVÁ, HANA: Farmakoterapie diabetu mellitu sledovaná v diabetologické poradně (Pharmacotherapy of diabetes mellitus followed up in diabetes clinic), 11 . 2 . 2019, PharmDr . Mgr. BREITEROVÁ, KATEŘINA, Ph.D.: Alkaloidy rostlin čeledi Amaryllidaceae jako potenciální léčiva v terapii civilizačních onemocnění (Alkaloids of the Amaryllidaceae family as potential drugs in therapy of diseases of affluence), 12. 8. 2019, PharmDr. Mgr. BRŮŽA, ZBYNĚK, Ph.D.: Syntéza a využití polysubstituovaných pyranonů (Synthesis and application of polysubstituted pyranones), 9 . 12 . 2019, PharmDr . Mgr . CARAZO FERNÁNDEZ, ALEJANDRO, Ph .D .: Nuclear receptors – new ligands study and importance of the genetic variability, 10 . 10 . 2019, PharmDr . Mgr. CICHÝ, JAKUB: Faktory ovlivňující purifikaci a stabilitu biokonjugátů azaftalocyaninů (Factors which affect the purification and stability of azaftalocyanines bioconjugates), 5. 6. 2019, PharmDr. Mgr. ČEČKOVÁ, PATRÍCIA: Studium interakcí léčiv s transportéry z rodiny OATP za využití střevních tkáňových řezů (Study of drug interactions with OATP family transporters using intestinal tissue slices), 26. 9. 2019, PharmDr . Mgr. ČEPA, ADAM, Ph.D.: Modifikace fragmentů protilátek, jejich značení nekonvenčními pozitronovými zářiči a biologické testování pro diagnostiku PET (Modification of antibody fragments and their radiolabeling by unconventional positron emitters and biological testing for PET diagnostics), 27 . 3 . 2019, PharmDr . Mgr. ČERMÁKOVÁ, VERONIKA: Ovlivnění pKa rozpoznávací části azaftalocyaninových sensorů (Modulation of pKa of the recognition moiety of azaphthalocyanine sensors), 12 . 11 . 2019, PharmDr . Mgr. ČERVINKOVÁ, TEREZA: Beneficial effects of 11β-HSD1 inhibition on cognitive performance in a mouse model of Alzheimer’s disease, 21 . 9 . 2018, PharmDr . Mgr. ČIKOVSKÁ, NATÁLIA: Analýza činnosti Liekového informačného centra II (Drug Information Centre service analysis II), 22 . 1 . 2019, PharmDr . Mgr. DOUDĚROVÁ, ANETA: Radiosensibilizace linie buněk nemalobuněčného karcinomu plic pomocí inhibitoru autofagie Lys05 (Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05), 17 . 6 . 2019, RNDr . Mgr. DUGASOVÁ, LUCIA: Vplyv doxorubicínu na vybrané myšacie mikroRNA (Effect of doxorubicin on selected mice microRNAs), 26 . 9 . 2019, RNDr . Mgr. DUCHAČOVÁ, KATEŘINA: Vliv glutamátem navozené obezity na detoxikační enzymy obsahující glutathion (Influence of glutamate-induced obesity on detoxification enzymes contains glutathione), 13. 2. 2019, PharmDr . Mgr . FABRIKOVÁ, DANIELA, Ph .D .: Molekulární mechanizmy patogeneze mikroba Francisella tularensis (Molecular mechanisms of Francisella tularensis pathogenesis), 15 . 3 . 2019, RNDr . Mgr. FIBIGR, JAKUB, Ph.D.: Využití HPLC techniky v analýze doplňků stravy na bázi rostlinných extraktů (Application of HPLC technique in analysis of food supplements based on plant extracts), 7 . 11 . 2019, PharmDr . Mgr. FLANDERKOVÁ, MICHAELA: Reologické vlastnosti gelů na hojení ran (Rheological properties of the scar treatment gels), 30 . 9 . 2019, PharmDr . Mgr. FLAXOVÁ, MICHAELA: Studium rezistence v nádorové terapii – vliv inhibitorů protein kinas na aktivitu vybraných lidských reduktas II (Study of resistance in cancer therapy – protein kinase inhibitors influence on activity of selected human reductases II), 17 . 6 . 2019, PharmDr . Mgr. GAJDOŠ, JAKUB: Radioaktivní značení ramucirumabu s následnou studií jeho internalizace in vitro (Radio labeling of ramucirumab followed with the study of its internalization in vitro), 17 . 6 . 2019, RNDr . Mgr . GAJDOŠOVÁ, BARBORA: Vývoj on-line SPE-HPLC metody pro stanovení zearalenonu ve vzorcích piva (On-line SPE-HPLC method development for determination of zearalenone in beers), 6 . 5 . 2019, RNDr . Mgr . GÓRECKI, LUKÁŠ, Ph .D .: Development of novel cholinesterase modulators (Development of novel cholinesterase modulators), 10 . 10 . 2019, PharmDr .