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Embryotoxicity testing of psychopharmacs using the CHEST method
Pavlovič, Ondřej ; Peterka, Miroslav (advisor) ; Maňáková, Eva (referee)
Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...
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The comparation of embryotoxical effect of insulin and glucose by the method CHEST.
Turková, Aneta ; Peterka, Miroslav (advisor) ; Likovský, Zbyněk (referee)
If gravid women suffer from diabetes,their unborn children have 10x higher risk of development of malformation,prenatal and postnatal death and post partum complications than children of women belonging to healthy population.The main and very controversial potential teratogenic factors are glucose and insulin.However,there are very ambivalent opinions on which one of these two substances causes damage to embryo. Therefore,the aim of this diploma thesis was to contribute to solving of this problem and test direct embryotoxicity of insulin and glucose. For solving of this issue, the so-called CHEST.The principle of this method is creation of a window in eggshell and consequent subgerminal or intraamnial application of the substance being tested.Embryos were tested from the second until the sixth incubation day.Firstly, two types of insulin were injected.Injected doses varied between 3µg/3µl to 0,003µg/3µl. Then glucose was tested,with dosage of 300µg/3µl and 30µg/3µl. Embryotoxic effect was detected for both types of insulin. The beginning of embryotoxicity line of insulin's lies between the dosage of 0,03µg/3µl and 0,003µg/3µl. From embryotoxic effect, death of embryos predominated over development of congenital malformations. Only after application on the second incubation day, there was increased...
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New psychotropic drugs and their effect on developing embryo
Košťalová, Jana ; Maňáková, Eva (advisor)
In my diploma thesis, I researched the effect of mirtazapine on a developing embryo. Nowadays, new drugs are being developed and used for the treatment of depression. These drugs also include mirtazapine. The risk of using mirtazapine during pregnancy has not been documented yet and therefore it can not be used by pregnant women. These drugs are often very effective and well tolerated so it is very important to recognize the effect on a developing embryo. In our research, we used the method of CHEST (chick embryotoxicity screening test). We applied a dose of mirtazapine solution dissolved in DMSO to 4-day old chickens. The doses were 0.2µg, 0.15µg, 0.1µg, 0.05µg, 0.03µg in 3µl of the solution. As controls, we applied 3µl DMSO and 3µl destilled water. Embryos were being incubated for 5 days in an incubator and on the 9th day, we evaluated dead and malformed embryos and the spectrum of defects. From our observations, we have obtained the lethal dose, which was above 0.15µg and the dose that was equivalent to the LD50 - 0.05µg. Lower doses were safe, although these embryos were malformed. These malformations, however, were not statistically significantly different from the malformations occurring in controls. It is neccessary to continue and complete data for 2 -and 3-day old embryos, so that we cover all...
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Drugs in pregnancy - strategy at selection optimal therapy and survey situation in CR
Marková, Gabriela ; Hubičková Heringová, Lucie (advisor) ; Dzúrová, Dagmar (referee)
Medication during pregnancy are frequently used for the treatment of maternal disease. Chronic diseases, like depression, anxiety, autoimmune diseases have to be treated during the pregnancy. Acute diseases, in case of need, must be treated as well. In both situation the strategy of the treatment should reflect the risk for mother and fetus. Optimal therapy is to take the effective drug for mother with minimalisation of therisk for fetus. We analyzed database of cases of prospectively followed pregnancies exposed to certain drugs and evaluate the medication with respect to the risk for the fetus. We recorded the most frequent health care providers in Czech Republic, who seek the information about risk of pharmacotherapy during pregnancy by Czech Teratology Information Service and compared the medication with optimal choice.
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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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Embryotoxicity testing of psychopharmacs using the CHEST method
Pavlovič, Ondřej ; Peterka, Miroslav (advisor) ; Maňáková, Eva (referee)
Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...
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|
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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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The comparation of embryotoxical effect of insulin and glucose by the method CHEST.
Turková, Aneta ; Peterka, Miroslav (advisor) ; Likovský, Zbyněk (referee)
If gravid women suffer from diabetes,their unborn children have 10x higher risk of development of malformation,prenatal and postnatal death and post partum complications than children of women belonging to healthy population.The main and very controversial potential teratogenic factors are glucose and insulin.However,there are very ambivalent opinions on which one of these two substances causes damage to embryo. Therefore,the aim of this diploma thesis was to contribute to solving of this problem and test direct embryotoxicity of insulin and glucose. For solving of this issue, the so-called CHEST.The principle of this method is creation of a window in eggshell and consequent subgerminal or intraamnial application of the substance being tested.Embryos were tested from the second until the sixth incubation day.Firstly, two types of insulin were injected.Injected doses varied between 3µg/3µl to 0,003µg/3µl. Then glucose was tested,with dosage of 300µg/3µl and 30µg/3µl. Embryotoxic effect was detected for both types of insulin. The beginning of embryotoxicity line of insulin's lies between the dosage of 0,03µg/3µl and 0,003µg/3µl. From embryotoxic effect, death of embryos predominated over development of congenital malformations. Only after application on the second incubation day, there was increased...
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New psychotropic drugs and their effect on developing embryo
Košťalová, Jana ; Maňáková, Eva (advisor)
In my diploma thesis, I researched the effect of mirtazapine on a developing embryo. Nowadays, new drugs are being developed and used for the treatment of depression. These drugs also include mirtazapine. The risk of using mirtazapine during pregnancy has not been documented yet and therefore it can not be used by pregnant women. These drugs are often very effective and well tolerated so it is very important to recognize the effect on a developing embryo. In our research, we used the method of CHEST (chick embryotoxicity screening test). We applied a dose of mirtazapine solution dissolved in DMSO to 4-day old chickens. The doses were 0.2µg, 0.15µg, 0.1µg, 0.05µg, 0.03µg in 3µl of the solution. As controls, we applied 3µl DMSO and 3µl destilled water. Embryos were being incubated for 5 days in an incubator and on the 9th day, we evaluated dead and malformed embryos and the spectrum of defects. From our observations, we have obtained the lethal dose, which was above 0.15µg and the dose that was equivalent to the LD50 - 0.05µg. Lower doses were safe, although these embryos were malformed. These malformations, however, were not statistically significantly different from the malformations occurring in controls. It is neccessary to continue and complete data for 2 -and 3-day old embryos, so that we cover all...
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