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Local steroidogenesis in peripheral tissues and its regulation
Langová, Veronika ; Ergang, Peter (advisor) ; Hudcovic, Tomáš (referee)
The innate and adaptive immune processes are modulated by hormones including glucocorticoids and by microbiota. The exact mechanisms underlying the microbial and hormonal contributions to this control are not completely clear. Present study is therefore focused to crosstalk between microbiota and de novo biogenesis or local regeneration of glucocorticoids. In particular, the study analysed the effect of commensal microbiota on expression of genes encoding steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp21a1, Cyp11b1) and regeneration of glucocorticoids (Hsd11b1) in adrenal glands, colon, spleen and mesenteric lymph nodes using conventional and germ-free mice. The expression of all 5 components of steroidogenesis was identified only in the adrenal gland and colon, whereas the lymphoid organs expressed predominantly Star, Cyp11a1 and Hsd3b1 indicating the ability to produce only progesterone but not corticosterone. Microbiota decreased the expression of Star in all studied tissues but the expression of other genes was insensitive to microbiota or did not respond homogenously depending on the tissue and gene. Hsd11b1 expression was upregulated by microbiota in the spleen but not in other tissues. Similarly, the in vitro treatment of immune cells isolated from mesenteric lymph nodes by microbial...
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MicroRNA expression in glucocorticoid-treated patients with systemic autoimmune
Uher, Martin ; Kuchařová, Monika (advisor) ; Nováková, Veronika (referee)
Rheumatoid arthritis is the most common joint disease of autoimmune origin. It is accompanied by inflammatory conditions that lead to irreversible changes in the joints, their deformities ending with permanent disability. Treatment of the disease involves routine regimens, surgical, as well as pharmacological treatment, which is necessary for advanced forms. Glucocorticoids play an important role in the therapeutic intervention in the course and progression of the disease. In spite of their anti-inflammatory effect, which is a key to improving the condition of the patient, they have a number of side effects in the long term- use. In this study, we have focused on the impact of these drugs on microRNA expression changes in arthritic patients treated with pulsed doses of glucocorticoids. MicroRNAs are nowadays widely studied due to their possible use as biomarkers in monitoring disease progression and the effect of treatment. MiRNA expression analysis was performed by quantitative real-time PCR array of 754 miRNAs with reverse transcription using stem-loop primers that allow amplification of short sequences that microRNAs are. Data analysis revealed 29 miRNAs differentially expressed at the significance level p ≤ 0.05, 14 miRNAs were at significance level p ≤ 0.025 (respectively 7 miRNAs at p ≤ 0.005...
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MicroRNA expression in glucocorticoid-treated patients with systemic autoimmune
Uher, Martin ; Kuchařová, Monika (advisor) ; Nováková, Veronika (referee)
Rheumatoid arthritis is the most common joint disease of autoimmune origin. It is accompanied by inflammatory conditions that lead to irreversible changes in the joints, their deformities ending with permanent disability. Treatment of the disease involves routine regimens, surgical, as well as pharmacological treatment, which is necessary for advanced forms. Glucocorticoids play an important role in the therapeutic intervention in the course and progression of the disease. In spite of their anti-inflammatory effect, which is a key to improving the condition of the patient, they have a number of side effects in the long term- use. In this study, we have focused on the impact of these drugs on microRNA expression changes in arthritic patients treated with pulsed doses of glucocorticoids. MicroRNAs are nowadays widely studied due to their possible use as biomarkers in monitoring disease progression and the effect of treatment. MiRNA expression analysis was performed by quantitative real-time PCR array of 754 miRNAs with reverse transcription using stem-loop primers that allow amplification of short sequences that microRNAs are. Data analysis revealed 29 miRNAs differentially expressed at the significance level p ≤ 0.05, 14 miRNAs were at significance level p ≤ 0.025 (respectively 7 miRNAs at p ≤ 0.005...
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Impact of glucocorticoid treatment on musculosceletal system of pediatric patients with acute lymphoblastic leukemia.
Petráčková, Karolína ; Jevič, Filip (advisor) ; Šrámková, Lucie (referee)
This bachelor thesis aims to provide a general overview of complications of musculoskeletal system in pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) undergoing chemotherapy treatment involving high cumulative doses of glucocorticoids. Musculoskeletal complications include steroid myopathy, osteonecrosis and reduced bone mineral density. The first part describes their basic pathophysiological mechanisms and the risk factors of their origin. The second part presents the current possibilities of muscle strength assessment and available exercise programs. Furthermore, diagnosis of osteonecrosis and bone mineral density are presented together with current possibilities of therapeutic intervention. The thesis also covers characteristics of muscle strength measuring methods and exercise programs along with presentation of the results of individual studies. In the discussion part, there are broken down the limits, advantages and disadvantages of using the muscle strength measuring methods and exercise programs in clinical practice.
