|
|
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,...
|
|
|
Evaluation of gene expression of selected ABC and SLC transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines
Pokorná, Petra ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petra Pokorná Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Dudičová Title of diploma thesis: Evaluation of gene expression of selected ABC and OATP transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines Placenta is the first and the largest fetal organ that gradually develops during pregnancy and plays an essential role in the development of the fetus. It fulfills the entire spectrum of functions, ensures the transport of nutrients to the fetus and the removal of waste substances back into the maternal circulation, protects the fetus from toxins, and at the same time fulfills a certain mechanical and especially immunological barrier between mother and fetus. One of the main functions of the placenta is the transport function which is made possible by membrane transporters present mainly in the syncytiotrophoblast layer of the placenta. Transporters in the human placenta can be divided into two families, SLC and ABC which are further divided into several subfamilies. The expression of transporters changes physiologically during pregnancy, but pathological conditions such as inflammation can also influence the expression....
|
|
|
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,...
|
|
|
Precision-cut placental slices as a model to study inflammatory response
Bolboli, Bahareh ; Štaud, František (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bahareh Bolboli Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: Kasin Yadunandam Anandam, Ph.D. Title of the diploma thesis: Precision-cut placental slices as a model to study inflammatory response. Maternal inflammation during pregnancy is a recognized factor linked to an array of complications and potential neurodevelopmental and neuropsychiatric risks for offspring. Placenta isthe crucial interface between maternal and fetal domains. This organ not only shapes fetal development but also possesses the ability to respond to inflammatory stimulations, potentially in a sex-specific manner. Nonetheless, the fundamental immunoregulatory mechanisms orchestrating such responses remain unclear. To bridge this knowledge gap, our study harnessed an innovative approach: the ex vivo precision-cut placental slice model using rat placentas. This experimental design was tailored to probe acute inflammatory responses. Precision-cut placental slices, precisely 200 µm thick, were meticulously generated from both male and female rat placentas. These slices were subjected to varying concentrations of Lipopolysaccharide (LPS) or Polyinosinic: polycytidylic acid (Poly I:C) for discrete periods of 4...
|
|
|
In vitro models for studying Syncytin-1-induced fusion of trophoblast cells
Jech, Lukáš ; Trejbalová, Kateřina (advisor) ; Zíková, Martina (referee)
Trophoblast cell fusion is essential for human placenta development. Apart from initiating blastocyst implantation, syncytialization is critical for optimal nutrient and gas exchange between mother and fo- etus. Multicellular syncytia called syncytiotrophoblast covers the surface of the branched structure of chorionic villi, which is in direct contact with maternal blood. Impairment of the syncytialization process leads to insufficient fetal nutrition and severe pregnancy complications. Syncytia formation is induced by the interaction of the surface glycoprotein of retrovital origin, Syncytin-1, with its receptor. Despite the significance of these processes, the details of cell fusion and trophoblast differentiation remain unk- nown. Furthermore, because of its uniqueness, the human placenta cannot be covered by animal models. As a result, research into human placental development, especially Syncytin-1-induced trophoblast cell fusion, is limited to in vitro trophoblast models. These models include primary trophoblast cell cultures and trophoblast cell lines, which can be obtained by immortalizing cell cultures or extracted from trophoblast tumours. Dedifferentiated trophoblast stem cell cultures were also established. The most recent approach, however, involves the direct reprogramming of dermal...
|
|
|
Circadian system and reproduction
Hrubá, Anežka ; Lužná, Vendula (advisor) ; Ladislavová, Lucie (referee)
Due to the alternation of day and night, mammals have developed internal circadian clocks, helping to synchronize physiological processes with the external environment. The circadian system is hierarchically organized, with central clocks located within suprachiasmatic nuclei of the hypothalamus (SCN). The main signal for setting the clocks to the external time is light, which enters the SCN through retina. The SCN communicate with peripheral oscillators in other organs, including reproductive ones, via hormonal signals, thereby synchronizing a variety of physiological processes. At the molecular level, clocks are controlled by clock genes. Cicradian system has a significant impact on reproduction. It is manifested by rythmical expression of clock genes and production of hormones in reproductive organs, as well as a success in reproduction if the clock's function is proper, and problems with reproduction if it is not. From a gender perspective, a several differences between women and men has been found throughout the SCN. Likewise, there are differences in chronotypes between both sexes over the course of their lives. Biological rhythms also include circannual rhythms, contributing to the timing of reproduction at the proper season of the year. Animals mate at different time depending on the length...
