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Transport of selected drugs in the renal cells
Lysá, Tereza ; Trejtnar, František (advisor) ; Melicharová, Ludmila (referee)
7. ABSTRACT Somatostatin analogues labelled with radionuclides are used for diagnosis and therapy of some tumours, mainly neuroendocrine ones, in which receptors specifically binding these radiolabelled analogues of somatostatin are occurred. However, the therapeutic usage of these radiolabelled analogues of somatostatin is limited due to nefrotoxic undesirable effects originated because of their accumulation in the renal proximal tubules after reabsorption from the glomerular filtrate. The aim of the study was to contribute to knowledge in the renal transport systems responsible for reabsorption of radiolabelled somatostatin analogues in the renal tubular cells and then on the base of such data to find some substances which could reduce the renal accumulation and prevent the damage of the renal tissue. In experiments, the isolated renal cells obtained from rat kidney by collagenase method were used. After the verification of presence and function of transport mechanism by known indicators of active and passive transport, the accumulation of two somatatostatin analogues labelled with radionuclides - 111In-DOTA-NOC and 125IDOTA- Tyr3-octreotate were studied on these renal cells. The active transport of these radiopeptides was verified by reduce of incubation temperature. Then changes of accumulation of these...
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The changes in expression of selected drug-metabolizing enzymes in parasites after exposition to sublethal doses of drugs
Pasák, Michael ; Skálová, Lenka (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michael Pasák Supervisor: prof. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: The changes in expression of selected drug-metabolizing enzymes in parasites after exposition to sublethal doses of drugs The parasite, which causes significant losses of small ruminants through a disease called haemonchosis, is the abomasal nematode Haemonchus contortus. IVM is one of the anthelmintics used in veterinary medicine to eliminate haemonchosis. The main problem with this parasite is the presence of drug resistance to almost all administered anthelmintics including IVM. It is believed that xenobiotic-metabolizing enzymes such as cytochromes P450 (CYPs) and membrane efflux transporters P- glycoproteins (P-gps), play the role in resistance in H. contortus. This study focuses on the effect of sublethal doses of IVM on expression of selected CYPs and P-gps. Females and males of susceptible ISE strain H. contortus were separated before our experiment. After incubation of nematodes with three different concentrations of IVM, RNA was isolated and the changes in expression of selected genes were analyzed using qPCR. Significant sex-differences were observed in inducibility of tested genes. Significant...
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Review on clinical effects of vitamins
Chrudimská, Klára ; Trejtnar, František (advisor) ; Melicharová, Ludmila (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Klára Chrudimská Supervisor: Doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: Clinical effects of vitamins Abstract Vitamins are popular and often used group of substances that are administered in clinical practice. They are administered to the patiens both due to prevent their insufficiency and to cure different pathologic state to aim some pharmacological effect. But often the vitamins are not applied rationally and on scientific proof. Today a number of accessible information increases but there is not enough number of summarizing information and critical evaluation of clinical studies results. The aim of this dissertation was to create an overview of present knowledge in the area of clinical effects of vitamins. The performed analysis of the latest knowledge available in accessible specialized databases that relate to clinical studies dealing with both preventive and therapeutical impact of substances from the group of vitamins suggests that the number of information concerning usage of vitamins in indication other than substitution of insufficience therapy are still quite incomplete and in some cases contradictory. Analysed clinical studies often have considerably small...
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Determination of radiochemical purity and stability of new radiopharmaceuticals
Vorlová, Nikola ; Lázníček, Milan (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Nikola Vorlová Supervisor: Prof. PharmDr. Ing. Milan Lázniček, CSc. Title of diploma thesis: The determination of radiochemical purity and stability of newly developed radiopharmaceuticals. The theme of this thesis is determination of radiochemical purity and stability of newly developed radiopharmaceuticals from the group of receptor specific peptides and antibodies by using liquid chromatography - HPLC and thin layer chromatography ITLC -SG method. The antibody sample 177Lu-hR3-I has been studied in the theses( 177 Lu enters in to relation with modified antibody Nimotuzumab), which blocs EGF receptors and due to this fact the growth of tumor cells too. It has been detected, that it is necessary for reaching sufficient radiochemical purity to clean this radio-labeled antibody by the gel chromatography after labeling. Radio-chemical purity of this sample circulate from 99,46 % to 88,77 % during period of 6 days. Another samples have been studied, 111In-minigastrin - radioisotope 111 In linked up to three different minigastrins I, II, and III. Minigasrins are gastrin derivates , which have a very good absorptive capacity to receptors for cholecystokinin (CCK-B receptors) occurring in...
