5. února 2020 P R O G R A M . VĚDECKÁ KONFERENC E XXIV

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UNIVERZITA KARLOVA,

LÉKAŘSKÁ FAKULTA V HRADCI KRÁLOVÉ A FAKULTNÍ NEMOCNICE HRADEC KRÁLOVÉ

XXIV. VĚDECKÁ KONFERENCE

P R O G R A M

5. února 2020

Velká posluchárna budovy Teoretických ústavů Lékařské fakulty

v Hradci Králové

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Vydavatel: Univerzita Karlova, Lékařská fakulta v Hradci Králové

ISBN: 978-80-907700-0-3

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T e c h n i c k é p o k y n y

V programu jsou uvedeny názvy řešených projektů a jména odpovědných řešitelů.

Věcná část publikovaných abstrakt dodaných řešiteli nebyla editována.

Ústní sdělení 1. Doba sdělení:

I. sekce 10 minut, diskuse 5 minut II. sekce 10 minut, diskuse 5 minut.

2. K dispozici je dataprojekce.

Plakátová sdělení

Postery budou vyvěšeny po celou dobu konání konference. Prohlídka plakátových sdělení je možná v průběhu přestávky.

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UNIVERZITA KARLOVA,

LÉKAŘSKÁ FAKULTA V HRADCI KRÁLOVÉ A FAKULTNÍ NEMOCNICE HRADEC KRÁLOVÉ

XXIV. VĚDECKÁ KONFERENCE

P R O G R A M

5. února 2020

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Velká posluchárna

Lékařské fakulty v Hradci Králové

10:00 – 10:15 Zahájení konference

prof. MUDr. Jiří Manďák, Ph.D.

děkan Lékařské fakulty v Hradci Králové

prof. MUDr. Vladimír Palička, CSc., dr. h. c.

ředitel Fakultní nemocnice Hradec Králové

Sekce I Předsedající: prof. MUDr. Petr Hejna, Ph.D.

(10 min. sdělení + 5 min. diskuse)

10:15 – 10:30 Objasnění role kadherinů a EMT v rozvoji chemoterapeutické rezistence u metastatického kolorektálního karcinomu

prof. PharmDr. Emil Rudolf, Ph.D.(Ústav lékařské biologie a genetiky) Přednášející: RNDr. Veronika Skarková, Ph.D.

GA ČR 17-10331S

10:30 – 10:45 Role kanonické signální dráhy Wnt v neurogenezi.

prof. MUDr. Jaroslav Mokrý, Ph.D. (Ústav histologie a embryologie) Přednášející: Rishikaysh Pisal, M.Sc., Ph.D.

GA ČR 17-05466S

10:45 – 11:00 Mikrovaskulární abnormality jakožto endofenotyp schizofrenie prof. MUDr. Ladislav Hosák, Ph.D. (Psychiatrická klinika) AZV MZ ČR 16-27243A

11:00 – 11:15 Péče zaměřená na zvláštnosti pacienta: individualizovaná péče (teorie, diagnostika, intervence)

prof. PhDr. Jiří Mareš, CSc. (Ústav sociálního lékařství) AZV MZ ČR 16-28174A

11:15 – 11:30 "Lipozomy (drug delivery systems) v kineticky řízené léčbě platinarezistentního karcinomu ovarií doxorubicinem pomocí plazmafiltrace.

prof. MUDr. Stanislav Filip, Ph.D. (Klinika onkologie a radioterapie) AZV MZ ČR 16-30366A

11:30 – 11:45 "Neinvazivní detekce intraamniální infekce stanovením dominantní bakterie v cervikální tekutině“

doc. MUDr. Marian Kacerovský, Ph.D. (Porodnická a gynekologická klinika FN HK)

AZV MZ ČR 16-28587A

11:45 – 12:15

Přestávka – občerstvení

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Sekce II Předsedající: doc. MUDr. RNDr. Milan Kaška, Ph.D.

(10 min. sdělení + 5 min. diskuse)

12:15 – 12:30 Vývoj nových insekticidů proti komárům přenášejícím malárií šetrných pro životní prostředí (CBV FN HK)

prof. PharmDr. Kamil Musílek, Ph.D. (Centrum biomedicínského výzkumu FN HK)

AZV 16-34390A

12:30 – 12:45 Nová účinná léčiva v terapii narkolepsie

PharmDr. Jan Korábečný, Ph.D. (Centrum biomedicínského výzkumu FN HK)

GA ČR 17-08596S

12:45 – 13:00 Vliv složení pooperační výživy na intenzitu zánětové odpovědi lidského imunitního systému/ organismu na operační trauma

doc. MUDr. RNDr. Milan Kaška, Ph.D. (Chirurgická klinika FN HK) Interní projekt č. 8155

13:00 – 13:15 Inovace infuzních roztoků podle nejnovějších poznatků s protektivním účinkem na glykokalyx

prof. MUDr. Zdeněk Zadák, CSc. (Centrum pro vývoj a výzkum FN HK) MPO ČR - FV 10454

13:15 – 13:30 Diabetes mellitus v graviditě

Monika Esterková (III. int. GMK FN HK) Junior projekt IGS

13:30 – 13:45 Deregulace mikroRNA u sinonasálního karcinomu Albína Přikrylová (ÚKBD FN HK)

Junior projekt IGS

13:45 – 14:00 Rozvoj nových diagnostických postupů Natálie Birknerová (ÚKBD FN HK) Junior projekt IGS

14:00 – 14:15 Operační trauma a nové operační postupy

Petr Smolák (Kardiochirurgická klinika FN HK) Junior projekt IGS

14:15 – 14:30 Vývoj a hodnocení léčiv

Jan Schönbauer (Centrum biomedicínského výzkumu FN HK) Junior projekt IGS

14:30 – 14:45 Ukončení konference

prof. MUDr. Jiří Manďák, Ph.D.

děkan Lékařské fakulty v Hradci Králové

prof. MUDr. Vladimír Palička, CSc., dr. h. c.

ředitel Fakultní nemocnice Hradec Králové

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Projekty prezentované formou plakátových sdělení

Implementace laserové spektroskopie v analýze kožních nádorů

MUDr. Kateřina Kubíčková (Chirurgická klinika FN HK) GAUK 1193819

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Na Lékařské fakultě v Hradci Králové a ve Fakultní nemocnici Hradec Králové se v roce 2019 dále řešily následující projekty

(abecedně podle jmen řešitelů)

V tomto přehledu jsou uvedeny ostatní smluvně podložené projekty a spolupráce na projektech.

Péče o nemocné staršího věku (>65 let) s Non-Hodgkinovými lymfomy – analýza faktorů ovlivňujících volbu léčby a osod nemocných

MUDr. David Belada, Ph.D.

(odp. řešitel: prof. MUDr. Marek Trněný, CSc. – VFN Praha) AZV MZ ČR 16-31092A (FN)

Genetické polymorfismy, MiRNA a vybrané bioindikátory aktivity - vzájemné vztahy při diagnostice a léčbě těžké familiární hypercholesterolemie

prof. MUDr. Vladimír Bláha, CSc. (Ing. J. Hubáček, CSc., DSc. – IKEM, prof.

MUDr. M. Bláha, CSc. – FN) AZV MZ ČR 17-28882A (LF)

Biomarkery v diagnostice a terapii v interních oborech prof. MUDr. Jan Bureš, CSc.

SVV 260396 (LF)

Vliv experimentálního gastrointestinálního poškození na farmakokinetiku léčiv Alzheimerovy choroby

prof. MUDr. Jan Bureš, CSc. (doc. PharmDr. J. Žďárová Karasová, Ph.D. – FN) GA ČR 18-13283S (LF)

Nové postupy ve výzkumu, diagnostice a terapii civilizačních chorob a onemocnění spojených se stárnutím populace

prof. MUDr. RNDr. Miroslav Červinka, CSc.

Progres Q40 (LF)

Jaterní mitochondrie - zaměření na vliv věku, životního stylu a prostředí prof. MUDr. Zuzana Červinková, CSc.

