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Circulating miRNAs as biomarkers in the diagnosis and treatment of rheumatic diseases
Prajzlerová, Klára ; Filková, Mária (advisor) ; Hrnčíř, Zbyněk (referee) ; Procházková, Leona (referee)
Background: MicroRNAs (miRNAs) are small non-coding single-stranded RNAs involved in the posttranscriptional inhibition of gene expression and thereby regulating all cellular functions. Their dysregulation contributes to the pathophysiology of many diseases, including rheumatic diseases. MiRNAs can also be found extracellularly in body fluids and represent promising diagnostic and prognostic biomarkers. Our study aimed to investigate miRNAs as biomarkers of stage and activity and predictors of therapeutic response of two most common inflammatory rheumatic diseases: spondyloarthritis (SpA) and rheumatic arthritis (RA). Results: We found several circulating miRNAs differentially expressed in SpA patients reflecting the severity of axial involvement and/or disease activity. The decrease in circulating miR-145 in plasma of patients with ankylosing spondylitis 3 months of anti-TNF therapy predicted a good therapeutic response and low disease activity after a year of therapy. Circulating and intracellular expression of miR-125b in peripheral blood mononuclear cells (PBMC) was lower in treatment-naïve patients with early RA than in healthy controls. Baseline expression of miR-125 in PBMC predicted a (non)adequate therapeutic response. We also found the increased expression of miR-451 in PBMC in...
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Pilot Testing of Usability of the Nine Hole Peg Test in Occupational Therapy in Patients with Rheumatoid Arthritis and in Patients with Hand Osteoarthritis
Nováková, Barbora ; Rybářová, Kateřina (advisor) ; Pluhaříková-Pomajzlová, Jana (referee)
Title: Pilot Testing of Usability of the Nine Hole Peg Test in Occupational Therapy in Patients with Rheumatoid Arthritis and in Patients with Hand Osteoarthritis Abstract: Occupational therapists can objectively assess manual dexterity in patients with rheumatoid arthritis (RA) or hand osteoarthritis (OA) using Nine Hole Peg Test (NHPT). It is performed according to a manual that includes precise instructions. The subject is required to place nine pegs from the container into the pegboard as quickly as possible and return them straight away. The time required to complete the test is measured with a stopwatch. The aim of the bachelor thesis is to perform a pilot testing of usability of a new Czech translation of the NHPT manual in patients with RA or with OA. The partial goal is to obtain video documentation during the administration of the Nine Hole Peg Test and to create recommendations for using this test in practice in patients with RA or with OA. With an approval of the Ethics Committee of the Institute of Rheumatology Prague, 19 patients (8x RA, 11x OA; 14 female, 5 male) were tested using NHPT. Analysis of the data revealed that the instructions were comprehensible for the administrator and all patients. Some ambiguity was found in the part of the instructions where the patient should only listen and...
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Analysis of the therapy in patients with juvenile idiopathic arthritis
Procházková, Martina ; Malý, Josef (advisor) ; Rozsívalová, Petra (referee)
Abstarct Analysis of the Therapy in Patients with Juvenile Idiopathic Arthritis Author: Martina Procházková Tutor: PharmDr. Josef Malý, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction and aims: Methotrexate (MTX) is an effective and safe drug used for the treatment of juvenile idiopathic arthritis (JIA) and is well-known like a golden standart in the treatment of this serious illness. The aim of this study was analysis of therapy in patients with JIA focusing on MTX and faktors affecting its intolerance. Methods: The study was undertaken from January 2017 to February 2018 at the Department of Paediatrics and Adolescent Medicine, 1st Faculty of Medicine, Charles University in Prague. Patients younger than 18 years old, who have become ill with JIA for the first time or repeatedly between years 2015-2017 and were treated by MTX were included in this study. The prevalence of MTX intolerance was measured by "Methotrexate Intolerance Severity Score" questionaire every 3 months during regular rheumatological examinations. Simultaneously, medical records were reviewed. Data analysis was performed by means of descriptive statistics, correlation dependence and statistical signifikance of dependence was assessed with statistical two-choice...
