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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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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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The male equivalent of polycystic ovary syndrome
Dušková, Michaela ; Stárka, Luboslav (advisor) ; Haluzík, Martin (referee) ; Kittnar, Otomar (referee)
Polycystic ovary syndrome, the most common endocrinopathy in women (with a prevalence of 5-10 %), is characterized by hormonal and metabolic imbalance. Complexity of symptoms of close relatives of women with PCOS as a mendelian trait raised a hypothesis about the existence of a male equivalent of PCOS. Premature alopecia was suggested as one of the signs of a male phenotype of this syndrome. Androgenetic alopecia is the most common cause of balding in men. AGA is the risk factor of cardiovascular diseases, glucose metabolism disorders and also benign prostate hyperplasia and prostate carcinoma. Polycystic ovary syndrome and metabolic syndrome are the risk factors of obesity and diabetes mellitus. The existence of mendelian form of PCOS initiated a hypothesis about the existence of a male equivalent of PCOS. Premature alopecia was suggested as one of the signs of a male phenotype of this syndrome. However, it can be the sign of metabolic syndrome as well. PCOS is characterized by hyperandrogenaemia while metabolic syndrome is characterized by low androgens.
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The metabolic profile of the milch cow of holstein breed in the period of lactation
HORČIČKOVÁ, Michaela
Diploma work was concentrated on the evaluation of two metabolic profiles on the milch cows of Holstein breed on the basic of compilated nutritive rations for individual phases of lactation. The metabolic tests were evaluated in the milch cows in the period of making cow milk, the top of lactation and the second phase of lactation. The balance of nutriments was counted out in the nutritive rations. The haemotological and biochemical parameters, macromineral and urinary profiles were evaluated in the metabolic profiles. The work in the both metabolic profiles evidenced the reduced number of erythrocytes which can be connected with the occurence of anaemia. In the period of the top of lactation it is possible to speculate about an energetical deficit with regard to the low content of triacylglycerols. In the profile tests the presence of ketone bodies substances in urine was found out in the period of making cow milk. This finding connects with the negative energetic balance that occurrs in the course of the first two months after calving. Within of mineral profile an attention should be paid to especially the content of calcium, which was reduced in the both profiles. In comparison with the profiles perfomed in 2011 we find out that reached modifications of the nutrive ration and the increase in the content of main nutriments, which shoved in the milch cows by improvement of metabolic effects. Neverthless in breeding of the milch cows the increased emphasis should be put on the period of making cow milk and the recommendation for prevention from anaemia or other disorders is carrying out of the selective metabolic test.
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The effect of physiotherapy on cardio-respiratory parameters in patients with chronic heart failure indicated for cardiac surgery intervention
MELECHOVÁ, Dominika
The bachelor thesis deals with the preoperative physiotherapy in patients with chronic heart failure who are indicated for cardiac surgery intervention and with the description of physiotherapy procedures utilized before and after the operation. The cardiovascular disease is in developed countries still the main cause of morbidity and mortality. (UNIFY, 2008) The improved treatment of acute conditions allows so that more patients reached a stage of the chronic heart failure. (Špinar, Vítovec, Hradec, 2012) The chronic heart failure is a sign for a number of symptoms that are caused by disruption of the heart work. It is a disorder in which despite adequate ventricular filling drops a cardiac output and the heart is unable to cover metabolic needs of the tissues (supply of oxygen and nutrients and removing of carbon dioxide and metabolic waste products). (Štejfa a kol., 2007) In the theoretical part is described the anatomy of the heart, the physiology of the heart and the blood circulation, the chronic heart failure, the response and the adaptation of the organism to physical load, the cardiovascular rehabilitation and physiotherapy procedures carried out before and after the operation. The practical part of the bachelor thesis is performed by method of the qualitative research with the using techniques: the anamnesis, the kinesiology analysis and the data analysis. The research set was formed by 2 patients of the cardiac surgery department of Hospital České Budějovice a. s. who were indicated for cardiac surgery intervention. The total time of the research was 4 weeks. The first purpose of this thesis was chart the effect of the preoperative physiotherapy on cardio-respiratory parameters and the condition of the patient. The second purpose was describe physiotherapy procedures carried out before and after the operation. I chose 2 research questions for the research: 1. What effect has the preoperative physiotherapy on cardio-respiratory parameters in patients with the chronic heart failure? 2. What are possibilities of physiotherapy procedures before and after the operation? The preoperative physiotherapy was carried out 5 times a week for 1 month in the home of the patient. It included a physical therapy, a respiratory physiotherapy and relaxation methods. Selected cardio-respiratory parameters were taken before and after each training unit. Results of therapy are processed through case studies. The component of the bachelor thesis is also a list of references, key words and abbreviations. Next it includes image attachments and graphs. The thesis can be a benefit for physiotherapists, general and professional public and for possible further research in this issue.
