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Preparation of radiolabeled albumin
Suchan, Martin ; Trejtnar, František (advisor) ; Lázníček, Milan (referee)
Objectives: This senior thesis was aimed at determining a method of albumin labelling with a particular radionuclide - technetium 99m Tc. Our task was to review the various possible methods needed for working out a procedure for albumin labelling with the mentioned radioisotope and also to test the behavior of labelled albumin in vitro in experiments with newly-isolated rat kidney cells. The next objectives of this work were to analyze the performed experiments, compare the results with other known procedures of albumin labelling with technetium 99m Tc and cast the results in the form of a scientific statement. Methods: A low pH and high concentration of albumin were useful for the albumin labelling experiments. A solution of SnCl2.2H2O was used for the reduction of pertechnetate. Purification of labelled albumin was performed by gel chromatography with a Sephadex G-50. The locations of albumin peaks in the chromatographic fractions were determined by the bicinchonic method. The location of pertechnetate was found by investigating the chromatographic spectrum of pertechnetate. Investigation of the elution spectrum was used to check for proper labelling. The radiochemical purity of labelled albumin was verified by paper chromatography and subsequent detection. Newly- labelled albumin was used in the...
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Role of ABC transporters in pharmacoresistant epilepsy
Hanousková, Tereza ; Pávek, Petr (advisor) ; Trejtnar, František (referee)
The diploma thesis summarizes the recent knowledge on the possible role ABC transporters in mechanisms of refractory epilepsy. Approximately 30% of patients with epilepsy are refractory to treatment. An important characteristic of pharmacoresistant epilepsy (PE) is that most patients are at the same time resistant to several antiepileptics (AED) even though these drugs act by different mechanisms. It was suggested that one of the main cause of pharmacoresistance is the decreased drug uptake into the brain mediated by multidrug transporters in the blood-brain barier (BBB). The ABC transporters studied in relation to PE are the following: P-glycoprotein (Pgp, coded by MDR1 gene), some members of the multidrug resistance protein (MRP) family and the breast cancer resistance protein (BCRP). The over-expression of the ABC transporters was demonstrated in capillary endothelial cells of BBB, and astrocytes and neurons of epileptogenic brain tissue. Therefore modulation of ABC efflux transporters of the BBB could be a novel strategy to enhance the penetration of AED into the brain. Coadministration of inhibitors with less toxicity, higher potency and specifity to Pgp together with AED could thus reverse PE and achieve seizure control in epilepsy. The characterization of variations in the MDR1 gene and...
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The attitudes and experiences of the university students with drugs of abuse
Fleischlingerová, Simona ; Melicharová, Ludmila (advisor) ; Trejtnar, František (referee)
Experiences of the students and their attitudes to the addictive drugs Simona Fleischlingerová The main dissertation's aim has been to find out the attitudes of the students of the third year of Faculty of Pharmacy in Hradec Králové to smoking and compare this with the results, which were given from the students of Medicine, Stomatology and Nursing. The data were compiled from the individual completed questionnnaire. The conclusions didn't show important differences in attitudes and opinions to smoking among the individual medical field of study. The importance of the smoking restriction in the closed room, the position of the medic as a consultant in stopping smoking and the knowledge of the therapy of nicotine addiction - These are students' opinions, which are very positive.
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Study of renal bioelimination of xenobiotics at the cellular level II
Popadičová, Lýdia ; Trejtnar, František (advisor) ; Melicharová, Ludmila (referee)
STUDY OF RENAL BIOELIMINATION OF XENOBIOTICS AT THE CELLULAR LEVEL II. Synthetic somatostatin analogues labeled with suitable metal radionuclides are used in nuclear medicine for scintigraphy. Recently, they are also used for targeting radiotherapy in some types of malignant tumors with higher expression of somatostatin receptors. Their therapeutical use is restricted due to a potential radiotoxic effects on kidneys. This is a consequence of accumulation of those radiopeptides in the renal tubular cells. The reason of this cumulation is the reabsorption of radiopeptides in renal tubules. The mechanism of accumulation has not been expained so far. The aim of this work was to study the accumulation of an experimental receptor specific derivate of somatostatin, DOTA-NOC (DOTA-1-Nal3 -oktreotid) labeled with indium-111 (111 In-DOTA- NOC). The experiments were mainly focused on a study of the mechanism of renal uptake and on possibilities how to modify an unfavourable accumulation of the studied radiopeptide in the renal cells. Freshly isolated renal rat cells, which we obtained by the collagenase method, were used as an experimental model. Verification of the viability of renal cells was made by trypan blue exclusion test. The preparates of renal cells showed viability approximately 90% and therefore...
