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Study of the novel phtalocyanines for the vascular-targeted photodynamic therapy of tumors
Brázdová, Petra ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Petra Brázdová Supervisor: Mgr. Miloslav Macháček Title of diploma thesis: Study of the novel phthalocyanines for the vascular-targeted photodynamic therapy of tumors Cancer is one of the leading causes of death in developed countries, therefore a big effort is devoted on research of novel anticancer drugs. Photodynamic therapy (PDT) is currently a well-established method in this area, but targeting its effect on tumor vasculature has not been considered until recently. In comparison with PDT, vascular-targeted photodynamic therapy (VTP) takes the advantage of a much shorter interval between administration of the photosensitizer (PS) and irradiation (drug-light interval) and thus turning the effect of cytotoxic agents to tumor vasculature. It is intended to disrupt the oxygen and nutrients supply to malignant cells and thus cause their damage and death. Aim of this work is to evaluate the efficacy of newly synthesized PSs from the group of phthalocyanines and azaphthalocyanines using the VTP protocol under in vitro conditions. The PSs used in this study have been investigated recently with classical PDT protocol, in which they have demonstrated very promising activity against tumor cells...
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Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line
Katrnošková, Simona ; Ramos Mandíková, Jana (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Mgr. Simona Katrnošková Supervisor: PharmDr. Jana Ramos Mandíková, Ph.D. Title of Thesis: Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line During pharmacologic therapy, tissues of liver and kidney are frequently exposed to high doses of xenobiotics. Via in vitro assays during preclinical testing, we are able to predict potential toxicity which helps to prevent the possible serious adverse drug reactions in clinical practice. The aim of this rigorous thesis was to state the cytotoxic profile of 4 potential antituberculotic drug candidates using appropriate cell models and in vitro assays. Another aim was to compare the cytotoxic effect of the tested compounds among themselves and to 4-aminosalicylic acid (PAS) which antituberculotic activity is known for many years. The tested substances were 3 salicylanilide diethyl phosphate-based derivatives and 4-(trifluormethyl)benzoic acid. For the cytotoxic potential assessment, we used the parameter half maximal inhibitory concentration IC50. We have used methods determining the cell metabolic activity, aminopeptidase activity, lactate dehydrogenase leakage and activity of 3/7 caspases in this...
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Study of interspecies differences in plasma protein binding of 18F-labeled radiopharmaceuticals
Nováková, Dana ; Lázníček, Milan (advisor) ; Bárta, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Dana Nováková Consultant: Prof. PharmDr. Ing. Milan Lázníček, CSc. Title of Thesis: Study of interspecies differences in plasma protein binding of 18 F-labeled radiopharmaceuticals In this thesis, the binding ability of three radiopharmaceuticals containing radionuclide 18 F to the plasma proteins was examined in bovine, pig, human and rat plasma, and the interspecies comparison was performed. Examined radiopharmaceuticals included 18 F-FDG, 18 F-fluorocholine and 18 F-thymidine. The two main methods used are equilibrium dialysis and ultrafiltration. These methods are based on separation of free ligand from the linked component. During the separation, semi-permeable membrane and special filters (AMICON and VIVASPIN) were used for equilibrium dialysis and ultrafiltration, respectively. Free fraction of drugs is considered to be an important parameter for the availability of the drug distribution into the tissues and cells, interaction with receptors, excretion and metabolism. All experiments were carried out at the physiological temperature of 37řC. Obtained results indicate low plasma protein binding of the three radiopharmaceuticals in all studied species, which suggests...
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Creation of Web Sites Consider a Legal and Illegal Drugs.
Bartoňová, Jitka ; Koula, Václav (referee) ; Klusoňová, Hana (advisor)
Bartoňová Jitka Creating interactive websites conversant problems of dependecies Diploma thesis Charles University in Prague, fakulty of Pharmacy in Hradec Králové field of study: Pharmacy Background:The innovation of working system with informations concerned dependencies. The formation of logical articles database and its publication on an internet. Working with checklists, continuum maintaining of questionaire research, creating question forms on an internet and its scoring. Methods:Working with computer, studying programm Joomla, self generating guide to this programm. Results: Begining new website: www.zavislosti.ic.cz Conclusions: Online questionaire searching is place and time limitless, personally undemanding, easily workable, faster, cheaper and globally preferable to research trough the paper questionaire.
