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Study of bilirubin and its oxidation products
Capková, Nikola ; Dvořák, Aleš (advisor) ; Vejražka, Martin (referee) ; Holendová, Blanka (referee)
Phototherapy (PT) with blue-green light (420-490 nm) is the standard treatment for severe neonatal jaundice to prevent infants from toxic bilirubin (BR). Upon blue-green light exposure, BR is converted to more polar photoisomer (PI) lumirubin (LR) and the other oxidation products (mono-, di-, tripyrrols) which can be more easily disposed of the body via urine and/or bile. Although generally considered to be safe, PT is accompanied by an increased risk of various pathophysiological conditions (inflammatory processes, allergies, diabetes, and some types of cancer), in extremely low-birth-weight newborns. Thus, to account for these consequences, our study aimed to understand the mechanism of BR secretion in different tissues and cell lines and investigate the bioactive properties of BR and its main photooxidation product LR. At first, we focused on the detection of BR in the bile and feces of hyperbilirubinemic Gunn rats. Simultaneously, we tested the antioxidant and pro-oxidant effects of unconjugated BR in human hepatoblastoma (HepG2), proximal tubular (HK2), neuroblastoma (SH-SY5Y), and murine endothelial (H5V) cells by exposing them to progressively increasing concentrations of BR. To compare the BR and LR effects on metabolic and oxidative stress markers, the biological activities were...
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Application of monosubstituted cyclodextrins in chiral separation of omeprazole by capillary electrophoresis
Dvořák, Aleš ; Čabala, Radomír (advisor) ; Coufal, Pavel (referee)
Chiral separation of omeprazole was the subject of this work. Five diferent monosubstituted derivatives of α- and β-cyclodextrins, two of them cationic and three anionics, were used as chiral selectors in various buffers of different pH. The influence of CD and buffer concentrations on chiral separation was studied. Voltage of 25 kV, UV detection in the range from 202 to 303 nm and constant temperature of 20 řC was used for all measurements. Concentration of CDs between 0 and 7 mmol.l-1 was used. Fused silica capillary of 50 µm ID and 375 µm OD, 48,5 cm total and 40 cm effective lenght was used as separation capillary. Dimethylformamide was used in stock solution of omeprazole as solvent, and was simultaneously applied as EOF marker. Succesfull chiral separation of omeprazole was achieved under the application of 2'-O-carboxymethyl-β-cyclodextrin (2'-CM-β-CD) and mono-6-deoxy-6-N,N,N',N',N'-pentamethylethylendiammonio- cyclomaltoheptaose dichloride (PEMEDA-β-CD) where the resolution of 1,42 (pH = 5,1) and 4,29 (pH = 11,1) was measured, respectively.
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Mitochondria as a target of anticancer therapy.
Dvořák, Aleš ; Ježek, Petr (advisor) ; Poučková, Pavla (referee) ; Vecka, Marek (referee)
Mitochondrial isocitrate dehydrogenase 2 (IDH2) catalyzes reductive carboxylation (RC, reverse Krebs cycle pathway) and 2HG synthesis (2HG) - metabolite of which many scientists are interested. 2HG may be concurrently synthetized in cytosol by IDH1. RC is involved in anabolic reactions necessary for cell proliferation - produces citrate, fatty acid precursor - especially in hypoxia. IDH2 and IDH1 are not the only enzymes that are involved in 2HG synthesis. Recently, several enzymes, which participate in 2HG production, have been discovered. 2HG is useful in cancer diagnostics due to its overproduction by transformed cells. Moreover, 2HG may cause epigenetic changes via inhibition of 2-oxoglutarate dependent dioxygenase. In this work, the importance of RC and 2HG synthesis in cancer and healthy cells was investigated by gas chromatography with mass spectrometry detection as well as IDH2 influence. We found that IDH2 significantly participates in reverse RC and 2HG synthesis in breast cancer cell lines and uses glutaminolysis as a supplementary anaplerotic pathway. RC is increased by hypoxia, inhibition of respiration, and decreased by activation of respiration or hypocapnia. We confirmed 2HG synthesis and RC in healthy cells (fibroblasts, breast epithelial cells etc.) as well as in cancer cells....
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Mitochondria as a target of anticancer therapy.
Dvořák, Aleš
RK se podílí a prolifera i ádorový h u ěk ve stíže ý h zkrá e é Kre sově klu v tváří reverz í reak í z OG itrát, který ůže ýt e portová do tosolu, kde slouží jako prekurzor ast ý h k seli a další h olekul. )ároveň IDH při RK spotře ovává stej ě tak i při s téze HG NADPH. RK se tak z výzku u zdá ještě zají avější, e oť ůže ovliv it produk i ROS a íru o idač ího stresu. HG ůže ýt s tetizová a IDH i ěkolik další h e z ů. HG regulač í olekul součas é do ě je v užívá Bývá oz ačová jako ož ý i hi itor α DD , jež se pod í a růz ý h epige eti ký h z ě á h a zv šují alig itu rakovi ého fe ot pu spoje ou se z ě ou prolifera e u ěč ý h li ií h kar i o u prsu a další h uňká h, včet ě pri ár í h potka í h fi ro lastů a aktivitě respira e. de o strují, že HG ádorový h uňká h, a aví že ve zdravý h uňká h z ě hladi ovlivňují prolifera i. elkově jeví jako vhod ý íl proti ádorové terapie, zej é a ve světle edáv ý h o jevů, ve který h se ukázalo, že utova á íře s tézu α Klíčová slova: MS, uňk prs ího 6, fi ro last , HG/ OG po ěr, C izotopi ké z ače í, prolifera e fi ro lastů, h po ie
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Mitochondria as a target of anticancer therapy.
