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Side and teratogenic effects of valproic acid in pregnancy nad in calcium metabolism
Veselá, Kristýna ; Pávek, Petr (advisor) ; Zimčíková, Eva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Sciences Candidate: Kristýna Veselá Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Adverse and teratogenic effects of valproic acid in pregnancy and calcium metabolism Valproic acid and sodium valproate (VPA) are substances with a broad spectrum of anticonvulsive effects. The VPA is mainly used in the treatment of bipolar disorder and epilepsy. The combination therapy with other antiepileptic drugs (AEDs) has been established in the treatment of acute mania, when compared with monotherapy. Various molecular mechanisms of action are responsible for the broad spectrum of VPA effects. VPA interpheres with GABA and glutamate brain neurotransmission, as well as affects intracellular mechanisms. Adverse drug reactions affect 10-20% of patients. They are mostly transient and usually resolve spontaneously or after dose reduction of VPA. Most of the VPA adverse effects, such as weight gain, gastrointestinal problems, sedation, hepatotoxicity and others, are dose dependent. The use of VPA in pregnancy and polytherapy is undesirable due to increased risk of congenital defects. It appears that other AED in this regard, potentiate the effect of VPA. The teratogenicity of VPA was...
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Problems of active scar
Zádrapová, Veronika ; Dudová, Agnieszka (advisor) ; Pánek, David (referee)
Name of thesis: Problems of active scar Aims: The purpose of this thesis is to create a comprehensive overview of the process and issues of active scars. Highlight the "hidden" meaning soft tissue and active scars in functional disorders of musculoskeletal conditions. Find the answer to the clinical question - What lies beneath the scars activity? Methods: This thesis is elaborated in the form of literature review. This thesis is divided to two parts. The first part deals mainly theoretical basis for the special section. Includes mainly anatomical and physiological knowledge of soft tissue, healing process, scar tissue types and so on. A special part is engaged directly active scar. Because, assessment and treatment of "active" scar tissue may comprise an important component of the management of locomotor dysfunction and associated pain syndromes. Key words: active scar, soft tissue lesions, the barrier phenomen, impaired function of the motor system, collagen,
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Marketing focused on patients with phenylketonuria (PKU)
Lifková, Hana ; Zamazalová, Marcela (advisor) ; Šantavá, Michaela (referee)
The master's thesis deals with inherited metabolic disorder phenylketonuria from a marketing point of view. The theoretical basis of this thesis points out to differences between the marketing mix in the pharmaceutical industry and other industries. Analysis of marketing mix of Nutricia company in relation to patients with phenylketonuria is based on these facts. Secondary and primary data are used in this master's thesis. There were several research methods used to get the information, such comparison and telephone interviews. The work provides insights and recommendations in relation to the potential competitive advantages of the Nutricia company, which can help to maintain its position as market leader in the future. Attention is mostly paid to project such Home Deliveery and on-line communication.
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Systematic Review of Researches Trstiny Movement and Body Techniques in the Treatement of Eating Disorders
Adámková Ségard, Milena ; Hátlová, Běla (advisor) ; Hošek, Václav (referee) ; Kebza, Vladimír (referee)
Title: Systematic Review of Researches Testing Movement and Body Techniques in the Treatment of Eating Disorders. Goal: The goal of this research is to organize the knowledge of past therapeutic researches and cross- connect this knowledge gained through experiments for the benefit of daily psychotherapeutic work and future researches. Methods: The design of the study follows the design of Systematic Review, which carries the highest evidence in the hierarchy of scientific evidence, and which offers the strongest knowledge for practical use. In this research were included studies testing Movement and Body Techniques on samples of patients with Eating Disorders and which were published in English till the year 2008. Results: This research confirms that for the treatment of eating disorders, therapies using body and movement oriented techniques have been used, tested and published since 1970. By the end of the year 2008 there are 41 published researches in the English language. The evidence-based quality of the researches in this field is very good. In 59% of the studies, the strength of the evidence reaches the third of four levels of scientific evidence. The studies included in the review, show that the treatments under discussion have positive effects in the healing of eating disorders. The study also...