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Computational Investigations of Biomolecular Systems and Comparison with Experiments in Various Environmental Conditions
KHABIRI, Morteza
Computational methods were used to study two different types of biological systems. The first study is related to the effect of three different organic solvents (formamide, acetone and isopropanol) on the structure and behavior of three globular proteins. These enzymes belong to the haloalkane dehalogenase family: DhaA, LinB, and DbjA. Moreover, the effect of mutation in the presence of DMSO was also investigated in two variants of DhaA; DhaA57 (L95V+A172V) and DhaA80 (Thr148Leu+Gly171Gln+Ala172Val+Cys176Phe). The simulation results showed that except for DhaA80, organic solvents entered the active site and influence its hydration. Not only the active site but also the enzyme?s hydration shell is influenced by organic molecules. The results showed that the water molecules are stripped out from the enzyme surfaces. It seems that the dual nature of organic molecules makes them favorable to solvate the enzymes. Radial Distribution Function (RDF) of the different parts of each organic molecule reveals that the behavior of each organic solvent in the vicinity of hydrophobic surfaces is similar to their behavior at the air-water interface. Structural analysis of root-mean-square-deviations (RMSD) and B-factors reveals that the flexibility of the enzymes decreased in the presence of most organic solvents, mainly in the CAP domain. Changes of other structural properties like radius of gyration and total solvent accessible surface areas are minimal. DbjA exists as a dimer and is more influenced by organic molecules. They penetrate to the amino acid network between monomers and influence their motion. The second study is the interaction of voltage-gated potassium channel Kv1.3 wild type and its mutants (Kv1.3_V388C, Kv1.3_V388C_H399T) with scorpion toxin (ChTX). Since there is no structure for Kv1.3, 94% sequence identity with Kv1.2 structure was used to make a homology model based on the Kv1.2 structure. MD structural analyses reveal that mutation of V388C changes the stability of selectivity filter by interrupting the amino acid network interactions behind the selectivity filter. The interaction of ChTX is also affected by the single mutant. ChTX is able to block wild type and double mutant channels but cannot occlude the pore entirely. Introducing the second point mutation H399T in the pore region reverts the structural changes back to the wild type. These results are entirely consistent with experimental results. Additionally, the binding energy of ChTX with the wild type mKv1.3 was investigated by the potential of mean force method, in the presence and absence of KCl solution. The results both in experiment and simulation show that, even though the unbinding process and dissociation rate is changing in the present of K+ ions, the binding energy is independent of K+ concentration. All together, the combination of computer simulations together with experiments provides new knowledge about channel-toxin interactions which could be helpful for drug design.
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The Use of Separation Methods for the Study of Selected Drugs and Pesticides in Water
Burešová, Jitka ; Hajšlová, Jana (referee) ; Chýlková, Jaromíra (referee) ; Kráčmar, Stanislav (referee) ; Vávrová, Milada (advisor)
This work is focused on the study of penetration of pesticides and pharmaceuticals in the aquatic environment. The aim was to develop and verify the optimal method for long-term monitoring of the occurrence of selected pesticides and pharmaceuticals in surface waters. Two frequently used analgesics ibuprofen and diclofenac, and carbamazepine that is used to treat epilepsy, were chosen from the group of drugs. A group of 41 pesticides were selected for monitoring too. The attention was focused on a group of urea pesticides and phenoxyacetic acids, as well as on selected pesticides falling to the group of priority substances or identified as environmental quality standards. Some of pesticides were selected because their consumption in the Czech Republic exceeds 30 tons a year. Liquid chromatography with tandem mass spectrometry (LC / MS / MS) was used for the determination of selected analytes in surface waters. Two optimized analytical method were developed. Ten analytes were determined in negative ion mode and 34 analytes in positive ion mode. Solid phase extraction (SPE) was used for purification and concentration of the samples. Developed methodology was validated and used for monitoring of selected compounds in samples of surface waters from the Morava River basin. Samples were collected on the rivers Morava and Svratka monthly for two years. Samples from the river Blata and stream Nivnička were collected for one year. Surface water samples were also collected from the river Litava. Four samples were taken throughout the length of the flow during one day. Smaller streams were chosen for monitoring because of the probability of occurrence of pesticides. They flow abundantly agriculturally cultivated areas. Drugs ibuprofen and diclofenac were detected in all taken samples, carbamazepine mostly. Among the most commonly occurring pesticides were bentazon, diuron, isoproturon, carbendazim, MCPA, MCPP, propiconazole, tebuconazole and 2,4-D.
