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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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Epidemiological aspects of inflammatory rheumatic diseases and diffusional diseases of binding tissue.
Hánová, Petra ; Pavelka, Karel (advisor) ; Bencko, Vladimír (referee) ; Horák, Pavel (referee)
v anglickém jazyce Introduction: No information was known about frequency of common inflammatory disorders in rheumatology in the Czech Republic. Aims of the study: To estimate the standardized annual incidence (INC) and point prevalence (PREV) of six diseases (rheumatoid arthritis-RA, juvenile idiopathic arthritis-JIA, gout, psoriatic arthritis-PsA, ankylosing spondylitis-AS, reactive arthritis-ReA) in a population-based study in two regions of the Czech Republic (CR). Methods: INC: Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. PREV was studied on the basis of identification of established diagnoses at a time point. Crude rates were standardized for age and sex. Results: Both INC and PREV are shown per 100.000 inhabitants. RA INC:31 (95%CI 20-42), PREV:610 (95%CI 561-658). Gout-INC:41 (95%CI 28-53), PREV:300 (95% CI 266-334). JIA-INC: 13 (95% CI 1-20), PREV:140 (95%CI 117-280). PsA-INC:3,6 (95% CI 1-8), PREV:49 (95%CI 40-60). AS-INC:6 (95% CI 3-11), PREV:94 (95% CI 94-109). ReA-INC:9 (95% CI 6-15), PREV:91 (95% CI 78-106). Conclusion: This is the first population-based study estimating annual incidence and prevalence rates of the most common rheumatological disorders in the Czech...
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Molecular Pathophysiology of Primary Hyperuricemia and Gout
Bohatá, Jana ; Stibůrková, Blanka (advisor) ; Hrnčíř, Zbyněk (referee) ; Friedecký, David (referee)
Primary hyperuricemia, as a condition of elevated serum uric acid levels, is caused by various factors and necessarily precedes a form of inflammatory arthritis referred to as gout. Uric acid is the end product of purine catabolism and requires specialized proteins for its transport. Pathogenic variants in the genes for these transport proteins can have a major negative impact on their function, thereby affecting the resulting serum uric acid levels. However, chronically elevated uric acid levels are not the only predisposition to the development of gout. Other factors, such as epigenetic mechanisms or genetic predispositions to inflammatory conditions caused by immune dysregulation, are likely to play a role in disease progression. The aim of the study was to analyse damaging variants in genes for important urate transporters ABCG2, SLC22A12 and SLC2A9, which may cause impaired excretion or reabsorption of uric acid and thus contribute to the development of primary hyperuricemia and gout, or rare hereditary renal hypouricemia. We also focused on circulating miRNAs in the plasma of patients with primary hyperuricemia, gout and gout attack. We identified and functionally characterized over ten rare nonsynonymous variants in the ABCG2 gene. Most of these variants had a negative impact on protein...
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Pathophysiology of urate transporters in primary gout
Pavelcová, Kateřina ; Stibůrková, Blanka (advisor) ; Doležel, Zdeněk (referee) ; Hrnčíř, Zbyněk (referee)
There are localised proteins (so-called urate transporters) in the renal proximal tubules and in the intestine, which excrete and reabsorb uric acid. Polymorphisms in the genes coding these proteins can result in the disruption of the transport function and development of hyperuricemia and gout. However the serum level of uric acid is also determined by other factors which include the intake of exogenous purines in food, synthesis of endogenous purines and degradation of nucleic acids, but also certain conditions. In 250 patients with primary hyperuricemia and gout we used Sanger sequencing to analyse the exons and adjacent intron regions in ten genes coding urate transporters: ABCG2, ABCC4, SLC2A9, SLC22A12, SLC22A11, SLC22A13, SLC17A1, SLC17A3, SLC22A6 and SLC22A8. We examined a possible connection between the identified genetic variants and primary hyperuricemia and gout based on a comparison of allele frequencies with the European population, according to topological models, according to programs predicting the functional impacts of variants and searches in specialised literature. We also took into account the conclusions of functional studies analysing the impact of nonsynonymous variants in the ABCG2 and SLC2A9 genes. We also focused on the effect of the concomitant occurrence of several...
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Nutraceuticals: possibilities in decreasing of hyperuricemia and alleviating gout
Lorencová, Štěpánka ; Hošťálková, Anna (advisor) ; Opletal, Lubomír (referee)
1 ABSTRACT Lorencová Š.: Nutraceuticals: possibilities in decreasing of hyperuricemia and alleviating gout. Diploma thesis, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Botany and Ecology, Hradec Kralove 2020, 82 p. This research work was conducted on the basis of literature analysis, reviewing papers mainly from international but also domestic journals. The review describes pathophysiology of gout and discusses options to mitigate the disease with the aid of dietary supplements. This work presents symptoms and a clinical picture of the disease as well as its origin and risk factors, pathological processes leading to the development of the disease, and a short overview of current pharmacotherapy. Furthermore this work summarises natural substances including plant extracts that may be utilised in the prevention and support of gout treatment. In particular, these include vitamins, unsaturated fatty acids, polyphenols and peptides. This work also describes plants used in the traditional treatment of gout and gives a brief overview of natural substances including plant extracts contained in food supplements that are available on the market in Czech Republic. This work also describes the role of purines, fructose, alcoholic drinks and tomatoes in triggering...
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Gout diet
KOZÁK, Martin
This Bachelor's thesis, that is concerned with the disease gout, is divided into 3 parts. Theoretical part of this thesis is dedicated to the description of this disease, including its treatment and related diet measures, which have to be followed. Part of this study is a research of respondents with gout disease. This research was made as an interview with the respondents and it discovers necessary information including their diet. Results of this research are described at the end of this thesis and it shows that gout disease cannot be treated only with pharmaceutical means, but it is important to follow appropriate diet including an overall change of a life style
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Epidemiological aspects of inflammatory rheumatic diseases and diffusional diseases of binding tissue.
Hánová, Petra ; Pavelka, Karel (advisor) ; Bencko, Vladimír (referee) ; Horák, Pavel (referee)
v anglickém jazyce Introduction: No information was known about frequency of common inflammatory disorders in rheumatology in the Czech Republic. Aims of the study: To estimate the standardized annual incidence (INC) and point prevalence (PREV) of six diseases (rheumatoid arthritis-RA, juvenile idiopathic arthritis-JIA, gout, psoriatic arthritis-PsA, ankylosing spondylitis-AS, reactive arthritis-ReA) in a population-based study in two regions of the Czech Republic (CR). Methods: INC: Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. PREV was studied on the basis of identification of established diagnoses at a time point. Crude rates were standardized for age and sex. Results: Both INC and PREV are shown per 100.000 inhabitants. RA INC:31 (95%CI 20-42), PREV:610 (95%CI 561-658). Gout-INC:41 (95%CI 28-53), PREV:300 (95% CI 266-334). JIA-INC: 13 (95% CI 1-20), PREV:140 (95%CI 117-280). PsA-INC:3,6 (95% CI 1-8), PREV:49 (95%CI 40-60). AS-INC:6 (95% CI 3-11), PREV:94 (95% CI 94-109). ReA-INC:9 (95% CI 6-15), PREV:91 (95% CI 78-106). Conclusion: This is the first population-based study estimating annual incidence and prevalence rates of the most common rheumatological disorders in the Czech...
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