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The pharmacotherapy of dyslipidemia
Řeháčková, Renata ; Melicharová, Ludmila (advisor) ; Trejtnar, František (referee)
Dyslipidemia (DLP) represents one of the most significant risk factors of atherosclerosis. Results of many clinical studies proved that effective treatment of dyslipidemia markedly decreases cardiovascular risk. Hypolipidemic treatment becomes one of the most effective treatment options (modalities) in prevention of CHD (coronary heart disease) and other cardiovascular diseases. Basic approach of the DLP treatment is nonpharmacologic therapy, e.g. change of life habits, stop of smoking, change of dietary habits, regular exercise, reduction of abnormal weight. In primary prevention settings the pharmacotherapy should commence after the failure of 3 to 6 months nonpharmacologic measures. In secondary prevention in patients with CHD it is recomended to start DLP treatment immediately, at the latest on release from the hospital. The care for the patient with hyperlipoproteinemia is comprehensive and should include rational control of diabetes, hypertension, obesity, adequate treatment of CHD and complications of atherosclerosis. The statins are the choice of medication in isolated hyperlipoproteinemia. If the target values are not reached by monotherapy, combination therapy by statin end ezetimib may be tried. The choice of lipid lowering drug should be decided on the major metabolic abnormality. When...
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Importance of Transport Proteins and Biotransformation Enzymes for Defending Role of the Placenta
Vacková, Zuzana ; Štaud, František (advisor) ; Trejtnar, František (referee) ; Mičuda, Stanislav (referee)
Placenta is a unique organ which ensures a number of vital functions necessary for normal course of pregnancy and development of a new individual. In addition to its main function of oxygen supply and nutrient and waste product exchange, placenta also serves as an endocrine, metabolic and protective organ. Placenta is considered to be one of the physiological barriers of the organism which regulates transport of both endogenous and exogenous compounds between two compartments - maternal and fetal blood circulations. Up to recently, the placental barrier was supposed to be formed only by cellular layers which separate maternal and fetal blood - syncytiotrophoblast and fetal capillary endothelium. However, it has been demonstrated that the activity of placental efflux transport proteins and metabolic enzymes contributes considerably to the protective function of placental barrier. Efflux transporters are membrane proteins which actively (along with consumption of ATP) "pump" a diversity of substrates out of the cell. It has been shown that the kinetics of transport of various substances across the placenta is affected predominantly by two transporters: P-glycoprotein (P- gp) and breast cancer resistance protein (BCRP). Compared to these transporters, placental biotransformation enzymes are considered...
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Progress in pharmacotherapy of parkinsonism
Tahovský, Tomáš ; Melicharová, Ludmila (referee) ; Trejtnar, František (advisor)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Tomáš Tahovský Supervisor: Doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: Progresses in pharmacotherapy of parkinsonism During the last few decades, there has been a remarkable progress in our understanding of the biology of Parkinson's disease (PD), which has been translated into the development of numerous antiparkinsonian drugs. There are different therapeutic strategies for patients in an early stage versus patients in a late stage of the disease. The current therapeutic arsenal includes levodopa preparations, MAO-B inhibitors, dopamine agonists, COMT inhibitors and several other compounds that target non- dopaminergic systems. Much interest is focused on the potential neuroprotective effect of the already available drugs, as well as on new research approaches for the development of disease-modifying agents. These include mainly antiglutamategic compounds, antiapoptotic and antioxidative agents. Future pharmacotherapy might include targeted delivery of genes involved in the pathogenesis of the disease.
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