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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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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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Immunogenetic and hormonal markers of predisposition to systemic rheumatic diseases particularly systemic lupus erythematosus
Fojtíková, Markéta ; Pavelka, Karel (advisor) ; Hrnčíř, Zbyněk (referee) ; Rovenský, Jozef (referee)
Fojtikova 2011 INTRODUCTION: Several factors like genetic susceptibility is required for systemic rheumatic diseases development. Immunomodulatory PRL effect supports autoimmunity. AIMS: 1. To detect the immunogenetic background (alleles HLA class I, II and microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene) of SLE and PsA. 2. To detect PRL serum and synovial fluid with regard to clinical and laboratory RA activity. 3. To find the role of the functional polymorphism -1149G/T SNP PRL of extrapituitary promoter of PRL gene in SLE, RA, PsA, SSc and inflammatory myopathies development. METHODS: Genetic analyses of pateints with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47) a DM (n=68) and 123 healthy individuals: PCR-SSP (HLA clase I and II), PCR-fragment analysis (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). In 29 RA a 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. RESULTS: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03-DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in Czech population. In SLE versus controls allele MIC-A5.1 was increased (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 increases the risk for SLE development, pc <0.000001; OR 9.71....
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Prolactin And Systemic lupus erythematosus
Moszkorzová, Ludmila ; Dostál, Ctibor (advisor) ; Pokorný, Jaroslav (referee) ; Hrnčíř, Zbyněk (referee)
Prolactin (PRL) is a polypeptide hormone of 23 kDa molecular weight made up of 199 amino acids, and produced by lactotropes, acidophilic cells of the anterior lobe of the pituitary. PRL is also synthetized in some other parts of the brain and in certain peripheral blood elements. Whether this extra-pituitary PRL, also known as PRL-like hormone, interferes with serum PRL radioimmunoassay (RIA) and whether it also has a feedback effect on PRL secretion in the pituitary, has yet to be elucidated. There is, however, proof of its apocrine and paracrine function of cellular growth factor, a function enhancing mitogenesis and lymphocyte differentiation at the site of inflammation and thereby their own production of yet other mediators and immunomodulators - including interleukines (IL) and growth factors. PRL also directly interferes with the synthesis of some acute-phase proteins in the liver (stimulating, e.g., alpha-2-macroglobulin synthesis). As a result of these discoveries, PRL was classed among immunomodulators, and the hypothesis was advanced of its part in the pathogenesis of autoimmune diseases. The aim of the thesis was to verify the presence of hyperprolactinemia (hyper- PRL) in SLE patients compare to patients with other auto-immune diseases and to healthy controls and to find its association...
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The Imaging of Brain Pathological Lesions in Systemic Lupus Erythematosus Patients
Podrazilová, Lucie ; Dostál, Ctibor (advisor) ; Hrnčíř, Zbyněk (referee) ; Seidl, Zdeněk (referee)
Objective: Our project study presents the results of measuring the volume of pathological foci in the brain tissue of patients suffering from systemic lupus erytematodes (SLE) with or without neuropsychiatric manifestations (NP). Magnetic resonance (MR) scans of patients with SLE and, in particular, signs of neuropsychiatric involvement show pathological foci in the cerebral white matter. Methods: A total of 53 SLE patients, 29 with signs of neuropsychiatric syndromes (NPSLE), 24 without, and 16 healthy controls underwent prospective volumetric magnetic resonance imaging in a flow attenuated inversion recovery (FLAIR) sequence. The disease activity was expressed in terms of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results: All of the patients in this study were found to have a larger volume of pathological foci in the brain tissue than the healthy controls. The NPSLE subgroup had a larger volume of pathological foci than the SLE patients without NP (p<0.001). The largest volume of such foci was found in patients with a history of cerebrovascular disease (p<0.05). These were also noted for a correlation between the duration of the disease and the period of time elapsed from the onset of the first signs of neuropsychiatric lupus (p<0.01). Correlation with SLEDAI-rated disease activity...
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Mechanisms of muscle inflammation and clinical manifestations in patients polymyositis and dermatomyositis
Studýnková-Tomasová, Jana ; Vencovský, Jiří (advisor) ; Bartůňková, Jiřina (referee) ; Hrnčíř, Zbyněk (referee)
Idiopathic inflammatory myopathies (IIM) is a heterogeneous group of acquired diseases with varying course and prognosis nehnisavým caused by inflammation of striated muscle. Clinically they are characterized primarily by proximal muscular weakness. On the basis of specific clinical, histopathological, immunological and demographic features of the breakers can be divided into three subgroups dermatomyositis (DM), polymyositis (PM) and inclusion bodies with myositis (IBM). The aetiology of these diseases is unknown and there is also rooted difficulties with their treatment. The common objective of the project was to try to map out the mechanisms leading to inflammatory infiltration of muscles, muscle tissue edema and tissue damage, and subsequently to clinical manifestations of disease in patients with PM and DM.
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Optimalize Application of Cascade Convection of a Heat Pumps
Hrnčíř, Zdeněk ; Šenk, Josef (referee) ; Gregor, Jan (advisor)
The introductory part of this diploma work contains a basic thought for the application of the heat pumps cascade connection and further I describe its function and define the notion of an optimum middle temperature.Then the direct comparison of two heats pumps cascade connection with an one-stage heat pump is shown there in a concrete example. The main part of the work is aimed to the determination of the most suitable variant for the heating and for the preparation of a hot service water in a benchmark family house. The systems of heatings are provided in options of a low-temperature floor heating and hot-water radiators. Both types of the heat pumps supply the warm to every heating system. It results into four possibles alternatives of the building heating.Besides of the alternatives mentioned above, a new variant of optimalised cascade connection was arisen during this work elaboration . The first stage of this connection which supplies the warm to the floor heating is disconnected out of the heating season and the second stage provides only a hot service water warming. The results of this work showed us that just this variant of a cascade connection causes savings in energy in comparison with an one-stage heat pump. In the conclusion of this work there are discussed the reached results and indicated the possibilities of a practical exploitation.
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