Huntingtons's disease (HD) is devastating neurodegenerative disorder manifesting by motor disturbances, cognitive decline and personal changes. The huge effort to find a cure for HD has brought several promising therapeutic treatments on the scene. Each of the prospective approaches needs to be investigated for safety, tolerability and efficacy. Mouse and rat models were a lot helpful in examination of pathological mechanisms of HD, but they are not sufficient for completion of pre-clinical testing. Therefore, we aimed to generate transgenic HD minipig to overcome the gap between rodents and humans. Minipig transgenic for the first 548 aminoacids of human mutant huntingtin gene (TgHD) under the control of human HD promotor was manipulated by lentiviral transduction of porcine one-cell stage embryos. Currently, six generations of minipigs expressing single copy of N-truncated human mutant huntingtin protein (mtHtt) with a repetition of 124 glutamines are at disposal. The more the model simulates the disease symptoms the better it is for translational research as the efficacy of the cure can be finer evaluated. Hence, the second aim was to demonstrate HD-like phenotype in our model. Testicular degeneration that preceded the clinical symptoms onset was observed as a consequence of expression of mtHtt....

Alzheimer's disease is a chronic, progressive, neurodegenerative disease. It belongs to the most common type of dementia and worldwide it is statistically the fifth cause of mortality. The most common morphological markers are insoluble β amyloid plaques, hyperphosforylated tau proteins and formation of neurofibrilar tangles. Among the manifestations of the disease is amyloid angiopathy, synaptic transmission disorders and subsequent apoptosis, deterioration of cognitive functions and brain atrophy. Studies have shown that administration of mesenchymal stem cells (MSC) has an immunomodulatory effects and it can reduce the production and storage of β amyloid and thus improve cognitive functions. In preclinical studies, which are conducted in transgenic mice and often use xenografts, administration of immunosuppresion may lead to variety of positive or negative effects which can affect the results of the experiment. The subject of the master's thesis was to determine the effect of immunosuppression on experimental therapy with MSC in various time windows of AD progression (model 3xTg). At which scale and combination of immunosupression will influence the cell therapy's effects, the length of graft survival, mortality of experimental animals and changes at the cellular level. We have also assessed...

This thesis is focused on evaluation of the education of social workers in social services who work with patients who suffer the Alzheimer's disease. It is concretely about workers who do the direct service care within the special regime homes in Plzeň Region. The thesis consists of the theoretical and empiric parts. The theoretical part includes the description, symptoms and phases of the disease. It talks about forms and availability of those services for specific needs of people with dementia in Plzeň Region. The important chapter is concentrated on education of social workers with relation to the legislative area of education, its planning and realization, the training courses for the social workers with the direct care. The empiric part evaluates the training courses for the social workers and the way which are selected. For finding of the answers was used questionnaire rating, the aim was to evaluate the training courses from the point of view of social workers. How are these courses chosen was discussed with executives in the form of a semi-structured interview. These executives coordinate the education of social workers in these special regime homes. The research took place in 10 deliberately selected special regime homes. The conclusion of this research indicates that social workers...

Author: Bc. Anežka Zasadilová Title: The effect of physiotherapy on patients with gastroesophageal reflux disease Objectives: The aim of this thesis is to design a therapeutic unit and evaluate its effect on long-term treatment in the therapy of selected patients with gastroesophageal reflux disease Methods: The group of patients treated for esophageal reflux disease was examined using a standardized questionnaire, esophageal manometry and postural tests. This was followed by a two-month therapy aimed at stretching and strengthening the diaphragm using several physiotherapeutic methods. After completing the therapy, the probands were measured again as in the same way as in the initial examination. The obtained data were evaluated by statistical analysis using a nonparametric test for one selection (Wilcoxon test). Results: The evaluation of the questionnaire survey resulted in the value of p-value = 0.007265, ie less than the selected level of alpha significance (= 0.05). Based on the Wilcoxon test, it was confirmed that the input score was statistically significantly higher than the output score. The evaluation of the esophageal manometry gave the value of p-value = 0.6956, ie greater than the selected level of significance alpha (= 0.05). Based on the Wilcoxon test, it was not confirmed that the...

Huntington's chorea is a dominantly inherited disease caused by trinucleotide (Cytosine-Adenine -Guanine) expansion in a gene coding huntingtin protein. Carriers of these mutation show symptoms associated with motor impairment, a cognitive and psychiatric disturbance, which is called Huntington's disease (HD). The major sign of HD is striatal atrophy in the middle age of life. Since it is known that huntingtin protein participates in a lot of cellular processes, such as transcriptional regulation and metabolism, these processes change by its mutation. One of the features observed in HD pathogenesis is the presence of oxidative stress. The aim of the work was to monitor the molecular changes preceding the HD manifestation in the knock-in minipig model. As a material for monitoring molecular changes leading to this condition, primary fibroblasts were used. Whereas, the oxidative stress arises from an imbalance between oxidants and antioxidants, level of reactive species and lipid peroxidation together with expression of antioxidant response associated genes was measured. At the same time, expression of metabolic and DNA repair related genes was monitored. Although the differences in oxidative stress level or the expression of antioxidative response genes were not detected, the changes in the...