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The Quality and Safety of Transfusion Products - a Study on Critical Aspects of Quality and Important Factors in Quality Control
Zimová, Renata ; Bláha, Milan (advisor) ; Gašová, Zdenka (referee) ; Turek, Petr (referee)
The quality and safety of transfusion products - a study on critical aspects of quality and important factors in quality control Products made from blood (transfusion products and blood derivatives) represent a special group of therapeutic preparations that have specific properties (danger of allergic reactions, transfer of infections etc.). The aim of this study was to show critical points of the process of producing safe, first-rate transfusion preparations at the level reflecting the progress in medicine and technology. Secondary aim was to analyze whether inspections of the State Institute for Drug Control, strict requirements and implementation of EU legislative have influence on the quality of work in blood establishments (BEs) and whether there are some relations between selected BEs with similar characteristics (the size and type of facility) and quality of work as this is presently a heated topic in discussions about restructuralization of transfusion service. The author analyzed her own experience gained during 129 inspections from the view of Good Manufacturing Practice (GMP) in BEs in the Czech Republic and abroad. The survey of results The most frequent and most important shortcomings (key and critical points) in production of transfusion products are parameters described in the chapter...
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The duration of the defensive reaction to a sudden attack
Straus, Jiří
Reaction time research is an important parameter for the examination of possible human motor responses, especially in forensic biomechanics. Factors influencing the reaction time can be classified by many criterions. The most relevant theoretical and practical factors are alcohol, stimulating drugs, age, training, fatigue, subject's orientation towards stimulus, warning of incoming stimulus and psychical tension. Primary, we were interested in impairment of human's reaction time as a result of alcohol administration. This article refers to presentation of results of our pilot research project, which treats of the reaction time on random stimulus that requires complex motor response. We found no impairment up to 0,3‰ BAC, but overall relationship is expressed by quadratic regression.
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Magnetic nanostructures with application potential
Bittová, Barbara ; Kalbáčová Vejpravová, Jana (advisor)
Title: Magnetic structures with application potential Author: Bc. Barbara Bittová Department: Department of condensed matter physics Supervisor: RNDr. Jana Poltierová Vejpravová Ph.D. Supervisor's e-mail address: jana@mag.cuni.cz Abstract: The thesis is mainly focused on the investigation of macroscopic and microscopic magnetic properties of selected nanomaterials containing cobalt and iron, and also the capability of our new device, scanning probe microscope Multimode V by Veeco, to directly visualise morphology and magnetic structure of these samples (Magnetic Force Miscroscopy, MFM). Investigated materials, such as CoFe2O4 nanoparticles and SiO2_Co_Si(111) thin films and multilayers are in general promising materials in many fields. In the medicine, the nanoparticles are used as the drug targets or contrast agents whereas in electronics, the (nano)granular thin films are the starting point in fabrication of high density storage media. The macroscopic magnetic properties of our samples are discusses in a view of superparamagnetic phenomena. The interactions in systems of nanoparticles are presented theoretically within the up-to date knowledge and also experimentally by demonstrating the behavior of the strongly-interacting, super-spin-glass system. The thin films are studied in term of their granular...
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