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The role of S100 proteins in the pathogenesis of rheumatic diseases
Andrés Cerezo, Lucie ; Šenolt, Ladislav (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Recent findings and better understanding to the pathogenesis of rheumatic diseases contributed to the development of biological therapies targeting cytokines and immune cells. Several S100 proteins exert cytokine-like effects and participate in the regulation of the inflammatory process. The aim of this work was to study the role of selected S100 proteins in the activity and in the pathogenesis of the rheumatic diseases. Results: Our data show for the first time an association of S100A4 proteinwith RA disease activity and decrease of the bioactive form, but not the total amount of S100A4, after aplication of tumour necrosis factor (TNF) blocking biologic therapy in patients with RA. We demonstrated that in vitro S100A4 acts as a potent pro-inflammatory mediator inducing production of TNFα, interleukin (IL)-1β and IL-6 in PBMCs via Toll-like receptor 4 (TLR-4), transcription factor NFκB and tyrosine kinases erk1/2 and p38. Moreover, S100A4 can play an important role in the pathogenesis of inflammatory myopathies. S100A4 is present in the inflammatory infiltrate of the affected muscles and in the regenerating muscles and may act as a cytokine-like factor indirectly promoting muscle fiber damage by stimulating mononuclear cells to increase the synthesis of pro-inflammatory cytokines. We...
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Social demokratic publicists in the post-February exile (1948-1953)
Horák, Pavel ; Čechurová, Jana (advisor) ; Sekera, Martin (referee)
This diploma thesis (Journalism of Social Democratic Exile after February 1948 /1948- 1953/) studies the history of social democratic party in exile between the years 1948 and 1953 with special focus on journalism, news service and propaganda. The thesis describes formation of party fractions and deals with how they defined themselves, communicated and presented themselves in the media. The thesis then goes on to analyse the newspaper format, production and financing thereof as well as the number of copies. It looks into broadcasting activities of social democrats and their plans related to the setup of illegal radio. Based on the cases of party secretary Vilím Blažej and Bohumil Laušman, the last party chairman prior to February 1948, the thesis analyses the question whether single groups within the party in the given time period tried by its journalistic activities to primarily influence events in Czechoslovakia or whether these efforts slowly faded due to rivalry between fractions and frustration over hopeless political situation and lack of audience in such an extent that media outputs were later on confined only to discussions within the party and to barely expressing political views.
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Application of renewable and recyclable raw materials for preparation of new polymers
Horák, Pavel ; Beneš, Hynek (advisor) ; Cajthaml, Tomáš (referee)
This thesis deals with optimalization of flexible polyurethane foam recycling with using of natural polyols based on rape seed oil and fish oil and it explores applications of depolymerized polyol product by formulations of new polyurethane materials. The experiments of depolymerisation showed that both tested natural oil (rape seed oil and fish oil) can be used as effective reagents for polyurethane recycling. Reaction conditions of depolymerisation were optimised with model flexible polyurethane foam and applied on waste foam from real conditions. Gain of depolymerisation is one-faze low viscosity (to 1500 mPa.s) liquid polyol products with content of hydroxyl groups ca 3 mmol/g. These polyols can be used for polymerisation of new materials. First application of recycled polyols was formulation of polyurethane foam systems. Through optimising of formula was prepared low-density semirigid foam containing 100 percentage of recycled polyol. Properties of these foams correspond to commercial foams. To prepare of homogenous cast polyurethane system based on recycled polyols it was necessary to add proper solvent, therefor extent of application has been lowered. On that account the systems were tested for study of polyaddition reaction and for following properties of the material. In these tests, the reactivity...
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Political ideas of Bohumil Laušman in the years 1941-1944
Horák, Pavel ; Čechurová, Jana (advisor) ; Kuklík jun., Jan (referee)
Socialdemocratic parties played a very important role in the tactics of communists in the countries of Sovieťs interest after the World War II. It was based on cooperation with social democrats and then on "unification" of both of the "labour" parties in conditions of so called popular, respectively national fronts. The very beginning of these cooperations could have started in the middle ofthe year 1941 after the US SR had entered the War. The initiation to cooperation of the left-wing partie s was coming out of the "left-wing" fraction of social democrats in London's exile at that time. Its representative was Boumil Laušman, whose obvious left-wing tendency and non-constructive behaviour are possible to be seen after the failure of his political formation of Czechoslovakia's resistance movement in Paris and London. So he left in the middle of the year 1942 to the USSR to get to know c10ser the political ideas of the representatives of the Czechoslovakia' s resistance living there, possibly to get their politi cal support. In the negotiations he offered communists mainly the possibility of advancement together with "lef-wing" group of the social democrats in London's exile institutions, at first the participation in the government. This cooperation was to be done with the perspective of uni:fYing the...