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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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Molecular aspects of musculoskeletal diseases and the role of small regulatory RNAs
Pleštilová, Lenka ; Vencovský, Jiří (advisor) ; Šedivá, Anna (referee) ; Hrnčíř, Zbyněk (referee)
Rheumatic diseases are common, usually chronic, painful and to some extent invalidating medical conditions. Understanding of the disease pathogenesis is still very fragmentary. Hyperreactivity of the immune system and defect of autotolerance are probably contributed by local factors, which helps to explain, why some joints/muscles are more affected than others. All this results from a complex net of interactions between immune cells, synovial fibroblasts, chondrocytes, osteocytes, myocytes and other cells. In the submitted PhD thesis I have focused on three groups of molecules: regulatory RNAs, S100 proteins and autoantibodies. In the theoretical part, I sum up the current knowledge on their biogenesis, function and the role in rheumatology. In the investigative part, I present six original publications and one review on the role of those molecules in development of rheumatoid arthritis (RA) and idiopathic inflammatory myositis (IIM). One of the main studies was focused on expression of PIWI-interacting RNAs (piRNAs) in RA synovial fibroblasts (SF). piRNAs are small regulatory RNAs which in complex with PIWIL proteins regulate gene expression and silence transpozoms. piRNA expression was considered to be limited to germline and cancer cells. We have found 267 PIWI-interacting RNAs to be expressed...
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"DASH molecues" in local and systemic pathogenetic processes of rehumatoid arthritis
Šromová, Lucie ; Šedo, Aleksi (advisor) ; Borovanský, Jan (referee) ; Prokešová, Ludmila (referee)
The biological half-life of several pro-inflammatory mediators involved in the pathogenesis of rheumatoid arthritis (RA) is controlled by molecules exhibiting dipeptidyl peptidase-IV (DPP-IV)-like enzymatic activity (Dipeptidyl peptidase-IV activity and/or structure homologues- DASH). The aim of this thesis was to identify the molecular source of the DPP-IV-like enzymatic activity in the peripheral blood and synovial fluid in patients with rheumatoid arthritis as compared to control patients with osteoarthritis (OA), and to evaluate the association of DPP-IV with the disease activity. We found that the main source of the DPP-IV-like enzyme activity in the plasma and in the synovial fluid in patients with RA is the canonical DPP-IV. DPP-IV-like enzymatic activity and canonical DPP-IV were also detected on the cell surface of blood and synovial fluid mononuclear cells. Significantly lower DPP-IV-like enzymatic activity and DPP-IV expression in the synovial fluid mononuclear cells was found in RA as opposed to OA patients. In the synovial fluid of RA patients there was also a negative correlation between the concentration of the pro-inflammatory DPP-IV substrate SDF (stromal cell-derived factor-1 and the proportion of the DPP-IV+ T cells. The blood plasma DPP-IV-like enzymatic activity and...
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Cell and Molecular Characterization of Failed Human Corneal Grafts. The Role of Matrix Metalloproteinases in Recurrent Corneal Melting.
