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Interaction of selected anti-HCV drugs with placental OCTN2 transport protein
Machalová, Vanda ; Čečková, Martina (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Mgr. Vanda Machalová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of rigorous thesis: Interaction of selected anti-HCV drugs with placental OCTN2 transport protein. The aim of this rigorous work was to test the interaction of paritaprevir and daclatasvir with the placental OCTN2 transporter, which ensures the transport of L-carnitine as a cofactor of the fatty acid oxidation process to obtain sufficient energy for correct intra-arterial fusion growth. No drugs in this group have been approved for the treatment of chronic hepatitis C in pregnancy, therefore examining their effect on the transport of L-carnitine via OCTN2 can create certain image concerning to the fetal and maternal safety. In the first part of my thesis the transport and accumulation of radioactively labeled L- carnitine via monolayers of BeWo b30 cells in the presence of paritaprevir and daclatasvir was assayed and the concentration of radiolabeled L-carnitine inside the cell layer. In the second part of my thesis we focused on the evaluation of the presence of paritaprevir and daclatasvir on its gene expression of the OCTN1 and OCTN2 carnitine transporters (or their coding genes SLC22A4 and SLC22A5) by qRT-PCR. The...
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In vitro evaluation of novel Toll-like receptor ligands II.
Machalová, Vanda ; Trejtnar, František (advisor) ; Janočková, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Vanda Machalová Supervisor: doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: In vitro evaluation of novel Toll-like receptor ligands II. The aim of this diploma thesis was to test the new substances at Toll-like receptors (TLR), namely TLR4 and TLR8 subtypes, as potential vaccine adjuvants. Adjuvants are required for new subunit vaccines to promote stimulation of a sufficient immune response. Stimulation of TLR receptors is safe and leads to the activation of both innate and adaptive immunity and to subsequent specific immune response. Testing was carried out on cell lines stable co-expressing the respective receptors, with colorimetric activity detection. In this work, both agonist and antagonist activity at TLR4 and TLR8 receptors was investigated and a half maximal effective concentration (EC50) of resiquimod was determined. Based on the results, the respective substances cannot be considered as potential adjuvants to the TLR8 receptor and DM014 exhibits the potential for agonist activity on the TLR4 receptor, whereas the substance DM015 can be used on further investigation of immunosuppression in autoimmune diseases and diseases associated with excessive activation of the...
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Interaction of selected anti-HCV drugs with placental OCTN2 transport protein
Machalová, Vanda ; Čečková, Martina (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Mgr. Vanda Machalová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of rigorous thesis: Interaction of selected anti-HCV drugs with placental OCTN2 transport protein. The aim of this rigorous work was to test the interaction of paritaprevir and daclatasvir with the placental OCTN2 transporter, which ensures the transport of L-carnitine as a cofactor of the fatty acid oxidation process to obtain sufficient energy for correct intra-arterial fusion growth. No drugs in this group have been approved for the treatment of chronic hepatitis C in pregnancy, therefore examining their effect on the transport of L-carnitine via OCTN2 can create certain image concerning to the fetal and maternal safety. In the first part of my thesis the transport and accumulation of radioactively labeled L- carnitine via monolayers of BeWo b30 cells in the presence of paritaprevir and daclatasvir was assayed and the concentration of radiolabeled L-carnitine inside the cell layer. In the second part of my thesis we focused on the evaluation of the presence of paritaprevir and daclatasvir on its gene expression of the OCTN1 and OCTN2 carnitine transporters (or their coding genes SLC22A4 and SLC22A5) by qRT-PCR. The...
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In vitro evaluation of novel Toll-like receptor ligands II.
Machalová, Vanda ; Trejtnar, František (advisor) ; Janočková, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Vanda Machalová Supervisor: doc. PharmDr. František Trejtnar, CSc. Title of diploma thesis: In vitro evaluation of novel Toll-like receptor ligands II. The aim of this diploma thesis was to test the new substances at Toll-like receptors (TLR), namely TLR4 and TLR8 subtypes, as potential vaccine adjuvants. Adjuvants are required for new subunit vaccines to promote stimulation of a sufficient immune response. Stimulation of TLR receptors is safe and leads to the activation of both innate and adaptive immunity and to subsequent specific immune response. Testing was carried out on cell lines stable co-expressing the respective receptors, with colorimetric activity detection. In this work, both agonist and antagonist activity at TLR4 and TLR8 receptors was investigated and a half maximal effective concentration (EC50) of resiquimod was determined. Based on the results, the respective substances cannot be considered as potential adjuvants to the TLR8 receptor and DM014 exhibits the potential for agonist activity on the TLR4 receptor, whereas the substance DM015 can be used on further investigation of immunosuppression in autoimmune diseases and diseases associated with excessive activation of the...
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