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Analysis of novel members of FAHFA lipid class derived from omega 3-PUFA by LC-MS/MS and LC-MS/MS/MS
Rombaldová, Martina ; Kuda, Ondřej ; Březinová, Marie ; Slavíková, Barbora ; Pošta, Martin ; Beier, Petr ; Janovská, Petra ; Veleba, J. ; Kopecký Jr., J. ; Kudová, Eva ; Pelikánová, T. ; Kopecký, Jan
White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obesity, contributes to the development of insulin resistance and type 2 diabetes. Omega-3 polyunsaturated fatty acids (PUFA) of marine origin play an important role in resolution of inflammation and exert beneficial metabolic effects. Using LC-MS/MS method, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids (FAHFA), which were present in murine and human serum and WAT after omega-3 PUFA supplementation in diet. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) termed 9-DHAHLA and 13-DHAHLA, and were synthesized in WAT. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed toomega-3 PUFA, in both miceandhumans.
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Less common metabolites of steroid hormones in human physiology and pathophysiology.
Máčová, Ludmila ; Hampl, Richard (advisor) ; Rauch, Pavel (referee) ; Černý, Ivan (referee)
The thesis focuses on selected, yet unsolved question of the role of less common steroids and SHBG as a junction of three endocrine systems. Answering these questions may help to understand the complex mechanism of action of these hormones on the human organism. This thesis is based on five author and co-written studies mostly published in foreign scientific journals. In the case of studies of metabolites 16α-OH-DHEA and 7-oxo-DHEA (Zamrazilová et al., 2007; Kazihnitková et al., 2007) were focused on the development of appropriate methodological approach because recently used methods showed a low sensitivity and specificity. We developed and statistically evaluated new RIA methods which are rapid, sensitive and inexpensive. Both of them can be used in other research even in routine practice. New methods were also used to determine the metabolites in a statistically significant sample of healthy human population. In another study (Zamrazilová et al., 2010) we examined the relationships of selected steroid metabolites and SHBG in patients with CAH. We assumed that SHBG may act as a non-steroidal laboratory parameter reflecting the effectiveness of substitution therapy in these patients. Our assumption was not confirmed. We observed lower levels of SHBG which at least in women reflect effects of...
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Problem of the undernourishment and the food water resources
Polzová, Tereza ; Kuna, Zbyněk (advisor) ; Petr, Petr (referee)
The main focus of the final thesis are the problems related to the problem of undernourishment in affected
regions of the world, sea fishing and aquaculture.
In the beginning, the definition of the food problem in the world is introduced. The potential contribution of proteins from the sea production to human dietary is emphasized. Further, the exponential population growth is mentioned, influencing the future development and the food problem itself.
The second part of thesis is dedicated to fisheries and aquaculture. The importance and benefits of sea water resources as well as aquaculture is mentioned from the nutritional and livelihood point of view. Sea management and international regulations are playing
crucial role in the sustainability of the fisheries stocks. These are needed to eliminate the problems of fisheries and aquaculture and the degradation of sea ecosystems due to unsuitable fishing techniques.
At the end of the thesis a summary of all important information is listed. Followed
by possible solutions of these global problems.
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Air transport in Czech Republic after accession to the European Union
Malá, Marie ; Vošta, Milan (advisor) ; Bartušková, Hana (referee)
The aim of this bachelor's thesis is to provide readers with overview of Czech air transport, its importance, system of regulation and presentation of the most important players in the air transport market and their roles. Furthermore, this thesis focuses on changes that occured as a result of Czech republic's accession to the European Union and to the Schengen Area. It also deals with common legislation, projects and developmet after 2004.
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Distribution of medicines in Slovak republic
Čechová, Kristína ; Mervart, Michal (advisor) ; Zrubcová, Dana (referee)
The Master thesis is dedicated to distribution of drugs and medicines in Slovak republic. The first chapter includes definition of logistics and describes the basic concepts of supply chain management. It also explains the main reasons for including distributors and pharmacies in distribution channel and what are their main roles. The Slovak health policy, legislation, and specificities of pharmaceutical industry are described in the thesis too. The last chapter of the first part deals with the price regulation and explains how the prices are created. The practical part includes the analysis of Slovak pharmaceutical market. The last chapters are crucial to understand the problem. I described here how three real companies -- pharmacies and a distributor work and operate on the market and I tried to find the best ways how to optimize their processes. The current trends in data synchronization and standardization are also included.
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Molecular Pathology of Rett Syndrome
Záhoráková, Daniela ; Martásek, Pavel (advisor) ; Kubala Havrdová, Eva (referee) ; Mazura, Ivan (referee)
Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder affecting almost exclusively girls. It belongs to autistic spectrum disorders and it is characterized especially by psychomotor regression, loss of acquired speech, microcephaly, repetitive stereotypic hand movements, and seizures. Most of RTT cases are caused by de novo mutations in the gene for the methyl-CpG-binding protein 2 (MECP2) and familial cases are extremely rare. The MECP2 gene product plays an important role in chromatin remodeling, regulation of gene expression and is also involved in RNA splicing. Some atypical RTT cases are caused by mutations in other genes, such as CDKL5, FOXG1 or NTNG1. In this paper we give an overview of RTT, its clinical aspects, molecular basis, diagnostic criteria, medical management and DNA diagnosis.