Brejchová, Kristýna ; Jirsová, Kateřina (advisor) ; Smetana, Karel (referee) ; Heissigerová, Jarmila (referee)
The aim of this work was to investigate the contribution of matrix metalloproteinases (MMPs) to recurrent corneal melting. Twenty three melted corneas from seven patients were separated into three groups: a) patients with primary Sjögren's syndrome, b) those with rheumatoid arthritis and c) those with other corneal melting underlying pathologies. Eleven cadaverous corneas served as controls. The presence of MMP-1, -2, -3, -7, -8, -9, and -13 was detected using indirect enzyme immunohistochemistry. The active forms of MMP-2 and -9 and MMP- 3 and -7 were examined by gelatin and casein zymography, respectively. The concentrations of active MMP-1 and -3 were measured using activity assays. Increased immunostaining intensity for MMP-1, -2, -3, -7, -8 and -9 was shown in the corneal epithelium and the stroma of almost all melted corneas from all three groups compared to the negative or slightly positive staining of the controls. In the endothelium, immunostaining for MMP-2 and MMP-9 was increased in most specimens of groups II and III and group I, respectively. A markedly higher level of active MMP-2 was detected in six, and active MMP-9 in all, pathologic specimens compared to the controls. In contrast to the completely negative controls, the proenzymes of MMP-3 and -7 were detected in almost all melted...
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Quality of life with scleroderma
Bendlová, Iva ; Tomášková, Anežka (advisor) ; Anděl, Michal (referee)
This bachelor thesis deals with the evaluation of the quality of life with scleroderma, a chronic autoimmune disease. The work is focused on determining the health-related quality of life of patients with localized and systemic scleroderma. The values obtained are then compared with the quality of life of the healthy population and with the health-related quality of life of the patients with selected diseases (psoriasis, systemic lupus erythematosus, rheumatoid arthritis and breast cancer). The research was conducted in the form of a randomized SF-36 questionnaire, a globally used tool for assessing the quality of life in chronically ill patients, which evaluates 8 areas of life. The results of the SF-36 questionnaire were further evaluated by T-test to determine statistically significant values. This questionnaire was further extended by supplementary questions. The results show that patients with scleroderma do not achieve the same quality of life as a healthy population in all evaluated areas. Patients with scleroderma rate their quality of life worse than all selected diseases (except for patients with localized scleroderma compared to those with systemic lupus erythematosus). Keywords - scleroderma - localized scleroderma (morphea) - systemic scleroderma - quality of life (QoL) - health related...
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Treatment of rheumatoid arthritis in health resort
Šachová, Aneta ; Babková, Lenka (advisor) ; Janečková, Alexandra (referee)
Tato bakalářská práce se zabývá léčebnou rehabilitací v lázeňském prostředí u pacientů s revmatoidní artritidou. Skládá se ze dvou hlavních částí. První část práce je terapeutické postupy tohoto onemocnění se zaměřením na lázeňskou léčbu. V této části jsou také uvedena specifika Léčebných lázní Bohdaneč, historie, přírodní léčivé zdroje, indikace a metody aplikované u pacientů s ou. V praktické části jsou zpracovány tři kazuistiky pacientů, kterým byla revizním lékařem schválena komplexní lázeňská léčba a absolvovali pobyt v Léčebných lázních Bohdaneč po dobu čtyř týdnů. Cílem této práce je zhodnotit stav tří konkrétních pacientů před a po ukončení rehabilitace v lázeňském prostředí a upozornit tak na mimořádný význam léčebné lázeňské rehabilitace u pacientů s
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Treatment of rheumatoid arthritis in health resort
Šachová, Aneta ; Babková, Lenka (advisor) ; Janečková, Alexandra (referee)
Tato bakalářská práce se zabývá léčebnou rehabilitací v lázeňském prostředí u pacientů s revmatoidní artritidou. Skládá se ze dvou hlavních částí. První část práce je terapeutické postupy tohoto onemocnění. Druhá část práce pojednává o specifikách Léčebných lázní Bohdaneč, historii, přírodních léčivých zdrojích, indikacích a metodách aplikovaných u pacientů s této praktické části jsou také uvedeny tři kazuistiky pacientů, kterým byla revizním lékařem schválena komplexní lázeňská léčba a absolvovali pobyt v Léčebných lázních Bohdaneč po dobu čtyř týdnů. Cílem této práce je zhodnotit stav tří konkrétních pacientů před a po ukončení v lázeňském prostředí a upozornit tak na mimořádný význam léčebné lázeňské rehabilitace u pacientů s
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