Inter Cost LTC17044 (LF)

Texderm-textilie a oděvy se zvýšeným komfortem pro specifické potřeby dětí s kožními problémy

doc. MUDr. Karel Ettler (LF) MPO ČR FV20287

Genetická variabilita BKV v ČR a její vliv na patogenezi infekce u pacientů po transplantaci ledvin

MUDr. Miroslav Fajfr, Ph.D.

(odp. řešitel: RNDr. Martina Saláková, Ph.D.) AZV MZ ČR 17-29992A (FN)

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Role deficitu železa a Mrp2 transportéru v rozvoji estrogeny-indukované cholestázy Fatemeh Alaei Faradonbeh, M.Sc.

GA UK 556218 (LF)

Lipozomy (drug delivery systems) v kineticky řízené léčbě platinarezistentního karcinomu ovarií doxorubicinem pomocí plazmafiltrace

prof. MUDr. Stanislav Filip, Ph.D. (prof. MUDr. Milan Bláha, CSc. – FN) AZV MZ ČR 16-30366A (LF)

Kompozitní nanočástice s magneticky a světelně řízeným uvolňováním biologicky aktivních látek

RNDr. Radim Havelek, Ph.D.

(odp. řešitel: Ing. Mgr. Ondřej Kaman, Ph.D. – FÚ AV ČR Praha) GA ČR 18-13323S (LF)

Trajektorie kvality života seniorů v počáteční fázi demence prof. MUDr. Roman Herzig, Ph.D.

(odp. řešitel: PhDr. Helena Kisvetrová, Ph.D. – UP FZV Olomouc) AZV MZ ČR 16-28628A (FN)

Hodnocení investic do vývoje zdravotních prostředků Mgr. Jan Honegr, Ph.D.

(odp. řešitel: doc. Ing. Mgr. Petra Marešová, Ph.D.) GA ČR 17-03037S (FN)

Mikrovaskulární abnormality jakožto endofenotyp schizofrenie

prof. MUDr. Ladislav Hosák, Ph.D. (prof. RNDr. Omar Šerý, Ph.D. – ÚŽFG AV) AZV MZ ČR 16-27243A (LF)

Rozvoj výuky paliativní medicíny na lékařských fakultách Univerzity Karlovy MUDr. Jana Hrubešová, Ph.D.

(odp. řešitel: MUDr. MgA. K. Rusinová, Ph.D. – UK 1. LF Praha) NF AVAST č. SADK18_3/100013

Neinvazivní detekce intraamniální infekce stanovením dominantní bakterie v cervikální tekutině

doc. MUDr. Marian Kacerovský, Ph.D. (doc. MUDr. O. Šimetka, Ph.D., MBA – FN Ostrava; MUDr. P. Janků – FN Brno)

AZV MZ ČR 16-28587A (FN)

Rozvoj diagnostiky a terapie v chirurgických oborech doc. MUDr. RNDr. Milan Kaška, Ph.D.

SVV 260399 (LF)

Nová účinná léčiva v terapii narkolepsie PharmDr. Jan Korábečný, Ph.D.

GA ČR 17-08596S (FN)

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In vitro kožní penetrace - optimalizace testovacích metod MUDr. Lenka Kotingová Ph.D.

(odp. řešitel: Ing. Petra Plodíková – VÚOS Rybitví) TA ČR TH03010279

Charakteristika aterosklerotického plátu a riziko mozkové ischemie při stentingu vnitřní karotidy

prof. MUDr. Antonín Krajina, CSc.

(odp. řešitel: prof. MUDr. David Školoudík, Ph.D., FESO – FN Ostrava) AZV MZ ČR 16-30965A (FN)

Morfologické charakteristiky aterosklerotického plátu v karotické tepně spojené s progresí plátu a rizikem cévní mozkové příhody

prof. MUDr. Antonín Krajina, CSc.

(odp. řešitel: MUDr. Tomáš Belšan, CSc. – VFN Praha) AZV MZ ČR 17-31016A (FN)

Zlepšení kvality života u pacientů se stabilní makulopatií prostřednictvím implantace intraokulární makulární čočky a modulací zrakové plasticity transkraniální elektrickou stimulací

doc. RNDr. Jan Kremláček, Ph.D. (prof. MUDr. Naďa Jirásková, Ph.D., FEBO – FN)

AZV MZ ČR NV18-06-00484 (LF)

Osvojování si kontrastní kvantity: input a percepční zpracování samohláskové délky v prvních měsících života

doc. RNDr. Jan Kremláček, Ph.D.

(odp. řešitel: MUDr. Kateřina Chládková, M.A. – FF UK Praha) PRIMUS/17/HUM/19 (LF)

Ověření diagnostických možností nového mobilního přístroje k vyšetřování zrakových evokovaných potenciálů

prof. MUDr. Miroslav Kuba, DSc.

AZV MZ ČR NV18-08-00314 (LF)

Studium specifických faktorů ovlivňujících toxicitu hypertermické intraperitoneální chemoterapie

doc. RNDr. Lenka Kujovská Krčmová, Ph.D.

(odp. řešitel: prof. MUDr. Bohuslav Melichar, Ph.D. – UPOL LF) AZV MZ ČR NV18-03-00130 (FN)

Komplexní morfologická, imunohistochemická, molekulárně genetická a klinicko- pathologická analýza vzácných typů karcinomů ovaria

prof. MUDr. Jan Laco, Ph.D.

(odp. řešitel: MUDr. Kristýna Němejcová, Ph.D. – UK 1. LF Praha) AZV MZ ČR NV19-03-00007 (LF)

Proprotein konvertáza subtilisin/kexin 9 (PCSK9) v patofyziologii a léčbě věkem podmíněné suché formy makulární degenerace

prof. MUDr. Hana Langrová, Ph.D. (prof. MUDr. Vladimír Bláha, CSc. – FN)

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AZV MZ ČR 17-29241A (LF)

Vliv kardiovaskulárních léčiv na rozvoj nealkoholové steatohepatitidy Ing. Hana Laštůvková

GA UK 346218 (LF)

Vývoj nových radioprotektivních látek na bázi malých molekulárních inhibitorů PharmDr. Jan Marek, Ph.D.

(odp. řešitel: doc. MVDr. Zuzana Šinkorová, Ph.D.) GAČR 17-13541S (FN)

Vývoj polyvalentního dekontaminačního činidla PharmDr. Jan Marek, Ph.D.

(odp. řešitel: doc. PharmDr. Daniel Jun, Ph.D. – FVZ HK) AZV NV18-09-00181 (FN)

Péče zaměřená na zvláštnosti pacienta: individualizovaná péče (teorie, diagnostika, intervence)

prof. PhDr. Jiří Mareš, CSc.

AZV MZ ČR 16-28174A (LF)

Mechanizmy orgánových patologií – rizikové faktory a možnosti nových diagnostických a terapeutických intervencí

prof. MUDr. Stanislav Mičuda, Ph.D.

SVV 260397 (LF)

Studium dynamiky genové regulace nukleárními receptory: porozumění detoxifikačních funkcí a přínos pro optimalizaci farmakoterapie

(odp. řešitel: prof. PharmDr. Petr Pávek, Ph.D. – UK FaF HK) GA ČR 17-06841S (LF)

Nové terapeutické možnosti ovlivnění metabolismu triglyceridů, cholesterolu a žlučových kyselin prostřednictví ligandů lidského CAR receptoru

(odp. řešitel: prof. PharmDr. Petr Pávek, Ph.D. – UK FaF HK) GA ČR 19-14497S (LF)

Role kanonické signální dráhy Wnt v neurogenezi.

prof. MUDr. Jaroslav Mokrý, Ph.D. (Mgr. J. Pacherník, Ph.D. – MU Brno) GA ČR 17-05466S (LF)

Vývoj nových insekticidů proti komárům přenášejícím malárií šetrných pro životní prostředí

doc. PharmDr. Kamil Musílek, Ph.D.

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Reaktivátory butyrylcholinesterasy pro přípravu pseudo-katalytických scavengerů využitelných při intoxikacích organofosforovými sloučeninami

doc. PharmDr. Kamil Musílek, Ph.D. (prof. Ing. K. Kuča, Ph.D. – UHK; doc.

