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The Study of the DNA of Tumor Cells Exposed to Doxorubicin
Belhajová, Marie ; Poljaková, Jitka (advisor) ; Mrízová, Iveta (referee)
Cancerous diseases are among the most serious problems of modern medicine and their occurrence is constantly increasing. Despite the significant development of therapeutic methods during recent years, this disease remains difficult to treat. Neuroblastoma (NB) is a malignant embryonal tumor in children, emerging from the peripheral nervous system and is the most frequent tumor in children. It is treated surgically and also with chemotherapy using cytostatic drugs. The cytostatic drug Doxorubicin has become very significant in treating cancer. Doxorubicin is a anticancer medication whose cytotoxic effect is based on a number of mechanisms, one of which is the intercalation into DNA molecules. Spectrophotometry was used to detect the presence of doxorubicin in the DNA derived from human neuroblastoma cell lines UKF-NB-4 and UKF-NB-4DOXO , exposed to this substance. This method, however, failed to detect the presence of doxorubicin. Keywords: neuroblastoma, doxorubicin, intrecalation, spectrophotometry
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Functional activity of opioid receptors in membrane domains
Cechová, Kristína ; Hudeček, Jiří (advisor) ; Mrízová, Iveta (referee)
7 ABSTRACT In this Thesis, we examined the influence of morphine administration to the laboratory rats on the amount of µ-opioid receptors and caveolins in their cerebral cortex. Effect of morphine is known to be caused by its binding to opiod receptors, in particular to the µ subtype, and a long-term exposure to morphine reduces the functionality and number of these receptors as part of the resulting tolerance and addiction. Caveolins are proteins essential for formation of the membrane microdomains of caveolae, although it is known today that presence of these proteins is not limited to caveolae and their function is probably independent of these domains (they may participate in the regulation of cell signaling pathways, lipid transport, etc.). The function of caveolins in brain cells is not precisely known yet. In the experimental part of this work, we used the Western blot method to estimate the presence of caveolin-1 and caveolin-2 in the cerebral cortex of the rats after ten-days morphine application and in control animals. A significant increase of caveolin-1 was observed after morphine treatment as compared to control animals; a smaller, non-significant increase of caveolin-2 was also found. The amount of μ-opioid receptors in morphine affected animals was significantly decreased compared to...
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The mechanism of action of anticancer drug ellipticin in target tissues of its effect
Mrízová, Iveta
Ellipticine is an alkaloid isolated from Apocynaceae plants exhibiting significant antitumor and anti-HIV activities. Cytochromes P450 (CYP) and peroxidases are the enzymes participating in metabolism of ellipticine. This process provides activation and detoxication metabolites of ellipticine. The CYP enzymes, which participate in oxidation of ellipticine in different tissues (liver, lung and kidney) of rat, a model organism simulating the fate of ellipticine in humans have already been identified. In this work, the effects of ellipticine on contents and catalytic activities of CYPs and other components of the mixed-function oxidase (MFO) system in this animal system were studied. For detection of contents of CYPs and other components of the MFO system, spectroscopic and electrochemical methods were used. To determine catalytic activities of CYPs and NADPH:cytochrome P450 reductase, reactions with specific substrates of these enzymes were utilized. The results found in this study demonstrate that expression and catalytic activity of CYP1A is induced by ellipticine in all of the tested organs (liver, kidney and lung) of rats treated with the drug. Moreover in liver, the cytochrome b5 expression is also induced. In addition, in this organ, expression and catalytic activity of CYP3A was increased by...
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Comparison of the determination of hormones (Follicle stimulating hormone, Luteinizing hormone, Prolactin, Testosterone, Progesteron) by two analytical systems. Converting accredited method and its verification.
Kucejová, Soňa ; Martínková, Markéta (advisor) ; Mrízová, Iveta (referee)
Analytical system ARCHITECT i2000SR was verified according to requirements of ÚLBLD VFN and 1. LF UK laboratory in Prague. Repeatability, intermediate precision, and measurement uncertainty were determined as performance parameters for verification of analytical assays for testosterone, progesterone, luteinizing hormone, follicule stimulating hormone and prolactin. Results of Lyphochek control samples, which were measured, were consistent with values given by manufacture. Repeatability: coefficients of variation for testosterone Lyphochek 1 6,81%, for Lyphochek 3 6,40%, progesterone 2,4% and 1,8%, luteinizing hormone 5,38% and 1,89%, follicle stimulating hormone 5,12% and 3,24% prolactin 1,45% a 1,83%. Intermediate precision: coefficients of variation for testosterone Lyphochek 1 6,02%, Lyphochek 2 3,60%, Lyphochek 3 3,07%, progesterone 7,9%, 4,9% and 5,8%, luteinizing hormone 4,50%, 5,51% and 5,83%, follicle stimulating hormone 4,00%, 3,72% and 4,87%, prolactin 4,60%, 4,20% and 5,00%. Measurement uncertainty: testosterone 6,02%, progesterone 7,9%, luteinizing hormone 5,83%, follicle stimulating hormone 4,87%, prolactin 5,00%. Analytical System Architect i2000SR was compared with previously used ADVIA Centaur system to find out, whether it is possible to convert the method Centaur Testosterone,...
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Comparison of adsorption capacity and adsorption efficiency of diosmectite and charcoal on selected compounds that often cause acute intoxication in adult population of the Czech Republic
Mináriková, Michaela ; Martínková, Markéta (advisor) ; Mrízová, Iveta (referee)
In the treatment of acute intoxications, one of the treatment procedures is an antidote submission, e.g. diosmectite and activated charcoal, where an antidote is a substance which acts antagonistically and disturbingly with the toxic effect of a toxic substance. The aim of this work was to compare the adsorption capabilities of activated charcoal and diosmectite in selected model compounds which are the most common originators of acute intoxications in the adult population of the Czech Republic. The actual comparison of adsorption capabilities of these sorbents was preceded by issues search processing of ten groups of substances that cause the most acute intoxications and subsequent testing of the proposed method for future detailed testing of adsorption and adsorption efficiency of different sorbents. Of the ten groups of substances five model compounds were selected: dosulepin, acetylsalicylic acid, ibuprofen, promethazine and phenobarbital, on which adsorption of diosmectite, activated charcoal, and mixture of these sorbents was compared in the experimental part of this work. This comparison of the adsorption capabilities of sorbents was carried out not only under neutral conditions, but also in an alkaline and acidic environment which simulated physiological conditions in different parts of the...
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