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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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Effect of Synthetic Magnolol Derivatives on Activity of Nuclear Receptors PPARγ and RXRα
Dymáková, Andrea ; Szotáková, Barbora (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences University of Vienna Faculty of Life Sciences Department of Pharmacognosy Candidate: Andrea Dymáková Supervisors: Mag. Simone Latkolik, doc. Ing. Barbora Szotáková, Ph. D. Title of diploma thesis: Effect of Synthetic Magnolol Derivatives on Activity of Nuclear Receptors PPARγ and RXRα The nuclear receptors, peroxisome proliferator-activated receptor γ (PPARγ) and its heterodimerization partner retinoid X receptor α (RXRα) are drug targets in the treatment of diseases like the metabolic syndrome and diabetes mellitus type 2. The effort has been made to develop new agonists for PPARγ to obtain ligands with more favourable properties than currently used drugs (Berger et al. 2002, Berger et al. 2005). Magnolol was previously described as a dual agonist of PPARγ and RXRα (Fakhrudin et al. 2010, Zhang et al. 2011). Based on the bi- aryl structure of magnolol, the effort has been made to design and synthesize linked magnolol dimers. The aim of this thesis was to investigate the agonistic potential of these compounds with respect of the nuclear receptors PPARγ and RXRα in comparison to magnolol. We evaluated the ligand binding properties of the compounds and their functionality as PPARγ agonists in vitro...
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Review of adverse effects of oral contraceptives
Dřevojánková, Barbora ; Trejtnar, František (advisor) ; Melicharová, Ludmila (referee)
Scientific data describing benefits and unprofitablenesses of oral contraception (OC), may diverse in many cases or could be also controversial. Therefore we have decided to draw up a background research diplomathesis, whose main objective was to summarize the currently available knowledge of the adverse effect in connection with the use of OC. To assess the relative benefits and risks of OC, we also examined the potential positive effects of OC use. More than half of the women terminate the use of OC because of the side effects. Irregular bleeding, nausea, weight gain, mood changes, feeling the tension in the chest and headache were reported as the most common side effects. Most of them disappear with the length of use. The clearly demonstrated serious risks of OC use include cardiovascular complications - stroke, thrombembolic disease, myocardial infarction and hypertension. The risk of this problem increases with higher content of estrogen, e.g. ethinylestradiol (EE). So far, however, there hasn't been proved that a reduction of EE below 50 g results in a further significant reduction of thrombembolic events. The risk of cardiovascular problems is not dependent only on the estrogen content in OC. Contraceptives containing desogestrel or gestodene have been shown to have a higher risk of...
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Advances in the treatment of rheumatoid arthritis
Papoušková, Kateřina ; Melicharová, Ludmila (advisor) ; Trejtnar, František (referee)
Charles Univerzity in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Papoušková Supervisor: PharmDr. Ludmila Melicharová Title of diploma thesis: Advances in the treatment of rheumatoid arthritis Rheumatoid arthritis is a serious systemic inflammatory autoimmune disease whose origin isn't precisely known. In the last decade there has been significant progress in the treatment of rheumatoid arthritis, which is the main topic of this dissertation. Major treatment advances have been based around the introduction of new drugs, including synthetic disease modifiying drugs, but primarily biological drugs (inhibitor). Diagnostic techniques for rheumatoid arthritis have also improved significantly, becoming more accurate, especially in the early stages, enabling earlier treatment and better outcomes. In particular a detailed description of the negative prognostic indicators for the destructive development of rheumatoid arthritis, together with improved evaluation of rheumatoid arthritis activity, have been the basis for the development of a new algorithm for the treatment of rheumatoid arthritis. The complex therapy of rheumatoid arthritis is increasingly sophisticated, incorporating both pharmacological and non-pharmacological treatment methods...
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