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Clinical Applicability of Cognitive Testing in Huntington Disease
Mühlbäck, Alžbeta ; Klempíř, Jiří (advisor) ; Rusina, Robert (referee) ; Horáková, Hana (referee)
Introduction: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder manifested by motor, behavioural and cognitive deficits with fatal consequences. Aims: This study aims to validate the psychometric properties of a standard cognitive battery used in HD and establish language-specific normative values. Methods: In the first study, cognitive performance was compared in 106 patients at different stages of HD and 100 healthy controls matched for age, sex, and education. The neuropsychological battery included the Symbol Digit Modalities Test, Stroop Word Reading Test, Stroop Colour Naming Test, Stroop Interference Test, Trail Making Test-A and B, Category and Letter Verbal Fluency. In addition, patients were comprehensively assessed for motor and functional status. In the second study, the cognitive performance of 3,267 healthy subjects was assessed. The work focused on the stratification of cognitive performance concerning age, gender, language and level of education. Another aim was to establish the language-specific normative values and implement a web-based normative calculator to assess the degree of cognitive deficit in different languages (English, German, Spanish, Italian, Polish, French, Dutch, Danish). Results: In the first study, analysis of variance showed that healthy...
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Nutritional disorders in patients with Huntington's disease
Procházková, Tereza ; Klempíř, Jiří (advisor) ; Kosheleva, Svetlana (referee)
OF THE BACHELOR THESIS This thesis deals with the issue of nutritional disorders in Huntington's disease. Huntington's disease is an incurable, neurodegenerative, autosomal dominant inherited disease. The prevalence of Huntington's disease in Western society is 10.6-13.7 / 100,000 individuals. The disease is manifested by disorders of free motor control, speech, swallowing, postural instability, cognitive deterioration and various behavioral changes. An integral part of the disease is unwanted weight loss. In the various stages of the disease, the causes of the development of nutritional disorders may differ and combine with each other. In the theoretical part, the chapters are devoted to the etiology and pathogenesis, pathology, clinical manifestations, forms and stages of the disease, nutritional disorders and their classification, methods of nutritional status examination and specific causes of nutritional disorders that occur in each stage of the disease. A special chapter focuses on the classification of nutritional disorders according to the European Society for Clinical Nutrition and Metabolism, which was applied in the research. The practical part aims to examine the nutritional status and evaluate eating habits in a group of patients with Huntington's disease through clinical and...
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Sarcopenia in patients with Huntington's disease
Šoltésová, Mária ; Klempíř, Jiří (advisor) ; Růžičková, Lucie (referee)
Introduction: This cross-sectional, non-interventional, non-randomized, prospective and observational study aims to determine whether sarcopenia and its types occur in a cohort of 16 patients with Huntington's disease and, if so, at which stages of the disease. The study also aspives to identify patients with Huntington's disease who are at risk of sarcopenia (so-called presarcopenia). In addition, the study also compares the results of nutritional and functional status tests between a group of patients and healthy controls who were of the same sex, age and with no further acute or chronic disease that could significantly affect their nutritional and functional status. This was done to determine to what extent the patients exhibit reduced nutritional and functional parameters as compared with the healthy population. Methods: Individuals with clinically diagnosed Huntington's disease who agreed to participate were recruited. These individuals are outpatients of the Department of Neurology, VFN in Prague and the 1st Faculty of Medicine, Charles University in Prague. A series of tests were performed to assess the nutritional and functional status of the individual - questionnaires of functional status, self-sufficiency and sarcopenia, bioimpedance testing, strength tests using a hand dynamometer and...
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Monitoring of the development of the Huntington's disease in transgenic minipigs with N-terminal part of human mutated huntingtin: biochemical and motoric changes of F0, F1 and F2 generation
Kučerová, Šárka ; Ellederová, Zdeňka (advisor) ; Klempíř, Jiří (referee)
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...
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Nutritional Status in Patients with Huntington's Disease and Nutritional Support
Kosheleva, Svetlana ; Klempíř, Jiří (advisor) ; Růžičková, Lucie (referee)
Huntington's disease is a dominantly-inherited autosomal neurodegenerative disease manifested by disorders of motility, cognitive function, behaviour, and weight loss, which is conditioned multifactorially. The aim of the study was to determine whether there are eating disorders in Huntington's disease, as well as its etiology and severity. Neurological scaling, anthropometric examinations, evaluation of three-day diet records, measurements with a manual dynamometer, bioimpedance analyses, indirect colorimetry and predictions of energy expenditure were performed on 10 patients. Algorithms were applied for the diagnosis of sarcopenia and malnutrition. Unwanted weight loss was observed in all patients and 4 out of 10 showed malnutrition. No difference was found between the values of measured resting metabolism and calculated according to the predictive equation. However, it has been shown that strict nutritional recommendations based on this data can be misleading for some patients with HN, as real energy consumption can be significantly higher. All our patients had a positive energy balance. A new diagnostic algorithm for the early diagnosis of sarcopenia has proven its worth. Using bioimpedance analysis and examination of the force of the handshake, we identified possible sarcopenia and already-present...
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Following the phenotype development of TgHD minipigs by invasive and noninvasive approach
Ellederová, Zdeňka ; Baxa, Monika ; Vidinská, Daniela ; Bohuslavová, Božena ; Vochozková, Petra ; Šmatlíková, Petra ; Klíma, Jiří ; Valeková, Ivona ; Ardan, Taras ; Juhás, Štefan ; Juhásová, Jana ; Konvalinková, R. ; Klempíř, J. ; Pokorný, M. ; Krupička, R. ; Kauler, J. ; Hansíková, H. ; Motlík, Jan
Recent promising treatments for Huntington’s disease (HD) may require pre-clinical testing in large animals. In 2009, we generated HD transgenic (TgHD) minipigs with one copy encoding the N-terminal part (548 aa) of human huntingtin (HTT) with 124 CAG/CAA repeats integrated into chromosome 1 q24-q25. The successful germ line transmission occurred through four successive generations.
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Monitoring of the development of the Huntington's disease in transgenic minipigs with N-terminal part of human mutated huntingtin: biochemical and motoric changes of F0, F1 and F2 generation
Kučerová, Šárka ; Ellederová, Zdeňka (advisor) ; Klempíř, Jiří (referee)
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...
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Protein analysis of selected mitochondrial proteins in the muscle tissue of porcine model of Huntington's disease
Dosoudilová, Žaneta ; Klempíř, Jiří (advisor) ; Baxa, Monika (referee)
Huntington's disease (HD) is an autosomal dominant hereditary neurodegenerative disease characterized by motor, cognitive and behavioral disorders. HD is caused by expansion of CAG triplet (cytosine-adenosine-guanine) located in a gene on the short arm of the fourth chromosome. This expansion encodes an aberrant polyglutamine chain in the protein huntingtin. Physiological and mutated huntingtin (in case of HD) are expressed in almost all tissues and influences many cellular functions. The prevalence of HD in population is about 1 per 10.000. The disease is currently incurable and its mechanisms are not sufficiently understood. Besides affecting the central nervous system HD also affects peripheral tissues, including skeletal muscles. HD disrupts mitochondrial function and damages oxidative phosphorylation system, which has the task of producing energy in the form of ATP in cells. Research of transgenic minipig model for HD could help elucidate the mechanisms of disease's pathogenesis and potential therapeutic strategy. In this diploma thesis, immunodetection with help of specific antibodies to detect changes in amount of 14 selected mitochondrial proteins in skeletal muscle tissue of three age groups of transgenic HD minipigs - 24, 36 and 48 months old was used. Gradual progression in reduced...
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