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Cytotoxicita beauvericinu, citrininu, deoxynivalenolu a T-2 toxinu stanovena metodou in vitro v buňkách Vero
Macáková, Petra ; Štaud, František (advisor) ; Vopršalová, Marie (referee)
Mycotoxins are secondary metabolites of moulds. Contamination of food and feed by mycotoxins is a major problem for human and animal health. Ingestion of mycotoxins may cause a range of toxic responses, from acute toxicity to long term or chronic health disorders. Several mycotoxins, either from the same or from different fungal species, occur simultaneously in plant products. However, its implication for food safety assessment is generally not known, as there is relatively little information on the interaction between concomitantly occurring mycotoxins and the consequence for the toxicity. Mycotoxins with similar mode of action would be expected to have at least additive effects. Conversely, some interactions could have subtractive effects. An understanding mode of action in simple in vitro systems can provide a rational basses for predicting interactions between mycotoxins. The aim of this study was to obtain cytotoxicity data (EC50 values) of Penicillium and Fusarium mycotoxins, nominally BEA, CIT, DON and T-2 toxin. For this purpose, Vero cells viability was evaluated in the presence of these four mycotoxins using the NR assay. All mycotoxins tested diminished cell viability in a concentration and incubation time-dependent manner on Vero cells. Individual mycotoxins increase cytotoxicity as...
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Primary Cilia and its Importance in Cell Response to Ionizing Radiation Exposure and Chemotherapy Drugs.
Filipová, Alžběta ; Řezáčová, Martina (advisor) ; Hampl, Aleš (referee) ; Hofer, Michal (referee)
Primary cilia and its importance in cell response to ionizing radiation exposure and chemotherapy drugs. Ionizing radiation, metabolic and genotoxic stress affect the cytoskeletal stability and morphology of cells by causing DNA damage in the form of single or double stranded breaks, the latter being the most critical. When DNA damage occurs the cell cycle becomes arrested and the repair machinery is engaged; however, if this damage is not repaired the cell enters programmed cell death by apoptosis. Primary cilia have been shown to act as physical- chemical sensors and their biological functions include the perception of the extracellular milieu, the regulation of organogenesis and cell polarity, as such, they are dynamically regulated during cell cycle progression. Further, the impairment or loss of primary cilia leads to the development of ciliopathies and other diseases including cardiovascular disorders, arthritis and, ultimately, cancer. Moreover, the presence and temporary formation of primary cilia is essential for the repair process of certain cell types. This work is focused on the evaluation of primary cilia changes caused by ionizing radiation, metabolic stress or cytostatic drugs (taxol and doxorubicin) in vitro. Our results showed a significantly higher number of ciliated C2C12 cells observed...
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Biochemistry of polyphenols effects in the treatment of vascular disease
Kondrashov, Alexey ; Štípek, Stanislav (advisor) ; Pecháňová, Olga (referee) ; Matouš-Malbohan, Ivan (referee)
This Ph.D. thesis deals with the deep analysis of polyphenols effects toward vascular disorders. This work provides a number of experimental results of studying both the effects of natural bioactive compounds in red wines and potatoes, and their application to the experiments which includes experimental animal models with spontaneous hypertension. Methods and equipment used in experimental studies allowed us to make several new statements regarding the universal nature of the relationships between the antioxidant capacity and the polyphenolic content in examined foodstuffs. Besides this it is also recognized that food is a source of minerals which also contribute to the total antioxidant capacity and therefore may have influence the endogenous antioxidant enzyme system by providing the essential cofactors. Experimentally we have found that the concentrations of magnesium known for its therapeutic action in wine and red wine extract are comparable to the mineral waters recommended for the treatment and prevention of cardiovascular and metabolic diseases. Moreover, synergistic interactions between selected minerals have been found. The key issue of bioavailability of polyphenols for supporting the idea of the beneficial effects of diet rich in fruits and vegetables toward vascular disease prevention...
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EVALUATION OF BONE MINERAL DENSITY AND CALCIUM SCORE IN HEMODIALYSIST PATIENTS
Ohlídalová, Kristýna ; Kreuzberg, Boris (advisor) ; Neuwirth, Jiří (referee) ; Tůma, Stanislav (referee)
Origin of renal osteodystrophy and cardiovascular complications are multifactorial. This complications are caused by disorders of calcium - phosphate metabolism already at the beginning of patient's irreversible renal failure. The factors playing the most important part in the development o renal ostedystrophy and are hypocalcemia and increasing serum phosphate levels associated with a declining glomerulal filtration. Two main types of renal osteodystrophy can be described - high turnover bone disease and low turnover disease. High turnover forms of renal osteodystrophy are characterized by rapid bone turnover caused by abnormally high PTH levels. The two types of high turnover renal osteodystrophy are predominant hyperparathyroid bone disease, and mixed uremic osteodystrophy. Low turnover forms of renal osteodystrophy are characterized by a dramatic drop in the rate of bone remodeling, caused by oversuppression of PTH and/or by aluminum accumulation. The bones become thin and overly flexible, and bowing may occur. The two types of low turnover renal osteodystrophy are low turnover uremic osteodystrophy and aluminum-related bone disease. Patients who have end-stage renal disease with increased serum phosphate levels and calciumphosphate products are associated with an increased prevalence of ectopic...
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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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