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Interaction of 7,8-dihydroxyflavone with physiological metals
Streďanská, Aneta ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Aneta Streďanská Supervisor: prof. Přemysl Mladěnka, Pharm.D., PhD. Consultant: Zuzana Lomozová, Pharm.D., PhD. Title of thesis: Interactions of 7,8-dihydroxyflavone with physiological metals 7,8-dihydroxyflavone belongs to the phenolic substances collectively referred to as flavonoids. Flavonoids are bioactive components abundantly distributed in the daily diet with the ability to modulate health and disease through miscellaneous mechanisms including their antioxidant activity. However, they can also exhibit prooxidative effects under certain conditions. Due to this fact, which is related to individual factors, i.e. presence of various substitutions on the flavonoid come, it is therefore essential to understand the redox behavior based on the relationship between structure and effect and to understand their physiological, pharmacological and thus also potential toxic properties. The interaction with physiological metals is determined by the structure of the molecule through the dihydroxy moiety in positions 7 and 8. These mentioned metals are essential for many biochemical processes in biological systems. Their homeostasis is strictly regulated in the human body and disruption of this...
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Study of interactions of betrixaban with antiretrovirals in an intestinal barrier model
Lukáčová, Ivana ; Vokřál, Ivan (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Ivana Lukáčová Supervisor: PharmDr. Vokřál Ivan, Ph.D. Title of diploma thesis: Study of interactions of betrixaban with antiretrovirals in an intestinal barrier model Oral administration of drugs is a practical and simple choice for the patient, which ensures high adherence to the treatment, and thanks to that, it is the most frequently used dosage form. The vast majority of these drugs penetrate intestinal barrier after oral administration, and many clinically significant drug interactions can occur right in this place. Several determinants, including membrane transport systems, have an impact on whether or not the effect is manifested. The most observed and studied transporter from the superfamily of ABC transporters in the small intestine is undoubtedly P-glycoprotein (P-gp). It functions as an efflux pump preventing the transfer of xenobiotics, including drugs, into the systemic circulation, thereby protecting the organism and thus creating a barrier against the possible toxic effect of substances. The direct-acting anticoagulant betrixaban is a substrate of P-gp in the intestinal barrier, and therefore simultaneous administration with drugs inhibiting or inducing this transporter can...
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Study of intestinal transporters and their role in drug absorption
Huličiak, Martin ; Červený, Lukáš (advisor) ; Mladěnka, Přemysl (referee) ; Chládek, Jaroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Kralove Training Workplace Department of Pharmacology and Toxicology Doctoral Degree Program Pharmacology and Toxicology Candidate Mgr. Martin Huliciak Supervisor Assoc. Prof. PharmDr. Lukas Cerveny, PhD. Advisor PharmDr. Ivan Vokral, PhD. Title of Doctoral Thesis Study of intestinal transporters and their role in drug absorption Oral drug administration is a widely accepted method due to its convenience and cost- effectiveness, with the small intestine playing a crucial role in drug absorption, thus affecting bioavailability and serving as a potential site for drug-drug interactions (DDIs). Efflux drug transporters such as P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), along with metabolizing enzymes such as cytochrome P450 3A4 (CYP3A4) at the intestinal barrier, significantly contribute to DDIs. Risk factors for DDIs include comorbidities, advanced age, and polypharmacotherapy. People living with HIV requiring antiretroviral therapy (ART) are particularly susceptible to DDIs, especially when co-infected with HCV. Antivirals, commonly used in ART and in the treatment of HCV infection, can interact with efflux transporters and CYP enzymes, affecting drug efficacy and safety. Therefore, this study mainly focuses on the DDIs of...
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Effect of abacavir on the expression of nucleoside transporters, adenosine receptors, and enzymes involved in adenosine synthesis and biodegradation in trophoblasts
Gala, Viktor ; Červený, Lukáš (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Viktor Gala Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Effect of abacavir on the expression of nucleoside transporters, adenosine receptors, and enzymes involved in adenosine synthesis and biodegradation in trophoblasts The nucleoside reverse transcriptase inhibitor (NRTI) abacavir (ABC) is now the mainstay of combination antiretroviral therapy (cART) for HIV in pregnant women. The introduction of cART, along with several other measures, has reduced mother-to-fetus transmission of HIV to less than 1% in recent years. The placenta is a key organ for the health of both the fetus and the mother. Imbalances in placental development can result in adaptive changes and fetal programming errors. cART recommended in pregnancy is known for its good safety profile, but some epidemiological studies suggest a higher risk of reduced fetal weight, preterm birth, etc. The placenta is a rapidly growing organ dependent on the supply of building materials that resembles tumor growth in certain aspects. Nucleosides are promoters of tumor proliferation and are involved in the development of immunotolerance. The placenta is complexly equipped for nucleoside synthesis, uptake,...
