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Effect of darunavir and atazanavir on ABCB1 and CYP3A4 expression in human precision-cut intestinal slices
Hradecká, Tereza ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Student: Tereza Hradecká Department of Pharmacology & Toxicology Supervisor: PharmDr. Vokřál Ivan, Ph.D. Oral administration of drugs is currently the most common and most convenient method of drug administration. Most drugs administered in this way are subsequently absorbed in the intestine and enter the systemic circulation. The absorption of drugs in the intestine can be influenced by a number of factors. Factors influencing drug absorption include, for example, efflux transporters or biotransformation enzymes. Currently, the most studied intestinal transporter is P-glycoprotein (P-gg), which is able to transport various substances back into the lumen of the intestine. Another factor affecting the absorption of drugs is intestinal metabolism, which in the first phase often takes place through enzymes from the cytochrome P450 family, while most drugs are metabolized through CYP3A4, which is also widely represented in the intestine. The activity of efflux transporters and biotransformation enzymes can be reduced (inhibition) or, conversely, increased (induction) by some drugs. This can subsequently lead to a whole range of drug interactions. The possible pharmacokinetic consequences of enzyme or transporter induction depend on the specific...
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Effect of dexamethasone on ABCB1 and CYP3A4 expression in human precision-cut intestinal slices
Podhorná, Pavla ; Vokřál, Ivan (advisor) ; Ambrož, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Pavla Podhorná Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Effect of dexamethasone on ABCB1 and CYP3A4 expression in human precision-cut intestinal slices Dexamethasone is a corticosteroid that has anti-inflammatory, immunosuppressive, and anti-allergic effects. The mechanism of dexamethasone action involves its ability to bind to intracellular glucocorticoid receptors, which are present in many types of cells, including intestinal mucosal cells. Upon binding to these receptors, it translocates to the nucleus of the cells and affects gene expression. This mechanism also affects the expression of genes important for the metabolism and transport of xenobiotics in the intestinal mucosa. The most important such genes include ABCB1, an important intestinal transporter, and CYP3A4, a significant biotransformationenzyme.Their localizationinthe wall of the small intestine can significantlyaffect the absorptionof orallyadministereddrugs.Studyingdrug interactions with this transporter and biotransformation enzyme is important for safe and effective pharmacotherapy. To determine whether dexamethasone affects the expression of these genes in the intestinal barrier,we used the method of...
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Effect of darunavir and atazanavir on ABCB1 and CYP3A4 expression in human precision-cut intestinal slices
Hradecká, Tereza ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Student: Tereza Hradecká Department of Pharmacology & Toxicology Supervisor: PharmDr. Vokřál Ivan, Ph.D. Oral administration of drugs is currently the most common and most convenient method of drug administration. Most drugs administered in this way are subsequently absorbed in the intestine and enter the systemic circulation. The absorption of drugs in the intestine can be influenced by a number of factors. Factors influencing drug absorption include, for example, efflux transporters or biotransformation enzymes. Currently, the most studied intestinal transporter is P-glycoprotein (P-gg), which is able to transport various substances back into the lumen of the intestine. Another factor affecting the absorption of drugs is intestinal metabolism, which in the first phase often takes place through enzymes from the cytochrome P450 family, while most drugs are metabolized through CYP3A4, which is also widely represented in the intestine. The activity of efflux transporters and biotransformation enzymes can be reduced (inhibition) or, conversely, increased (induction) by some drugs. This can subsequently lead to a whole range of drug interactions. The possible pharmacokinetic consequences of enzyme or transporter induction depend on the specific...
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Effect of vitamin D on ABCB1 and CYP3A4 expression in human precision-cut intestinal slices
Mazurová, Tereza ; Vokřál, Ivan (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Tereza Mazurová Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Effect of vitamin D on the expression of ABCB1 and CYP3A4 in human intestinal slices When drugs are administered orally, their absorption is significantly affected by the intestinal barrier. This barrier expresses a variety of efflux and uptake transporters, as well as first and second-phase biotransformation enzymes. The most important efflux transporter in the intestinal barrier is P-glycoprotein, which has a broad substrate specificity. Among the first-phase biotransformation enzymes, cytochrome P450 3A4 is the most important. Their function is to protect the human body from the toxic effects of xenobiotics, including drugs. Many clinically important drugs act as substrates, inhibitors or inducers in relation to these proteins, which may result in an increased risk of drug interactions. A plethora of dietary supplements or medicines containing vitamin D can be found in the pharmacy. It is used for the proper development of bones and teeth, for the proper function of the immune system or for the treatment of osteomalacia, rickets or osteoporosis. Limited information is available on its effects on P-gp and...
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Postnatální změny střeva králíka.
ŠTĚCHOVÁ, Kristýna
The small intestine is an important organ of the gastrointestinal tract. It is undergoing the influence of internal and external factors significant adaptive changes in the postnatal life. The aim of the thesis was to provide information about the morphometric changes in various sections of the small intestine of rabbits during the 19 days of postnatal development study. It was measured length of the individual sections of the small intestine at the age of 0, 5, 10, 14 and 19 days and it was sampled for morphometric examination mucosa. The length and width of villi, the depth of crypts of Lieberkühn and the height of enterocytes were evaluated under a light microscope. The average length of the small intestine was 61,4?2,4 cm at new born rabbits and when they were 19 days old it was 106,5?9,1 cm. The most noticeable increase was observed at ileum (124,4 %). On the contrary the lowest increase was observed at jejunum (63,1 %). In the duration of 19 days development of the rabbits, the highest size of villi and crypts of Lieberkühn was in duodenum, on the other hand the lowest was in jejunum. We could also observe temporary stagnation of the growth of enterocytes in all parts of the small intestine. From the results follow that in the duration of the early postnatal development, it is duodenum, which is able to adapt in the fastest way
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