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Interaction between TiAl melt and coated oxide refractories
Dočekalová, Kateřina ; Dlouhý, Antonín ; Zemčík, L. ; Fiala, J.
The present study focuses on reactions between ceramic crucibles and molten TiAl intermetallics. Coating strategies are investigated that exhibit a potential in slowing down the decomposition of the crucible wall. Uncoated crucibles (system TiAl melt - Al2O3 crucible) and crucibles with the coat (system TiAl melt - CaO coat - Al2O3 crucible) were used in melting and casting experiments. The reference state of the coated crucible before the melting trial was also investigated. Results of the SEM, EDAX and X-ray diffraction analysis contributed to the identification of the reaction zone and its chemical composition. The melt contamination with oxide inclusions results from the erosion process in which individual components of the melt diffuse along grain boundaries of the refractory and activate chemical reactions that decompose the crucible wall. Assessment of thermodynamic parameters associated with the chemical reactions helped in identifying the nature of the erosion process.
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Molecular factors of artherogenesis in chronic kidney disease with experimental model of chronic inhibition of Nitric Oxide Synthesis and its Effect of HMG-CoA reductase inhibitoin
Lecian, Dalibor ; Matouš, Bohuslav (advisor) ; Tesař, Vladimír (referee) ; Zadražil, Josef (referee)
The experimental part of the thesis covered the markers involved in nitric oxide deficiency model in rats. The analogue of arginine N-nitro- L -arginine-methyl ester ( L -NAME) was used. L -NAME administration resulted in sustained elevation of BP, decreased GFR, and in higher albuminuria compared to control animals. The administration of hypolipidemic drug - atorvastatin to Wistar rats was studied. The statin used caused lower albuminuria and prevented decreases in GFR in L -NAME rats without having an impact on hypertension. CAV1 protein expression was similar in all groups of rats. In contrast, VEGF expression and RhoA activity was increased in L -NAME-treated animals, and normalized with coadministration of atorvastatin. Clinical part of the thesis focused on the analysis of markers of oxidative stress in obese and non-obese patients with CKD and after kidney transplantation. The patients with CKD had elevated serum concentrations of AGEs, sRAGE and ADMA with the maximal concentrations of AGEs in the patients on hemodialysis. The successful kidney transplantation decreases the AGEs, sRAGE and ADMA concentrations but not to normal value according to general population. Patients with obesity exhibited lower concentrations of sRAGE in CKD as a protective factor for cardiovascular disease. Concentrations of...
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STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS
Jansová, Hana ; Šimůnek, Tomáš (advisor) ; Hrdina, Radomír (referee) ; Jun, Daniel (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF BIOCHEMICAL SCIENCES Candidate: Mgr. Hana Jansová Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of Doctoral Thesis: STUDY OF POTENTIAL PHARMACOLOGICAL PROTECTION OF CARDIAC CELLS AGAINST OXIDATIVE STRESS AND ANTRACYCLINE ANTICANCER DRUGS Development of cardiovascular disorders is associated with various risk factors and oxidative stress plays an important role in many of them. Iron-catalysed production of highly toxic and reactive hydroxyl radicals may contribute to oxidative stress. Chelation of free iron seems to be a promising strategy to prevent the propagation of oxidative stress. However, the use of classic iron chelators in pathological conditions without iron overload is associated with the risk of toxicity due to the iron depletion. Hence, this study deals with cardioprotective properties of iron chelators as well as prochelators derived from them. We focused on prochelators with almost no affinity for iron ions until they are activated under disease-specific oxidative stress conditions. For a long time, it has been assumed that oxidative stress is also the main denominator in an anthracycline-induced cardiotoxicity. However, the previous studies suggested alternative mechanism(s). Therefore in the...
