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Sexual dimorphism of rat gut microbiota composition and intestinal immunity
Kalousová, Pavla ; Kovařík, Miroslav (advisor) ; Jílek, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Pavla Kalousová Supervisor: PharmDr. Miroslav Kovařík, Ph.D. Title: Sexual dimorphism of rat gut microbiota composition and intestinal immunity Background and Aim: Many factors can influence the composition of gut microbiota and the immune system. It is well-known that one of those factors is sex. This sexual dimorphism can lead to a specifically adjusted treatment of diseases for different gender and nutritional interventions. This study focuses on analysing sexual differences in gut microbiota and intestinal immunity in adult rats. Methods: Caecal content from 12-week-old female and male Wistar rats were collected and analysed by DNA-sequencing technique to characterize microbiota composition. ELISA test was performed to quantify the concentration of IgA in faeces and gut wash. Flow cytometry determined the concentration of IgA-coating bacteria in faecal samples. Results: Metagenomic analysis revealed that female gender presents 1 phylum, 4 families, 13 genera, and 13 species which are not present in male rats. Only one male-specific colonization was observed at the species level. Quantitative analysis showed a higher proportion of Firmicutes phylum in males which was associated with...
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Study of interactions of antiviral drugs with intestinal drug efflux ABC transporters
Huličiak, Martin ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martin Huličiak Supervisor: PharmDr. Lukáš Červený, Ph.D Title of diploma thesis: Study of interactions of antiviral drugs with intestinal drug efflux ABC transporters P-gp, MRP2 and BCRP are efflux transporters, members of the family of ATP binding cassette (ABC) transporters. These transporters are located on the apical membrane of the intestinal epithelium, where they may limit absorption of orally administered drugs. Study of drug interactions with/on intestinal efflux transporters is necessary to provide safe and effective treatment. The Caco-2 cell line is FDA recommended in vitro model of intestinal barrier and it is used for bidirectional testing of substrates and inhibitors of ABC transporters in preclinical research. However, this methodology has several shortcomings, so the need of introduction of new experimental models is increasing and the ex vivo method based on human or rat intestine is a promising option. Precision-cut intestinal slices (PCIS) represent a mini-model of the organ and contain all types of cells of the tissue. We used both in vitro model using Caco-2 cell monolayers for drug transport study and in our lab established ex vivo method of PCIS for accumulation study...
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In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters
Jahodová, Michaela ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Michaela Jahodová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters The absorption of orally administered drugs takes place especially in the intestine, where it can affect by the activity of drug's ABC transporters located on the apical membrane of the intestinal epithelium. Study of drug interactions in intestinal ABC transporters is essential to ensure effective and safe pharmacotherapy. Testing of bi- directional transport on Caco-2 cells is generally the preferred method for in vitro evaluation of substrates and inhibitors of ABC transporters. Drawbacks of the Caco-2 model increase the need and necessity to introduce new models. A great potential is the involvement of ex vivo methodologies in the human or rat intestine. The aim of the work was to introduce an in vitro methodology using the Caco-2 cell monolayer and the ex vivo methodology of precision-cut rat intestinal slices. By the bi-directional transport method, we analyzed drug interactions of the model substrate P-gp and BCRP Rhodamine 123 (RHD123) and clinically-used tenofovir...
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee) ; Herichová, Iveta (referee)
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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Linguistic picture of the particular somatisms in Czech
Škanderová, Adéla ; Janovec, Ladislav (advisor) ; Chejnová, Pavla (referee)
The bachelor thesis deals with a lingvistic picture of the world of the particular somatisms, namely the components of the digestive system (stomach, bile, gall bladder, heartburn, intestine). The theoretical part covers the term cognition, cognitive science and, logically, cognitive linguistics. Furthermore, it includes the indispensable and key topics which have to be taken into account to understand the concept of the linguistic picture of the world, i.e. conceptualization, categorization, metaphor, anthropocentrism etc. The practical part is interested in the real occurence of the somatisms in various language contexts. In particular, their occurence in collocations, phraseology and idiomatic expressions. The analysis is based on the profile theory and its image schema. The lingustic backround is supplemented with the psychosomatic knowledge because it appears to be a helpful science branch while completing and considering the possible connection between the occurence of somatism in the language of the specific culture and extralinguistic reality.
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