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Interaction of gilteritinib with OCT1 and OCT2 transporters; relation to conventional therapy of acute myeloid leukemia.
Novotná, Kateřina ; Čečková, Martina (advisor) ; Hofman, Jakub (referee)
Univerzita Karlova Farmaceutická fakulta v Hradci Králové Katedra Farmakologie a toxikologie Student: Kateřina Novotná Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Interaction of gilteritinib with OCT1 and OCT2 transporters; relation to conventional therapy of acute myeloid leukemia. Gilteritinib is one of the recently approved drugs which is primarily used in the treatment of relapsed/refractory acute myeloid leukemia (AML) with mutated FMS-like tyrosine kinase 3 (FLT3) receptor. In this project, gilteritinib was investigated in terms of its ability to interact with solute carrier (SLC) membrane transporters, namely with OCT1 and OCT2. These membrane proteins play a role in uptake of endogenous compounds and also drugs into the cells of main elimination organs (liver, kidney), but also to cancer cells. In particular, we wanted to examine potential interaction with daunorubicin and mitoxantrone, drugs traditionally used in AML therapy. First, we performed accumulation study and evaluated, whether gilteritinib is potential inhibitor of OCT1 and OCT2 studying differential uptake of daunorubicin and mitoxantrone into MDCKII-OCT1 and MDCKII-OCT2 cells based on OCT1 and OCT2 inhibition by gilteritinib. Secondly, the study evaluating the transfer of gilteritinib across the...
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Analysis of interdisciplinary approach to children with orofacial clefts
Novotná, Kateřina ; Korandová, Zuzana (advisor) ; Klenková, Jiřina (referee)
The topic of this diploma thesis is an analysis of interdisciplinary approach to children with orofacial clefts. The first chapter deals with theoretical base and defines terminology - communication, communication disabilites. It also defines anatomy and physiology of nasal cavity and oral cavity. The second chapter relates to issues of orofacial clefts. It describes classification, etiology, symptomatology, prevention, aestetic and psychosocial impacts and orofacial cleft children care. The third chapter deals with occurence of communication disabilites of children with orofacial clefts. It focuses on the definition of palatholaly, velopharyngeal inadequacy and it describes various linguistic levels and speech therapy and intervention. The fourth chapter is empiric and it deals with analysis of interdisciplinary approach to children with orofacial clefts. In research processes there were used scientific literature analysis, anamnestic data analysis and available specialized materials analysis. Based on all of these materials six case studies were created. Main goal of this empiric chapter was to analyze interdisciplinary approach to children with orofacial clefts. Partial goals were to analyze whether information provided by experts and doctors to parents of newborn children with orofacial cleft...
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Roles of environmental factors and microbiome in type 1 diabetes
Novotná, Kateřina ; Funda, David (advisor) ; Cahová, Monika (referee)
Type 1 diabetes mellitus (T1DM) is an insulin-dependent autoimmune disease. Its onset is characterized by an autoreactive self-destruction of β-cells within pancreatic islets. T1DM is influenced by multiple genetic predispositions, but since the incidence of the disease has increased dramatically in the past decades, especially in developed, western-type countries, the importance of the environmental factors has become obvious. There are various significant environmental influences that need to be addressed in the equation of variables. This bachelor thesis deals with the environmental variables and their mechanisms in T1DM and focuses on several areas of interest. It introduces frequently used spontaneous animal model of T1DM, pathogenetic mechanisms and T-cells in T1DM as well as regulatory immune cells and their mechanisms, in the light of hygiene and another hypothesis. Next it addresses the role of intestinal microbiota, dietary factors, mucosal immunity, their mechanisms and interactions in T1DM and extends to other, less researched, but important environmental variables such as circadian rhythm in connection with circadian gene expression depending on the rhythmicity of light/dark rotation and timing of food intake throughout the day, psychological/oxidative stress, and the effects of...
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The GAP in Brno
Novotná, Kateřina ; Likavčanová, Lenka (referee) ; Palaščák, Michal (advisor)
BACHELOR'S WORK SOLVES THE DESIGN OF AN APARTMENT BUILDING WITH POLYFUNCTION IN THE OLD BRNO LOCATION ON KŘÍŽOVÁ STREET NEAR MENDLOVO SQUARE. THE Plot IS INTERESTED IN THE ENTIRE UNSTOPPED LENGTH OF THE STREET. IN MY DESIGN, I CONSIDERED FOLLOW-UP TO THE PLANNED REVITALIZATION OF MENDLOV SQUARE. OBJECT DESIGNED AS AN APARTMENT BUILDING WITH PARTIAL POLYFUNCTION. THIS FUNCTION IS THE MOST BENEFICIAL DUE TO THE LOCATION IN THE CITY CENTER. THE SIZE OF APARTMENTS IS OPTIMAL, THANKS TO WHICH WE CAN CONSIDER OVER LARGE DEMAND. GLASS WINDOWS FOR STYLE RECOVERY ARE PARTIALLY LOCATED IN THE PARTERY. ANOTHER POINT OF INTEREST IS AN UNUSUAL CASCADE FACADE, WHICH CAN ATTRACT THE VIEWS OF LOCALS AND TOURISTS. THE TOTAL MASS OF THE OBJECTS WAS DECIDED BY THE SHAPING OF THE NORTH SHIELD OF THE EXISTING HOUSE WITH THREE SURFACES TO WHICH I FOLLOWED. THE CONCEPT OF THE BUILDING WAS A FAN ROTATION. SO THAT THE PARTER DOES NOT OPEN, IT IS PARTIALLY OPENED INTO THE INTERIOR BLOCK, WHERE THE PUBLIC GREENERY, RESIDENT PARKING AND ACCESS TO THE APARTMENTS ARE THROUGH OPEN GALLERY.