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The use of (nano)oxides for metal and metalloid stabilization in contaminated soils
Michálková, Zuzana ; Komárek, Michael (advisor) ; Luke, Luke (referee)
The main objective of the thesis was to evaluate the potential of selected Mn and Fe (nano)oxides for the stabilization of metals and metalloids in contaminated soils. The research was focused basically on three materials - commercial nanomaghemite (Fe III), nanomagnetite (Fe II,III) and a synthetic amorphous Mn oxide (AMO). The main aim of the work was to provide a complex view on the chosen stabilizing amendments regarding not just their direct influence on contaminants mobility and stabilization mechanisms, but also their stability and alterations in soil conditions together with influence on soil microorganisms and higher plants. Firstly, adsorption properties of the tested materials towards Cd, Cu, Pb and As were investigated. In this context, the most effective material showed to be the AMO reaching one to two orders of magnitude higher adsorption capacities than Fe III and Fe II,III under given experimental conditions. Interestingly, the rate of As(V) adsorption onto AMO was increasing with increasing pH as a result of high pHzpc of the AMO (8.1) and significant dissolution of this phase at lower pH values. As a next step, the influence of (nano)oxides on metal(loid)s mobility and other physico-chemical soil characteristics after application to contaminated soil was examined. Again, the AMO proved to be the most efficient in reducing mobile pools of Cd, Cu, Pb, Zn and As. On the other hand, Fe III and Fe II,III addition had generally less significant effects on contaminants mobility. AMO application further resulted in an increase of soil pH connected with AMO dissolution and unwanted decomposition of soil organic matter. When (nano)oxides alterations in soil conditions were observed, MnCO3 coatings were identified on AMO surface while no significant changes were recorded for Fe III and Fe II,III. As the MnCO3 formation was connected with increased AMO stability, AMO particles synthetically covered with MnCO3 coating (denoted as SM AMO) were prepared. Although the SM-AMO had a lower mass loss in soil than pure AMO, the stabilizing efficiency was almost the same for both materials. The differences in surface composition of both materials were decreasing with time as MnCO3 naturally precipitated on the AMO surface in soils while the SM AMO coating was gradually dissolving. When investigating the effect on soil microbiota, AMO efficiently promoted soil microbial activity while no significant changes were observed in the case of Fe III and Fe II,III. The AMO was also able to reduce the uptake of Cd, Pb and Zn by sunflower (Helianthus annuus L.), eliminate Zn phytotoxicity symptoms and increase biomass yield. On the other hand, toxic levels of Mn released from the AMO in an acidic soil were found in sunflower tissues. AMO application is thus recommended for contaminated neutral or slightly alkaline pH with a higher cation exchange capacity in order to avoid unwanted release of Mn. Finally, various types of AMO-biochar composite sorbents were recently prepared and field experiment focused on stabilization of Cd, Pb, Zn and As using studied materials is currently under preparation. The combined results from the thesis highlight the importance of a complex experimental approach dealing with all parts of the contaminated soil environment in order to obtain complete information about the efficiency and usefulness of any newly developed stabilizing amendment.
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Study of signal systems with special focus on the role of nitric oxide: gene expression, regulation and pharmacological modulation in hepatocytes and adipocytes
Kutinová Canová, Nikolina ; Farghali, Hassan (advisor) ; Červinková, Zuzana (referee) ; Martásek, Pavel (referee)
Nitric oxide (NO) is involved in surprising array of vital physiological and pathophysiological phenomena. The expression of nitric oxide synthases, endothelial (eNOS) and inducible (iNOS), was demonstrated in rat liver and white adipose tissue among others. Therefore, the goals of the present thesis were to provide in vitro data about NO in the liver and white adipose tissue and to assess: 1) the effects of selective immunosuppressive drugs, cyclosporin A (CsA) and tacrolimus (FK 506), and nonspecific and specific iNOS inhibitors on NO production and iNOS expression during endotoxemic insult using primary rat hepatocyte culture; 2) spontaneous NO production under various culture conditions with comparison of its influence on functional status of hepatocytes in conventional cell culture and in hepatocyte bioreactors; 3) effects of S-nitroso-N-acetyl penicillamine (SNAP), D- galactosamine (D-GalN), lipopolysaccharide (LPS), LPS+D-GalN and thapsigargin (TG), a selective inhibitor of a sarco-endoplasmic reticulum-Ca2+ -ATPase, on apoptotic/necrotic markers in relation to NO production; 4) the effect of LPS on lipolysis in relation to iNOS stimulation; and 5) the interplay between NO production and β3-adrenoreceptor (β3- AR)/cAMP pathway on lipolysis in rat epididymal adipocyte culture. We found that CsA, FK...
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The oxidative DNA damage and its relationship to the cytotoxic effect.
Blahová, Hana ; Hochmann, Jiří (advisor) ; Polívková, Zdeňka (referee)
This work has been focused on the study of oxidative DNA damage induced with hydrogen peroxide and on the relationship of this damage to cytotoxic effect . The repair of the oxidative DNA damage and the cell survival was followed both in normal Chinese hamster cells and their mutant derivative UV-20. The modified single cell gel electrophoresis (the comet assay,) was used to estimate the DNA damage. The cytotoxiciy was measured using the inhibition of colony forming capacity of cells. Both normal AA8 and mutant UV-20 cells repair the oxidative DNA damage with approximately the same velocity, and they show also the same sensitivity towards the hydrogen peroxide. These results indicate, that the defect in the nucleotide excision DNA repair in UV-20 cells does not play any important role in the response of these cells to the oxidative DNA damage, and therefore this mechanism is not involved in the removal of this damage. This may indicate, that the main mechanism of the repair of oxidative DNA damage is the base excision repair. Keywords: Oxidative DNA damage, hydrogen peroxide, comet assay, excision repair.
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