National Repository of Grey Literature 34 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
The effect of natural compounds on transport by OATP drug transporters
Zemčíková, Lucie ; Trejtnar, František (advisor) ; Mičuda, Stanislav (referee) ; Szotáková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: MSc. Lucie Zemčíková Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Title of doctoral thesis: The effect of natural compounds on transport by OATP drug transporters OATP membrane transporters belong to carrier proteins responsible for transporting certain drugs (e.g. hypolipidemics from the group of statins) and other xenobiotics across the biological membranes and tissue barriers within the body. These transport proteins play an important role in pharmacokinetic processes such as absorption, distribution and elimination. The potential modulation of their transport function by natural compounds commonly present in plant food or food supplements may result in the changes of the concentration of their substrate (drug) in the cells and body fluids, that may affect the effect and toxicity of these drugs. The aim of this study was to obtain data on the interactions of selected natural compounds with human transporters OATP2B1 and OATP1A2 and their ability to affect drug transport mediated by these transporters. These two OATP transporters are involved in the drug uptake especially in organ barriers important for pharmacokinetics. For the study natural compounds from the group of...
Alterations in gene expression of hepatobiliary transporters as potential mechanisms for drug-induced cholestasis by amoxicillin and clavulanic acid
Řepová, Veronika ; Pávek, Petr (advisor) ; Mičuda, Stanislav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Řepová Supervisor: Prof. PharmDr. Petr Pávek, Ph.D., Prof. Ramiro Jover Atienza, Ph.D. Title of diploma thesis: Alterations in gene expression of hepatobiliary transporters as potential mechanisms for drug-induced cholestasis by amoxicillin and clavulanic acid The combination of amoxicillin and clavulanic acid (AMO/CLA) represents one of the most frequent causes of the idiosyncratic type of drug-induced liver injury (DILI) nowadays. Despite difficulties in diagnosis and causality assessment, the clinical features have already been reported and in most of the cases categorized as cholestatic damages. Number of descriptions of the molecular mechanisms of drug-induced cholestasis has been rising recently and the role of hepatobiliary transporters has turned out to be crucial in the pathogenesis. However, the mechanisms of AMO/CLA-induced DILI at the molecular level still remain indistinct. In order to investigate the hepatotoxic effects of AMO/CLA and AMO alone in vitro, HepG2 and human Upcyte hepatocytes were used as hepatocellular models. The mRNA levels of key bile acid (BA) transporters, enzymes and nuclear receptors (NRs) were measured by quantitative real-time polymerase chain...
The effect of natural compounds on transport by OATP drug transporters
Zemčíková, Lucie ; Trejtnar, František (advisor) ; Mičuda, Stanislav (referee) ; Szotáková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: MSc. Lucie Zemčíková Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Title of doctoral thesis: The effect of natural compounds on transport by OATP drug transporters OATP membrane transporters belong to carrier proteins responsible for transporting certain drugs (e.g. hypolipidemics from the group of statins) and other xenobiotics across the biological membranes and tissue barriers within the body. These transport proteins play an important role in pharmacokinetic processes such as absorption, distribution and elimination. The potential modulation of their transport function by natural compounds commonly present in plant food or food supplements may result in the changes of the concentration of their substrate (drug) in the cells and body fluids, that may affect the effect and toxicity of these drugs. The aim of this study was to obtain data on the interactions of selected natural compounds with human transporters OATP2B1 and OATP1A2 and their ability to affect drug transport mediated by these transporters. These two OATP transporters are involved in the drug uptake especially in organ barriers important for pharmacokinetics. For the study natural compounds from the group of...
Alterations in gene expression of hepatobiliary transporters as potential mechanisms for drug-induced cholestasis by amoxicillin and clavulanic acid
Řepová, Veronika ; Pávek, Petr (advisor) ; Mičuda, Stanislav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Řepová Supervisor: Prof. PharmDr. Petr Pávek, Ph.D., Prof. Ramiro Jover Atienza, Ph.D. Title of diploma thesis: Alterations in gene expression of hepatobiliary transporters as potential mechanisms for drug-induced cholestasis by amoxicillin and clavulanic acid The combination of amoxicillin and clavulanic acid (AMO/CLA) represents one of the most frequent causes of the idiosyncratic type of drug-induced liver injury (DILI) nowadays. Despite difficulties in diagnosis and causality assessment, the clinical features have already been reported and in most of the cases categorized as cholestatic damages. Number of descriptions of the molecular mechanisms of drug-induced cholestasis has been rising recently and the role of hepatobiliary transporters has turned out to be crucial in the pathogenesis. However, the mechanisms of AMO/CLA-induced DILI at the molecular level still remain indistinct. In order to investigate the hepatotoxic effects of AMO/CLA and AMO alone in vitro, HepG2 and human Upcyte hepatocytes were used as hepatocellular models. The mRNA levels of key bile acid (BA) transporters, enzymes and nuclear receptors (NRs) were measured by quantitative real-time polymerase chain...
Biological effects of edible algae.
