The number of rheumatic diseases has been increasing in Europe. It is estimated that currently up to a quarter of Europeans suffer from some type of rheumatism. Rheumatoid arthritis and Bechterew's disease (ankylosing spondylitis) are chronic diseases manifested by pain, stiffness, inflammation of joints and the back. The theoretical section is divided into two parts; the first part defines rheumatoid arthritis and Bechterew's disease from the health point of view. The second part is devoted to the social area that is often neglected. The aim of the practical section of the thesis is to reveal how rheumatoid arthritis differs from Bechterew's disease in terms of the use of social assistance, as well as employability or participation in social life. For the data collection, qualitative research methods and interviewing techniques were used. The addressed respondents were patients of rheumatology consulting rooms of the Medipont Plus Ltd., who were divided into two groups ? patients with rheumatoid arthritis and those with Bechterew's disease. The research has shown that persons suffering form rheumatoid arthritis are more likely to get a disability pension than those with Bechterew's disease and they also more often use social contributions, most frequently the extra benefits for people with disabilities ? ZTP cards. This is related to a lower work capability in patients with rheumatoid arthritis compared to those with Bechterew's disease. The research results are influenced by the age of the respondents, the length of the illness, the difference in the roles of men and women and last but not least, by personality characteristics. The research has proved that patients suffering from rheumatic diseases as well as those suffering from Bechterew's disease and undergoing biological treatment are more self-sufficient due to this modern treatment. It has also been found that the respondents who are not fully self-sufficient are not informed about the possibilities to get social benefits and contributions and do not know where to get this information. The thesis could provide an impetus for the strategy when rheumatic diseases are not considered only a medical issue, because these diseases significantly influence the lives of the people affected and thus become a serious psychosocial issue.

CMT disease is the most frequently type of the hereditary polyneuropathy. In the Czech republic are some 2 - 4 thousand people with this disease. Clinical picture is characterized by deterioration peripheralnerves, that faces to muscular atrophy and mobility disorders. Lower limbs are affected early than upper limbs. On the lower extremitywe observe typical deformity progress - pes cavus. Fingers on the hand are in claw position. The disturbed peripheral nerves and foot deformity affect balance, movement and stability. The scope of my work was assessment of the value of the Vojta's reflective locomotion for the hereditary polyneutopathy. Powered by TCPDF (www.tcpdf.org)

Rýdlová Kateřina: Alkaloids Narcissus 'Dutch Master' (Amaryllidaceae) and their biological activity III. Diploma thesis 2017. Charles university in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology. The aim of this work was isolation of compounds from the selected fraction ND 3 - 5 obtained by column chromatography of a Narcissus 'Dutch Master' alkaloid extract. Preparation of the extract and its column chromatography was performed by Mgr. Daniela Hulcová as a part of her doctoral study. Two substances NDM-1 and NDM-2 were isolated from fraction ND 3 - 5 by column chromatography and preparative TLC. The structures were determined as (+)-masonine and (+)-homolycorine on the basis of NMR, GC-MS analysis, optical rotation and their comparison with literature data. Isolated alkaloids were tested on inhibitory activity against human erythrocyte acetylcholinesterase, plasma butyrylcholinesterase and prolyloligopeptidase. Activity of alkaloids was expressed as IC50 values: (+)-masonine (IC50 AChE = 305 ± 34 μM, IC50 BuChE = 229 ± 24 μM, IC50 POP = 314 ± 34 μM), (+)-homolycorine (IC50 AChE = 63.7 ± 4.3 μM, IC50 BuChE = 151 ± 20 μM, IC50 POP = 173 ± 41 μM). In comparison with standards of galanthamine (IC50 AChE = 1.710 ± 0.1 μM, IC50 BuChE = 42.3 ± 1.3 μM),...

Numerous epidemiological and experimental studies have shown that patients suffering from metabolic disorders such as type 2 diabetes mellitus (TDM2), insulin resistance or obesity are at a higher risk of cognitive functions impairment and developing Alzheimer's disease (AD). Impairment of insulin signalling in the brain could contribute to two pathological changes which leads to AD development that include insoluble senile plaques and neurofibrillary tangles, containing an abnormally hyperphosphorylated tau protein (Tau). This work is focused on investigating of insulin signaling in hippocampi in the brains of mice models of insulin resistence, impact of disturbed insulin signaling on hyperphosphorylation of Tau, and possible benefical efect of insulin sensitizing agents on insulin signaling and Tau phosphorylation in the hippocampi of diabetic mice. The first, we examined insulin signaling and phosphorylation of Tau in hippocampi in two mouse models of TDM2 - lipodystrofic A-ZIP F-1 mice and monosodium glutamate obese mice (MSG mice). We did not observe any changes in insulin signaling and Tau phosphorylation in hippocampi of A-ZIP F-1 mice compared to controls. In the hippocampi of MSG mice there was attenuated phosphorylation of kinases of insulin signalling including Ser9 of glycogen synthase...

