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Importance of Transporter Proteins for Fetal Protection
Hahnová, Lenka ; Štaud, František (advisor) ; Anzenbacher, Pavel (referee) ; Geršl, Vladimír (referee)
Doctoral thesis Mgr. Lenka Hahnová (Cygalová) Placenta, which represents a unique link between the mother and fetus, fulfills many functions essential for normal course of pregnancy and uncomplicated development of the fetus. Nutrient supply, gas exchange and metabolic waste product removal belong to its main roles. In addition, placenta serves as an endocrine, metabolic, immune and protective organ, since during pregnancy mother may be, either unconsciously or deliberately, exposed to a wide range of substances toxic for the fetus. Originally, it was supposed that the physiological barrier between maternal and fetal circulation is created only by cellular layers of syncytiotrophoblast and endothelium of fetal capillaries. However, it has been demonstrated that besides this mechanical component of protection, activity of drug efflux transporters and metabolic enzymes localized in the polarized syncytiotrophoblast layer contribute considerably to the protective function of placental barrier. Efflux transporters are ATP dependent membrane proteins capable of actively removing different molecules out of cells. So far, the best described drug efflux transporters are P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), significantly affecting kinetics of transplacental passage of various...
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Preemptive analgesia & the role of drugs affecting nervous system in potentiatio n of analgesics efficacy
Slíva, Jiří ; Kršiak, Miloslav (advisor) ; Geršl, Vladimír (referee) ; Kozák, Jiří (referee)
The aim of our research is was to determine whether new and already clinically successfullyused anticonvulsant levetiracetam has a preemptive or therapeutic effects in the model of postoperative pain in rats. The second objective of our research was to determine whether guaifenesin increases the efficiency even analgesic NSAIDs, with different selectivity for COX-2 (ibuprofen, nimesulide and celecoxib) in the model of visceral pain in mice. As Previously, it was discovered that guaifenesin increases theabsorption of paracetamol, we investigated whether guaifenesin also affect plasma levels of one of the NSAIDs tested, andnimesulide. The third main objective of our research was therefore to determine whether cannabinoid receptor agonist CP-55940 increases the analgesic activity of diclofenac in amodel of visceral pain model in mice and inflammatory pain in rat.
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Adhesion Molecules and their Role in Model of Pathological Conditions
Pospíšilová, Naďa ; Semecký, Vladimír (advisor) ; Geršl, Vladimír (referee) ; Stingl, Josef (referee)
Souhrn/Summary 1 Atherosclerosis is one of the major causes of cardiovascular morbidity. This chronic inflammatory disease is characterized by endothelial dysfunction with accumulation of lipids, leukocytes, smooth muscle cells and extracellular matrix within the vessel intima. This process results in reducing of the vessel lumen that can lead to the obstruction of vessel blood flow. The initiation of atherogenic process is characterized by the alteration of endothelial function which is so-called endothelial dysfunction. The endothelial dysfunction is characterized by the expression of cell adhesion molecules and increased endothelial permeability for monocytes, T-cells and lipoproteins. This is beginning of "vicious"circle of atherosclerosis. On of the most important cell adhesion molecules participating in the beginning of atherogenesis are members of the immunoglobulin superfamily, VCAM-1 (vascular cell adhesion molekule-1), ICAM-1 (intracellular cell adhesion molekule-1) and PECAM-1 (platelet-endothelial cell adhesion molekule-1).VCAM-1 and ICAM-1 are transmembrane glycoproteins participacing predominantly in the stabilization leukocyte of interaction with endothelium and transmigration of leukocytes into vessel intima. In this dissertation thesis, the first studies were focused on the endothelial...
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New iron chelators and antioxidants in acute myocardial model / / infarction and oxidative stress-induced catecholamine / / - effect on the basic biochemical parameters
Mladěnka, Přemysl ; Hrdina, Radomír (advisor) ; Geršl, Vladimír (referee) ; Patočka, Jiří (referee)
I. SUMMARY Background: Iron is an essential element necessary for many physiological processes involving oxygen transport, DNA-synthesis and ATP-formation. The fate of iron in the organism is tightly regulated especially at the absorption and distribution level probably mainly due to lack of specific active iron excretion mechanism. Any derangement of iron homeostatis may lead to appearance of free (unbound or loosely bound) iron, which can catalyse reactive oxygen species (ROS) production by Haber-Weiss chemistry. Cardiovascular diseases, particularly coronary heart disease (CHD), remain notwithstanding recent scientific advances important therapeutic problem. The most serious form of CHD represents acute myocardial infarction (AMI). The pathophysiology of AMI involves in most cases initial ischaemic period caused by coronary blood flow derangement due to a thrombus formation. Ischaemia alters substantially tissue homeostasis with subsequent cytosolic free iron appearance. Reconstitution of coronary blood flow (reperfusion) represents the only way for myocardial tissue recovery although on the other hand, it is linked with a release of free redox-active iron in the circulation and formation of ROS both intracellularly as well extracellularly. Iron chelators are a large group of drugs with very...
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