PharmDr. D. Jun, Ph.D. – UO FVZ HK) GA ČR 18-01734S (FN)

Exprese biotransformačních enzymů u primárních nádorů jater RNDr. Jana Nekvindová, Ph.D.

Účinnost chodecké intervence s využitím krokoměru na fyzickou zdatnost a neurohumorální modulaci u pacientů s chronickým srdečním selháním MUDr. Radek Pelouch

(odp. řešitel: doc. MUDr. Jan Bělohlávek, Ph.D. – VFN) AZV MZ ČR NV18-09-00146 (FN)

Klinicko-patologické a molekulární faktory detekované v metastázách, které předpovídají odpověď na léčbu karcinomu tlustého střeva

prof. MUDr. Jiří Petera, Ph.D. (ing. V. Vymetálková, Ph.D. – ÚEM Praha) AZV MZ ČR NV19-09-00237 (LF)

Objasnění role kadherinů a EMT v rozvoji chemoterapeutické rezistence u metastatického kolorektálního karcinomu

prof. PharmDr. Emil Rudolf, Ph.D. (prof. MUDr. A. Ryška, Ph.D. – FN) GA ČR 17-10331S (LF)

Nové metody a postupy v diagnostice a hledání prediktivních a prognostických markerů nádorových onemocnění

prof. MUDr. Aleš Ryška, Ph.D.

SVV 260398 (LF) Banka klinických vzorků

prof. MUDr. Aleš Ryška, Ph.D.

(odp. řešitel: prof. MUDr. Dalibor Valík, Ph.D. – MOÚ Brno) MŠMT BBMRI_CZ (LF)

Vývoj nových radioprotektivních látek na bázi malých molekulárních inhibitorů prof. MUDr. Martina Řezáčová, Ph.D.

(odp. řešitel: doc. MVDr. Z. Šinkorová, Ph.D. – UO FVZ HK) GA ČR 17-13541S (LF)

Onemocnění orofaciálního systému – výskyt, mechanizmy, prevence, léčba, interakce doc. MUDr. Radovan Slezák, CSc.

Progres Q29 (LF)

Centrálně účinná antidota pro léčbu otrav organofosfáty PharmDr. Ondřej Soukup, Ph.D.

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Vliv funkčních polymorfismů ovlivňujících zánět a oxidační stres na průběh chronické lymfocytární leukémie a volbu individuální léčebné strategie

MUDr. Martin Šimkovič

(odp. řešitel: prof. MUDr. T. Papajík, CSc. – UPOL LF) AZV MZ ČR 16-32339A (FN)

Studium jednotlivých isoforem topoisomerasy II v protinádorovém a kardiotoxickém působení antracyklinů a jejich modulací bisdioxopiperaziny

doc. PharmDr. Martin Štěrba, Ph.D.

(odp. řešitel: prof. PharmDr. Tomáš Šimůnek, Ph.D. – UK FaF HK) GA ČR 18-08169S (LF)

Katetrizační uzávěr ouška levé síně versus terapie novými orálními antikoagulancii u rizikových pacientů s fibrilací síní (studie PRAGUE-17)

doc. MUDr. Josef Šťásek, Ph.D.

(odp. řešitel: doc. MUDr. Pavel Osmančík, Ph.D. – 3. LF UK Praha) AZV MZ ČR 15-29565A (FN)

Porovnání účinnosti kolonické kapslové endoskopie a optické kolonoskopie u osob s pozitivním imunochemickým testem na okultní krvácení do stolice

MUDr. Ilja Tachecí, Ph.D.

(odp. řešitel: MUDr. Štěpán Suchánek, Ph.D. – ÚVN Praha) AZV MZ ČR 16-29614A (LF)

Mechanismy IFNgama-indukované buněčné senescence a fenotypové plasticity Mgr. Vojtěch Tambor, Ph.D.

(odp. řešitel: MUDr. Zdeněk Hodný, CSc. – ÚMG AV Praha) GA ČR 17-07635S (FN)

Vztah solubilního endoglinu k hypercholesterolémii u pacientů s diabetes mellitus 2 typu a vliv léčebné intervence.

MUDr. Jakub Víšek, Ph.D.

(odp. řešitel: doc. PharmDr. Petr Nachtigal Ph.D. - UK FaF HK) AZV MZ ČR 17-31754A (FN)

Nové analytické metody pro efektivní stanovování biologických markerů.

prof. MUDr. Zdeněk Zadák, CSc.

(odp. řešitel: Ing. Michal Bartoš – Výzkumný ústav organických syntéz, a.s.) TA ČR TA04010954 (FN)

Inovace infuzních roztoků podle nejnovějších poznatků s protektivním účinkem na glykokalyx

prof. MUDr. Zdeněk Zadák, CSc.

(odp. řešitel: Ing. Milan Máchal – Ardeapharma a.s. Ševětín) MPO ČR FV10454 (FN)

Variabilita a změny ve složení nazofaryngeálního mikrobiomu u pacientů s transplantací kmenových krvetvorných buněk

doc. MUDr. Helena Žemličková, Ph.D.

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XXIV. vědecká konference LF v Hradci Králové a FN Hradec Králové, 5. února 2020

__________________________________________________________________________

SOUHRNY VÝZKUMNÝCH ÚKOLŮ

ŘEŠENÝCH NA LF UK A VE FN V HRADCI KRÁLOVÉ

(ABECEDNĚ)

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Title of the project: Comparison of platinum-sensitive and platinum-resistant methylomes in ovarian cancer cell lines

Grant Agency: Internal Agency of UHHK Project Number: 8148 Principal Investigator: I. Baranová

Co-investigators: M. Chmelařová, H. Kovaříková, A. Mrkvicová

Starting date: 01.02.2019 Duration (years): 1

Total funds allocated for project - Kč (thousands): 438 Summary of 2019 results

Title of the presentation: Differentially methylated gene patterns between platinum-sensitive and platinum-resistant ovarian cancer cell lines

Authors: I. Baranová (1), H. Kovaříková (1), A. Mrkvicová (2), M. Chmelařová (1)

(1) Inst. of Clinical Biochemistry and Diagnostics, Fac. Med., Charles Univ. and Univ. Hospital Hr. Králové; (2) Dept. of Medical Biochemistry, Fac. Med., Charles Univ., Hr. Králové

Ovarian cancer is the most fatal cancer of female reproductive system. The current standard treatment consists of primary cytoreductive surgery followed by an adjuvant platinum-based chemotherapy combined with taxane or alternatively biological treatment. However, more than 20 % of patients exhibit primary chemo-resistance and the rest of them usually become platinum resistant with subsequent relapses. Multiple molecular mechanisms including epigenetic changes have been implicated in chemotherapy resistance. Several studies have supported an association between hypermethylation of various genes and chemo-resistance. The aim of the project was to compare genome-wide DNA methylation profiles of platinum-sensitive (OVCAR3) and platinum-resistant ovarian cancer cell lines (OVCAR3-CP-R) with purpose to identify changes in methylation associated with platinum resistance. For whole-genome DNA methylation analysis next-generation sequencing was used. Significant differences were observed in the methylation profiles of OVCAR3 and OVCAR3-CP-R. N-cadherin (CDH2) was selected from a large number of genes with different methylation for further confirmation. In OVCAR3-CP-R, an average methylation of 91.4 % was observed in the promoter region of the gene. Methylation in OVCAR3 was below 1 %. Moreover, analysis of relative expression showed statistically significant downregulation of CDH2 in OVCAR3-CP-R. Our results suggest that CDH2 hypermethylation and related silencing of the gene could be connected to platinum resistance which may be potentially used in prediction of chemotherapy resistance in ovarian cancer patients.

Supported by Ministry of Health, Czech Republic – conceptual development of research organization (UHHK, 00179906).

Address for correspondence: I. Baranová, Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Sokolská 581, Hradec Králové 500 05, Czech Republic;

ivana.baranova@fnhk.cz

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Title of the project: Population of Elderly Patients with Non-Hodgkin´s Lymphomas- the Analysis of Factors Affecting the Management and Outcome.