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Structural-Functional Correlations of Hydroxymethylbilane synthase
Douděrová, Dana
Acute intermittent porphyria (AIP) is an autosomal dominantly inherited disorder, classified as acute hepatic porphyria. It is characterized by a deficiency of hydroxymethylbilane synthase (HMBS, EC 4.3.1.8), the third enzyme in heme biosynthesis. Clinical features include gastrointestinal, neurologic and cardiovascular symptoms, but the most common clinical presentation is abdominal pain caused by neurovisceral crises. The purpose of this study was first to perform molecular analysis of the AIP patients. Once a mutation is detected in a patient, molecular testing is offered to family members. In each affected family, this becomes an important tool for individualised medicine, allowing for careful drug prescription; in addition, it is very important for the asymptomatic carriers to be warned of precipitating factors, thus avoiding an acute attack. The proper DNA diagnostics can be achieved by a combination of a robust and effective pre-screening method and a confirmatory DNA sequencing step. We decided to establish a new generation pre-screening method, which will be highly sensitive and relatively time- and cost-effective. Our method of choice was high-resolution melting (HRM) analysis using the LightScanner instrument. Another important aspect of this project was to study the molecular...
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Study of mitochondrial ultrastructure and functions in selected mitochondrial and lysosomal storage disorders
Kostková, Olga ; Hansíková, Hana (advisor) ; Šmíd, František (referee) ; Hyánek, Josef (referee)
This thesis has been worked out in The laboratory for study of mitochondrial disorders (Departement of Pediatrics, 1st Faculty of Medcine, Chales university in Prague) and in cooperation with The Institute of Inherited Metabolic Disorders. Mitochondrial disorders represent a heterogeneous group of diseases with the onset at any age from neonatal period till adulthood, mostly presented with very severe clinical courses of disease. The mammalian organism is fully dependent on mitochondrial oxidative phosphorylation system as on the major energy producer of the cell. Therefore the mitochondrial disorders affect mainly high energy demanded tissues such as brain, heart or muscle. Simillar phenotype is observed in many lysosomal storage disorders. Despite of expanding knowledge of molecular basis of mitochondrial and lysosomal disorders, it may be still difficult to explain the exact pathogenesis of disease as well as the prognosis for patients and their families. Mitochondrial functions affect more than just energy production; they contribute in initiation of apoptosis, in cellular calcium homeostasis, and in production of reactive oxygene species. Disturbed mitochondria become a goal of autophagy mediated by the lysosomal compartement. The results of our study enable: 1. better understanding of the tissue...
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Comparison of iron-chelating properties of synthetic iron chelators
Zárubová, Pavla ; Mladěnka, Přemysl (advisor) ; Pourová, Jana (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Pavla Zárubová Tutor: Přemysl Mladěnka, Ph.D. Name of thesis: Comparison of iron-chelating properties of synthetic iron chelators Iron is an essential element for living cells. Both lack of iron (sideropenia) and iron overload can be dangerous for the organism. Thus, iron homeostasis is maintained on the cellular and whole body levels. Sideropenia may occur as a consequence of increased blood loss/ increased iron need (menarche, gravidity, lactation), lack of iron in food or in derangements of gastrointestinal tract. Iron excess can be caused by acute intoxication, dangerous mainly in children, and also in chronic poisoning, caused by hereditary disorders or especially by frequent blood transfusions during the treatment of some haematological diseases. Iron chelators are a wide group of chemical substances with very variable structure. They have been used therapeutically in different indications for many years and other indications are being researched recently. Traditionally, they are used for chelation therapy in acute intoxication and in chronic iron overload, nowadays they are in the center of research attention in association with cancer and neurodegenerative...
