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TRANSPORT OF NSAIDs ACROSS A BLOOD-BRAIN BARRIER IN VITRO MODEL BASED ON CELL LINE PBMEC/C1-2
Nováková, Iveta ; Štaud, František (advisor) ; Červený, Lukáš (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Iveta Nováková Consultant: Prof. PharmDr. František Štaud, Ph.D. Title of Thesis: Transport of NSAIDS across a blood-brain barrier in vitro model based on cell line PBMEC/C1-2 The blood-brain barrier (BBB) has a prominent role in regulation of the transport of substances into and out of the central nervous system (CNS). Partly, the BBB inhibits the entrance of substances harmful for the brain, it regulates the delivery of needed substances and it takes part in efflux of useless substances as well. The equilibrium of these regulation systems is essential for the correct function of the CNS, without which the homeostasis would be disturbed. Non-steroidal anti-inflammatory drugs (NSAIDs) are very well known for their anti- inflammatory effect, for reduction of fever and pain. Due to their bright, everyday usage, some side effects on the brain were observed (sleepiness, giddiness, nausea). This has evoked the question, how NSAIDs can cross the BBB. PBMEC/C1-2 cell monolayer was used as an in vitro model of the BBB. The transport of following NSAIDs was investigated: celecoxib, diclofenac, ibuprofen, lornoxicam, meloxicam, piroxicam and tenoxicam. The experiments were carried out...
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Transport nesteroidních antiflogistik přes hematoencefalickou bariéru in vitro
Nováková, Iveta ; Červený, Lukáš (referee) ; Štaud, František (advisor)
The migration of substances between the blood circulation and the central nervous system (CNS) is regulated by the blood-brain barrier (BBB). Small, lipophilic molecules such as carbon dioxide, oxygen or ethanol can pass the BBB by passive, transcellular diffusion, while the paracellular transport of hydrophilic substances is restricted by intercellular tight junctions. Due to accessory transport systems, the BBB is able to regulate specifically the permeation of substances (e.g. nutrients) (Ballabh et al., 2004). Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used substances world-wide, yet little is known about their ability to cross the BBB. Since NSAIDs may exhibit CNS side effects including dizziness, headaches and drowsiness we sought to study the transport of several NSAIDs (celecoxib, diclofenac, ibuprofen, lornoxicam, meloxicam, piroxicam and tenoxicam). Both single studies and group studies were carried out applying either a single substance or several substances simultaneously across the BBB in vitro model based on the human cell line ECV304. The permeability data were normalized to the internal standards diazepam and carboxyfluorescein to account for cell layer's variabilities. According to our studies, it was confirmed that crossing of ibuprofen and...
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Serological evidence of Lyme borreliosis
NOVÁKOVÁ, Iveta
This bachelor thesis deals with Lyme borreliosis (Lyme disease). Lyme disease has a worldwide distribution. It is caused by several species of the Borrelia bacteria that vary according to geographic occurrence. In our country, this disease is transmitted, above all, by hard ticks of the genus Ixodes ricinus (Other genera are prevalent in other parts of the world.). These ticks are present in a wet environment, e.g. in the woods or in high grass. This poses a higher risk for people who stay or work in similar sites; i.e. lumberjacks, but also for children who spend their free time in the great outdoors. According to symptoms Lyme disease can be divided into three stages: stage 1 is called early localized Lyme borreliosis, stage 2 is called early disseminated Lyme disease, and stage 3 is called late disseminated, or persistent Lyme disease. The most frequently reported typical early sign is a rash called erythema migrans (EM). EM is an oval reddish skin eruption created at the site of the tick bite; this skin condition may gradually disappear. Other symptoms are: borrelial lymphocytoma, conjunctivitis, neuroborreliosis, Lyme carditis, etc. Therefore, generally recommended preventive measures should be used before each trip to an area infested with ticks in order to avoid contact with the ticks. Lyme disease is treated with antibiotics that are administered to a patient upon confirmation of the disease. As a rule the following antibiotics are prescribed: cephalosporin, macrolide, tetracycline or penicillin, depending on at what stage of the disease medication is prescribed and whether the patient shows typical Lyme disease symptoms. Laboratory diagnostics of Lyme disease relies on direct and indirect methods. The direct methods include: cultivation of Borrelia, hybridization, immunoelectron microscopy, and the PCR method (polymerase chain reaction) applied to prove the presence of borrelial DNA. Of all the methods, PCR is most often the method of choice. The indirect diagnostic methods are: indirect immunofluorescence, Western blot (WB) and ELISA tests (enzyme linked Immunosorbent Assay). These methods are used mainly to establish specific antibodies of the class IgM and IgG. The aim of this thesis was to analyze patients' samples for the presence of Lyme disease by means of the ELISA test and the Western blot, to test these methods, and to evaluate their results. The