Grant Agency: Ministry of Health Project Number: 16-31092A Principal Investigator: Marek Trneny, prof.

Co-investigators: doc.Andrea Janikova, dr.David Belada,doc.Vít Procházka, Dr.Heidi Móciková, Dr.Kateřina Kubáčková, Dr.J.Ďuraš, doc.S.Vokurka

Title of the presentation: Population of Elderly Patients with Non-Hodgkin´s Lymphomas- the Analysis of Factors Affecting the Management and Outcome.

Authors: Dr.David Belada, doc.Andrea Janikova, doc.Vít Procházka, Dr.Heidi Móciková, Dr.Kateřina Kubáčková, Dr.J.Ďuraš, doc.S.Vokurka and prof.Marek Trneny

This project is focused on elderly patients with Non-Hodgkin´s lymphoma (NHL). The data on the management, therapy, effect, toxicity is limited, especially at the age ≥ 80 years. Project is based on prospective collection of data from NIHIL - Czech Lymphomy Study Registry. There is already registered more than 7600 patients at the age ≥ 60 years. The inclusion about 700 newly diagnosed patients is anticipated in the prospective part of the project per year.

The project objectives are:

1. Analysis of currently included patients according to diagnosis (NHLS subtype), biological characteristic, age, furthe prognostic factors, analysis of therapy, its effect and toxicity, farmacoeconomy of targeted therapy.

2. In prospective part the from 2015 analysis of treatment outcomes in individual diagnosis is performed

3. National guidelines for management of lymphoma patients including chapter of specifics of elderly pts were introduced in 2018 and will be updated in 2020

During 2019 we continued with several analysis of elderly patients with NHL from the Czech Lymphoma Registry. Data with treatment results of elderly patients with lymphoma focusing on patients with DLBCL, primary CNS lymphoma, Hodgkins lymphoma, peripheral T-cell lymphoma and follicular lymphoma were presented. New treatment options for elederly patients with relapsed DLBCL are studied - including combination of bendamustine, rituximab and polatuzumab vedotin. Publication "First-line therapy for T cell lymphomas: a retrospective population-based analysis of 906 T cell lymphoma patients. has been published. Several another publications on this topic were published in 2018 and some another are now prepared. New diagnostic and therapeutic guideilnes for lymphoma patients are planned in 2020.

Address for correspondence: David Belada, M.D., Ph.D., Charles University and Medical School, 4-th Clinic of Internal Medicine, Haematology Dept., Sokolska street 581, Hradec Kralove 5, 500 05, Czech Republic; david.belada@fnhk.cz

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Title of the project: Analysis of allelic variants in thymidylate synthase and dihydropyrimidine dehydrogenase genes to predict hematological toxicity of chemotherapy in colorectal cancer – a retrospective study

Grant Agency: Internal Agency of University Hospital HK Project Number: 8142 Principal Investigator: M. Beránek

Co-investigators: J. Grim

Title of the presentation: Analysis of allelic variants in thymidylate synthase and dihydropyrimidine dehydrogenase genes to predict the toxicity of chemotherapy in patients with colorectal cancer

Authors: Beránek M. (1), Grim J. (2)

University Hospital Hradec Králové: Institute of Clinical Biochemistry and Diagnostics (1), Department of Oncology and Radiotherapy (2)

Adjuvant and palliative treatment of colorectal cancer is based on combination of 5-fluorouracil (5-FU) and oxaliplatin. Complete adjuvant chemotherapy, however, is performed only in one- third of patients because of its toxicity. The worse tolerance to 5-FU could be linked to low activity of repair (thymidylate synthase, TS) and biotransformation (dihydropyrimidine dehydrogenase, DPD) enzymes. The aim of this study was to explore possible relationships between allelic variants in TS (rs34743033 polymorphism/28R*2 and *3 alleles and 1494del6 polymorphism, respectively), and DPD (IVS14+1G>A, DPYD*13, D949V and IVS10) genes and 5-FU toxicity. Genomic DNA of 41 subjects (24 women and 17 men, age median 68 years, range 40–78 years) with developing toxicity to chemotherapy and 11 controls (5 women and 6 men, age median 68 years, range 39–81 years) was extracted from EDTA blood specimens and stored at -70 °C until analysis. The rs34743033 polymorphism was analyzed by standard PCR followed by horizontal electrophoresis in 3% agarose gels. In 1494del6 polymorphism, the fragmentation analysis in the ABI 3500 Genetic Analyzer (Life Technologies) was used. DPD variants were examined by the Easy DPYD Kit (Diatech Pharmacogenetics). In rs34743033, no significant difference in genotype distribution between the experimental and control groups was found. The frequency of 28R*3 variant in both groups reached 60 % and 73 %, respectively.

Neither 1494del6 polymorphism showed significant differences in the distribution of genotypes, the frequency of 1494del6 deletion variant was 32 % and 27 % in the groups. In both TS polymorphic sites, similar allelic frequencies in subjects suffering from hematological, skin or mucous toxicity, and controls were apparent (p>0.05). Our data show that the presence of allelic variants in rs34743033 and 1494del6 TS polymorphisms does not probably influence the toxicity of FOLFOX therapy of colorectal cancer. No IVS14+1G>A, DPYD*13, D949V and IVS10 variants in the DPD gene were discovered in the patients and controls. Thus, DPD genotyping does not seem to be useful for predicting the toxicity of 5-FU therapy in patients of Czech origin.

Address for correspondence: M. Beránek, Institute of Clinical Biochemistry and Diagnostics, University Hospital, Sokolská 581, 500 05 Hradec Králové, Czech Republic

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Title of the project: DNA methylation changes in oropharyngeal cancer (student project)

Grant Agency: Internal Agency of UHHK Project Number: Junior - 1 Principal Investigator: N. Birknerová - student

Co-investigators: M. Chmelařová - supervisor

Title of the presentation: Dna methylation changes of specific genes in oropharyngeal cancer Authors: N. Birknerová (1), H. Kovaříková (2), I. Baranová (2), J. Laco (3), M. Vošmik (4), M.

Chmelařová (2)

Fac. Pharmacy, Charles Univ., Hr. Králové, Dept. of Biochemisty (1); Fac. Med., Charles Univ.

and Univ. hospital, Hr. Králové: Inst. of Clinical Biochemistry and Diagnostics (2), The Fingerland Dept. of Pathology (3), Dept. of Oncology and Radiotherapy (4).

Oropharyngeal carcinoma (OP) is a type of head and neck cancer (HNC) emerging in the tissue of the base of the tongue, tonsils, soft palate and pharynx. Traditional risk factors include excessive alcohol and tobacco consumption. Recently, human papillomavirus (HPV) has been identified as an additional independent risk factor for the development of these tumors [1].

Epigenetic alterations, such as DNA methylation, refer to heritable changes in gene expression that occur without changes in the underlying DNA sequence and can contribute to carcinogenesis [2]. The aim of this study was to investigate methylation levels of selected tumor suppressor genes in oropharyngeal squamous cell carcinoma (OPSCC) by comparsion with normal oropharyngeal tissue.

DNA methylation levels of selected tumor suppressor genes were analysed using Methylation- Specific Multiplex Ligation-dependent Probe Amplification (ME002-Tumour suppressor mix 2 kit, MRC-Holland) in metastatic tumor samples, metastases samples, non-metastatic tumor samples and control tissue samples (non-cancerous palatine tonsils). From 25 analyzed genes (using a 15% cut-off for methylation) we observed statistically significantly higher methylation in the RARB, PAX5, KLLN (P<0.05) and WT1, CADM1 (P<0,01) genes of patients with oropharyngeal carcinoma compared to control group.

The findings of this study show promising candidates for prognostic OPSCC biomarkers and may have implications for future individualised therapies based on epigenetic changes.

1. ZARAVINOS, A.: Oncotarget, 2014, 5(12), 3956–3969.

2. VAN KEMPEN et al.: Epigenetics, 2014, 9(2), 194–203.

The study was upported by MH CZ - DRO (UHHK, 00179906).

