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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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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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Consequences of perinatal insult on brain excitability in immature and adult rats
Fábera, Petr ; Mareš, Pavel (advisor) ; Pokorný, Jaroslav (referee) ; Ošlejšková, Hana (referee)
Perinatal insult may lead to a permanent impairment of brain function resulting in the development of epilepsy. Status epilepticus (SE) in immature rats leads to hippocampal hyperexcitability. The functional and morphological changes of the hippocampus are similar to those seen in human temporal lobe epilepsy. The excitability may be influenced by adenosine. Adenosine acts its anticonvulsant effect by activation of A1 receptors (A1R). The concentration of adenosine is regulated by adenosine kinase (ADK) present in two isoforms - ADK-L and -S. The main goal of the thesis is to elucidate the changes in A1R and ADK isoforms expression during intact brain development and after SE. A1R agonist 2-chloro-N6- cyclopentyladenosine (CCPA), as well as inhibition of ADK by 5-iodotubercidin (5-ITU), may bolster the anticonvulsant effect, but their action may correspond with the level of A1R and ADK. Hippocampal excitability in immature rats after LiCl-pilocarpine SE was studied by the model of hippocampal afterdischarges (ADs) and correlated with changes of A1R and ADK in the hippocampus. ADs demonstrated significantly decreased hippocampal excitability shortly after SE induction, whereas significant hyperexcitability accompanied by spontaneous seizures in older rats was shown. Increasing ADK-S expression...
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