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Study of expression and maturation of mitochondrial oxidative phosphorylation system during mammal's prenatal period
Mrhálková, Andrea ; Hůlková, Martina (advisor) ; Ješina, Pavel (referee)
Postnatal adaptation of neonate to extrauterine life is among others dependent on maturation of mitochondrial oxidative phosphorylation system (OXPHOS). It depends on effective mitochondrial biogenesis during fetal developement. The inadequate capacity of mitochondrial OXPHOS system plays an important role in the neonatal mortality and morbidity. Therefore the study of mitochondrial biogenesis on molecular and biochemical level is important to improve the care of very premature neonates, especially critically ill premature neonates. This thesis has been worked out in The laboratory for study of mitochondrial disorders (Department of Pediatrics, 1st Faculty of Medicine, Charles University in Prague). The thesis is based on molecular genetic analyses, which are focused on characterisation of ATP synthase gene expression and on changes in mitochondrial DNA content during human and rat fetal development. The results provide the better insight into mitochondrial respectively ATP synthase biogenesis during human and rat fetal development.
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Human F1Fo-ATPsynthase deficiency
Suldovská, Sabina ; Tesařová, Markéta (advisor) ; Černá, Leona (referee)
F1FO-ATPsynthase is a key enzyme in energy metabolism of the cell. Its deficit is caused usually by mutations in two structural genes MT-ATP6 and MT-ATP8 encoded by the mitochondrial DNA or in nuclear genes ATPAF2 and TMEM70 encoding the biogenesis factors and structural gene ATP5E. Deficiency of the F1FO-ATPsynthase leads to progressive and serious phenotype affecting organs with high energy demands. The first symptoms usually occurs in neonatal age and prognosis of the disease is fatal. Mutations in these genes result in both qualitative and quantitative defects of the F1FO-ATPsynthase. The study of molecular bases of mitochondrial disorders including F1FO-ATPsynthase deficiency uses large number of biochemical and molecular-genetic methods to determine a proper diagnosis which is essential for the symptomatic therapy and genetic counselling in affected families. The aim of the diploma thesis was to characterise the F1FO-ATPsynthase deficiency in isolated mitochondria from the lines of cultured cells by the determination oligomycin- sensitive ATP-hydrolytic activity of the F1FO-ATPsynthase, enzymatic activities of the respiratory chain complexes and to analyse changes in the steady-state levels of the representative subunits and whole complex of the F1FO-ATPsynthase in comparison with controls. 3...
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Developmental defects of reproductive system in selected species of mammals
Vedralová, Petra ; Chmelíková, Eva (advisor) ; Krejčířová, Romana (referee)
Genital organs of males and females provide the reproduction and survival of the species. If the gonads or efferent tract are formed abnormally or missing, reproductive anomalies arise. Then development of female or male gametes are not normal and fertilization and pregnancy or sexual act can not be performed. It is in all livestock but also in all mammals.
Developmental disorders of reproductive system are usually inherited and they are passed from parents to offspring. Defects may occur at the chromosomal, gonadal or phenotypic level.
Monosomy and trisomy are serious disorders of chromosomal sex and they cause infertility of affected individual. Sex reversal is included among the defects of gonadal sex. Anomalies of phenotypic sex are hermaphroditism and pseudohermaphroditism. Hypoplasia of the ovaries and testes and frequent cryptorchidism belong to defects of the gonads. The most common anomalies of the efferent genital tract are aplasia of Müllerian and Wolffian ducts, hypospadia and diphallia.
Developmental defects are grave. Because of them the reproduction is not successful or even impossible. Animals in testing or breeding with disorders are excluded from breeding programme to defects not get among descendants.
The occurrence of genital tract defects causes reproductive disorders and infertility. It is linked closely with the economy mainly in livestock. So the breeding is lossy. Breeding is healthier and more successful if methods for describing are improved and selection is realized.
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