Address for correspondence: N. Birknerová, Institute of Clinical Biochemistry and Diagnostics,University Hospital Hradec Králové, Sokolská 581, 500 05, Hradec Králové, Czech Republic; birknerovan@faf.cuni.cz

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Title of the project: Genetic polymorphisms, MicroRNAs and bioindicators of activity:

interrelations in the diagnostics and therapy of severe familial hypercholesterolemia

Grant Agency: Ministry of Health Project Number: 17-28882A Principal Investigator: Prof. MUDr. Vladimír Blaha, CSc.

Co-investigators: Ing. Jaroslav Hubáček CSc., DSc., Prof. MUDr. Milan Blaha, CSc., MUDr.

Jakub Víšek, PhD., MUDr. Martina Lášticová, PhD., RNDr. Dana Dlouhá, PhD., doc. MUDr.

Jan Piťha, CSc., MUDr. Alena Paříková, MUDr. Miriam Lánská, doc. RNDr. Lenka Kujovská Krčmová, PhD.

Title of the presentation: Influence of lipoprotein apheresis on circulating plasma levels of miRNAs in patients with high Lp(a)

Authors: D. Dlouha (1), I. Prochazkova (1), Z. Eretova (2), V. Blaha (3), M. Blaha (3), J. A.

Hubacek (1), J. Pitha (4)

Centre for Experimental Medicine (1), Clin. Nephrology (2), Institute for Clinical and Experimental Medicine, 3^rd Dept. Internal Medicine Hradec Kralove (3), Dept. Internal Medicine, 2nd Medical Faculty Prague (4), Charles University, Czech Republic

Background: Lipoprotein apheresis (LA) is a well-established therapy for lowering lipid levels in serious cases of dyslipidaemia, including high levels of lipoprotein(a) [Lp(a)]. This method lowers both LDL cholesterol and Lp(a) by more than 60% in most of patients; however, because randomized clinical studies could be extremely difficult, also other markers of the effect of this procedures on vascular health are of importance. Therefore, in addition to changes in plasma lipids and Lp(a) during LA, we also analysed the response of biomarkers associated with vascular integrity: small non-coding microRNAs (miRNAs).

Materials and methods: We analysed the changes in miRNAs in two women (age 70 and 72 years) with clinically manifest extensive and progressive atherosclerotic disease and high levels of Lp(a) and with different clinical course who were treated by LA. In both women we analysed changes of 175 circulating plasma miRNAs using pre-defined serum/plasma focus panels at the beginning of and one year after the therapy.

Results: In addition to reduced levels of plasma lipids and Lp(a), circulating plasma levels of miR-193a-5p; -215-5p; -328-3p; -130a-3p; -362-3p; -92b-3p decreased, and levels of miR-125a- 5p; -185-5p; -106a-5p; -320b; -19a increased (all P < 0.05) in both women. Moderate differences were found between both women with regard to the different course of atherosclerotic disease.

Conclusions: Long-term LA substantially changes circulating plasma miRNAs associated with vascular integrity reflected different clinical course in both women. If confirmed, this approach could improve the assessment of the effectiveness of this therapy on an individual basis.

Address for correspondence: prof. MUDr. Vladimír Blaha, CSc., IIIrd Department of Internal

|Medicine - metabolism and gerontology, Medical Faculty Charles University and University Hospital, Sokolska 581, 500 05 Hradec Kralove, Czech Republic

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Title of the project: Clinical and experimental gastroenterology

Grant Agency: Internal Agency of University Hospital HK Project Number: 8161 Principal Investigator: Jan Bureš

Co-investigators: Darina Kohoutová, Miroslava Forstlová, Paula Moravková, Jiří Cyrany, Juraj Bosák, David Šmajs, Stanislav Rejchrt, Ladislav Douda, Tomáš Douda, Marcela Drahošová, Tomáš Fejfar, Miloš Hroch, Veronika Knoblochová, Marcela Kopáčová, Věra Králová, Jaroslav Květina, Jana Nekvindová, Jaroslav Pejchal, Eva Peterová, Věra Radochová, Rudolf Repák, Tomáš Soukup, Ilja Tachecí, Jaroslava Vávrová, Doris Vokurková, Barbora Voxová, Jana Žďárová Karasová

Title of the presentation: Bacteriocin production by mucosal bacteria in current and previous colorectal neoplasia

Authors: D Kohoutova (1,2), M Forstlova (3), P Moravkova (1), J Cyrany (1), J Bosak (4), D Smajs (4), S Rejchrt (1), J Bures (1)

(1) 2nd Dept Med - Gastroent, Charles Univ Fac Med, Univ Hospital, Hradec Králové; (2) The Royal Marsden Hospital, London; (3) Dept Clin Microbiol, Charles Univ Fac Med, Univ Hospital, Hradec Králové; (4) Dept Biol, Masaryk Univ Fac Med, Brno

Optimal therapy for colorectal carcinoma (CRC), a frequently diagnosed malignancy, does not exist. Some of colicins and microcins, ribosomally synthetized peptides by gramnegative bacteria, have shown significant biological activity specifically against different cancer cells in vitro and in vivo conditions. The aim of this prospective study was to evaluate natural colicin and microcin production by large intestinal mucosal bacteria in each stage of colorectal neoplasia and in those with a history of colorectal neoplasia.

A total of 21 patients with non-advanced adenoma (non-a-A; 13/21 with current and 8/21 with history of non-a-A), 20 patients with advanced colorectal adenoma (a-A; 11/20 with current and 9/20 with history of a-A), 22 individuals with CRC (7/22 with current and 15/22 with history of CRC) and 20 controls were enrolled. Mucosal biopsies from the caecum, transverse colon and the rectum were taken during colonoscopy in each individual. Microbiological culture followed. Production of colicins and microcins was evaluated by PCR methods. A total of 239 mucosal biopsies were taken. Production of colicins and microcins was significantly higher in individuals with non-a-A, a-A and CRC compared to controls. No significant difference in colicin and microcin production was found between patients with current and previous non-a-A, a-A and CRC. Significantly higher production of colicins was observed in men compared to women at the stage of colorectal carcinoma. A later onset of increased production of microcins during the adenoma-carcinoma sequence has been observed in males compared to females.

Strains isolated from large intestinal mucosa in patients with colorectal neoplasia produce colicins and microcins more frequently compared to controls. Bacteriocin production does not differ between patients with current and previous colorectal neoplasia. Fundamental differences in bacteriocin production have been confirmed between males and females.

This paper was accepted for publication in BMC Cancer; DOI: 10.1186/s12885-020-6512-5 (a Q1 journal).

Address for correspondence: Assoc. Professor Darina Kohoutová, 2nd Department of Internal Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové; e-mail: darina.kohoutova@fnhk.cz

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Title of the project: The influence of experimental gastrointestinal injury and inflammation on pharmacokinetics of Alzheimer disease drugs

Grant Agency: Grant Agency of the Czech Republic Project Number: 18-13283S Principal Investigator: Jan Bureš

Co-investigators: J Květina, V Radochová, I Tachecí, E Peterová, D Herman, R Doležal, M Kopáčová, S Rejchrt, T Douda, V Šetsák, L Douda, J Žďárová Karasová

Title of the presentation: The Pharmacokinetic Parameters and the Effect of a Single and Repeated Doses of Memantine on Gastric Myoelectric Activity in Experimental Pigs

Authors: J Bures, J Kvetina, V Radochova, I Tacheci, E Peterova, D Herman, R Dolezal, M Kopacova, S Rejchrt, T Douda, V Sestak, L Douda, J Zdarova Karasova

Memantine is an antagonist of the N-methyl-D-aspartate type of glutamate receptors.

Memantine administration is associated with different gastrointestinal dysmotility side effects (vomiting, diarrhoea, constipation, motor-mediated abdominal pain), thus limiting its clinical use. Mechanism of these motility disorders has not been clarified yet.

The aim of this study was to evaluate the impact of a single and repeated doses of memantine on porcine gastric myoelectric activity evaluated by means of electrogastrography (EGG).

