|
|
Atherosclerosis and cadiovascular risk in selected rheumatic diseases
Oreská, Sabína ; Tomčík, Michal (advisor) ; Horák, Pavel (referee) ; Soukup, Tomáš (referee)
Cardiovascular (CV) diseases due to atherosclerosis are the leading cause of morbidity and mortality worldwide. CV risk in rheumatic patients is caused by both traditional and non- traditional risk factors associated with autoimmune diseases. Unlike the relatively more prevalent rheumatic disease, there is a lack of evidence on CV risk in rare rheumatic diseases. The aim of this study was to evaluate the CV risk in 90 patients with idiopathic inflammatory myopathies (IIM), compared to 180 healthy controls (HC) with similar age and gender distribution, without clinically manifested CV diseases. The results of this cross-sectional cohort study showed a significantly higher prevalence of traditional risk factors as well as of subclinical atherosclerosis in IIM compared to HC. In comparison to carotid ultrasonography, SCORE, SCORE2, and modified SCORE was proved to underestimate the CV risk, while SCORE2 appeared to be the most accurate. The most severe CV risk profile was observed in patients with statin-induced necrotizing myopathy. Overall, higher CV risk in IIM was associated with higher age, disease activity, body composition parameters, and higher blood pressure values. We confirmed a higher CV risk as well as a higher prevalence of traditional risk factors in patients with IIM compared to the...
|
|
|
Prevalence and severity of sexual dysfunctions in patients with selected rheumatic diseases and the effect of specialized physiotherapeutic intervention on the sexual health of these patients
Heřmánková, Barbora ; Tomčík, Michal (advisor) ; Horák, Pavel (referee) ; Suchý, David (referee)
Introduction: Rare rheumatic diseases, such as systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), are severe autoimmune diseases characterized by multiorgan involvement and often significant functional impairment that are chronic and progressive in nature. Severe clinical manifestations of SSc and IIM are often associated with significant deterioration of all aspects of quality of life, including sexual function. Only a low number of studies have addressed sexual health in patients with SSc and IIM, which are limited by small sample size, the use of non-standardized scales, or poor methodological quality. In addition, none of the studies evaluated pelvic floor function and its relationship to sexual function in patients with these diseases. Objectives: The aim of this work was a cross-sectional evaluation of the prevalence and severity of sexual dysfunction and pelvic floor dysfunction in women and men with SSc and IIM compared to sex-/age-matched healthy controls (HC). Furthermore, we aimed to evaluate the association between sexual dysfunction/pelvic floor dysfunction and disease-related features. Finally, our goal within the pilot project was to evaluate the effect of an 8-week physiotherapy program on sexual function in women with SSc and IIM. Methods: This work consists of...
|
|
|
Selected aspects of methotrexate treatment in patients with rheumatoid arthritis
Hloch, Karel ; Pávek, Petr (advisor) ; Souček, Miroslav (referee) ; Tomčík, Michal (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Social and Clinical Pharmacy Doctoral Degree Program Clinical and Social Pharmacy Candidate MSc. Karel Hloch Supervisor prof. PharmD. Petr Pávek, Ph.D. Advisor assoc. prof. MUDr. Tomáš Soukup, Ph.D.; PharmD. Martin Doseděl, Ph.D. Title of Doctoral Thesis: Selected aspects of methotrexate treatment in patients with rheumatoid arthritis Introduction and objectives Rheumatoid arthritis (RA) is an autoimmune disease typically connected with chronic inflammation of the joints, causing their swelling and pain. The prevalence of RA is about 1% in the general population. A crucial role in higher morbidity and mortality in RA patients has been associated with increased inflammatory activity. Methotrexate (MTX), a drug with immunosuppressive activity, is the most frequent drug of choice used in RA therapy. It seems that main anti-inflammatory effect is mediated via release of purine nucleoside adenosine. The status of patients with inflammatory diseases is influenced by activation of A2a and A3 adenosine receptors. High caffeine (adenosine receptor antagonist) consumption may therefore lead to alteration of MTX treatment efficacy. 1) The aim of first study was to determine whether RA patients who had discontinued...
|
|
|
Body composition in patitents with systemic sclerosis
Česák, Michal ; Tomčík, Michal (advisor) ; Coufalová, Klára (referee)
Title: Body composition of patients with systemic sclerosis Objectives: The aim of this study was to compare selected parameters of body composition in patients with systemic sclerosis (SSc) with a group of age- and sex-matched healthy individuals (CG). Another objective was to evaluate the effect of selected clinical parameters in patients with SSc on the detected variability of the parameters of body composition and on physical activity of patients. Methods: The research group N = 95, group SSc (n = 59), control group (n = 36). Anthropometry (body height [cm], weight [kg], BMI [kg/m2 ]), bioelectrical impedance analysis - BIA 2000 (body fat - BF [%], total body water - TBW [%], lean body mass - LBM [kg], body cell mass - BCM [kg], BCM of FFM [%], the ECM / BCM); DEXA - Lunar Series iDXA (bone mineral density - BMD [g/m3 ], lean body mass - LBM [kg] body fat - BF [%], visceral fat - VF [kg] questionnaire on physical activity Human Activity Profile. Statistics: T test/Mann-Whitney U test, Cohen's d/partial eta squared (η2 ). Results: The results are presented as mean ± SD: body height: SSc 166.5 ± 7.1 cm, CG 171.2 ± 8.3 cm; body weight: SSc 62.4 ± 10.7 kg, CG 77.3 ± 11.9 kg; BMI: SSc 22.4 ± 4.3 kg/m2 , CG 26.4 ± 3.3 kg/m2 ; BF % BIA: SSc 24.6 % ± 7.8 %; CG 31.1 % ± 6.4 %; BF % DEXA: SSc 32.6 ± 8.2...
