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Adhesive Properties of Branched Oligoesters Plasticized with Triethyl Citrate and Drug Release from These Carriers
Dvořáková, Petra ; Šnejdrová, Eva (advisor) ; Mužíková, Jitka (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ Department of Pharmaceutical Technology Rigorous Thesis Adhesive properties of branched oligoesters plasticized with triethyl citrate and drug release from these carriers Mgr. Petra Dvořáková SUMMARY The aim of this thesis was the study of adhesive properties of branched terpolymers of D,L-lactic acid, glycolic acid and dipentaerythritol, and release of fluconazole and aciclovir from these carriers. All tested carriers were plasticized with 30% of triethyl citrate (TEC). In the theoretical part of this thesis mechanisms of bioadhesion, biological substrates, polymers used in drug delivery systems and mechanisms of drug release are described. In the experimental part adhesivity of plasticized oligoesters was measured. Hydrated mucin isolated from porcine stomach was used as a model substrate for bioadhesion. The rate of adhesivity is the maximal force Fmax [N], which is required for the detachment of tested samples from the substrate. This force was related to the size of the contact surface and expressed in units mN/mm2 . The highest adhesivity was measured in oligoesters labelled 5D and 8D, which had low dynamic viscosity. However, it is impossible to state linear relationship between adhesivity and dynamic viscosity. The release of...
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Effect of temperature on gill morphology and ion transporter distribution in the gills of Koi carp (\kur{Cyprinus carpio L.})
KRATOCHVILOVÁ, Hana
The effect of temperature on the gill morphology and ion transporter distribution in the branchial epithelium of a freshwater teleost, the Koi carp (Cyprinus carpio, L.) was examined. Three different water temperatures were used to detect changes in expression level of transporter proteins in the gill epithelial cells. With increasing temperature, the expression level of all three ion transporters studied declined, and the gill lamellae protruded out of the cell mass, thus increasing the surface area of the branchial epithelium. A hypothetical organization of the transporter proteins within the ionocytes is proposed.
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Sensitive Layers for Optical Biosensors and Protein Chips
Rodriguez Emmenegger, César ; Brynda, Eduard (advisor) ; Lynn, Nicholas Scott (referee) ; Shukurov, Andrey (referee)
Sensitive layers for optical biosensors and protein chips The goal of this thesis was the development of sensitive surfaces for optical affinity biosensors detecting in complex biological media. The practical application of these surface-based technologies has been hampered by protein fouling from biological media, in particular blood plasma, where the vast majority of relevant analytes are present. The work of the thesis was centred in three main foci: Design and preparation of antifouling and non-fouling surfaces Evaluation and conceptualisation of their resistance to fouling from blood plasma and serum as well as other biological fluids Preparation of sensitive layers for detection in complex biological media Three approaches were used to prepare protein resistance surfaces, i) ω-functional self-assembled monolayers (SAM), ii) end-tethered polymers and iii) polymer brushes prepared by surface initiated controlled radical polymerisation. Investigation of proteins in the blood plasma deposits on PEG- based surfaces revealed that some fouling is unavoidable in PEG-based surface modifications. A novel type of non-fouling polymer brushes based on poly[N-(2-hydroxypropyl) methacrylamide] challenged the accepted ideas for the design of protein resistant surfaces. For the first time a...
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Construction of mouse polyomavirus chimeric VLP bearing melanoma epitopes
Kojzarová, Martina ; Drda Morávková, Alena (advisor) ; Tachezy, Ruth (referee)
Major capside protein of Polyomaviridae family viruses is able to selfassemble into virus-like particle (VLP) even without the presence of minor proteins, bind exogenous DNA non-specifically and recognise the receptor on the cellular surface. These characteristics determine its use as vector in gene therapy or immunotherapy. It was discovered before that MPyV VLPs significantly stimulate immune system and have strong adjuvant effect. Chimeric VLP derived from mouse polyomavirus carrying exogenous antigene or epitop is supposed to elicit specifically targeted immune response after immunisation. The main obstacle is choice of immunogene that is strong enough to cause adequate immune response. The goal of this thesis was to construct chimeric particles carrying epitop of malignant melanoma, one of the most immunogenic tumours, on their surface, using methods of genetic engineering. For future research of particle's immunogenic properties three types of particles were developed - particles with human and mouse melanoma epitopes, respectively and control particles with ovalbumine epitop. For the purpose of production of chimeric protein was used baculovirus expression system. It was verified then, with the use of electron microscopy, that introduction of tumour antigen into one of surface loops of VP1...
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Therapy of hematologic cancer
Baniková, Lucia ; Štaud, František (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucia Baniková Supervisor: Doc. PharmDr. František Štaud, PhD. Title of diploma thesis: Therapy of hematological malignancies Hematologic malignancies are cancers of the blood, bone marrow or lymph nodes. Individual hematological malignancies are defined and distinguished from one another essentially according to four parameters: clinical features, microscopic morphology, immunophenotype and molecular/genetic features. Despite the progress made in the last decade in the treatment of haematological malignancies, most of the patients still have a dismal prognosis. However, the improved knowledge of tumour biology opened the possibility to develop new 'intelligent' therapeutic strategies, the so-named targeted therapies. These approaches aim to selectively kill cancer cells by basing this selectivity on both the expression of a specific molecule on their surface or the activation of particular molecular pathways secondary to malignant transformation. Extensive research has led to the understanding that there are many more subtypes of haematological malignancies. Each of these subtypes behaves in its own particular way and requires its own particular therapy. Correct treatment depends...