Single dose of memantine significantly increased DF, from basic values (1.65±1.05 cycles per min.) to 2.86 cpm after 30 min. (p=0.008), lasting till 75 min. (p=0.014). Basal power (median 452; inter-quartile range 280 – 1312 μV^2) raised after 15 min. (median 827; IQR 224 - 2769;

p=0.386; NS), lasting next 30 min. Repetitively administrated memantine caused important gastric arrhythmia. Basal DF after single and repeated administration was not different, however, a DF increase in the second part was more prominent (up to 3.18±2.16 after 15 and 30 min., p<0.001). In comparison with a single dose, basal power was significantly higher after repetitively administrated memantine (median 3940; IQR 695 – 15023 μV^2; p<0.001). Next dose of 20 mg memantine in the second part induced a prominent drop of power after 15 min.

(median 541; IQR 328 – 2280 μV^2; p<0.001), lasting till 120 min. (p<0.001).

Both single and repeated doses of memantine increased DF. Severe gastric arrhythmia and long-lasting low power after repeated administration might explain possible gastric dysmotility side effects in the chronic use of memantine.

This paper was accepted for publication in PLOS ONE; doi: 10.1371/journal.pone.0227781 (a Q1 journal).

Address for correspondence: Professor Jan Bureš, 2nd Department of Internal Medicine - Gastroenterology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, Czech Republic; e-mail:bures@lfhk.cuni.cz

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Title of the project: New procedures in research, diagnostics and therapy and therapy of lifestyle diseases and diseases connected with population ageing

Grant Agency: Charles University Project Number: Q 40 Principal Investigator: M. Červinka

Co-investigators: J. Bureš, Z. Červinková, S. Dusilová Sulková, Z. Fiala, M. Kaška, J. Krejsek, M. Kuba, S. Mičuda, J. Mokrý, R. Pudil, A. Ryška, E. Rudolf, L. Sobotka, R. Slezák, P. Žák

Title of the presentation: New procedures in diagnostics and therapy of lifestyle diseases and diseases connected with ageing of population

Authors: M. Červinka, J. Bureš, Z. Červinková, S. Dusilová Sulková, Z. Fiala, M. Kaška, J.

Krejsek, M. Kuba, J. Malý, S. Mičuda, J. Mokrý, A. Ryška, E. Rudolf, R. Pudil, L. Sobotka, R.

Slezák

Anticancer properties of selected compounds on several malignant models were studied. Beta- hydroxy-beta-methyl butyrate increases concentrations of branched-chain amino acids in blood plasma and has detrimental effect on the course of experimental liver cirrhosis induced by carbon tetrachloride.

Therapeutic dose of Sorafenib (10 µM) induced mitochondrial membrane depolarization, oxidative stress, reduction of mitochondrial oxygen consumption and apoptosis in HepG2. In vitro and in vivo pharmacokinetics of dexrazoxane and its active metabolite ADR-925 was studied on cardiomyocytes and myocardium. Attention was payed to detection of cardiotoxicity, arterial hypertension, coronary artery disease, heart failure and cardio surgery procedures.

Human bone marrow-derived mesenchymal stem cells were used to improve bone neoformation.

Human mesenchymal stem cells were used for treatment of femoral bone defects.

Electrophysiological group has reported brain changes (evoked potentials) in HIV+ adults, electrophysiological correlates of complex behavioural pattern, bone side effects of antiepileptic therapy, visual outcome in fungal keratitis and development of portable evoked potentials device.

We continue study of organism's response to selected chemical, physical and social factors related to civilization diseases and aging population. Immunological group studied premature rupture of maternal envelopes in the context of inflammatory response. Analysis of DNA methylation and microRNA expression in SMARCB1-deficient sinonasal carcinoma and prognostic significance of dendritic cell infiltration in ovarian cancer were published. The influence of lipid metabolism on development of age-related macular degeneration and potential of antibodies against PCSK9 in the treatment was described.

The effect of glucose based parenteral nutrition on plasma FFA was described in the new cohort of intensive care patients. Porcine experimental model of inflammatory bowel disease was published. Study of different acetylcholinesterase-modulators on gastric myoelectric activity was performed and published.

Address for correspondence: M. Červinka, Charles University, Faculty of Medicine in Hradec Králové, Šimkova 870, 50038 Hradec Králové, Czech Republic

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Title of the project: Liver mitochondria - focus on Age, Lifestyle, Environment

Grant Agency: Ministry of Education Project Number: LTC17044 Principal Investigator: Z. Červinková

Co-investigators: O. Kučera, H. Lotková, P. Staňková, R. Endlicher, D. Rychtrmoc, O. Sobotka

Title of the presentation: Age-dependent changes of calcium retention capacity in rat liver mitochondria.

Authors: R. Endlicher (2), P. Staňková (1), O. Kučera (1), Z. Drahota (1), Z. Červinková (1) Fac . Med. Charles Univ., Hr. Králové: Dept. of Physiology (1)

Fac . Med. Charles Univ., Hr. Králové: Dept. of Anatomy (2)

Mitochondrial dysfunction and oxidative stress are crucial mechanisms involved in the aging process and the pathogenesis of many age-related diseases. In accordance with the work plan, we focused on the evaluation of mitochondrial sensitivity to calcium ions in relation to age. In mitochondria, calcium ions regulate mitochondrial permeability transition pore (MPTP).

Increased Ca2+ concentration, in addition to other changes (inorganic phosphate concentration, oxidative stress), causes MPTP opening and may lead to induction of cell death. Various studies document that mitochondrial sensitivity to Ca2+ ions is changing throughout ontogenesis.

Mitochondria were isolated from adult male Wistar rat liver by differential centrifugation. The sensitivity of isolated mitochondria to calcium ions was evaluated by measuring mitochondrial swelling (turbidimetric analysis at 520 nm - Shimadzu UV-1601) and calcium retention capacity (CRC) in mitochondria (fluorescent probe Calcium Green - AMINCO-Bowman Series 2).

We have found that CRC is significantly dependent on rat age. The highest values of CRC were measured in the sexual maturity of rats (7 weeks, 200 g). During adolescence CRC gradually increases. Younger rats (3 weeks, 50 g and 5 weeks, 100 g) show significantly lower CRC compared to sexually mature animals. Mitochondria isolated from older rats again exhibited lower CRC. Significant decrease in CRC was seen already after three weeks (10 weeks, 300 g) compared to the maximal value. Retention capacity further decreased with increasing age of rats (13 and 15 weeks).

We have shown that hepatic mitochondria isolated from older rats respond to the same Ca2+

concentration by much more intensive swelling. The time of maximum change in optical density (MPTP opening) was also significantly lower in older rats. Mitochondria isolated from 7-week- old rats showed the highest resistance (the lowest swelling rate) to calcium ions. Swelling in mitochondria isolated from older rats (10, 13, 15 weeks) indicate an increasing rate of mitochondrial swelling. In conclusion, hepatic mitochondria isolated from older rats showed increased sensitivity to calcium ions.

Address for correspondence: Z. Červinková, Dept. of Physiology, Charles University, Faculty of Medicine in Hradec Králové, Šimkova 870, 500 03 Hradec Králové, Czech Republic

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Title of the project: Gestational diabetes mellitus according to the new diagnostic criteria – prevalence, data and treatment.

Grant Agency: Internal Agency of University Hospital HK

Project Number: Junior - 2 Principal Investigator: Monika Esterková

Co-investigators: MUDr. Markéta Kubíčková

Starting date: 01. 02. 2018 Duration (years): 1 Total funds allocated for projekt – Kč (thousands): 50 thousands Kč

Summary of 2019 results Title of the prentation:

Retrospective statistics of the patients diagnosed with Gestational diabetes mellitus in the Diabetes center FN HK focused on the impact of current treatment using the new

diagnostic criteria for the period of 1. 1. 2013 – 31. 12. 2018.

