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Localisation of FUBP3 protein in human cervical cancer cell line
Kunrt, Josef ; Jirkovský, Eduard (advisor) ; Macháček, Miloslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Josef Kunrt Supervisor: Eduard Jirkovský, PharmD, PhD.; Assist. Prof. Nika Lovšin, M.Chem., PhD Title of Diploma Thesis: Localisation of FUBP3 Protein in Human Cervical Cancer Cell Line Osteoporosis is a skeletal disorder characterised by an impaired bone mass, strength and microarchitecture which leads to a higher risk of fracture. The disease is predominant in postmenopausal women but also affects older men and other risk groups, such as oncological patients. To ascertain the genetic basis of osteoporosis, multiple genome-wide association studies have been performed with the aim to identify genes with a role in the diseases. These studies discovered multiple genetic loci associated with a higher risk of osteoporotic fractures, one of which was far upstream element-binding protein 3 (FUBP3). Works studying the properties of this protein such as cellular localisation are scarce. Therefore, we focused on establishing a protocol for visualisation of FUBP3 and its co-localization with other cellular structures in a human cervical cancer cell line (HeLa). The visualisation was done using immunostaining of FUBP3 and GM130, a matrix protein of Golgi apparatus, and subsequent imaging with...
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Expression of selected membrane transporters in placentas of pregnant women diagnosed for preterm rupture of membranes
Michalská, Martina ; Čečková, Martina (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martina Michalská Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Expression of selected membrane transporters in placentas of pregnant women diagnosed for preterm rupture of membranes Placenta is a key organ for pregnancy maintenance. One of its main functions is transport of compounds between mother and her fetus. The transplacental penetration is ensured due to membrane transporters that are present in the apical or basal side of trophoblast. Their expression level is affected by many physiological and pathological factors, among others it can be influenced by infection and inflamatory reaction. Inflammation is also one of the risk factors of preterm deliveries and it can be therefore assumed that these pathological states are accompanied by changes in expression of placental transporters. This study was performed using 51 placentas obtained from Faculty hospital in Hradec Králové from women who underwent preterm delivery and on 15 placentas delivered in term. The study employed quantitative RT-PCR approach. The mRNA expression of membrane transporters ABCB1, ABCG2, OATP1A2, OATP1B3, OATP2A1, OATP2B1, OATP3A1, OATP4A1 was assessed and the results were compared to...
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Involvment of PDA3 in oxidative stress response
Ženklová, Lucie ; Vokřál, Ivan (advisor) ; Jirkovský, Eduard (referee)
Charles University, Faculty of pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Ženklová Supervisors: Prof. Fabio Altieri and PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Involvement of PDIA3 in oxidative stress response PDIA3 is a member of the protein disulfide isomerase family (PDI) and it is a stress- responsive protein. It is also involved in various cellular signalling pathways and has various functions in the cell. The best-known location is in the endoplasmic reticulum where it plays a major role mainly in the proper folding and quality control of glycoproteins, and participation in the assembly of the major histocompatibility complex class I. However, its existence has also been described in many other cell compartments, such as nucleus, mitochondria, cell surface or cytosol, where it interferes in various processes. While in some instances these roles need to be confirmed by further studies, a lot of observations confirmed its involvement in the signal transduction (for example releated with STAT protein) from the cell surface and the regulatory processes in the nucleus. Recent studies have also confirmed its increased expression in various pathological states. The aim of our work was to find out what is its role in the exposure of the MDA-MB 468...
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Misuse of doping substances
Valová, Katarína ; Vopršalová, Marie (advisor) ; Jirkovský, Eduard (referee)
Charles University in Prague Faculty of pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Katarína Valová Supervisor: PharmDr. Marie Vopršálová, CSc. Title of diploma thesis: Misuse of doping substances My diploma thesis describe the term doping, possible causes of doping and its prevalence. It contains the outline of doping substances and methods, the characteristics of individual groups, the mechanism of action as well as the adverse effects of the substances on the health of sportsmen. I also focused on anti-doping organs and testing methods or describing new possibilities in in the fight against doping. I briefly described the process of the doping control and as well as the sanctions.
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Assessment of the complex stoichiometry of the active dexrazoxane metabolite ADR-925 with iron and copper by the standard Job's method
Szotáková, Tereza ; Mladěnka, Přemysl (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Tereza Morávková Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of Thesis: Assessment of the complex stoichiometry of the active dexrazoxane metabolite ADR-925 with iron and copper by the standard Job'smethod Iron and copper are important trace elements which participate on many physiological processes in humans. Their kinetics in the organism is tightly regulated since both lack or excess of these elements are associated with pathological states. Free ions of iron and copper can catalyse reactive oxygen species (ROS) production and hence cause damage to proteins and DNA. Imbalance in these metals is linked with diabetes, cardiotoxicity, cirrhosis of the liver and neurodegenerative diseases as Alzheimer's disease or Parkinson's disease. Dexrazoxane is a drug with documented protecting effect against cardiotoxicity of anthracyclines. A former theory associated its protective effects against these cytotoxic drugs with the iron-chelating properties of its active metabolite ADR-925. The goal of this diploma thesis was to explore if ADR-925 is able to chelate Fe2+ , Fe3+ , Cu+ a Cu2+ ions at physiologically and pathophysiologically relevant pH values (4,5; 5,5; 6,8 and 7,5) and...