|
|
|
Evaluation of gene expression of selected ABC and SLC transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines
Pokorná, Petra ; Čečková, Martina (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petra Pokorná Supervisor: Assoc. Prof. PharmDr. Martina Čečková, Ph.D. Consultant: Mgr. Simona Dudičová Title of diploma thesis: Evaluation of gene expression of selected ABC and OATP transporters in the HTR-8/SVneo cell line during stimulation with pro-inflammatory cytokines Placenta is the first and the largest fetal organ that gradually develops during pregnancy and plays an essential role in the development of the fetus. It fulfills the entire spectrum of functions, ensures the transport of nutrients to the fetus and the removal of waste substances back into the maternal circulation, protects the fetus from toxins, and at the same time fulfills a certain mechanical and especially immunological barrier between mother and fetus. One of the main functions of the placenta is the transport function which is made possible by membrane transporters present mainly in the syncytiotrophoblast layer of the placenta. Transporters in the human placenta can be divided into two families, SLC and ABC which are further divided into several subfamilies. The expression of transporters changes physiologically during pregnancy, but pathological conditions such as inflammation can also influence the expression....
|
|
|
Placental homeostasis of monoamines; effect of gestation age
Mahrla, Filip ; Štaud, František (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Filip Mahrla Supervisor: Prof. PharmDr. František Štaud, Ph.D. Consultant: PharmDr. Rona Karahoda, Ph.D. Title of diploma thesis: Placental homeostasis of monoamines; effect of gestation age Catecholamines norepinephrine and dopamine have been implicated in numerous physiological processes within the central nervous system. Emerging evidence suggests their involvement in placental development and functions and a crucial role in fetal development and programming. Nonetheless, a comprehensive characterization of catecholamine synthesis, degradation, and transport in the fetoplacental unit is still lacking. Thus, in this thesis, we aimed to provide a comprehensive evaluation of catecholamine metabolism and transport in the fetoplacental unit. Gene and protein expression was evaluated using quantitative polymerase chain reaction (PCR) and Western blot analysis, respectively. Firstly, using several placental cell models (BeWo, JEG-3, primary trophoblast cells), we identified components of cellular catecholamine handling associated with the trophoblast cells. Next, we determined the effect of advancing gestation on the placental catecholamine system in humans (first trimester vs. term placenta) and...
|
|
|
Placental transport of dopamine and norepinephrine
Turková, Helena ; Štaud, František (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Helena Turková Supervisor: prof. PharmDr. František Štaud, Ph.D. Title of diploma thesis: Placental transport of dopamine and norepinephrine During the whole course of pregnancy, it is important to maintain proper monoamine homeostasis, namely serotonin (5-HT), norepinephrine (NE), and dopamine (DA), which are crucial for proper placental function and fetal development. Monoamines are important neuromodulators, involved in cell proliferation, and differentiation. and neuronal migration. High fetal monoamine secretion during gestation demands a responsible clearance mechanism, as disruption of their balance may lead to long-lasting changes in brain structure and function, provoking a higher risk of attention deficit hyperactivity disorder (ADHD), autism or depression. However, uptake of NE a DA through the fetoplacental unit has not been fully and in detail described. Therefore, in this diploma thesis, we focus on the uptake of NE and DA through ex vivo isolated vesicles of microvillous (MVM) and basal (BM) membranes from healthy human term placentas. Our results show that NE and DA uptake is mediated via high-affinity and low-capacity serotonin (SERT) and norepinephrine (NET) transporters in...
|
|
|
Placental transport of dopamine and norepinephrine
Turková, Helena ; Štaud, František (advisor) ; Jirkovský, Eduard (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Helena Turková Supervisor: prof. PharmDr. František Štaud, Ph.D. Title of diploma thesis: Placental transport of dopamine and norepinephrine During the whole course of pregnancy, it is important to maintain proper monoamine homeostasis, namely serotonin (5-HT), norepinephrine (NE), and dopamine (DA), which are crucial for proper placental function and fetal development. Monoamines are important neuromodulators, involved in cell proliferation, and differentiation. and neuronal migration. High fetal monoamine secretion during gestation demands a responsible clearance mechanism, as disruption of their balance may lead to long-lasting changes in brain structure and function, provoking a higher risk of attention deficit hyperactivity disorder (ADHD), autism or depression. However, uptake of NE a DA through the fetoplacental unit has not been fully and in detail described. Therefore, in this diploma thesis, we focus on the uptake of NE and DA through ex vivo isolated vesicles of microvillous (MVM) and basal (BM) membranes from healthy human term placentas. Our results show that NE and DA uptake is mediated via high-affinity and low-capacity serotonin (SERT) and norepinephrine (NET) transporters in...
|
guest ::