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Influence of corticosteroids and movement disorder on development of osteoporosis in patients with multiple sclerosis (MS)
Týblová, Michaela ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Taláb, Radomír (referee)
Introduction: Multiple sclerosis (MS) is associated with impaired bone health in comparison to an equally healthy population, even already in patients at the onset of this disease. The main risk factors for development of osteoporosis in MS patients are known. The aim of the study was to find the relationship of the decrease in bone mineral density (BMD) to the administered cumulative dose of steroids and to other risk factors in MS, mainly to the degree of motor deficit. Further goal was to evaluate the occurence of the risk of low-trauma fractures in multiple sclerosis patients.. The BMD and muscle mass was compared in MS patients (women and men) and control subjects, to examine the effect of main ones - physical disability and long-term glucocorticoid (GC) therapy on BMD. Clinical values of bone remodeling markers were evaluated in assessment of rate of bone loss in patients with multiple sclerosis long term treated with low dose of GC. Patients and methods: We used dual -energy X-ray absorptiometry for a measurement of BMD in 591 MS patients (455 females and 136 males) in 2004 and in cross-sectional longitudinal study published in 2014 with 474 patients (353 women and 121 men). Out of the whole study group body composition was evaluated in 250 MS females, 104 males and 247 healthy controls (193...
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Effect of elevated levels of corticoid hormones on child growth and bone tissue
Brusová, Adéla ; Sedlak, Petr (advisor) ; Zemková, Daniela (referee)
The Bachelor's thesis deals with the elevated level of glucocorticoid hormones and their effect on bone tissue. In particular, reasons which cause hypercorticoisms in human body genetic diseases, tumors, autoimmune diseases, and so forth, are described in detail. Asthma and other diseases are treated by glucorticoid and increase hypercorticoism. This autoimmune disease are treated by glucocorticoid and increase the hypercorticoism. Therefore, this thesis focuses on research process consists of multiple scientific studies including the impact of glucocorticoid hormones on bone tissue, endocrine system hypothalamus-hypophyse-IGF-I and influence of endocrine system on child's growth. The main benefit of the Bachelor's thesis is the description of the outcome of inhalation glucocorticoid hormones on body height in childhood.
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Effect of elevated levels of corticoid hormones on child growth and bone tissue
Brusová, Adéla ; Sedlak, Petr (advisor) ; Zemková, Daniela (referee)
This Bachelor's thesis examines the effect of elevated level of corticoid hormons on growing organism. The negative effect of glucocorticoid hormones and their derivates is evidenced especially on child growth and growth of bone density. Primary source of the elevated level of corticoids in organism are medicaments. The anti-inflammatory and immunosuppressive effects of the glucocorticoids are used in medical treatment of various diseases (infections, chronical diseases - especially GIT, autoimmune diseases etc.). The rare source of the hypercorticoidism in childhood are hormonally active tumors (the tumor of the adrenal cortex). The main part of the Bachelor's thesis deals with impact of long-term inhalation of glucocorticoid hormones on body height and quality of bone tissue of the patients with astma bronchiale.
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Bone remodeling in rheumatic diseases: Bone loss in juvenile idiopathic arthritis
Brábníková Marešová, Kristýna ; Štěpán, Jan (advisor) ; Blahoš, Jaroslav (referee) ; Hrnčíř, Zbyněk (referee)
Introduction: The inflammation plays the essential role in the bone loss in juvenile idiopathic arthritis (JIA). Proinflammatory cytokines and also glucocorticoids (GCs) may activate bone resorption by osteoclasts. Simultaneously, bone formation can be attenuated, especially by inhibitors of proteins, which control the osteoblast differentiation. The aim was to verify the hypothesis that in patients with highly active JIA, reduction of bone formation via Wingless (Wnt) proteins inhibitors - Dickkopf 1 (Dkk-1) and sclerostin could be found. Except the densitometry measurements of bone and lean mass, we assessed markers of disease activity, bone metabolism and remodeling in young adult patients with JIA before and during 2 years of anti TNFα (tumour necrosis factor α) treatment, which decreases disease activity. Results: In patients with JIA before antiTNFα treatment, bone mineral density (BMD, g/cmš) was significantly reduced compared to controls. Values of BMD and body composition in JIA significantly depended on disease duration and GCs treatment. Serum concentration of sclerostin was significantly elevated in JIA compared to values in healthy controls. Values of the other monitored markers did not differ between JIA and controls. In patients with JIA, Dkk-1 correlated positively with C-reactive...
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