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Distribution of pharmaceuticals in wastewater treatment plants
Šilhánková, Lenka ; Čáslavský, Josef (referee) ; Vávrová, Milada (advisor)
This bachelor’s thesis deals with a trending topic – wastewater distribution of pharmaceuticals proven to be toxic to non-target organisms – specifically, the occurrence of beta-blockers, plentifully used in treating hypertension and other cardiovascular diseases, is discussed. Members of this group, Atenolol, Acebutolol and Bisoprolol were chosen for closer study. The elimination of these chemicals was observed in three wastewater treatment plants (WWTP) with different treatment technologies and various number of population equivalents. For said analytes, UHPLC with UV/VIS detection using diode array detector (DAD) method was optimalised. A part of this thesis also deals with optimalization of isolation and concentrating the analytes. Unfortunately, the described method was not suitable for real sample analysis, because in most samples, the limit of quantification or even the limit of detection was not exceeded. It would be best for an analytical method with higher sensitivity, e. g. mass detector, to be used. The data gained in this experiment do not hold any informational value about the effectiveness of WWTP, as the exact amount of Acebutolol in effluent was measured only in one case. Based on the to-date executed analysis, it is impossible to conclude whether the quality of the treated water, concerning the content of aforementioned pharmaceuticals, is in any way ideal.
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Drug repurposing for the inhibition of invasiveness and metastasis of cancer cells
Turchyna, Kateryna ; Brábek, Jan (advisor) ; Jakubek, Milan (referee)
Metastasis is the primary cause of death from cancer. Current lack of medicines for metastasis makes it a topical issue and encourages the global search for molecules that may potentially inhibit invasiveness of cancer cells, and thus prevent metastatic spread. Drug repurposing is a strategy of identifying new uses for approved drugs that are outside the scope of the original medical indication. The aim of this thesis is to summarize knowledge on the repurposing potential of selected groups of drugs with emphasis on molecular mechanisms of their action. In particular, the work is focused on selected antipsychotics, antidepressants, beta- blockers and statins, whose abilities to inhibit cancer invasiveness have been indicated.
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The impact of positive inotropic and antiarrhythmic drugs on cardiovascular system
Kočková, Radka ; Linhart, Aleš (advisor) ; Janoušek, Jan (referee) ; Štengl, Milan (referee)
Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo A significant increase in cardiovascular medication use during pregnancy has occurred in recent years but only limited evidence on its safety profile is available. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. We tested metoprolol, carvedilol, or ivabradine for embryotoxicity and their acute effect on chick embryonic model. We used video microscopy and ultrasound biomicroscopy. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared to controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, 53%, respectively (controls 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of -adrenergic receptors showed a downward tendency during embryonic development but a negative chronotropic effect of tested drugs was increasingly pronounced with embryonic maturity. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death....
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Determination binding constant of beta-blockers by capillary zone electrophoresis
Kanizsová, Lívia ; Zusková, Iva (advisor) ; Šteflová, Jana (referee)
Capillary zone electrophoresis identifies and determines various analytes based on their mobilities in a solution of the background electrolyte, which is exposed to an effect of the electric field. Besides that, it is a suitable method for determination of dissociation and complexation (stability) constants. In this paper the adrenergic β-blockers were chosen as analytes. β-blockers have at least one chiral center in the structure and separation of their enantiomers in presence of the chiral selectors by capillary electrophoresis is possible. For the enantioseparation, variously modified β-cyclodextrins are most often added to the background electrolyte. If the enantiomers of β-blockers have a different affinity to the chiral selector, they exhibit different effective mobilities. Based on a dependence of the effective mobility of analytes on the concentration of chiral selector, we are able to determine their stability constants. Key words: β-blockers, cyclodextrins, stability constant, capillary zone electrophoresis
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The impact of positive inotropic and antiarrhythmic drugs on cardiovascular system
Kočková, Radka ; Linhart, Aleš (advisor) ; Janoušek, Jan (referee) ; Štengl, Milan (referee)
Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo A significant increase in cardiovascular medication use during pregnancy has occurred in recent years but only limited evidence on its safety profile is available. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. We tested metoprolol, carvedilol, or ivabradine for embryotoxicity and their acute effect on chick embryonic model. We used video microscopy and ultrasound biomicroscopy. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared to controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, 53%, respectively (controls 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of -adrenergic receptors showed a downward tendency during embryonic development but a negative chronotropic effect of tested drugs was increasingly pronounced with embryonic maturity. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death....
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Distribution of pharmaceuticals in wastewater treatment plants
Šilhánková, Lenka ; Čáslavský, Josef (referee) ; Vávrová, Milada (advisor)
This bachelor’s thesis deals with a trending topic – wastewater distribution of pharmaceuticals proven to be toxic to non-target organisms – specifically, the occurrence of beta-blockers, plentifully used in treating hypertension and other cardiovascular diseases, is discussed. Members of this group, Atenolol, Acebutolol and Bisoprolol were chosen for closer study. The elimination of these chemicals was observed in three wastewater treatment plants (WWTP) with different treatment technologies and various number of population equivalents. For said analytes, UHPLC with UV/VIS detection using diode array detector (DAD) method was optimalised. A part of this thesis also deals with optimalization of isolation and concentrating the analytes. Unfortunately, the described method was not suitable for real sample analysis, because in most samples, the limit of quantification or even the limit of detection was not exceeded. It would be best for an analytical method with higher sensitivity, e. g. mass detector, to be used. The data gained in this experiment do not hold any informational value about the effectiveness of WWTP, as the exact amount of Acebutolol in effluent was measured only in one case. Based on the to-date executed analysis, it is impossible to conclude whether the quality of the treated water, concerning the content of aforementioned pharmaceuticals, is in any way ideal.
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