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Antiplatelet effects of flavonoids
Kopková, Nikola ; Mladěnka, Přemysl (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Nikola Kopková Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Antiplatelet effects of flavonoids The most common antioxidants in ordinary food are flavonoids. They show antioxidant and anti-aggregation effects and other positive effects on cardiovascular diseases. Flavonoids are promising candidates to be antiplatelet drugs. Although several mechanisms responsible for antiplatelet activity have been suggesteed, only a few have been documented by published studies. The inhibition of blood platelet aggregation by flavonoids is reversible, which is another important factor. Data on thrombin-induced aggregation are controversial, some claim that flavonoids have no effect, the others says they have positive effects. (In the case of quercetin and genistein, inhibition of aggregation induced by thrombin was documented). The effect on arachidonic acid in the aggregation cascade is well documented, but there are several inconsistencies resulting from the use of different materials. Other mediators of aggregation are phospholipase A2, which plays a key role in the formation of inflammatory mediators. In this case, it has been shown that mainly genistein is capable of...
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Effect of soluble endoglin on bile acids transport in livers
Kvasnicová, Lucia ; Doleželová, Eva (advisor) ; Jirkovský, Eduard (referee)
Lucia Kvasnicová Effect of soluble endoglin on bile acids transport in livers Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: Increased plasma levels of soluble form of endoglin (sEng) were observed in patients with hypercholesterolemia, cystic fibrosis associated liver disease, or hepatocellular carcinoma combined with cirrhosis. As there are not available data focused on functional aspects of sEng in the liver, the aim of this diploma thesis was to describe the effect of sEng on the mechanism of bile formation and transport of bile acids in the liver. Methods: In our study were used six months-old transgenic male mice overexpressing human sEng on CBAxC57BL/6J background (sEng) and control mice (n = 8, in each group). Expressions of transport proteins responsible for bile acids homeostasis in the liver at mRNA and protein level were assessed by qRT-PCR and Western blot. Results: High plasma levels of sEng led to decreased plasmatic levels of bile acids. mRNA and protein expression analysis revealed, that this change occurs due to posttranscriptional induction of canalicular transporters, Bsep and Mrp2. Expression of an efflux Mrp4 protein localized at the basolateral membrane of hepatocyte was decreaced, which explains the decreased plasma...
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CARDIOTOXICITY OF ANTHRACYCLINE ANTINEOPLASTIC DRUGS AND POSSIBILITIES OF PHARMACOLOGICAL CARDIOPROTECTION
Jirkovský, Eduard ; Štěrba, Martin (advisor) ; Kolář, František (referee) ; Hrdina, Radomír (referee)
- CARDIOTOXICITY OF ANTHRACYCLINE ANTINEOPLASTIC DRUGS AND POSSIBILITIES OF PHARMACOLOGICAL CARDIOPROTECTION Chronic anthracycline (ANT) cardiotoxicity is an important clinical problem which can have a substantial impact on morbidity and mortality of cancer survivors. Dexrazoxane (DEX) is the only agent with clearly evidenced cardioprotective effects in both experimental models and clinical trials. Despite intensive research, precise pathogenesis of chronic ANT cardiotoxicity and molecular mechanisms of cardioprotective effects of DEX remain unknown. Current clinical guidelines recommend not using DEX from the beginning of ANT therapy, but instead only from the cumulative ANT dose of 300 mg /m2. The aim of this work was to study functional, morphological and molecular changes associated with induction of chronic ANT cardiotoxicity and their further development in the post-exposure (follow up) period. Special attention was paid on the role of oxidative stress and possible response of protective antioxidant pathway regulated by Nrf2 as well as on mitochondrial impairment and response of mitochondrial biogenesis pathway. Chronic ANT cardiotoxicity was induced in rabbits by repeated intravenous injections of daunorubicin (DAU, 3 mg/kg, once weekly for 10 weeks). At the end of the treatment, the animals...
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Cardiotoxicity of anthracycline antineoplastic drugs and possibilities of pharmacological cardioprotection
Jirkovský, Eduard ; Štěrba, Martin (advisor) ; Kolář, František (referee) ; Hrdina, Radomír (referee)
- CARDIOTOXICITY OF ANTHRACYCLINE ANTINEOPLASTIC DRUGS AND POSSIBILITIES OF PHARMACOLOGICAL CARDIOPROTECTION Chronic anthracycline (ANT) cardiotoxicity is an important clinical problem which can have a substantial impact on morbidity and mortality of cancer survivors. Dexrazoxane (DEX) is the only agent with clearly evidenced cardioprotective effects in both experimental models and clinical trials. Despite intensive research, precise pathogenesis of chronic ANT cardiotoxicity and molecular mechanisms of cardioprotective effects of DEX remain unknown. Current clinical guidelines recommend not using DEX from the beginning of ANT therapy, but instead only from the cumulative ANT dose of 300 mg /m2. The aim of this work was to study functional, morphological and molecular changes associated with induction of chronic ANT cardiotoxicity and their further development in the post-exposure (follow up) period. Special attention was paid on the role of oxidative stress and possible response of protective antioxidant pathway regulated by Nrf2 as well as on mitochondrial impairment and response of mitochondrial biogenesis pathway. Chronic ANT cardiotoxicity was induced in rabbits by repeated intravenous injections of daunorubicin (DAU, 3 mg/kg, once weekly for 10 weeks). At the end of the treatment, the animals...
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