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Pathophysiological and genetic factors affecting serum uric acid level.
Hasíková, Lenka ; Závada, Jakub (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Serum uric acid level (SUA) depends on the balance between its production and excretion. SUA is associated with several transmembrane proteins responsible for reabsorption (mainly URAT1 and GLUT9) and secretion (ABCG2) on the apical and basolateral membranes of the proximal tubules in the kidney, and in the case of ABCG2, it also correlates with its significant excretion through the gastrointestinal tract. Gout is a metabolic disease caused by the deposition of urate crystals in the joints and tissues. Chronic hyperuricemia is a primary risk factor for the development of gout; however, gout patients usually have a lower SUA during an acute gout attack than in the intercritical periods. The exact mechanism of this phenomenon is unknown. It has been speculated that the systemic inflammatory response can explain this discrepancy. The aim of the study is to determine whether treatment with specific inhibitors of the proinflammatory cytokine TNF (TNFi) affects SUA in patients with systemic rheumatic disease (SRD), and whether changes in SUA correlate with changes in selected proinflammatory cytokines or with the biomarker of oxidative stress, allantoin. Another aim is to determine the frequency and effect of allelic variants in the ABCG2 urate transporter gene in patients with primary...
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Effectiveness and safety of biological therapy in inflammatory rheumatic diseases
Nekvindová, Lucie ; Závada, Jakub (advisor) ; Hendl, Jan (referee) ; Hrnčíř, Zbyněk (referee)
This thesis focuses on evaluating the effectiveness and safety of biological/targeted treatment in chronic inflammatory rheumatic diseases based on data from the ATTRA registry. The introductory chapters of the thesis give an overview of three rheumatic diseases - rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), characterising clinical manifestation, diagnosis, therapeutical options and current treatment guidelines. The work also contains a brief summary of information about planning, creating and maintaining a clinical registry and characterises specifics related to the analysis of registry data. The practical part of the thesis was aimed at two research questions. Recently, a treat-to-target (T2T) strategy was established for RA, PsA and axSpA. Studies from daily clinical practice concerning the advantage of following T2T over usual care are still lacking. Thus, the first goal of the thesis was to evaluate whether following a treat to target strategy after not reaching low disease activity within the first six months leads to a higher chance of meeting the treatment target at the twelve-month visit. Our second goal in the thesis was to evaluate the association between therapeutic response (achieving remission and drug retention) and patients'...
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The role of endothelial progenitor cells in the pathogenesis of anti - neutrophil cytoplasmatic antibody - associated vasculitis
Závada, Jakub ; Tesař, Vladimír (advisor) ; Haluzík, Martin (referee) ; Monhart, Václav (referee)
Summary: Introduction: Circulating endothelial progenitor cells (EPC) may provide an endogenous repair mechanism to counteract ongoing endothelial damage. Antineutrophil cytoplasmic antibody - associated vasculitis (AAV) is an inflammatory disorder of small- to medium-sized vessels with relapsing/remitting progression and endothelial injury is a major feature of AAV. EPC thus may play and an important role in the pathogenesis of AAV, or serve as a useful marker for monitoring and/or prediction of outcomes in patients with AAV. Hypotheses: EPC number in patients with AAV could be altered. The decreased capacity for endothelial regeneration paralleled by low EPC numbers could increase the risk of relapse in patients with AAV. Patients and methods: We have measured EPC in healthy volunteers, patients with AAV, chronic kidney failure (CKD) and atherosclerosis by a colony-forming assay. We have investigated the relation between the numbers of EPC, clinical and laboratory characteristics of the patients, and long-term outcomes of patients with AAV. Results: Patients with AAV had a significantly lower number of EPC than healthy subjects, but not than patients with CKD or atherosclerosis. The cumulative relapse-free survival increased stepwise across three increasing baseline levels of endothelial progenitor cells....
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