National Repository of Grey Literature 58 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Changes of internal organs after percutaneous exposure to sulfur mustard
Šulová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Šulová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. External supervisor: pplk. doc. MUDr. Jaroslav Pejchal, Ph.D. et Ph.D. Title of diploma thesis: Changes of internal organs after percutaneous exposure to sulfur mustard Sulfur mustard is a chemical warfare agent belonging to the group of blistering agents. The theoretical section of the thesis is mainly focused on the description of acute toxic effects, the mechanism of action, and deals with the current possibilities of poisoning therapy. The experimental section is focused on monitoring the effect of sulfur mustard poisoning in the liver, lung, and kidney of female C57BL/6J mice after the percutaneous administration. This work aimed to evaluate markers of oxidative stress and histopathological changes of the selected organs at 3, 5, and 7 days after the poisoning. Ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) methods were used to determine markers of oxidative stress. Histopathological changes were evaluated microscopically using the hematoxylin-eosin staining method. The airness of the lung parenchyma was also assessed by computer image analysis. First, the LD50 of sulfur mustard was...
In vitro cultivation of tapeworm Hymenolepis diminuta - 2
Jandura, Dominik ; Vokřál, Ivan (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Dominik Jandura Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: In vitro cultivation of tapeworm Hymenolepis diminuta - 2 Aim of this diploma thesis was to obtain cycticercoids of the rat tapeworm (Hymenolepis diminuta), excyst them and find out the conditions for the maximal in vitro incubation period. As the intermediate host mealworm beetle (Tenebrio molitor) infected by the rat feces containing tapeworm eggs was used. Excystment was done using L-cystein and sodium tauroglycocholate. Excysted larvae were cultured in vitro (37 řC, 5 % CO2) in RPMI 1640 medium enriched with other substances chosen according previously published methods. Mainly sheep, mouse or rat liver extracts eventually in combination with yeast extract and sheep bile were used. The effect of tested substances on the cultivation was evaluated by measuring of the tapeworm's growth. The best effect on the grow of the tapeworms was observed using medium containing serum, yeast extract and sheep liver extract where tapeworms achieved length of 1561 µm after 16 days of incubation. The further growth was limited by appearance of pathologic formations.
In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters
Jahodová, Michaela ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Michaela Jahodová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters The absorption of orally administered drugs takes place especially in the intestine, where it can affect by the activity of drug's ABC transporters located on the apical membrane of the intestinal epithelium. Study of drug interactions in intestinal ABC transporters is essential to ensure effective and safe pharmacotherapy. Testing of bi- directional transport on Caco-2 cells is generally the preferred method for in vitro evaluation of substrates and inhibitors of ABC transporters. Drawbacks of the Caco-2 model increase the need and necessity to introduce new models. A great potential is the involvement of ex vivo methodologies in the human or rat intestine. The aim of the work was to introduce an in vitro methodology using the Caco-2 cell monolayer and the ex vivo methodology of precision-cut rat intestinal slices. By the bi-directional transport method, we analyzed drug interactions of the model substrate P-gp and BCRP Rhodamine 123 (RHD123) and clinically-used tenofovir...
Study of drug-drug interactions of antiviral drugs on intestinal transporters
Záboj, Zdeněk ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zdeněk Záboj Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of drugs interactions of antiviral drugs with intestinal transporters Sofosbuvir is an antiviral agent widely used in the treatment of chronic hepatitis C. This orally administered prodrug is a designed substrate of ATP-binding (ABC) efflux transporters, P- glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). ABCB1 and ABCG2 are important determinants of intestinal absorption and are the site of significant pharmacokinetic drug interactions, leading to changes in drug exposure. Pharmacokinetic drug interactions may be undesirable (increasing the toxicity of the treatment) or desirable (allowing dose reduction). Because sofosbuvir is often administered in combination regimens with other anti(retro)virotics, the aim of this thesis was to study the ability to enhance intestinal absorption of sofosbuvir. To study the pharmacokinetic drug interactions on ABCB1 and ABCG2, a widely established in vitro bi-directional transport method through a polarized monolayer formed by the Caco-2 cell line derived from colorectal cancer has been used. We analyzed the drug interactions of sofosbuvir on these efflux...
Characterization of ligand binding to M1 muscarinic acetylcholine receptor using fluorescence anisotropy method
Danková, Hana ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Hana Danková Supervisors: Prof. Ago Rinken, PhD. MSc. Tõnis Laasfeld PharmDr. Ivan Vokřál, PhD. Title of diploma thesis: Characetrization of ligand binding to M1 muscarinic receptor using fluorescence anisotropy method Muscarinic acetylcholine receptors (mAChRs), members of the superfamily of G-protein coupled receptors (GPCRs), regulate vital physiological processes and are important targets in drug research. Five different subtypes (M1 - M5) have been identified. M1 mAChR is mainly distributed in the central nervous system and is linked to pathophysiology of neurodegenerative diseases. In recent years, fluorescent methods have been frequently used in studies of ligand binding to receptors. The fluorescence anisotropy (FA) is a homogenous assay to characterize ligand binding to receptors. In this work, we have evaluated the FA method with fluorescent ligand MK342 binding to M1 mAChRs expressed on budded baculovirus (BBV) particles. The fluorescence ligand was binding with the high affinity (4,4 nM) to M1 receptor in constructed BBV preparation. The apparent binding affinities (pKi) of eleven classical and three bitopic muscarinic ligands were screened and compared to previously published...