Authors: Monika Esterková, MUDr. Markéta Kubíčková

Diagnostics of Gestational diabetes mellitus (GDM) in the Czech Republic is subject to nationwide screenings and as of 2013 the diagnostic criteria were tightened. This caused rise of patients which are being cured in the Diabetes center of the Faculty Hospital Hradec Králové. Main goal of this project is to assess the impact of current treatment upon the course of pregnancy, birth and health of the child. Then the gathered data could be used to improve treatment for pregnant patients. This paper verifies the hypothesis that timely diagnosis and correct GDM treatment lowers morbidity and mortality of both mothers and children and also lowers the number of complications during pregnancy. Used methodology is retrospective statistics and data were gained from the Diabetes center of III. Internal Gerontology-Metabolic clinic FN HK database of patients. The data were selected according to the criteria for diagnoses O244 (GDM) and for the period of 1. 1. 2013 – 31. 12. 2018.

First phase of the project is focused on monitoring the patients matching the given criteria hospitalized in the Diabetes center. Aggregating criteria are: age, BMI, family anamnesis, glycemic metrics, OGT, medication, comorbidity. Processing of the patient data and birth reports from the Obstetrics-Gynecology clinic FN HK will result in verification or dismissal of the hypothesis.

Address for correspondence: Markéta Kubíčková, III. Internal Gerontology-Metabolic clinic, Faculty Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic

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Title of the project: TEXDERM - Comfortable textiles and clothing fulfilling specific needs of kids with skin problems

Grant Agency: Ministry of Industry and Trade, Trio Tr

Project Number: FV20287 Principal Investigator: K. Ettler, Dept. of Dermatology and Venereology, Medical Faculty of Charles University, Hradec Králové

Co-investigators: V.Wertzová, Dept. of Dermatology and Venereology, Medical Faculty of Charles University, Hradec Králové

Title of the presentation: Clinical testing of clothes for kids with skin problems Authors: K. Ettler, V. Wertzová

Two types of textile fibres have been prepared for clinical testing at the Institute of Cotton Research (VUB, a.s., Ústí n.O.): lyocel (Tencel)/polypropylen Ag+ (POP) and viscose Viloft/micromodal.

Technical University (Liberec) laboratories assessed their physical properties with the main stress on permeability, heat conductivity, sensoric comfort and permeability for water vapour.

Also the washability using commercial soap powders of each textiles was performed after staining the clothes with common dermatological topical ointments.

Some antimicrobial properties have been established by exposition to 2 bacterial strains and Candida yeast. Results of antifungal resistence tests are still expected.

As the ready-to-wear sample were choosen pyjamas with flat seams in natural colour pretreated by washing. Four sizes of pyjamas were prepared for testing in children aged 3 to 12 years according to the Study protocol for 2 months in each child (Dept.of Dermatology, Medical Faculty in Hradec Králové). Clinical examination of the skin and skin microbiom was monitored before and after wearing tests. Also some physical properties for each textile material were assessed.

Results: There were very good tolerance (without any irritation) of tested clothes in all children.

Textiles made from Tencel/POP Ag+ had a high tendency to lumping. Viloft/micromodal pyjamas were very wispy and had a tendency to shrink and loose a shape.

Conclusion: We will continue clinical testing of prepared samples of pyjamas. But some new textile materials are needed. Especially fine flax fibres are very promising for their toughness, natural origin and ability to absorb water.

Address for correspondence: K. Ettler, Dept. of Dermatology and Venereology, Charles University, Faculty of Medicine in Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic, e-mail: ettler@lfhk.cuni.cz

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Title of the project: Genetic variability of BKV in the Czech Republic and its influence on pathogenesis of infection in kidney transplant recipients

Grant Agency: Ministry of Health Project Number: 17-29992A Principal Investigator: RNDr. Martina Saláková, PhD.

Co-investigators: MUDr. M. Fajfr Ph.D., prof. MUDr. S. Dusilová Sulková, Ph.D., MUDr. P.

Navrátil, CSc.

Title of the presentation: BKV in patients after kidney transplantation in the University hospital in Hradec Kralove - partial results

Authors: M. Fajfr (1), S. Sulková Dusilová (2), P. Navrátil (3)

Institute of Clinical Microbiology, Charles University, University Hospital in Hradec Kralove (1); Haemodialysis Centre, Charles University, University Hospital in Hradec Kralove, (2);

Transplantation Centre of Urological Clinic, Charles University, University Hospital in Hradec Kralove (3)

Aim: We propose a prospective study of BKV infection in kidney transplant patients, aimed to evaluate the impact of genetic polymorphism of BKV, dynamics of BKV specific and BKV type-specific antibodies, including donor and recipient serostatus, in the context of other clinical indicators (recipient age, sex, type of immunosuppressive therapy, graft rejection) on the development of BKV infections after transplantation. We will evaluate the risk factors associated with the infection progression into the stage of PVAN disease.

Materials and Methods: from each patients were collected blood and urine samples from several time points – date of transplantation, and following samples from 1, 3, 6 and 12 months after transplantation. BKV viraemia/viruria were examined by QCMD controlled PCR reactions. And sera from 0 and 12 month were collected and stored for BKV serology examination (in the laboratory of Institute of Hematology and Blood Transfusion - co-investigator)

Results 2018: From the University Hospital in Hradec Kralove 52 donors and 104 recipients were already assigned to the project. In total 4 patients had to be excluded from the study - early graftectomy, exitus lethalis, and inappropriate transplantation for contraindications. The BKV positivity has been captured from 30 patients - 4 kidney donors and 26 recipients. The genetic variability of examined BKV isolates showed dominance of genotype 1 (G1b1 and G1b2). The other fond genotypes were genotype 4 an in 1 patient also genotype 2. The genetic variability will be assessed with clinical data in the last year of project.

Address for correspondence: M. Fajfr MD; Institute of Clinical Microbiology, University Hospital in Hradec Kralove, Sokolska 581, 500 05, Czech Republic; email address:

miroslav.fajfr@fnhk.cz

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Title of the project: Role of iron depletion and Mrp2 deficiency for development of estrogen-induced cholestasis

Grant Agency: Charles University Project Number: 5562/18 Principal Investigator: F. Alaei Faradonbeh

Co-investigators: S. Mičuda

Starting date: 13.03.2018 Duration (years): 3 Total funds allocated for project - Kč (thousands): 270

Summary of 2019 results

Title of the presentation: Effect of cardiovascular drugs on the development of non-alcoholic steatohepatitis.

Authors: H. Laštůvková (1), S. Mičuda (1). Fac. Med., Charles Univ., Hr. Králové: Dept. of Pharmacology(1)

Biliary secretion is essential pathway for elimination of lipophilic agents from the organism.

This pathway is modified by numerous liver diseases, which may worsen accumulation of toxic compounds and predispose for further liver impairment. Nonalcoholic steatohepatitis (NASH) is a frequent disease associated with numerous metabolic and cardiovascular risks. Recent works demonstrated that bile acid homeostasis and bile formation markedly contributes to pathophysiology of NASH. It is therefore important to describe modulation of these mechanisms by all drugs regularly prescribed for therapy of NASH and accompanying risks.

Primary aim of this project is to study in detail effects of drugs commonly used for these risks, carvedilol, metformin, and atorvastatin, and their combinations on the mechanisms of bile production and bile acid homeostasis using relevant mice model of NASH. During the second year of the project solution, we completed all in vivo studies based on continuous 24 week administration of high fat diet with glucose and fructose to induce NASH. Designed groups of animals received carvedilol, metformin, and atorvastatin or their combinations. The samples are currently analysed by analytical, histological, and molecular-biology methods. Preliminary data uncovered positive effects of metformin while carvedilol and atorvastatin neither improved nor worsened the course of NASH. The study will be finished during third year of the project.

Project was supported by the Charles University project No. GAUK 3462/18.

Address for correspondence: S. Mičuda, Dept. of Pharmacology, Charles University, Faculty of Medicine in Hradec Králové, Šimkova 870, 500 03 Hradec Králové, Czech Republic

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Title of the project: Liposoms (drug delivery systems) in kinetically guided therapy of ovaria platinum-resistant carcinoma with doxorubicin using plasmafiltration.

