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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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The influence of some factors on renal impairment in AA amyloidosis
Potyšová, Zuzana ; Ryšavá, Romana (advisor) ; Monhart, Václav (referee) ; Horák, Pavel (referee)
Introduction: Available data suggest an association between presence of secondary (AA) amyloidosis and MCP-1 (monocyte chemoatracttant protein-1) and MIP-1alpha (macrophage inflammatory protein-1 alpha) genes polymorphisms. Some studies have also shown an impact of polymorphisms in exon 3 of SAA 1 (serum amyloid A 1) gene on the incidence of AA amyloidosis in different populations. Methods: The incidence of single genotypes MCP-1, MIP-1alpha and SAA 1 genes was investigated. Serum levels of SAA, MCP-1 and MIP-1alpha were measured and potential relation between serum levels and genotypes were analyzed. All examinations were performed in patients with AA amyloidosis (43), rheumatoid arthritis (RA) without amyloidosis and healthy control group (100). Results: Significantly more frequent occurrence of 1.1/1.1 genotype in SAA 1 was recorded in AA amyloidosis group compared to RA group as well as in control group (p<0,001). No statistically significant differences in distribution of another genotypes were found. Distribution of neither 1.1/1.1 genotype nor another ones did not vary among RA group and control group. No significant difference in distribution of another examined genotypes was recorded among all three groups. Serum concentrations of SAA were statistically significantly higher in AA amyloidosis group...
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Political ideas of Bohumil Laušman - story of the democratic socialist
Horák, Pavel ; Čechurová, Jana (advisor) ; Gebhart, Jan (referee)
Bohumil Laušman (born August 30th, 1903) was a member of the Social Democratic Party. He was elected member of the National Assembly for the Pardubice region after ten years in regional politics. At the age of thirty-one he became the youngest Member of Parliament. He organised the foundation of the second parliament formation after the Munich events within the system of limited democracy, the National Labour Party. Not only did he show courage, he also showed sense for reality, when he was regulating some left-wing radicals in the weak party. He participated actively in the resistance after the establishment of the protectorate. In his resistance, he promoted collaboration across the political spectrum. That is why the selfconfident Laušman entered the exile with the idea that the left-wing party should have a moral right to determine political direction of exile institutions, which were forming at that time. His 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. He travelled to the USSR in the middle of the year 1942 to get acquainted with political ideas of the representatives of the Czechoslovak resistance residing there, possibly to get their political support. During...
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Biomarkers of subchondral bone damage caused by inflammation in axial spondyloarthritis.
Bubová, Kristýna ; Pavelka, Karel (advisor) ; Horák, Pavel (referee) ; Hrnčíř, Zbyněk (referee)
Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease affecting primarily the spine and its adjacent structures. The disease is characterized not only by destructive joint changes but also by excessive osteoproduction, which can lead to gradual ankylosis of the spine and thus significantly reduce the mobility and quality of life. The pathogenesis of the disease is not yet fully understood, but a strong genetic background is suggested, along with dysregulation of tissue metabolism resulting from an imbalance of pro- and anti-inflammatory immune mechanisms. We are still lacking biomarker with sufficient sensitivity and specificity which could help to identify early diagnosis, to monitor subchondral damage, and to differentiate rapidly progressing patients. The aim of this work was to determine the levels of potential biomarkers of connective tissue metabolism, fat metabolism and new promising biomarkers for both disease subtypes, their relationship to disease activity and progressive structural changes. Results: We have shown increased serum/plasma levels of connective tissue metabolism biomarkers (especially matrix metalloproteinase mediated metabolites), which were able to differentiate patients with early and late forms of axSpA from healthy individuals (HC), were...
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Vliv provenience Dodonaea angustifolia na klíčení a růst této dřeviny vhodné pro protierozní opatření v okolí jezera Awassa
Horák, Pavel
The bachelor thesis is focused on issues of Dodonaea angustifolia and its using for erosion control around Lake Awassa in Ethiopia. There is a theoretical part, where materials about this specimen are collected, about location and previous erosion control projects of MENDELU. In next part data about experimentally germinated individuals from different provenances with using various ways of stratification have been introduced. Based on this data most suitable provenance and way of stratification for direct sowing has been chosen. Statistically significant differences of the observed parameters occurred only in five cases. Seed treatment most often resulted in increased biomass in seedlings from treated seed. For use during anti-erosion measures, it seems that Umbulo Kajima is the best proveniency.
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The effect of physical activity interventions on the course and activity of selected rheumatic diseases
Špiritović, Maja ; Tomčík, Michal (advisor) ; Horák, Pavel (referee) ; Soukup, Tomáš (referee)
Introduction: This work focused on two rare rheumatic diseases systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM). Skin and musculoskeletal involvement in patients with SSc leads to disability and loss of functional abilities of an individual. Chronic inflammation of the muscles, subsequent muscle atrophy and permanent muscle damage in patients with IIM are the cause of a decrease in muscle strength and endurance. Moreover, both diseases also affect internal organs and manifest often with impaired lung and heart function. All of these involvements in both diseases lead to a decrease in the quality of life of patients. The data on efficacy of non-pharmacological care in SSc and IIM are very limited due to the heterogeneity of the studied interventions and/or outcomes. However, due to limitations in pharmacological therapy, non-pharmacological interventions could help bring patients back into their everyday life and improve their quality of life. Objectives: The main objective of this project was to evaluate the impact of physical intervention on disease course and activity in a substantial number of SSc and IIM patients, with the aim of minimizing the limitations of available studies, thereby improving the quality and reliability of the obtained results. Methods: This is a...
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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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