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Perception of foreigners in Czech society
Novotná, Kateřina ; Vávra, Martin (advisor) ; Černý, Karel (referee)
The submitted diploma thesis deals with the view of the majority society on the population of foreigners in the Czech Republic. In recent years, this is a frantically discussed topic, which is given a lot of space in terms of quantity, but not in terms of quality, taking into account the number of publications and research. The aim of the thesis is to find out how individuals belonging to the majority population perceive foreigners mainly with regard to partial topics, which are the actor's definition of foreigners, prejudices and stereotypes against foreigners, interest in this issue, attitudes towards foreigners from different countries or areas and experiences with foreigners. These views and attitudes were obtained through qualitative methodology, specifically through semi-structured interviews. The research involved informants across basic demographic indicators (gender, age, education, size of place of residence). Due to the qualitative nature of the research, it is not possible to generalize the results of the work directly to the entire majority population. However, they provide a comprehensive insight into the structure and conditionality of attitudes towards foreigners. Key words: foreigner, stay in the Czech Republic, prejudice, stereotype, attitude
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Design and Synthesis of Prodrugs of 6-Diazo-5-oxo-L-norleucine; Potential Treatment for Glioblastoma
Novotná, Kateřina ; Majer, Pavel (advisor) ; Rýček, Lukáš (referee)
6-Diazo-5-oxo-L-norleucine (DON, 1) is a non-standard amino acid with proven antitumor activity found in soil bacteria of the genus Streptomyces. However, due to the considerable systemic toxicity manifested mainly in the gastrointestinal tract, DON alone is not a suitable clinical candidate for the treatment of cancer. One of the ways to solve the problem of its toxicity is the reversible structural modification of this molecule by protecting both its amino group and carboxyl functional group, by preparing the so-called prodrug of DON. The prepared prodrug may suitably alter the distribution of DON in the body and at the same time increase its permeability to brain tissue. Due to this structural modification, its side effects can be eliminated and a substance for the treatment of brain tumors, such as glioblastoma multiforme (GBM), can potentially be formed. In my dissertation, five strategies for the specific delivery of DON to the brain using different types of its prodrugs are discussed. The new prodrugs are designed to be either capable of spontaneous penetration across the blood-brain barrier or of being a substrate for one of its influx transporters. At the same time, these prodrugs should be stable in other metabolically active organs and blood plasma in order to sufficiently reduce the...
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Assessment of primary students with a focus on verbal assessment in the bilingual programme
Richterová, Jana ; Novotná, Kateřina (advisor) ; Vallin, Petra (referee)
The thesis focuses on primary school pupil's assessment in the bilingual program. The research is based on the way that the pupils are being assessed in the program, particularly in the half-year and in the end of the school year. The theoretical part of the thesis refers to the definition of the important terms, which are connected with the assessment and bilingual education. The important terms are for example school assessment, assessment, also its forms, functions and principles. The thesis is focused above all on the term verbal assessment, which is also defined in the theoretical part for example as what is its principle, positive and negative parts or how is the verbal assessment formulated. Last but not least in the thesis is defined the difference between the bilingual education, teaching by CLIL and the selected programme. The practical part was realized as a qualitative research, whose main methods of collecting were interviews and analysis. The interviews were performed at the primary school where the programme operates with three different groups of people who are a part of the programme. These are the Czech teachers, English teacher and pupils. The document analysis of the verbal assessments was realized as its content categorization thanks to the coding, which afterwards led to the...
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Bilingual education from the perspective of a primary school pupil
Sochovská, Markéta ; Vallin, Petra (advisor) ; Novotná, Kateřina (referee)
The diploma thesis focuses on bilingual education from the perspective of primary school pupil and describes learning through two languages in broader context. The theoretical part characterizes the term of bilingual education and describes its various models and forms that are implemented in schools. The second part of the thesis employs semi-structured interviews and tries to find out what is the opinion of the pupils of Toscool bilingual program. The goal is to interpret the data and suggest a set of recommendations to improve the bilingual program. KEYWORDS bilingualism, bilingual education, mother language, bilingual family, language education, perspective of a student
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