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The role of accumulation of iron and other metals in the pathophysiology of neurodegenerative diseases
Mašková, Jana ; Dušek, Petr (advisor) ; Vymazal, Josef (referee) ; Bártová, Petra (referee)
The role of metal accumulation in the pathophysiology of neurodegenerative diseases has been a hot topic in recent years due to the possibility of its treatment by chelating agents. Although the mechanisms of neurodegeneration are well known, the role of metal accumulation is still unclear. The main limitation are unsatisfactory methods for in vivo metal imaging; the most widely used technique is magnetic resonance imaging (MRI). Our aim was to assess the possibility of using transcranial sonography (TCS) in differential diagnosis of neurodegenerative diseases and to further explore the underlying factors of echogenicity. In the first study, using TCS fusion with MRI, we focused on location verification of the commonly assessed structures (substantia nigra and nucleus lentiformis) and exclusion of possible focal structural changes affecting the echogenicity in WD and PD patients. Moreover, obtained MRI were used for semi-quantitative comparison with TCS images. Although TCS has been confirmed to be highly beneficial in differential diagnosis of Wilson's disease and it should be recommended as a screening method for extrapyramidal patients with atypical course of the disease, the direct relationship between TCS and metal deposits could not be proven. The obtained results from the ultrasound fusion...
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The role of accumulation of iron and other metals in the pathophysiology of neurodegenerative diseases
Mašková, Jana ; Dušek, Petr (advisor) ; Vymazal, Josef (referee) ; Bártová, Petra (referee)
The role of metal accumulation in the pathophysiology of neurodegenerative diseases has been a hot topic in recent years due to the possibility of its treatment by chelating agents. Although the mechanisms of neurodegeneration are well known, the role of metal accumulation is still unclear. The main limitation are unsatisfactory methods for in vivo metal imaging; the most widely used technique is magnetic resonance imaging (MRI). Our aim was to assess the possibility of using transcranial sonography (TCS) in differential diagnosis of neurodegenerative diseases and to further explore the underlying factors of echogenicity. In the first study, using TCS fusion with MRI, we focused on location verification of the commonly assessed structures (substantia nigra and nucleus lentiformis) and exclusion of possible focal structural changes affecting the echogenicity in WD and PD patients. Moreover, obtained MRI were used for semi-quantitative comparison with TCS images. Although TCS has been confirmed to be highly beneficial in differential diagnosis of Wilson's disease and it should be recommended as a screening method for extrapyramidal patients with atypical course of the disease, the direct relationship between TCS and metal deposits could not be proven. The obtained results from the ultrasound fusion...
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Chelating polymers for the therapy of Wilson's disease
Mattová, Jana ; Poučková, Pavla (advisor) ; Sedláková, Zdeňka (referee) ; Vávrová, Jiřina (referee)
Wilson's disease is a hereditary disorder of copper metabolism, which causes copper accumulation in organism, especially in the liver, kidneys and brain. Current treatment is based on using low-molecular weight copper chelators and high doses of zinc salts. Unfortunately, they can induce some severe side effects due to systemic action. The aim of this thesis is to improve the treatment of Wilson's disease by using of polymeric drug delivery systems. The size of polymer particles in tens of microns should provide non-resorbability of the drug after oral administration. Synthetic microparticles of poly(glycidyl methacrylate-co- ethylene dimethacrylate), natural microcrystalline cellulose and cross-linked chitosan were used as polymer matrices. N,N-di(2-pyridylmethyl)amine, triethylenetetraamine and 8-hydroxyquinoline were selected as specific copper chelators, which can complex copper cations with high efficiency. The principle of the proposed treatment is that the polymeric carrier-bound chelator complex copper directly from the food in digestive tract of the organism. Because of non-resorbability, the entire complex should be eliminated from the body together with stools. This virtually eliminates systemic side effects. The ability of adsorption of copper and the stability of polymer complex under...
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