The causative role of the huntingtin (HTT) gene in Huntington's disease (HD) has been identified more than 25 years ago. The extension of CAG repeat stretch over 39 repeats in exon 1 of one HTT allele results in full penetrance of this neurodegenerative disorder. While the identification of the causative mutation raised hopes that development of the therapeutic compound will be easily achievable, the patients and their families are still waiting for treatment until now. The main reason for that might be the complex cellular function HTT that makes the determination of the pathologic mechanism difficult and the development of treatments even more challenging. Although a lot of different animal models have been generated until now, establishing a suitable model has still not been achieved yet. Due to its anatomy, physiology, and genetics, the minipig seems to be a suitable candidate for neurodegenerative disease models. Indeed, the existing Transgenic (Tg) Libechov minipig model manifests signs typical for HD in patients, but on the other hand significant inconsistencies have also been observed. The finding of malformation that partially shows the situation in human patients is true for both, the male reproductive tract as well as for the brain. The reason for this might be the fact the genetic...

Optimization of biologic therapy in children with inflammatory bowel disease (IBD) using modern biomarkers Abstract to thesis Study programme: Biochemistry and Pathobiochemistry Introduction: In adults, infliximab (IFX) levels correlate with disease activity and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in paediatric population. Methods: This study was performed as a prospective observational study. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). We used multivariate analysis to identify the predictors of IFX levels. IFX and ATIs levels were meassured using ELISA. Results: Lower levels of IFX were associated with ATIs positivity (OR [odds ratio] 0.027, CI [confidence interval] 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) and CPT levels were found in patients with lower IFX levels. The optimal combination of specificity (50%) and sensitivity (74%) for disease activity was calculated for IFX levels ≥ 1.1 µg/ml using CRP level < 5 mg/l as a marker of laboratory remission. In a model that used CPT ≤...

Obesity is very widespread and detrimental to health. Obesity brings with it many changes including heightened immune function, and a higher prevalence of major cardiovascular disorders, cancer, diabetes, and Alzheimer disease. Obesity is also associated with shortened lifespan. The detrimental effects of obesity are linked to the "metabolic syndrome", a broad range of changes in metabolic processes and immune function. As a first approximation, we agree with this formulation but we will then proceed to document some of its weaknesses. (i) Crude mortality rates increase with increasing body mass index (BMI) but as the BMI approaches the normal range, mortality rates reverse (the now classic "J-shaped curve") so that individuals with reduced BMI have elevated mortality. (ii) A multiplicity of medical and surgical conditions have been reported where short term and medium term outcomes are better for overweight patients. These conditions are placed under the heading of "obesity paradox". (iii) The medical community has introduced a binary system for the metabolic syndrome ---- yes, patient has it or no, the patient does not have it, despite the fact that all of the changes that are considered components of the metabolic syndrome are continuous variables. Our work is focused on sharpening focus and improving...

The institute of preventive detention is a new protective measure in our penal law. The theme of this thesis is an analysis of the comission and goals of the new protective measure and focusing on a comparation of theoretical and practical function of this protective measure. The folowing chapters provide the characterization of the preventive detention and its legal framework in the Czech republic. The component part of the thesis is also a description of the preventive detention in a legal framework of other state, concretely Slovakia. At the end of the work there are explicated knowledges obtained during the visit of the Institute for preventive detention Brno. In this chapter not only functional equipment is described but also the compositon of the inmates and employees and their most important competencies. Programms, by which are the medical goals fullfiled are described at the end of the thesis.

This diploma thesis with the management of health support program in a hospital, because of increesing interest in relevance of health support nowadays. Theoretical section attempts to map out health supportin global context and also outline some health support programs, which are in progress in Czech Republic today. Another goal is to specify the most frequent noncommunicable chronic deseases and their risk factors. The last part of theoretical section deals with quality of health care, implementation of quality management and quality planning and also highlits quality as a result of modification of management process. Practical section analyzes data from questionaire survey, colected from in-patients with ischemic heart disease in The Hospital Pelhřimov. Results show, that patients wanted to change their life style. There is also a big group of patients, who don't think of changes of their habits. But this group is interested in informations about changes of their life style. The informations are provided by physicians. As for this group, group consists of patients with overweight or obesity, and patients who are suffering from their disease less then one year. Level of provided information in The Hospital Pelhřimov is very high. Patients are able to realise recommendations, which personal of the...