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The impact and influence of Action Commitees of the National Front in the chosen districts of Eastern Bohemia
Horák, Pavel
HORÁK Pavel, The impact and influence of Action Commitees of the National Front in the chosen districts of North-eastern Bohemia. Hradec Králové: Faculty of Arts, University of Hradec Králové, 2017, 257 p. Doctoral Dissertation. This doctoral dissertation is focused on impact and influence of Action Comittees of the National front (AC NF) in these districts: Hradec Králové, Náchod, Nový Bydžov and Trutnov in 1948- 1954. Based on analysis and comparation followed of the process of formation working of the AC NF in the chosen districts and the work reveals some local features which essentialy influenced National Front Action Committees working on regional basis. The aim of the dissertation is to contribute to better understanding of the issue of National Front Action Committee and to complete the gaps in history of the districts mentioned above. The author paid attention on the creation of AC NF itself, consequences of its decisions to local inhabitants but also difficulties which AC NF had to deal with. The issue of NF elements and their mutual co- working with Action Committee takes a big part in this work. Keywords: National Front Action Committees, Communist Party of Czechoslovakia, National Front, February 1948, Hradec Králové, Náchod, Nový Bydžov, Trutnov, North-eastern Bohemia, Czechoslovakia 1948-1954
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New cytokines in the pathogenesis of rheumatic diseases
Filková, Mária ; Šenolt, Ladislav (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Background: An imbalance between pro- and anti- inflammatory cytokine activities favors the induction of autoimmunity, chronic inflammation and joint damage in patients with rheumatoid arthritis (RA). Adipokines are bioactive proteins that are important regulators of inflammation. IL-35 is a new cytokine involved in the inflammatory processes in mouse models and is of unknown function in humans. The aim of the work was to study the levels and role of several adipokines and IL-35 in the joint and blood compartment and the association with the disease activity in patients with RA or other rheumatic diseases. Results: We found increased levels of adiponectin in serum of patients with erosive osteoarthritis (OA) of the hand, differential regulation of new adipokines vaspin and omentin in synovial fluid of patients with RA compared with OA and the effect of therapy using TNFα inhibitor on the expression profile of adipokines in subcutaneous adipose tissue of RA patients. B cell depletion therapy in RA resulted in decrease of serum levels of visfatin that correlated with following change of disease activity. The levels of IL-35 in synovial fluid are significantly higher in RA than in OA and correlate with the disease activity and functional status. IL-35 subunits p35 and EBI3 are overexpressed in RA...
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The role of new pro-inflammatory and/or pro-fibrotic molecules in the pathogenesis of systemic sclerosis.
Tomčík, Michal ; Bečvář, Radim (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Systemic sclerosis (SSc) is a generalized connective tissue disease affecting the skin and internal organs. The pathogenesis of SSc is characterized by inflammation, vasculopathy and fibrosis. To date, none of the tested drugs have demonstrated convincing efficacy in the treatment of SSc. S100A4 is involved in the regulation of cell motility, proliferation, apoptosis, angiogenesis and remodeling of the extracellular matrix. It was originally described as a promoter of metastasis in tumors, however, its pro-inflammatory properties have recently been demonstrated in inflammatory rheumatic diseases. The aim of this study was to assess the role of S100A4 in pathological activation of fibroblasts in SSc and in experimental models of dermal fibrosis. Results: The expression of S100A4 was increased in the skin of SSc patients, in SSc fibroblasts and in experimental fibrosis in a TGF-β / Smad dependent manner. Overexpression of S100A4 or stimulation with recombinant S100A4 induced an activated phenotype in resting normal fibroblasts. In contrast, inhibition of S100A4 or its complete deficit abrogated the pro-fibrotic effects of TGF-β and decreased the release of collagen. S100A4 knock-out mice (S100A4-/- ) were protected from bleomycin-induced skin fibrosis with reduced dermal thickening,...
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Relation of Soluble Factors of Immune System to Fenotype of Idiopathic Inflammatory Myopathies
Klein, Martin ; Vencovský, Jiří (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Idiopathic inflammatory myopathies (myositis, IIM) are heterogeneous group of rare autoimmune systemic diseases, characterized particularly by proximal skeletal muscle weakness. Heretogeneity of myositis is based on different pathogenetic mechanisms which may be reflected by variable imunophenotypic response in individual subtypes. Objectives: The aim of this work was to explore the associations and influence of soluble factors of immune system in patient's sera on phenotypic characteristics and subtypes of IIM, to describe their expression in inflammed muscle tissue and study their eventual role in pathogenesis by analysis of effect on immune and muscle cells in vitro. Results: We have described prevalence and characteristics of joint involvement in myositis patients and its significant association with anti-Jo-1 autoantibody. Further we confirmed the relation of anti-HMGCR antibody to immune mediated necrotizing myopathy, its tight relation to statins and recent increase in incidence. We showed inverse association of IFNα serum levels with muscle activity detected on MRI. Clinical activity positively correlated with IFN type-I pathway activation in patients with dermatomyositis. We also show positive correlation of resistin levels and clinical activity and correlation of activity...
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Application of renewable and recyclable raw materials for preparation of new polymers
Horák, Pavel
This thesis deals with optimalization of flexible polyurethane foam recycling with using of natural polyols based on rape seed oil and fish oil and it explores applications of depolymerized polyol product by formulations of new polyurethane materials. The experiments of depolymerisation showed that both tested natural oil (rape seed oil and fish oil) can be used as effective reagents for polyurethane recycling. Reaction conditions of depolymerisation were optimised with model flexible polyurethane foam and applied on waste foam from real conditions. Gain of depolymerisation is one-faze low viscosity (to 1500 mPa.s) liquid polyol products with content of hydroxyl groups ca 3 mmol/g. These polyols can be used for polymerisation of new materials. First application of recycled polyols was formulation of polyurethane foam systems. Through optimising of formula was prepared low-density semirigid foam containing 100 percentage of recycled polyol. Properties of these foams correspond to commercial foams. To prepare of homogenous cast polyurethane system based on recycled polyols it was necessary to add proper solvent, therefor extent of application has been lowered. On that account the systems were tested for study of polyaddition reaction and for following properties of the material. In these tests, the reactivity...
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