|
|
|
Selected aspects of methotrexate treatment in patients with rheumatoid arthritis
Hloch, Karel ; Pávek, Petr (advisor) ; Souček, Miroslav (referee) ; Tomčík, Michal (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Social and Clinical Pharmacy Doctoral Degree Program Clinical and Social Pharmacy Candidate MSc. Karel Hloch Supervisor prof. PharmD. Petr Pávek, Ph.D. Advisor assoc. prof. MUDr. Tomáš Soukup, Ph.D.; PharmD. Martin Doseděl, Ph.D. Title of Doctoral Thesis: Selected aspects of methotrexate treatment in patients with rheumatoid arthritis Introduction and objectives Rheumatoid arthritis (RA) is an autoimmune disease typically connected with chronic inflammation of the joints, causing their swelling and pain. The prevalence of RA is about 1% in the general population. A crucial role in higher morbidity and mortality in RA patients has been associated with increased inflammatory activity. Methotrexate (MTX), a drug with immunosuppressive activity, is the most frequent drug of choice used in RA therapy. It seems that main anti-inflammatory effect is mediated via release of purine nucleoside adenosine. The status of patients with inflammatory diseases is influenced by activation of A2a and A3 adenosine receptors. High caffeine (adenosine receptor antagonist) consumption may therefore lead to alteration of MTX treatment efficacy. 1) The aim of first study was to determine whether RA patients who had discontinued...
|
|
|
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,...
|
|
|
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...
|
|
|
Body composition in patitents with systemic sclerosis
Česák, Michal ; Tomčík, Michal (advisor) ; Coufalová, Klára (referee)
Title: Body composition of patients with systemic sclerosis Objectives: The aim of this study was to compare selected parameters of body composition in patients with systemic sclerosis (SSc) with a group of age- and sex-matched healthy individuals (CG). Another objective was to evaluate the effect of selected clinical parameters in patients with SSc on the detected variability of the parameters of body composition and on physical activity of patients. Methods: The research group N = 95, group SSc (n = 59), control group (n = 36). Anthropometry (body height [cm], weight [kg], BMI [kg/m2 ]), bioelectrical impedance analysis - BIA 2000 (body fat - BF [%], total body water - TBW [%], lean body mass - LBM [kg], body cell mass - BCM [kg], BCM of FFM [%], the ECM / BCM); DEXA - Lunar Series iDXA (bone mineral density - BMD [g/m3 ], lean body mass - LBM [kg] body fat - BF [%], visceral fat - VF [kg] questionnaire on physical activity Human Activity Profile. Statistics: T test/Mann-Whitney U test, Cohen's d/partial eta squared (η2 ). Results: The results are presented as mean ± SD: body height: SSc 166.5 ± 7.1 cm, CG 171.2 ± 8.3 cm; body weight: SSc 62.4 ± 10.7 kg, CG 77.3 ± 11.9 kg; BMI: SSc 22.4 ± 4.3 kg/m2 , CG 26.4 ± 3.3 kg/m2 ; BF % BIA: SSc 24.6 % ± 7.8 %; CG 31.1 % ± 6.4 %; BF % DEXA: SSc 32.6 ± 8.2...
|
|
|
New biomarkers and candidate molecules in antifibrotic therapy in systemic scleroderma
Štorkánová, Hana ; Tomčík, Michal (advisor) ; Javorková, Eliška (referee)
Systemic scleroderma (SSc) is a systemic connective tissue disease affecting skin and internal organs. The pathogenesis of SSc is characterized by inflammation, vasculopathy and fibrosis. No agent has been proven effective in the treatment of SSc. There is a lack of suitable biomarkers for monitoring the disease activity or the response to the treatment of SSc. Therefore our aim was to analyse the extracellular levels of S100A4, Hsp90 (Heat shock protein 90) and IL-35 (interleukin-35) in SSc. S100A4 and Hsp90 have been initially studied in tumours; in some of them considered as suitable prognostic markers and candidates for future therapies. We have recently described the profibrotic role of S100A4 and Hsp90 in the pathogenesis of SSc. Our results showed that inactivation of S100A4 and Hsp90 effectively prevented the development of experimental skin fibrosis. This was consequently confirmed by the analysis of S100A4 and Hsp90 in the peripheral blood of patients with SSc, where significant associations with disease activity and organ involvement were detected. IL-35 may become another potential biomarker of SSc. We detected increased expression of IL-35 in the affected skin, dermal fibroblasts and in serum of patients with SSc. Moreover, the main profibrotic mediator transforming growth factor...
|
|
|
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,...
|
guest ::
