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Význam laktátu v diagnostice mitochondriálních onemocnění u dětí
Magner, Martin ; Zeman, Jiří (advisor) ; Baxová, Alice (referee) ; Procházková, Dagmar (referee)
The lactate level assesment in various body fluids plays an important role in the diagnostics of mitochondrial disorders in children. However, the interpretation of lactate level is often difficult due to its unspecificity and variability even in particular mitochondrial disorders. Three specific aims have been stated in this PhD Thesis: 1. To analyse the role of lactate examination in the differential diagnosis between children with mitochondrial disorders and children with other diseases. 2. To study the lactate level differences in various mitochondrial syndromes. 3. To characterise the clinical and laboratory data of neonates with mitochondrial disorders and to suggest new diagnostic algorhytms. Clinical and laboratory data from patients hospitalized in the Department of Pediatrics were collected. Laboratory methods were provided in the cooperation with the Mitochondrial laboratory of the Department of Pediatrics and Institute of Inherited Metabolic Disorders. The study with lactate levels in 107 patients documented that brief seizures lasting less than 2 minutes did not increase lactate concentration in the CSF. CSF-lactate was a relialable marker in differential diagnosis in the children with mitochondrial disorders against children with epilepsy. 2. The severity of particular phenotype is more...
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Genetické příčiny deficitu cytochrom c oxidázy u dětí
Vondráčková, Alžběta ; Tesařová, Markéta (advisor) ; Brdička, Radim (referee) ; Procházková, Dagmar (referee)
Mitochondria are the key source of vital ATP molecules, which are largely produced within cells by a system of oxidative phosphorylation (OXPHOS). Genetic defects affecting any of the components of the oxidative phosphorylation system or the structure and function of mitochondria lead to mitochondrial disorders, which occur at an incidence rate of 1 in 5000 live births. Cytochrome c oxidase (COX) is the terminal enzyme and electron acceptor of a respiratory chain that catalyses oxygen to produce a water molecule. In addition to complex I deficiency, isolated or combined COX deficiency is the most common respiratory chain defect in paediatric patients, and it can arise from mutations located either in mitochondrial DNA or in nuclear genes encoding the structural subunits or corresponding assembly factors of the enzyme complex. However, the molecular basis of COX deficiency remains elusive in many patients despite advances in the identification of an increasing number of mutations and genes involved in the disease. This thesis focuses on the identification of the genetic causes of mitochondrial diseases in a cohort of 60 unrelated Czech children with clinically and laboratory confirmed COX-deficiency. With the use of a high-resolution melting analysis mutation screen, four heterozygous sequence...
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Genetické příčiny deficitu cytochrom c oxidázy u dětí
Vondráčková, Alžběta ; Tesařová, Markéta (advisor) ; Brdička, Radim (referee) ; Procházková, Dagmar (referee)
Mitochondria are the key source of vital ATP molecules, which are largely produced within cells by a system of oxidative phosphorylation (OXPHOS). Genetic defects affecting any of the components of the oxidative phosphorylation system or the structure and function of mitochondria lead to mitochondrial disorders, which occur at an incidence rate of 1 in 5000 live births. Cytochrome c oxidase (COX) is the terminal enzyme and electron acceptor of a respiratory chain that catalyses oxygen to produce a water molecule. In addition to complex I deficiency, isolated or combined COX deficiency is the most common respiratory chain defect in paediatric patients, and it can arise from mutations located either in mitochondrial DNA or in nuclear genes encoding the structural subunits or corresponding assembly factors of the enzyme complex. However, the molecular basis of COX deficiency remains elusive in many patients despite advances in the identification of an increasing number of mutations and genes involved in the disease. This thesis focuses on the identification of the genetic causes of mitochondrial diseases in a cohort of 60 unrelated Czech children with clinically and laboratory confirmed COX-deficiency. With the use of a high-resolution melting analysis mutation screen, four heterozygous sequence...
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Význam laktátu v diagnostice mitochondriálních onemocnění u dětí
Magner, Martin ; Zeman, Jiří (advisor) ; Baxová, Alice (referee) ; Procházková, Dagmar (referee)
The lactate level assesment in various body fluids plays an important role in the diagnostics of mitochondrial disorders in children. However, the interpretation of lactate level is often difficult due to its unspecificity and variability even in particular mitochondrial disorders. Three specific aims have been stated in this PhD Thesis: 1. To analyse the role of lactate examination in the differential diagnosis between children with mitochondrial disorders and children with other diseases. 2. To study the lactate level differences in various mitochondrial syndromes. 3. To characterise the clinical and laboratory data of neonates with mitochondrial disorders and to suggest new diagnostic algorhytms. Clinical and laboratory data from patients hospitalized in the Department of Pediatrics were collected. Laboratory methods were provided in the cooperation with the Mitochondrial laboratory of the Department of Pediatrics and Institute of Inherited Metabolic Disorders. The study with lactate levels in 107 patients documented that brief seizures lasting less than 2 minutes did not increase lactate concentration in the CSF. CSF-lactate was a relialable marker in differential diagnosis in the children with mitochondrial disorders against children with epilepsy. 2. The severity of particular phenotype is more...
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NO plant metabolism under stress
Schier, Jakub ; Procházková, Dagmar (advisor) ; Sedlářová, Michaela (referee)
This work handles the role of nitric oxide (NO) in both physiological, and stress metabolism of plants, it introduces the history of NO studies, including necessary inclusion of some facts related to the animal kingdom. It summarizes the physical and chemical properties of NO, which largely influence the way it acts in physiological processes. The work further discusses the various ways NO is synthetized in plants, including enzymatic, and non-enzymatic means. It further deals with various ways NO can influence different physiological processes, antioxidant mechanisms, and finaly concernes itself with various stress inducing facotrs, their impact on plants, and the role of NO in influencing physiological responses. Finally, this work includes a chapter discussing the so called "heavy metals", mechanisms of their toxicity and the role of antioxidant mechanisms, with emphasis to role of NO.
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Clinical impact of cytochrome c oxidase disorders
Böhm, Marek ; Zeman, Jiří (advisor) ; Procházková, Dagmar (referee) ; Doležel, Zdeněk (referee)
This thesis has been worked out in The Laboratory for Study of Mitochondrial Disorders, Department of Paediatrics, 1st Faculty of Medicine, Charles University in Prague. A retrospective multicentric study in 180 children with cytochrome c oxidase (COX) deficiency was designed in cooperation with the Division of Metabolic Diseases in Department of Paediatrics, The Children's Memorial Health Institute, Warsaw, Poland. The survey was focused on clinical manifestation, molecular background and prognosis of the disease and showed that COX deficiency in childhood represents a heterogeneous group of diseases with significantly unfavourable prognosis. Genetic counselling in affected families requires detailed characterization of COX deficiency at the molecular level. An underlying genetic defect was found in 42 % of patients by detection of mutation in mitochondrial DNA (mtDNA) or in nuclear coded genes for proteins surf1 and sco2 that contribute to COX assemblation. Isolated defects of COX were found in patients with mutations in SURF1 or SCO2 genes, whereas in the patients with mutations in mtDNA was the defect of COX combined with decreased activities of one or more other respiratory chain complexes. In the second part of the work, activities of respiratory chain complexes in isolated platelets were analysed in...
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