individual samples of serums, liquors and punctuates to be analyzed were provided by the Teaching Hospital in Pilsen, specifically by the Department of Serology and Parasitology. The samples must be diluted before examination. The method ELISA involved the use of a device manufactured by Dynex, DSX (an automated ELISA system). This device determines IgM and IgG antibodies in samples and facilitates analysis of up to 96 patient samples during a single measurement. The author of this thesis used this opportunity to try the manual determination of the ELISA test whose use is rather infrequent, especially in situations where a large number of samples need analyzing. The further examination of the IgM and IgG antibodies was accomplished with a Western blot, specifically by means of a commercial set for manual determination. The author applied the ELISA test to a total of 90 samples in the IgM class. 4 samples were borderline and 4 were positive. The same method was used to analyze the same 90 samples in the IgG class where 4 samples were positive. The Western blot method was used to examine 98 samples. The IgM class was borderline in 5 samples and positive in 18 samples. The IgG class was borderline in 5 samples and positive in 30 samples. Following laboratory examination the results of serological tests and clinical symptoms must be considered by a physician who suggests a suitable method to prove Lyme disease and exclude others.
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Study of thermal insulation properties of cement concrete exposed to high temperature
Nováková, Iveta ; Sitek,, Libor (referee) ; Bodnárová, Lenka (advisor)
Master`s thesis is divided in to two parts, practical and theoretical. In theoretical part are listed basic information’s about light weight concrete, special emphasis are given to characteristic and practical application of compact light weight concrete with Liapor aggregates. In this study is described influence of high temperature on concrete structure and chemical, mechanical and physical changes, which take place during exposal to high temperatures. Further is evaluated surface permeability of concrete and addition of polypropylene fibres to concretes resistive to high temperatures. The practical part deals with design, production and testing of cement based concrete with use of different aggregates (light weight aggregates Liapor, basalt). The properties and use for applications in high temperatures is also mentioned. The influence of high temperature on strength, absorption, thermal conductivity, changes of surface permeability and degradation of testing specimens due to heat loads according to normative heat curve (ISO 834). For better transparency are experimental tests divided in to five phases and the measured values are evaluated on the end of each phase. In conclusion are resumed all knowledge’s obtained by testing and evaluated the most suitable formulation. The approach for further research is also mentioned.
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Possibilities of using recycled concrete as fine aggregate replacement in cement screeds
Nováková, Iveta ; Brožovský,, jiří (referee) ; Hubáček, Adam (advisor)
The bachelor thesis deals with summary of knowledge about cement-based screed with partial replacement of natural aggregates by recycled aggregates. Special emphasis is given to describing and studying characteristics of cement-based flowscreed. In this study are described feedstocks with requirements which they must meet and test methods for testing properties of screeds. One part is also given to practical application of cement-based flowscreed with partial replacement of natural aggregates by recycled aggregates.
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Creation of the distribution chain for textile products
NOVÁKOVÁ, Iveta
The thesis is focused on the creation of the logistics chain for textile products. The issue was analyzed and suitable suppliers after their selection. Were then identified the best transportation options to the Czech Republic in accordance with the optimized cost effectiveness. The next stage of the analysis of demand forecast, which then followed the method cost-effective order quantities. In the last stage on the basis of analyzes to create the optimum distribution.
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The Product Mix of company Cais
NOVÁKOVÁ, Iveta
The aim of my thesis was to describe product mix in a chosen company. I chose bakery Vladimír Cais in Vlachovo Březí for this work. Another aim was to analyze the product portfolio by means of the Boston Matrix and to propose possible modifications of the product portfolio based on the results. There were also a SWOT analysis and a product life cycle compiled within the analytic part.
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Adaptation of employees in a company
Nováková, Iveta ; Stříteský, Marek (advisor) ; Šikýř, Martin (referee)
Bachelor Thesis focuses on adaptation of new employess at L'Oréal Česká republika s.r.o. The aim is to analyse adaptation process, evaluate it and propose measures that would lead to improvements. Using these proposals, the company could adjust its adaptation process and thus contribute to performance improvement, fluctuation stabilisation or higher employees satisfaction. Questionnaire has been used for this analysis.
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