National Repository of Grey Literature 263 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Metabolism and efficacy of new potential anthelmintics
Zajíčková, Markéta ; Skálová, Lenka (advisor) ; Várady, Marián (referee) ; Vadlejch, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Markéta Zajíčková Supervisor: Prof. RNDr. Lenka Skálová, Ph.D. Consultant: PharmDr. Ivan Vokřál, Ph.D. Title of Dissertation Thesis: Metabolism and efficacy of new potential anthelmintics Overpopulation of gastrointestinal nematodes represents global health and economical problem. Therefore, suitable solution in the form of effective anthelmintic treatment is needed. Several anthelmintics with distinct mechanism of action are available on the market, however, the widespread resistance limits their efficacy. As a consequence, finding a new possible alternative becomes important. In present dissertation thesis, the novel anthelmintic candidates were selected and their effect against model parasitic nematode Haemonchus contortus was examined. The studies encompassed three approaches within the field of drug discovery: new molecular entity identification and structure modification, drug repurposing, and medicinal plants screening. Newly synthesized compounds designated as BLK127, HBK4 and BLK127 derivatives, already known antipsychotic drug sertraline (SRT) and the extracts from eight European ferns species from genus Dryopteris, Athyrium and Blechnum were the subjects of our interests. Two...
Diagnostic potential of piwi-RNA molecules in the process of in vitro fertilization
Šeršeň, Dominika ; Skálová, Lenka (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Dominika Šeršeň, DiS. Supervisor: doc. RNDr. Lenka Skálová, PhD. Consultant: doc. RNDr. Miroslava Rabajdová, PhD. Title of diploma thesis: The diagnostic potentional of piwiRNA molecules in IVF procedure Infertility is currently a prevalent health problem affecting millions of couples of reproductive age worldwide and the use of in vitro fertilization techniques is increasing worldwide every year. For successful in vitro fertilization, it is essential to select a good quality embryo. Despite advances in in vitro fertilization, there is still an insufficient amount of non-invasive and reliable biomarkers for the selection of embryos with the highest developmental and implantation potential. Small non-coding RNAs, specifically piwiRNAs (piRNAs) and microRNAs (miRNAs), secreted into the extracellular environment, which is the culture medium, appear to be suitable biomarkers. This work describes the evaluation of the quality of the embryos, their morphological features on individual days as well as the annotation system itself using the TimeLapse system. The next chapter describes the composition of the media suitable for the cultivation of embryos and their analysis at the omic level, focusing on...
The effect of fenbendazole on drug-metabolizing enzymes in Haemonchus contortus
Šulcová, Kateřina ; Matoušková, Petra (advisor) ; Skálová, Lenka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Šulcová Supervisor: doc. Ing. Petra Matoušková, Ph.D. Title of diploma thesis: Effect of fenbendazole on biotransformation enzymes of Barber's pole Barber's pole worm (Haemonchus contortus) is a parasitic nematode in the gastrointestinal tract of small ruminants. In infected animals it causes a disease called haemonchoses. Its signs are anaemia, weight loss and animals are in general not thriving. In numerous cases it can cause death. For treatment of this disease substances called anthelmintics are used. Parasite resistance to all groups of these drugs has been a worldwide problem for several years. It is probably due to frequent and inaccurate use of anthelmintics when the parasites are exposed to sub-lethal doses of the drug. Mechanisms of resistence vary depending on anthelmintic group and its mechanism of action. This thesis focuses on studying mechanism of resistence of H. contortus to fenbendazole, a benzimidazole anthelmintic. Changes in expression of some biotransformation enzymes and efflux transporters genes could contribute to resistence. In this study expression of selected genes of biotransformation enzymes and efflux transporters from CYP (cytochromes P450), UGT...
Diagnostic potential of piwi-RNA molecules in the process of in vitro fertilization
Šeršeň, Dominika ; Skálová, Lenka (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Dominika Šeršeň, DiS. Supervisor: doc. RNDr. Lenka Skálová, PhD. Consultant: doc. RNDr. Miroslava Rabajdová, PhD. Title of diploma thesis: The diagnostic potentional of piwiRNA molecules in IVF procedure Infertility is currently a prevalent health problem affecting millions of couples of reproductive age worldwide and the use of in vitro fertilization techniques is increasing worldwide every year. For successful in vitro fertilization, it is essential to select a good quality embryo. Despite advances in in vitro fertilization, there is still an insufficient amount of non-invasive and reliable biomarkers for the selection of embryos with the highest developmental and implantation potential. Small non-coding RNAs, specifically piwiRNAs (piRNAs) and microRNAs (miRNAs), secreted into the extracellular environment, which is the culture medium, appear to be suitable biomarkers. This work describes the evaluation of the quality of the embryos, their morphological features on individual days as well as the annotation system itself using the TimeLapse system. The next chapter describes the composition of the media suitable for the cultivation of embryos and their analysis at the omic level, focusing on...
The changes in expression of carbonyl reductases during life cycle of nematode
Ňorková, Kateřina ; Skálová, Lenka (advisor) ; Szotáková, Barbora (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Ňorková Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The changes in expression of carbonyl reductases during life cycle of nematode Barber 's pole worm (Haemonchus contortus, from the family Trichostrongylidae) is a nematode attacking the mucosa of the gastrointestinal tract of small ruminants. Infections caused by this nematode are manifested by anemia and edema. Anthelmintics, drugs against parasitic worms, are used for prophylaxis and treatment of these infections. However, a huge problem is the worldwide growing resistance to all available anthelmintics. Therefore, it is very important to study the possible mechanisms of resistance and factors that contribute to the development of resistance. In recent years, one of the mechanisms of resistance to anthelmintics has been found to be increased expression and activity of some enzymes of metabolizing drugs. This work dealt with the monitoring of changes in the expression of selected genes from the detrinth of Dehydrogenas/Reductas with a short chain (SDR). Expression of 20 SDR genes was determined using the quantitative PCR method in all developmental nematode stages (eggs, larvaes, adults) of...