Grant Agency: Ministry of Health Project Number: 16-30366A Principal Investigator: Prof. MUDr. Stanislav Filip, Ph.D., DSc.

Co-investigators: M.Bláha, J.Martínková, O.Kubeček, M.Hodek, J.Maláková, M.Lánská, J.Špaček

Title of the presentation: Plasmafiltration as an effective method in the removal of circulating pegylated liposomal doxorubicin (PLD) and the reduction of mucocutaneous toxicity during the treatment of ovarial cancer.

Authors: S.Filip(1), M.Bláha(2), J.Martínková(1), O.Kubeček(1), M.Hodek(1), J.Maláková(3), M.Lánská(2), J.Špaček(4).

(1) Dept. of Oncology and Radiotherapy; (2) Dept. of IV. Internal Medicine, (3) Dept. of Clinical Biochemistry, (4) Dept. of Obstetrics and Gynecology.

Abstract.

Purpose. The present study evaluates the safety and efficacy of double-plasma filtration (PF) to remove the exceeding pegylated liposomal doxorubicin (PLD) in circulation, thus reducing mucocutaneous toxicity.

Methods. A total of 16 patients with platinum-resistant ovarian cancer were treated with 50 mg/m2 PLD applied in 1-h IV infusion every 28 days. PF was scheduled at 44–46 h post- infusion. The concentration of plasma PLD and non-liposomal doxorubicin (NLD) was monitored with high-performance liquid chromatography over 116 h post-infusion. A non-linear method for mixed-effects was used in the population pharmacokinetic model. The dose fraction of PLD eliminated by the patient prior to PF was compared with the fraction removed by PF.

PLD-related toxicity was recorded according to CTCAE v4.0 criteria and compared to historical data. Anticancer effects were evaluated according to RECIST 1.1 criteria.

Results. The patients received a median of 3 (2–6) chemotherapy cycles. A total of 53 cycles with PF were evaluated, which removed 31% (10) of the dose; on the other hand, the fraction eliminated prior to PF was of 34% (7). Exposure to NLD reached only 10% of exposure to the parent PLD. PLD-related toxicity was low, finding only one case of grade 3 hand–foot

syndrome (6.7%) and grade 1 mucositis (6.7%). Other adverse effects were also mild (grade 1–

2). PF-related adverse effects were low (7%). Median progression-free survival (PFS) and overall survival (OS) was of 3.6 (1.5–8.1) and 7.5 (1.7–26.7) months, respectively. Furthermore, 33% of the patients achieved stable disease (SD), whereas that 67% progressed.

Conclusion PF can be considered as safe and effective for the extracorporeal removal of PLD, resulting in a lower incidence of mucocutaneous toxicity.

Keywords Cancer therapy; Ovarian cancer; EPR effect; Population kinetics; Pegylated liposomal doxorubicin (PLD); Mucocutaneous toxicity; Hand–foot syndrome; Plasmapheresis.

Address for correspondence: S. Filip, Dept. of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Králové, Šimkova 870, 50003 Hradec Králové, Czech Republic, fillip@fnhk.cz

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Title of the project: The influence of ministernotomy approach on pulmonary functions in elderly patients after aortic valve replacement

Grant Agency: Internal Agency of UH HK Project Number: 8151 Principal Investigator: J. Gofus

Co-investigators: M. Voborník, A. Myjavec, V. Koblížek, J. Vojáček, M. Pojar

Title of the presentation: Ministernotomy for aortic valve replacement: Is it better in terms of pulmonary functions and quality of life?

Authors: J. Gofus(1), M. Voborník(1), A. Myjavec(1), V. Koblížek(2), J. Vojáček(1), M.

Pojar(1)

Department of Cardiac Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Czech Republic (1),

Department of Pneumology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kral(2)

Ministernotomy (upper hemi-sternotomy) is one of the most commonly used miniinvasive approaches for aortic valve replacement. It leads to lower blood loss, shorter arteficial ventilation time and shorter lenght of intensive care unit stay postoperatively. We aimed to prove that preserving lower half of throacic cage in this approach could lead to better postopulmonary functions, as well. Consequently we examined quality of life using SF-36 survey and excercise tolerance using one-minute sit-to-stand test.

We enrolled 30 patients into the study and randomised them prospectively to ministernotomy and full sternotomy group (15 vs 15). We examined pulmonary functions and one-minute sit-to- stand test preoperatively, on 7^th and 90^th postoperative day. Quality of life was evaluated preoperatively and on 90^th postoperative day.

Both groups were equal in terms of standard perioperative characteristics. There was significantly lower blood loss in ministernotomy group (p<0.01). Minimally invasive group had better preoperative pulmonary functions but showed more significant drop in obstructive parameters in early postoperative period (p=0.02 for FEV1, p=0.03 for FEV1/FVC, p=0.03 for MEF50%). On the other hand, ministernotomy lead to greater improvement in quality of life postoperatively (p=0.03 for physical functioning, p=0.05 for general health). There was no difference among the groups in one-minute sit-to-stand test outcomes (p=0.49).

Ministernotomy seems to be at least as safe as standard full sternotomy approach, as can be seen in our study in accordance with other papers. We were able to show lower blood loss in minimally invasive group. Ministernotomy could lead to greater drop in pulmonary functions postoperatively, nevertheless, our outcomes could be biased by difference in preoperative pulmonary functions. Implication of this finding remains questionable. Quality of life seems to be better after minimally invasive approach.

Address for correspondence: MUDr. Ján Gofus, Department of Cardiac Surgery, University Hospital Hradec Králové, Sokolská 581, 500 05 Hradec Králové, Czech Republic

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Title of the project: Composite nanoparticles with magnetically and light activated release of biologically active compounds

Grant Agency: Grant Agency Czech Republic Project Number: 18-13323S Principal Investigator: O. Kaman

Co-investigators: R. Havelek

Title of the presentation: Research progress overview on project grant Composite nanoparticles with magnetically and light activated release of biologically active compounds

Authors: O. Kaman (1), L. Kubíčková (1), J. Kuličková (1), Z. Jirák (1), K. Královec (2), M.

Majorošová (2), D. Koutová (2), R. Havelek (2); Department of Magnetics and Superconductors, Institute of Physics, Czech Academy of Sciences, Praha (1); Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové (2)

The aim of the project is to study novel theranostic nanosystems that enable magnetically guided delivery and release of therapeutically active compounds. These study objectives are executed according to the separate research milestones: synthesis of novel complex nanostructures, understanding their behaviour in magnetic fields in terms of their structure and elucidation of their biological effects.

During the second year of the project, a several distinct types of the magnetic nanoparticles (cores) were synthesized and their structure and ferrimagnetic order were characterized by different analytical methods. These experiments primary focused on structural (crystal structure, size and shape of particles) and magnetic behaviour relationships, which allow optimization with respect to intended applications. The biocompatibility of the magnetic cores and/or silica-coated particles and their potential as the functional platform for the development of complex nanosystems was also evaluated in vitro by using human cell cultures. For the determination of cytotoxic and cytostatic activity over a broad concentration range, we employed experiments on human adherent cell lines (A549, MCF-7 and HK-2) with simultaneous use of kinetic and endpoint determinations. The viability of cells treated with particles (e.g. γ-Fe2O3, Ga- substituted ε-Fe2O3, or Fe3O4) was monitored using Trypan blue dye exclusion assay. Next, cell viability, cell growth and cell adhesion kinetics responses were assessed in real-time using the label-free xCELLigence system measurements. The possible cytotoxic, cytostatic, genotoxic and pro-apoptotic mechanisms of particles were investigated using flow cytometric cell cycle analysis, analysis of Annexin V/propidium iodide-binding, fluorescence microscopic analysis of F-actin, paxillin, γH2AX or activated caspase-3/7. The studied silica-coated maghemite rods and Ga-substituted ε-Fe2O3 did not show any considerable toxic effects, which warrants their further investigation.

To date, four articles were published in journals with impact factor and other two manuscripts are now in the peer-review process.

Address for correspondence: O. Kaman (kaman@fzu.cz); R. Havelek (havelekr@lfhk.cuni.cz)