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Foreigns nationals interned in the Czech Republic
Čech, Pavel ; Polišenský, Miroslav (advisor) ; Gabriela, Gabriela (referee)
Diploma thesis describes foreign nationals imprisoned in the Czech Republic with more detailed focus on the characteristics of the selected groups. Based on the analysis, characterization and expert examination gives a comprehensive view on this issue and to help you navigate not only the interested persons.
The theoretical part focuses on the description of the Prison service of the Czech Republic as an institution, its role, structure and organization system. It also deals with the history and its evolution to the present time. It provides a comprehensive insight into the issue of foreigners in the Czech Republic, legislative regulation and crime. For purposes of this research work have been selected group of foreign nationals imprisoned in the Czech Republic, which are closer to the theoretical part, characterized, distributed and investigated.
Analytical part is focused on analysis of selected data, and layout (for clarity) into several sections, which always include one area of research interest of the issue. This section is arranged graphs providing an overview on the development of individual indicators.
In conclusion there is summary assessment and recommendations to individual areas of research.
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Mechanizmy regulace signální transdukce povrchovými proteiny leukocytu*.
Štěpánek, Ondřej ; Brdička, Tomáš (advisor) ; Brábek, Jan (referee) ; Vomastek, Tomáš (referee)
The core of the doctoral thesis "Regulation of signal transduction by leukocyte surface proteins" consists of three publications in international peer-reviewed journals dealing with leukocyte signaling both at the level of individual signaling pathways and in the context of a multicellular organism. Most attention is paid to signaling via the T cell receptor (TCR), which plays a central role in the development and function of T cells and represents a key signaling pathway for proper function of the adaptive component of the immune system. Transmembrane protein tyrosine phosphatase CD148 was considered a negative regulator of TCR signaling through dephosphorylation of LAT and PLCγ1 proteins. This study brings evidence that CD148 is able to modulate signaling also at the level of Lck, both positively and negatively. The net effect of CD148 activity on the TCR signaling is determined by the intracellular biochemical context, notably, the presence of another tyrosine phosphatase CD45. The second project dealt with the characterization of a transmembrane adaptor protein PRR7. This adapter inhibits TCR signaling via down-regulation of the intracellular Lck and cell surface TCR levels. The research concerning the signaling in the environment of a multicellular organism is represented by the analysis of...
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Regulation of alternative splicing
Dušková, Eva ; Staněk, David (advisor) ; Trejbalová, Kateřina (referee)
Alternative splicing is an important cellular mechanism. It allows to produce multiple protein isoforms from a limited number of genes. Regulation of alternative splicing involves cis-acting elements on pre-mRNA and trans-acting splicing factors (SR and hnRNP proteins). Because splicing occurs co-transcriptionaly, chromatin structure appears to have a role in the regulation of alternative splicing. We have studied the effect of histone acetylation on alternative splicing. We have prepared splicing reporter for alternative EDB exon, which is part of the fibronectin gene. We have shown, that the inhibition of histone deacetylases affects splicing pattern of EDB exon from the reporter in the same way as the splicing of the endogenous EDB exon. Furthermore, we have shown, that the structure of the promoter affects splicing of alternative EDB exon from splicing reporter. Currently we have found out, that the structure of the promoter influences the degree of histone H4 acetylation. Inclusion of alternative EDB exon in mRNA was inversely proportional to histon acetylation on the reporter. This work might explain why various promoters have different splicing patterns of alternative exons.
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Signalling of protein kinase B and expression of cyclooxygenase in early phases of diabetic nephropathy
Ždychová, Jana ; Komers, Radko (advisor) ; Haluzík, Martin (referee) ; Matoušovic, Karel (referee) ; Škrha, Jan (referee)
Introduction: Renal hypertrophy, extracellular matrix accumulation, aItered apoptosis as well as changes in regional hemodynamics have been implicated in the pathophysiology of nephropathy in diabetes mellitus (DM). On the molecular level the detailed mechanisms for development of diabetic nephropathy (DN) have becn intensively studied. Insulin induces a variety of biologicaI effects in a number of cell types via phosphatidylinositol-3 kinase (PI3K)/Akt kinase signaling pathway. Considering multiple function of Akt that incIude potentiaIly hannful pro-growth effects mediated by mTOR and cyclooxygenas-2 (COX-2), as well as protective effects mediated by endotheliaI nitric oxide synthase (eNOS), it is possible that aIterations in activities of Akt may play role in the pathophysiology ofDN. Renal corticaI activity and expression of Akt, its down-strearn effectors mTOR, eNOS, and "C<JIX-:Z. as well as PTEN, an endogenous Akt inhibitor, were investigated in streptozotocin (STZ): diabetic rats as a model of Type 1 DM with different levels of glycenůc control, and in Zucker ~d.iabetic fatty rats, a model ofDM2, and in nondiabetic rats as controls. Methods: Akt activity was measured by kinase assay. Protein expressions were measured by .immunoblotting and immunohistochemistry in renal cortex of 4- and 12- week old...
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