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Calculus Bovis effect on blood lipids and the expression of endothelial NO synthesis / / in ApoE-deficient mouse model of atherosclerosis
Studená, Romana ; Nachtigal, Petr (advisor) ; Trejtnar, František (referee)
Calculus Bovis is one of the most precious and commonly-used medicinal materials in China. It is consists predominantly bilirubin and bile acids. In this thesis we focused on possible effects of Calculus Bovis on lipids and atherogenesis in apoE-deficient mice. ApoE-deficient mice were fed standard diet for 2 weeks. At the age of 8 weeks the control group of animals were fed with the western type diet, which contained 21% fat and 0,15% cholesterol for 8 weeks. The same atherogenic diet was used in Calculus Bovis group, where Calculus Bovis was added to the atherogenic diet at the dosage of 50 mg/kg b.wt. Calculus Bovis (Artificial bezoar, Biopharma, Australia) per day. The biochemical analysis of lipid spectrum was done, area of atherosclerotic lesions was determined and imunohistochemical and stereological analysis of eNOS expression was performed as well. Calculus bovis treatment did not affect blood lipids, total cholesterol, VLDL, LDL, HDL and TAG when compared with control mice. Moreover Calculus bovis treatment did not decrease either atherosclerotic plaque area or endothelial expression of eNOS. The failure of Calculus Bovis treatment in this pilot study could be probably related to insufficient dose of Calculus Bovis.
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The attitudes and experiences of the university students with drugs of abuse
Fleischlingerová, Simona ; Melicharová, Ludmila (advisor) ; Trejtnar, František (referee)
Experiences of the students and their attitudes to the addictive drugs Simona Fleischlingerová The main dissertation's aim has been to find out the attitudes of the students of the third year of Faculty of Pharmacy in Hradec Králové to smoking and compare this with the results, which were given from the students of Medicine, Stomatology and Nursing. The data were compiled from the individual completed questionnnaire. The conclusions didn't show important differences in attitudes and opinions to smoking among the individual medical field of study. The importance of the smoking restriction in the closed room, the position of the medic as a consultant in stopping smoking and the knowledge of the therapy of nicotine addiction - These are students' opinions, which are very positive.
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Effect of Synthetic Magnolol Derivatives on Activity of Nuclear Receptors PPARγ and RXRα
Dymáková, Andrea ; Szotáková, Barbora (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences University of Vienna Faculty of Life Sciences Department of Pharmacognosy Candidate: Andrea Dymáková Supervisors: Mag. Simone Latkolik, doc. Ing. Barbora Szotáková, Ph. D. Title of diploma thesis: Effect of Synthetic Magnolol Derivatives on Activity of Nuclear Receptors PPARγ and RXRα The nuclear receptors, peroxisome proliferator-activated receptor γ (PPARγ) and its heterodimerization partner retinoid X receptor α (RXRα) are drug targets in the treatment of diseases like the metabolic syndrome and diabetes mellitus type 2. The effort has been made to develop new agonists for PPARγ to obtain ligands with more favourable properties than currently used drugs (Berger et al. 2002, Berger et al. 2005). Magnolol was previously described as a dual agonist of PPARγ and RXRα (Fakhrudin et al. 2010, Zhang et al. 2011). Based on the bi- aryl structure of magnolol, the effort has been made to design and synthesize linked magnolol dimers. The aim of this thesis was to investigate the agonistic potential of these compounds with respect of the nuclear receptors PPARγ and RXRα in comparison to magnolol. We evaluated the ligand binding properties of the compounds and their functionality as PPARγ agonists in vitro...
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Intracellular trafficking of an anti - Amyloid Protein Precursor antibody.
Zitko, Jan ; Doležal, Martin (advisor) ; Trejtnar, František (referee)
Intracellular trafficking of an anti-Amyloid Protein Precursor antibody Alzheimer's disease is characterized by over-accumulation of beta-amyloid peptide (Aβ) in the brain. Aβ is produced by proteolytic cleavage of beta-amyloid precursor protein (APP) by β- and γ-secretases. Novel monoclonal antibody, 2B12, has been shown to bind to β-secretase cleavage site of APP, reducing the production of APP, presumably by preventing the cleavage by steric hindrance. 2B12 is hypothesized to bind to APP molecules exposed on the cell surface and to be internalized in the form of complex with APP via natural endocytic pathway. This hypothesis was confirmed by San Pei Ho's (2007), who followed the internalization of 2B12 in living astrocytoma MOG-G-UVW, cells in time-course experiment. This project is focused on intracellular trafficking of 2B12 and its localization within specific cellular compartments. Experiments were performed with fixed astrocytoma MOG- G-UVW cells (constitutively expressing APP). Originally planned experiments with live cells could not be performed due to decreased stability of 2B12 (causes remain unknown). 2B12 was tested for colocalization with polyclonal affinity purified antibodies labelling subcellular markers (proteins) associated with compartments known to participate in APP...
