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Molecular mechanisms of action of antidepressants.
Brenišin, Martin ; Hejnová, Lucie (advisor) ; Valeš, Karel (referee)
Depression is a widely spread medical illness which affects people's thoughts, moods, physical health and general quality of their lives. Typical symptoms of this disorder are bad mood, lack of energy, sadness, insomnia or disability to feel happiness and enjoy life. Most people have encountered depression either directly or indirectly, through their family members or close friends. Number of patients with major depressive disorder grows globally every year. As much as half of the patients have got suicidal thoughts during their depressive episode while a quarter of them have tried to commit suicide. Therefore, the treatment of depression is very important. Antidepressants represent a large group of drugs focused on that treatment. Nowadays, there is a lot of antidepressants with different mechanism of action, their main effect being the increase in levels of monoamine neurotransmitters in brain. Selective reuptake inhibitors achieve this by blocking transporters of said neurotransmitters. Another type of antidepressants inhibits the activity of monoamine oxidase, which degrades serotonin, noradrenaline and dopamine. This paper reviews basic knowledge about main types of antidepressants and their mechanism of action. Key words: antidepressants, serotonin, depression, noradrenaline, monoamine...
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The role of calcium influx and calcium sensitization in contraction of isolated arteries of normotensive and hypertensive rat
Bencze, Michal ; Zicha, Josef (advisor) ; Neckář, Jan (referee) ; Chalupský, Karel (referee)
Vascular resistance is mainly determined by the contraction of vascular smooth muscle (VSM), which is regulated by the phosphorylation of myosin light chain (MLC). VSM contraction is initiated by calcium influx into the VSM cells, which is mediated by transient receptor potential (TRP) channels and L-type voltage- dependent calcium channels (L-VDCC). On the other hand, calcium sensitization is a mechanism enhancing vascular contractile response at a given level of intracellular calcium by RhoA/Rho kinase pathway-mediated inhibition of myosin light chain phosphatase. In this thesis I present the data about i) the role of TRP channels in the mechanisms of vascular smooth muscle contraction, ii) enhanced contractility of arteries from spontaneously hypertensive rats (SHR), and iii) the differences in contraction of arteries from normotensive and hypertensive rats related to the role of RhoA/Rho kinase pathway in three types of experimental hypertension (SHR, Ren-2 transgenic rats and salt-sensitive Dahl rats). In the study concerning TRP channels, I compared the effects of three commonly used non-selective TRP channels inhibitors (2-APB, SKF-96365, FFA) on isolated arteries. Among them 2-APB was the most interesting because the observed inhibitory effects of 2-APB were dependent on the type of...
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Determination of adrenaline and noradrenaline in plasma by HPLC
Kučerová, Tereza ; Klapková, Eva (advisor) ; Kotaška, Karel (referee)
The target of this bacalary work was to validate the metod for determination of adrenaline and noradrenaline in plasma by high performance liquid chromatography with electrochemical (coulometric) detection. The metod was first necessary to optimize for the coulometric detection because it was used the Bio-Rad kit, which was designed to determine with amperometric detection. The principle of this metod is the chromatographic separation of substances with subsequent oxidation of the determined analyte passes through the analytic cell with coulometric detection. The part of the analytical procedure is the solid phase extraction. The part of this work was the optimization of the metod for the coulometric detector. For the analysis were selected following potentials: channel 1 - 350 mV with range 100 nA, channel 2 - 0 mV with range 50 nA, guard channel 0 mV with range 50 nA. Furthermore, the chromatographic metod was fully validated (accuracy, precision, limit of detection, robustness). In the conclusion was made interlaboratory comparison of results of 42 patients samples with those obtained in the hospital Šternberk.
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