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Cost analysis of engineering structures
Klec, Martin ; Kudrna, Jan (referee) ; Výskala, Miloslav (advisor)
The thesis titled "Cost analysis of engineering structures" presents a comparison of the life cycle costs of linear structures with an asphalt surface against the life cycle cost of linear structures with a concrete surface. The thesis deals with prices, costs, calculations and budgets in its theoretical part. The following chapters present history and current status, road constructions, life cycle of the construction and differences between concrete and asphalt covering. Practical part of the thesis is divided into three parts. In each sub-section, there is a practical example of comparing the costs of the life cycle of linear structure with the asphalt surface against the costs of the life cycle of linear structure with the concrete surface. Everything is expressed in graphs.
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Impregnace keramických membrán anatasem
Vacík, M. ; Hofman, R. ; Mastný, L. ; Šrank, Z. ; Brožek, Vlastimil
Catalytic properties of anatase have been known for a certain time but its practical usage has been hindered by technological limits of preparation of either compact massive intermediate products of various shapes which are necessary as a component of catalytic reactors or nanosized anatase powder. Our aim was to prepare ceramic membrane which would contain catalytic form of titanium oxide - i.e. anatase in its entire volume or on its surface only. Ceramic membranes of any shape (mostly tabular or piped) may be prepared by hot spattering technology. If plasma torch is used we call this process plasma spraying. The advantage of plasma spraying is in chance to provide semi-finished membranes with high dimension accuracy with defined radius of voids and/or as functionally graded materials, i.e. with changing concentration of some ceramic, metallic or combined components. The pores developed in membranes can be readily filled up with substances that allow modification of its properties. In this area, the possibility to impregnate membrane ceramic intermediates with other functional components, e.g. photocatalytic forms of titanium oxide, arises as well.
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Cancer treatment with polymer-bound cytostatic drugs and its potentiation through immunomodulation
Chmelová, Helena ; Kovář, Marek (advisor) ; Drda Morávková, Alena (referee)
Cancer treatment with polymer-bound cytostatic drugs and its potentiation through immunomodulation Poly[N-2-(hydroxypropyl)-methacrylamide] (PHPMA) is a synthetic water soluble and biocompatible polymer which can be used as a carrier of a cytostatic drug and an antibody as a targeting moiety. The antibody ensures the site-specific delivery of the conjugate. Nevertheless, even polymeric conjugates without any tumor-specific targeting moiety are passively accumulated within solid tumors via so called Enhanced Permeability and Retention (EPR) effect, in case that their molecular wight is at least 40 kDa. Antibody-targeted polymeric drugs have been shown previously to have a cytostatic activity in vitro and an antitumor activity in vivo. Since treatment of cancer diseases in practice is far from such ideal conditions and many tumors have no strictly specific marker suitable for targeted therapy, upgrading of the treatment efficacy represents the major challenge. One of the possible ways how to improve insufficient chemotherapy outcome can be using of a combination of polymer-bound cytostatic drug and potent immunomodulation able to induce a robust anti-cancer immune response. In this study, we have used B cell leukemia BCL1 as an experimental tumor model. BCL1 cells express surface IgM with an unique...
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Implication of the Gabaergic System in Altered Responses to Stress Associated to Maternal Separation
Martišová, Eva ; Pávek, Petr (advisor) ; Štaud, František (referee)
in English language - diploma thesis Implication of the Gabaergic System in Altered Responses to Stress Associated to Maternal Separation Eva Martišová This diploma thesis studied whether the GABA system alters responses to stress induced by maternal separation in rats. The aim was to examine the influence of maternal separation on GABA neurotransmission, in particularly, the biochemical markers of the system (levels of the neurotransmitter GABA, GABA A receptor expression), and to study of gender-related differences in behavioral and neurochemical processes in rats induced by maternal separation. In order to pursue the objectives, it was necessary to develop a model of maternal separation in rats. Rat pups were separated from their mother for three hours a day from postnatal day 2 to postnatal day 21 (in the postnatal period, when the reduced ability to respond to stressful stimuli). At postnatal day 23 pups were removed from mothers, divided into groups of the same sex. Then pups were without significant manipulation left to grow into adulthood. After reaching adulthood (> 60 days) rats were divided into two groups. The first group was killed by decapitation and different brain regions (anterior and temporal cortex, corpus striatum and hippocampus) were used to determine the levels of GABA using...
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Francisella Tularensis infection of macorphage-like cell line J774.2 - changes of surface and intracellular molecules
Novosad, Jakub ; Krčmová, Irena (advisor) ; Raška, Milan (referee) ; Kročová, Zuzana (referee)
Summary: Background: Francisella tularensis (F.t.) is a facultative intracellular bacteria, enrolled at the list of Centre for Disease Control (CDC) as a high risk bioterrorism agent, category A. There is a long-term effort to understand to the immunopathogenesis of F.t. infection. The aim of our study was focused on phenotype analysis (CD54, CD16/32 and CD86) and nitric oxide (NO) production analysis of murine macrophage-like cell line J774.2 durig F.t. live vaccine strain (LVS) in vitro infection. J774.2 cells were either untreated or stimulated either before or after F.t. infection by interferon gamma (IFNγ), lipopolysaccharide (LPS) separately or in its combination. Method: We followed up the expression of cell surface markers and NO production 3, 6, 9, 12 and 24 hours after initiation of infection with or without stimulation using flow cytometry and Griess method respectively. The expression was followed as either absolute value of mean fluorescence index (MFI) or as relative change of MFI (∆MFI). Murine macrophage-like cells (J774.2) were incubated in cultivation flasks (2x106 cells/10ml of medium Dulbecco's MEM with Glutamax-1 with 10% BSA). The cells were activated with 10 or 50 ng of LPS / 1ml of medium or with 100 or 1 000 I.U. of IFNγ / 1ml of medium separately or in combination (10 ng/ml and 100...
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