Comparison of novel amphiphilic anionic phthalocyanine photosensitizers with their hydrophilic analogues
Hasoňová, Kateřina ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Hasoňová Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Comparison of new amphiphilic anionic photosensitizers based on phthalocyanines with their hydrophilic analogues. Currently, one of the most common causes of death in our population is cancer. There are a number of treatment modalities how to treat tumours, but none of them is ideal, and a large number of people are still dying of cancer. For this reason, intensive research and studies are ongoing, focusing on cancer treatment options. In recent years, photodynamic therapy has been increasingly used to treat both cancerous and non-malignant diseases. It is a modern method that has minimal side effects, is highly selective and minimally invasive. Its principle is a photochemical reaction, which proceeds when a combination of three basic components occurs - light, oxygen and photosensitizer. Separately, these components are nontoxic, but when the photosensitizer is exposed to oxygen, toxic reactive oxygen species are produced, whose subsequently cause destruction of the tumour tissue. A photosensitizer is a compound that is able to absorb radiation of a certain wavelength and then convert it into energy, which...
Constitutive expression of UDP-glucosyltransferases from Haemonchus contortus
Nekovová, Lucie ; Matoušková, Petra (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Nekovová Supervisor: Ing. Petra Matoušková, Ph.D. Title of diploma thesis: Constitutive expression of UDP-glucosyltransferases from Haemonchus contortus Haemonchosis is one of the most frequent parasitic disease on small ruminants caused by gastrointestinal nematode Haemonchus contortus. Attack of this blood sucking parasite does not mean only serious health damage but also lower productivity and economic losses. Anthelmintics are used as a medical treatment of haemonchosis however they are often insufficient because of worlwide developing resistence. Knowledge of mechanisms causing resistence is still not sufficient, therefore much effort is spent in order to find the factors which could be their source. It appears that changes of biotransformation enzymes and their expression might be one of the reason for resistence. At H. contortus more than 40 genes which code a different types of UDP- glucosyltransferases (UGTs) have been found. UGTs are the main enzymes in nematode which are connected with a deactivation of drugs (glycosylation). Therefore this thesis is focused especially on UGT family with the main goal to analyse changes in expression of these genes of susceptible (ISE) and...
Metabolism of flubendazole in human liver subcellular fractions
Holubová, Jana ; Skálová, Lenka (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Jana Holubová Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Metabolism of flubendazole in human liver subcellular fractions Flubendazole (FLU), a benzimidazole anthelmintic drug with a broad spectrum of activity and low toxicity has been used in veterinary as well as human medicine for a long time. Owing its mechanism of action, based on the specific binding to tubulin, FLU is now considered a promising anti-cancer agent. However, we do not have enough information about its biotransformation in human. In our project, subcellular fractions from the liver of 12 human patients (6 males and 6 females) were used to study the stereospecificity, cellular localization, coenzyme preference and possible inter-individual or sex differences in FLU reduction. In addition, the risk of FLU interaction with other drugs was evaluated. Results showed that FLU is predominantly reduced in cytosol and the NADPH coenzyme is preferred. The strict stereospecificity of FLU carbonyl reduction was proven and carbonyl reductase 1 was identified as the main enzyme of FLU reduction in the human liver. A higher reduction of FLU and a higher level of carbonyl reductase 1 protein was found in males than in...
Study of drug interactions with OATP family transporters using intestinal tissue slices
Čečková, Patrícia ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Patrícia Čečková Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Study of drug interactions with OATP family transporters using intestinal tissue slices An essential role in the action of orally administered drugs is their absorption through the intestinal barrier. It expresses a variety of transporters, including the OATP2B1 and OATP1A2 influx transporters, belonging to the SLC family. They are located on the apical membrane of enterocytes and allow the flow of endogenous and exogenous substances from the lumen of the intestines to the enterocyte. They affect not only the pharmacokinetics of drugs, but also their safety and efficacy. They represent sites of drug interactions with other drugs/food components that may altered drug efficacy or toxicity. Since FDA (The Food and Drug Administration) and EMA (European Medicines Agency) do not have intestinal OATP transporters included in their guidelines for preclinical studies, there is no single model of interaction study. The limitations of cell models and genetically modified organisms lead to the development of new methods such as the ex vivo method of precision cut intestinal slices (PCIS), which represents a tissue model...

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