Preparation of STAT3-knockout glioblastoma multiforme cell line using CRISPR-Cas9 editing
Papinčáková, Dominika ; Skálová, Lenka (advisor) ; Laštovičková, Lenka (referee)
Charles University Fakulty of Pharmacy in Hradec Králove Department of Biochemical Sciences Candidate: Bc. Dominika Papinčáková Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Preparation of STAT3-knockout glioblastoma multiforme cell line using CRISPR-Cas9 editing Glioblastoma multiforme (GBM) is one of the most common primary brain tumours in adults and one of the most fatal cancers in humans A key oncogene in GBM development and progression is the signal transducer and activator of transcription 3 (STAT3). It is one of the mediators of tumorigenesis, plays a strong pro-survival role in GBM, and is permanently activated in GBM, leading to increased cell proliferation, invasiveness, and angiogenesis. The aim of this work was to establish a GBM STAT3-knockout (STAT3-KO) cell line. The U87MG cell line and the CRISPR-Cas9 gene knockout method were used for this purpose. In a first step, we investigated the possibility of silencing STAT3 expression by siRNA and the suitability of this cell type to pinpoint the mechanism for CRISPR gene editing into the cell. In the second step, we transfected the cells using the STAT3 gene knockout kit (CRISPR) and tested the knockout success. In the established STAT3-KO GBM cell line, we confirmed STAT3-KO at the DNA, RNA and protein levels. We...
The changes in flubendazole metabolism during life cycle of nematode
Salvová, Martina ; Skálová, Lenka (advisor) ; Prchal, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Martina Salvová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The changes in flubendazole metabolism during life cycle of nematode The nematode barber's pole worm (Haemonchus contortus) is an infectious pathogen that causes gastrointestinal haemonchosis in ruminants. Its life cycle consists of egg, larval (L1, L2 and L3) and adult stages. Haemonchosis is a common and widespread disease of farm animals, which causes significant global economic losses. Whereas the treatment of haemonchosis is mainly based on pharmacotherapy using anthelmintics, the increasing drug resistance of barber's pole worm to these drugs is a big problem. Hence, the study of the mechanisms of the development of drug resistance in this parasite is in the foreground of scientific interest. One of the mechanisms of resistance may be an increased ability to deactivate the anthelmintics. In the case of the benzimidazole anthelmintic flubendazole, deactivation is based on a reduction of the carbonyl group by the enzymes aldo-ketoreductases and short-chain dehydrogenases/reductases. The metabolite with decreased anthelmintic efficacy is produced by the reduction of flubendazole, and in this way, nematodes...
Optimization of a new analytical system for selected biochemical and immunochemical methods
Dvořáková, Kristýna ; Skálová, Lenka (advisor) ; Matysová, Ludmila (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kristýna Dvořáková Thesis supervizor: prof. RNDr. Lenka Skálová, Ph.D. Consultant: Mgr. Martina Hrdinová Title of diploma thesis: Optimization of a new analytical system for selected biochemical and immunochemical methods Specific requirements for validation and verification of analytical methods according to the ČSN EN ISO 15189: 2013 standard must be met by every medical laboratory. The aim of the work was to meet the requirements of verification in the introduction of a new analytical system Cobas 8000 and also to compare the results with those obtained using older analyzer Cobas 6000 in the laboratory of clinical biochemistry. For the analysis of biochemical and immunochemical methods, we used diagnostic kits from the same supplier Roche s.r.o. We determined the selected clinic-biochemical markers by the basic methods using spectrophotometry, immunoturbidimetry and electrochemiluminiscence. We used certified calibration and control material in the process of method verification. The mixed patient serum was used for the evaluation of repeatability and comparability of the methods. We evaluated the verification and repeatability of methods using Microsoft Excel software. We compared the...
The effect of fern extracts on cell line SW480
Zacharská, Andrea ; Matoušková, Petra (advisor) ; Skálová, Lenka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Student: Andrea Zacharská Supervisor: doc. Ing. Petra Matoušková, Ph.D. Title of diploma thesis: Effect of fern extracts on the SW480 cell line Cancer is one of the leading causes of death in the world. Although we have several drugs available for the treatment of cancer, none of them are completely effective and safe. The fundamental problem is toxicity, which experts try to eliminate by looking for other treatment alternatives like plants and their secondary metabolites with antiproliferative and antioxidant effects against free radicals, that can cause cancer. Our work is focused on the antioxidant, as well as the prooxidant effect of 4 species of ferns (Athyrium filix - femina, Dryopteris dilatata, Dryopteris borreri, Blechnum spicant), whose extracts of different concentrations were studied as potentially beneficial substances against oxidative stress on the SW480 cell line. We used the fluorescent probe H2DCF-DA to detect the production of reactive oxygen species (ROS) in cells. In the initial setup the potential prooxidant effect was monitored alongside with the terc- butyl hydroperoxide solution as a positive control. The results demonstrated that these test substances did not induce the ROS...

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9 SKALOVÁ, Lucie
9 SKÁLOVÁ, Lucie
2 Skalová, Lenka
9 Skalová, Lucie
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