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Study of renal transport mechanisms of radiolabeled antibodies
Karasová, Jana ; Trejtnar, František (advisor) ; Bárta, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department: Department of Pharmacology and Toxicology Candidate: Mgr. Jana Kanokova Supervisor: Doc. PharmDr. Frantisek Trejtnar, CSc. Title of rigorous thesis: Study of renal transport mechanisms of radiolabeled antibodies Utilization of monoclonal antibodies belongs to one of the important strategies in the treatment of oncological diseases. This treatment has a great advantage in precise focusing on the target structure with minimal damage to surrounding non-target tissue. The antibodies against the receptor for epidermal growth factor (EGFR) expressed in higher rate by variety of tumor types represent one of the important group. Nowadays oncology utilizes both unconjugated antibodies, and the ones conjugated with other effector components, e.g. cytostatic agents, radionuclides, toxins. One of the important limits for the antibodies conjugated with radionuclides appears to be their potential accumulation in kidneys with subsequent radiotoxic damage to the kidney tissue. The aim of this experimental study was to investigate the accumulation of three 131 I- labeled anti-EGFR antibodies - panitumumab, cetuximab and nimotuzumab using a kidney model in vitro, and compare it with renal uptake of the natural peptide ligand EGFR which was...
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The Repair of Oxidative DNA Damage in the Chinese Hamster Cell Line Deficient in Nucleotide Excision Repair
Strejčková, Lada ; Trejtnar, František (advisor) ; Pávek, Petr (referee)
The repair of oxidative DNA damage in the Chinese hamster cell line deficient in nucleotide excision repair Abstract The aim of our work was to specify DNA oxidative damage repair in the Chinese hamster ovary cell line. Comet assay was used to detect the damage consequences - DNA breaks. We were capable of achieving high method sensitivity due to application of specific endonucleases and specific inhibitors of excision repair - inhibitor of poly(ADP- ribose)polymerase PARP 3-aminobenzamide (3-AB) and cytosine arabinoside with hydroxyurea (AraC/HU). PARP-1 is an important factor in the base excision repair (BER) process. PARP-1 deficient cells show recovery impairment both in LP-BER and SP-BER way. AraC/HU is known as the long-patch excision repair inhibitor. The results of our experiments showed the inhibiting effect of 3-AB on the repair of hydrogen peroxide-induced DNA damage. But in the same setting the AraC/HU effect on repair was not observed. To make the value of experimental results more significant and clear, we decided for additional experiments with monofunctional alkylating agent methyl methanesulfonate (MMS). Damage caused by MMS showed slower repair both when 3-AB or AraC/HU were present during the repair period. Based on all available results we suppose that the MMS and also hydrogen peroxide...
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Interactions of resveratrol derivatives with PXR receptor
Marešová, Veronika ; Pávek, Petr (advisor) ; Trejtnar, František (referee)
Charles University in Prague Department of Pharmacology & Toxicology Student: Supervisor: Prof Title of diploma thesis: Interactions of resveratrol derivatives with PXR receptor Derivatives of resveratrol belong between natural substances contained mainly in red wine and grapefruit. These compounds with stilbene-like structure show antioxidant activity. Pregnane X receptor (PXR) regulates expression of the most important biotransformation enzymes in human liver and intestine including cytochrome P450 3A4 (CYP3A4). Interaction of resveratrol and PXR have already been studied, but published data are contradictory. In my diploma thesis, I studied interaction of resveratrol and its derivatives with PXR. For this purpose, gene reporter assay with quantitative real-time polymerase chain reaction (qRT-PCR) was introduced. It was not possible to conduct experiments in standard way because both resveratrol and its derivatives inhibit lusiferase activities. I studied also effects of resveratrol and its derivatives on expression of CYP3A4 mRNA on differentiated HepaRG cell line. New method gene reporter method with qRT-PCR detection of luciferase was established on hepatoma cell line HepG2 transfected with CYP3A4 reporter construct. Concertation dependent effects of resveratrol and its derivatives were...
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