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Gabriela Kocurová Supervisor: Prof. MUDr. Jaroslav Dršata, CSc. Title of diploma thesis: Investigation of proteolytic enzymes expression in different tissues at the transgenic animal model of Huntington's disease by means of biochemical and immunohistochemical methods Background: Huntington's disease (HD) is a neurodegenerative disorder that is caused by an expansion of a polyglutamine (polyQ) domain in the huntingtin (Htt) protein. Because it is known that mutant Htt and especially its small proteolytic fragments are toxic to neurons (particularly those in the striatum and cortex), it has been suggested that proteolysis of mutant huntingtin (mHtt) might play an important role in HD pathogenesis. Therefore, the aim of the present study was to examine the expression of endogenous and mtHtt and possible participation of the proteolytic enzymes from the group of caspases, matrix metalloproteinases (MMPs), kallikreins (KLKs) and calpains in HD pathology of brain tissue. Methods: In this study we used WT and TgHD minipigs for N-terminal part of the human mtHtt (548aaHTT-145Q, both F2 generation, age 36 months; F3 generation, age 48 months in additional experiment), R6/2 mice were used as...

Gut microbiota is considered an important factor in the development of various diseases including inflammatory bowel disease (IBD, n = 127), Ulcerative colitis, Crohn's disease, and colorectal cancer (CRC, n = 64). A part of this thtesis is to prepare clinical material of different sorts (stool, biopsy) for sequencing on Illumina Miseq platform. This is achieved trough DNA isolation, amplification of 16S and internal transcribed spacer (ITS), normalization and ligation of sequencing adaptors. The aim of this project is to describe the differences between microbiota in healthy and diseased subjects in case of IBD or unimpaired and tumorous tissue for CRC patients. This research is also being based on cultivation, where a fresh stool samples (n = 3) are cultivated in a broad range of conditions, which enables us to obtain ecophysiological and species diversity of these samples by traditional and molecular methods. The cultivable fungi are also assigned reliable taxonomy by amplification of relevant genes (ITS1, β tubulin, second largest subunit of RNA polymerase II, RPB2) followed by both-sided Sanger sequencing. Selected species of fungi are processed into lysates, which are used for stimulation of mice macrofage cell line (RAW). Therefore the impact on immunity response is studied in vitro and...

Huntington's disease (HD) belongs to neurodegenerative disorders. It is a monogenic disease caused by trinucleotic CAG expansion in exon 1 of gene coding protein huntingtin. Even though the cause of HD is known since 1993, the pathophysiology and cure for HD reminds to be found. The animal models are being used for better understanding of HD. The most common animal models for HD are rodents, especially mice but it was also important to create large animal models, which will be more like human. Therefore, TgHD minipig was created in Academic of Science in Liběchov in 2009. This model was created by microinjection of lentiviral vector carrying N-terminal part of human HTT with 124 repetitive CAG in exon 1. This model is viable and in every generation, is part of the offspring transgenic. In this thesis, I specialized to biochemical and behavioral changes of this model. I compared transgenic and wild type siblings. I found that biochemical changes are manifested mostly by increased level of mtHtt fragments in testes and brain. In behavioral part of this thesis I established new methods for testing behavioral changes in this model. The introduced methods showed some changes between wild type and transgenic animals at the tested ages but these changes were not significant due to the low number of...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Tereza Červinková Supervisor: PharmDr. Lukáš Červený, Ph.D. Title: Beneficial Effects of 11β-HSD1 Inhibition on Cognitive Performance in a Mouse Model of Alzheimer's Disease The increased life expectancy goes hand in hand with ageing-related cognitive impairments. Alzheimer's disease (AD) is the most common type of dementia being an irreversible and progressive brain disorder with loss of cognitive functions. Recent studies suggest that excess of glucocorticoid (GC) action exerts deleterious effects on the hippocampus and causes impaired spatialmemory. In addition, it has been demonstrated that aged mice with cognitive deficits show increased gene expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the hippocampus and parietal cortex. The Senescence-Accelerated Mouse Prone 8 (SAMP8) strain is a spontaneous animal model of accelerated ageing. Many studies indicate that SAMP8 harbour the behavioural and histopathological signatures of AD. In the present study, we evaluated the neuroprotective effects of 11β-HSD1 inhibition by a potent pyrrolidine-based compound RL-118 and/or effects of diet on cognitive performance in different groups of SAMP8 by conducting behavioural and...

Huntington's disease (HD) is inherited fatal disorder caused by CAG triplet expansions in the huntingtin gene resulting in the expression of mutated huntingtin protein (mtHtt). The main symptoms of HD are neurodegeneration, osteoporosis, testicular degeneration, loss of muscle tissue and heart muscle malfunction, weight loss, metabolic changes, and sleeping disturbances. Since huntingtin protein (Htt) has a role in several biological processes, many molecular mechanisms, like oxidative stress, mitochondrial dysfunction, DNA-damage, and others, are affected by mtHtt. However, its exact pathogenic mechanisms in HD are still not well understood. Transgenic minipig model of HD (TgHD) serves an opportunity to isolate unlimited number of primary cells and unlike primary cells obtained from HD patients, often in the late stages of the disease, the TgHD minipig model allows to monitor molecular changes occurring gradually with age and progression of the disease. Thus, TgHD minipig model and primary cells isolated from it play an important role in investigating and understanding the underlying mechanistic cause of HD. We focused on molecular and cellular changes in primary cells isolated from TgHD minipigs and their wild type (WT) controls at different ages (24, 36, and 48 months). In mesenchymal stem cells...

5 ABSTRACT This thesis is focused on examining quality and range of care services for people with dementia and their family carers in the region of Ústí. Through the testimony of nine respondents provides a view of social awareness about this diagnosis. It also focuses on providing information of possibilities of prevention, medical treatment and social care that is currently available. Last but not least it deals with possibilities of development of the services within this area. Key words: Alzheimer disease, dementia, social services, healtcare services, family care.