Dvořák, Aleš
RK se podílí a prolifera i ádorový h u ěk ve stíže ý h zkrá e é Kre sově klu v tváří reverz í reak í z OG itrát, který ůže ýt e portová do tosolu, kde slouží jako prekurzor ast ý h k seli a další h olekul. )ároveň IDH při RK spotře ovává stej ě tak i při s téze HG NADPH. RK se tak z výzku u zdá ještě zají avější, e oť ůže ovliv it produk i ROS a íru o idač ího stresu. HG ůže ýt s tetizová a IDH i ěkolik další h e z ů. HG regulač í olekul součas é do ě je v užívá Bývá oz ačová jako ož ý i hi itor α DD , jež se pod í a růz ý h epige eti ký h z ě á h a zv šují alig itu rakovi ého fe ot pu spoje ou se z ě ou prolifera e u ěč ý h li ií h kar i o u prsu a další h uňká h, včet ě pri ár í h potka í h fi ro lastů a aktivitě respira e. de o strují, že HG ádorový h uňká h, a aví že ve zdravý h uňká h z ě hladi ovlivňují prolifera i. elkově jeví jako vhod ý íl proti ádorové terapie, zej é a ve světle edáv ý h o jevů, ve který h se ukázalo, že utova á íře s tézu α Klíčová slova: MS, uňk prs ího 6, fi ro last , HG/ OG po ěr, C izotopi ké z ače í, prolifera e fi ro lastů, h po ie
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Mitochondria as a target of anticancer therapy.
Dvořák, Aleš ; Ježek, Petr (advisor) ; Poučková, Pavla (referee) ; Vecka, Marek (referee)
Mitochondrial isocitrate dehydrogenase 2 (IDH2) catalyzes reductive carboxylation (RC, reverse Krebs cycle pathway) and 2HG synthesis (2HG) - metabolite of which many scientists are interested. 2HG may be concurrently synthetized in cytosol by IDH1. RC is involved in anabolic reactions necessary for cell proliferation - produces citrate, fatty acid precursor - especially in hypoxia. IDH2 and IDH1 are not the only enzymes that are involved in 2HG synthesis. Recently, several enzymes, which participate in 2HG production, have been discovered. 2HG is useful in cancer diagnostics due to its overproduction by transformed cells. Moreover, 2HG may cause epigenetic changes via inhibition of 2-oxoglutarate dependent dioxygenase. In this work, the importance of RC and 2HG synthesis in cancer and healthy cells was investigated by gas chromatography with mass spectrometry detection as well as IDH2 influence. We found that IDH2 significantly participates in reverse RC and 2HG synthesis in breast cancer cell lines and uses glutaminolysis as a supplementary anaplerotic pathway. RC is increased by hypoxia, inhibition of respiration, and decreased by activation of respiration or hypocapnia. We confirmed 2HG synthesis and RC in healthy cells (fibroblasts, breast epithelial cells etc.) as well as in cancer cells....
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Application of monosubstituted cyclodextrins in chiral separation of omeprazole by capillary electrophoresis
Dvořák, Aleš ; Coufal, Pavel (referee) ; Čabala, Radomír (advisor)
Chiral separation of omeprazole was the subject of this work. Five diferent monosubstituted derivatives of α- and β-cyclodextrins, two of them cationic and three anionics, were used as chiral selectors in various buffers of different pH. The influence of CD and buffer concentrations on chiral separation was studied. Voltage of 25 kV, UV detection in the range from 202 to 303 nm and constant temperature of 20 řC was used for all measurements. Concentration of CDs between 0 and 7 mmol.l-1 was used. Fused silica capillary of 50 µm ID and 375 µm OD, 48,5 cm total and 40 cm effective lenght was used as separation capillary. Dimethylformamide was used in stock solution of omeprazole as solvent, and was simultaneously applied as EOF marker. Succesfull chiral separation of omeprazole was achieved under the application of 2'-O-carboxymethyl-β-cyclodextrin (2'-CM-β-CD) and mono-6-deoxy-6-N,N,N',N',N'-pentamethylethylendiammonio- cyclomaltoheptaose dichloride (PEMEDA-β-CD) where the resolution of 1,42 (pH = 5,1) and 4,29 (pH = 11,1) was measured, respectively.
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Sound-aesthetic conceptcs in chamber acoustic jazz
Košulič, Jan ; DVOŘÁK, Aleš (advisor) ; PINKAS, Martin (referee)
The aim of presented work is the sound - aesthetic concept recordings of chamber jazz recordings. The work defines various criteria that can be used to issue of the aesthetic concept of jazz recordings. Several selected significant, settled and success in the music market-proven aesthetic concepts are briefly analyzed. The core of the work is the practical implementation of various aesthetic concepts in recording jazz music. Qualitative research, the results of this work presents were obtained from observations supplemented by discussions in the focus group consisting of jazz musicians. The work provides information about the views of musicians on each part of the process of recording jazz music and practical experience and knowledge based on a series of jazz recording. It also deals with the issue of communication between musicians and sound engineers. A sub- goal which work fulfilled is the opening of the debate over sound - aesthetic issues among jazz musicians and sound engineers.
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