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Changes of internal organs after percutaneous exposure to sulfur mustard
Šulová, Veronika ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Šulová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. External supervisor: pplk. doc. MUDr. Jaroslav Pejchal, Ph.D. et Ph.D. Title of diploma thesis: Changes of internal organs after percutaneous exposure to sulfur mustard Sulfur mustard is a chemical warfare agent belonging to the group of blistering agents. The theoretical section of the thesis is mainly focused on the description of acute toxic effects, the mechanism of action, and deals with the current possibilities of poisoning therapy. The experimental section is focused on monitoring the effect of sulfur mustard poisoning in the liver, lung, and kidney of female C57BL/6J mice after the percutaneous administration. This work aimed to evaluate markers of oxidative stress and histopathological changes of the selected organs at 3, 5, and 7 days after the poisoning. Ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) methods were used to determine markers of oxidative stress. Histopathological changes were evaluated microscopically using the hematoxylin-eosin staining method. The airness of the lung parenchyma was also assessed by computer image analysis. First, the LD50 of sulfur mustard was...
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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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Reactive extrusion of polymers by peroxides
Červený, Ladislav ; Petruš, Josef (referee) ; Kučera, František (advisor)
Diploma thesis deals with processing of two types of PP, HDPE, LDPE, PET, PA, PS, PMMA and ABS by reactive extrusion in presence of peroxides. The theoretical part summarizes existing knowledge about processing of used polymers. Reactive extrusion was carried out with a single screw extruder at 260 °C, 30 rpm and 60 rpm depending on peroxide used. One type of PP was processed in presence of Luperox 101, hydrogen peroxide, dicumyl peroxide and potassium persulfate. Luperox 101 and hydrogen peroxide were chosen for reactive extrusion of other polymers. The efficiency of selected peroxides on radical modifications of individual polymers during processing was evaluated by methods of rheological (MFI), structural (FTIR) and thermal (DSC) analysis.
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Rheological study of starch suspensions for surface coatings of glass fibres
Červený, Ladislav ; Řehoř, Radek (referee) ; Klučáková, Martina (advisor)
Bachelor thesis deals with the rheological study of model starch suspension systems which are intended for surface modification of glass fibers. The rheological methods were used to record a course of the gelatinization process in selected types of film-forming starch suspensions. Based on measured data were determined their initial and final gelatinization temperatures which can be used to save energy in the manufacturing process of surface coatings of glass fibers. The increase in apparent viscosity values of the measured samples during the gelatinization confirms that this process is temperature and time dependent.
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Interactions of antiretroviral drugs with membrane transporters
Martinec, Ondřej ; Červený, Lukáš (advisor) ; Boušová, Iva (referee) ; Chládek, Jaroslav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Ondřej Martinec Supervisor: Assoc. Prof. PharmDr. Lukáš Červený, Ph.D. Title of doctoral thesis: Interactions of antiretroviral drugs with membrane transporters Oral delivery is the most common, convenient, and economical form of drug administration. Absorption of orally administered drugs occurs mainly in the intestine. Intestinal absorption can be reduced by the activity of efflux drug ABC transporters, mainly p-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), located in the apical membrane of the intestinal epithelium. HIV-infected patients are dependent on lifelong pharmacotherapy, which includes a combination of three or more antiretroviral drugs. Hepatitis C (HCV) is a common co-infection of HIV. In addition, the HIV-positive population is aging, which is associated with burden of other comorbidities. This results in an indication of polypharmacy and thus an increased risk of drug-drug interactions. Many antiretroviral drugs used are substrates, inhibitors and /or inducers of ABCB1, so they might quantitatively affect the intestinal absorption of co-administered drugs (ABCB1 substrates), thereby affecting the efficacy/safety of treatment. As part of this...
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Effect of abacavir on the expression of nucleoside transporters, adenosine receptors, and enzymes involved in adenosine synthesis and biodegradation in trophoblasts
Gala, Viktor ; Červený, Lukáš (advisor) ; Čečková, Martina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Viktor Gala Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Effect of abacavir on the expression of nucleoside transporters, adenosine receptors, and enzymes involved in adenosine synthesis and biodegradation in trophoblasts The nucleoside reverse transcriptase inhibitor (NRTI) abacavir (ABC) is now the mainstay of combination antiretroviral therapy (cART) for HIV in pregnant women. The introduction of cART, along with several other measures, has reduced mother-to-fetus transmission of HIV to less than 1% in recent years. The placenta is a key organ for the health of both the fetus and the mother. Imbalances in placental development can result in adaptive changes and fetal programming errors. cART recommended in pregnancy is known for its good safety profile, but some epidemiological studies suggest a higher risk of reduced fetal weight, preterm birth, etc. The placenta is a rapidly growing organ dependent on the supply of building materials that resembles tumor growth in certain aspects. Nucleosides are promoters of tumor proliferation and are involved in the development of immunotolerance. The placenta is complexly equipped for nucleoside synthesis, uptake,...
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