Vaňková, Kateřina ; Vítek, Libor (advisor) ; Brůha, Radan (referee) ; Mičuda, Stanislav (referee)
Nutritional factors with antioxidant properties, such as those contained in edible algae or green plants, might be implicated in protection against cancer development. Chlorophyll and other tetrapyrrolic compounds, structurally related to heme and antioxidant bile pigment bilirubin, belong to important candidate molecules, which might be responsible for these effects. Based on our studies demonstrating antiproliferative effects of S. platensis edible alga extract on experimental model of human pancreatic adenocarcinoma we investigated in detail the effect of chlorophyll occurring abundantly in this alga. Since only scarce data exist on the antiproliferative effects of chlorophylls, the aim of our study was to assess these effects. The study was performed on experimental models of human pancreatic and prostate cancer. The inhibitory effects of chlorophylls (chlorophyll a, chlorophyll b, chlorophyllin and pheophytin a) on cell proliferation and cell viability were investigated in in vitro studies. Chlorophylls reduced the mRNA expression as well as activity of hemeoxygenase in tested pancreatic cancer cells. Simultaneously, chlorophylls played an important role in redox environment of studied cancer cell lines including modulation of mitochondrial membrane potential, reactive oxygen species (ROS)...
Tissue and soluble endoglin relation to the endothelial dysfunction and possible treatment
Blažíčková, Kateřina ; Nachtigal, Petr (advisor) ; Bláha, Vladimír (referee) ; Mičuda, Stanislav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Msc. Katerina Blazickova Supervisor: Assoc. Prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Tissue and soluble endoglin relation to the endothelial dysfunction and possible treatment Atherosclerosis is a complex inflammatory disease and it represents a major source of morbidity and mortality in the world as a part of cardiovascular diseases. Endothelial dysfunction represents the first step in the development of atherosclerosis and it is characterized by disruption of endothelial homeostasis. Statins are drugs of choice in the treatment of atherosclerosis and they can decrease LDL cholesterol levels and positively affect levels of HDL cholesterol. Statins, however have a wide range of other effects, which are referred to non-lipid or pleotropic effects. The most important non-lipid effects of statins are lipid- independent modulation of endothelial function, antioxidant, anti-inflammatory, antithrombogenic and antiproliferative effects. The most widely used animal model for the study of atherosclerosis is the mouse model. Thanks to a high fat diet and genetic modification, we are able to modify lipid profile in mice and induce atherosclerotic changes even at...
Novel approaches for development of in vitro liver cell models
Smutný, Tomáš ; Pávek, Petr (advisor) ; Mičuda, Stanislav (referee) ; Kollár, Peter (referee)
1 Abstract Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Tomáš Smutný, MSc. Supervisor: Prof. PharmDr. Petr Pávek, Ph.D. Title of doctoral thesis: Novel approaches for development of in vitro liver cell models. The liver is a main metabolizing organ in the body. Therefore, the evaluation of hepatic metabolism is a crucial step during drug development. Moreover, a liver damage induced by drugs is another task to be assessed in drug development. In vitro liver cell models allow addressing some of these concerns. Up to date, primary human hepatocytes are considered as a "gold" standard of in vitro liver cell models. Additionally, other liver model systems are used such as liver tissue slices, subcellular fractions, liver cancer cell lines and hepatocytes derived from stem cells. Despite the significant progress towards right estimation of pharmacokinetic and toxicological parameters of drug candidates during drug development, current in vitro systems still suffer from various drawbacks. One of these limitations is their insufficient similarity with in vivo-like phenotype associated with low metabolic capacity of the models. In last several years, we were victims of tremendous effort to improve existing models such as 3D models, co-culture and...
Nuclear receptors - new ligands study and importance of the genetic variability
Carazo Fernández, Alejandro José ; Pávek, Petr (advisor) ; Mičuda, Stanislav (referee) ; Vrzal, Radim (referee)
IN ENGLISH LANGUAGE Candidate: Mgr. Alejandro Carazo Fernández Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Nuclear receptors - new ligands study and importance of the genetic variability Nuclear receptors (NRs) constitute a superfamily of transcription factors, which regulate the expression of target genes upon the binding of a ligand. These receptors can be classified in steroid receptors, "orphan receptors" and "adopted orphan receptors" depending on the affinity to an endogenous ligand. Nuclear receptors play important roles in physiological processes and are widely distributed in the human body. Thus, adipogenesis, lipolysis, insulin sensitivity, oxidative metabolism, fatty acid homeostasis, cholesterol homeostasis, gluconeogenesis, glycogen homeostasis, triglyceride metabolism among other processes, are regulated by nuclear receptors. During my study, we have tested several sets of drugs, endogenous, natural and synthetic, in several nuclear receptors, focusing mainly on constitutive androstane receptor (CAR) and to a lesser extent on pregnane X receptor (PXR). My main aim was to find a new and reliable ligand or activator for human CAR. In addition, I aimed to study the mechanism of action by which these compounds interact with the receptor and how they trigger...
Tissue and soluble endoglin relation to the endothelial dysfunction and possible treatment
Blažíčková, Kateřina ; Nachtigal, Petr (advisor) ; Blaha, Vladimír (referee) ; Mičuda, Stanislav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Msc. Katerina Blazickova Supervisor: Assoc. Prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Tissue and soluble endoglin relation to the endothelial dysfunction and possible treatment Atherosclerosis is a complex inflammatory disease and it represents a major source of morbidity and mortality in the world as a part of cardiovascular diseases. Endothelial dysfunction represents the first step in the development of atherosclerosis and it is characterized by disruption of endothelial homeostasis. Statins are drugs of choice in the treatment of atherosclerosis and they can decrease LDL cholesterol levels and positively affect levels of HDL cholesterol. Statins, however have a wide range of other effects, which are referred to non-lipid or pleotropic effects. The most important non-lipid effects of statins are lipid- independent modulation of endothelial function, antioxidant, anti-inflammatory, antithrombogenic and antiproliferative effects. The most widely used animal model for the study of atherosclerosis is the mouse model. Thanks to a high fat diet and genetic modification, we are able to modify lipid profile in mice and induce atherosclerotic changes even at...

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