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Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method
Šinaľová, Lucia ; Hofman, Jakub (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Šinaľová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method This master thesis focuses on the prediction of tacrine derivatives permeability through blood- brain barrier and their cytotoxicity. We studied tacrine-benzothiazole and tacrine- thiaquinazoline derivates as potential drugs for treatment of Alzheimer's disease. The reason of testing new tacrine derivates was effort to find substances with same effect and lower toxicity, for which was the tacrine discarded from clinical practice. The probable permeability of the studied substances was determined in vitro by the PAMPA method. Based on the permeation coeficient values we have identified that tacrine-benzothiazole derivates A-D (Pe= 8,31- 16,9×10-6 cm/s) and tacrine-thiaquinazoline derivates 1, 3, 4 (Pe= 8,59-14,9×10-6 cm/s) were permeable through blood-brain barrier, tacrine-thiaquinazoline derivate 2 (Pe= 3,79×10-6 cm/s) had uncertain permeability and tacrine-thiaquinazoline derivate 5 (Pe= 2,0×10-6 cm/s) was not permeable. In the pre-clinical evaluation of...
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In vitro Methods for the Prediction of Blood Brain Barrier Penetration
Zálešáková, Helena ; Vopršalová, Marie (advisor) ; Čečková, Martina (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Helena Zálešáková Supervisor: PharmDr. Marie Vopršálová, CSc. Title of diploma thesis: In vitro Methods for the Prediction of Blood Brain Barrier Penetration This thesis deals with the correlation between two in vitro models simulating the blood- brain barrier (HEB, hematoencephalic barrier) and their comparison in terms of practical use. These are the PAMPA (Parallel Artificial Membrane Permeability Assay) method and the MDCK (Madin-Darby Canine Kidney) cell line, which are models for potential central nervous system (CNS) penetration screening. Within this work, a set of sixteen standard drugs were measured. The procedure was similar in both methods in order to obtain information on the amount of test substances passing through the membrane from the donor portion of the plate to the acceptor. The concentration in the donor portion was measured by UV-VIS spectrophotometry. The main difference between these methods is the membrane through which the substances penetrate. In the case of PAMPA, a lipid solution that has been isolated from pig brain (PBL, polar brain lipid) is used. This lipid simulates the phospholipid membrane of the brain capillary endothelium. In the MDCK model, the membrane...
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In vitro Methods for the Prediction of Blood Brain Barrier Penetration
Zálešáková, Helena ; Vopršalová, Marie (advisor) ; Čečková, Martina (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Helena Zálešáková Supervisor: PharmDr. Marie Vopršálová, CSc. Title of diploma thesis: In vitro Methods for the Prediction of Blood Brain Barrier Penetration This thesis deals with the correlation between two in vitro models simulating the blood- brain barrier (HEB, hematoencephalic barrier) and their comparison in terms of practical use. These are the PAMPA (Parallel Artificial Membrane Permeability Assay) method and the MDCK (Madin-Darby Canine Kidney) cell line, which are models for potential central nervous system (CNS) penetration screening. Within this work, a set of sixteen standard drugs were measured. The procedure was similar in both methods in order to obtain information on the amount of test substances passing through the membrane from the donor portion of the plate to the acceptor. The concentration in the donor portion was measured by UV-VIS spectrophotometry. The main difference between these methods is the membrane through which the substances penetrate. In the case of PAMPA, a lipid solution that has been isolated from pig brain (PBL, polar brain lipid) is used. This lipid simulates the phospholipid membrane of the brain capillary endothelium. In the MDCK model, the membrane...
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Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method
Šinaľová, Lucia ; Hofman, Jakub (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Šinaľová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method This master thesis focuses on the prediction of tacrine derivatives permeability through blood- brain barrier and their cytotoxicity. We studied tacrine-benzothiazole and tacrine- thiaquinazoline derivates as potential drugs for treatment of Alzheimer's disease. The reason of testing new tacrine derivates was effort to find substances with same effect and lower toxicity, for which was the tacrine discarded from clinical practice. The probable permeability of the studied substances was determined in vitro by the PAMPA method. Based on the permeation coeficient values we have identified that tacrine-benzothiazole derivates A-D (Pe= 8,31- 16,9×10-6 cm/s) and tacrine-thiaquinazoline derivates 1, 3, 4 (Pe= 8,59-14,9×10-6 cm/s) were permeable through blood-brain barrier, tacrine-thiaquinazoline derivate 2 (Pe= 3,79×10-6 cm/s) had uncertain permeability and tacrine-thiaquinazoline derivate 5 (Pe= 2,0×10-6 cm/s) was not permeable. In the pre-clinical evaluation of...
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Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method
Šinaĺová, Lucia ; Hofman, Jakub (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Šinaľová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method This master thesis focuses on the prediction of tacrine derivatives permeability through blood- brain barrier and their cytotoxicity. We studied tacrine-benzothiazole and tacrine- thiaquinazoline derivates as potential drugs for treatment of Alzheimer's disease. The reason of testing new tacrine derivates was effort to find substances with same effect and lower toxicity, for which was the tacrine discarded from clinical practice. The probable permeability of the studied substances was determined in vitro by the PAMPA method. Based on the permeation coeficient values we have identified that tacrine-benzothiazole derivates A-D (Pe= 8,31- 16,9×10-6 cm/s) and tacrine-thiaquinazoline derivates 1, 3, 4 (Pe= 8,59-14,9×10-6 cm/s) were permeable through blood-brain barrier, tacrine-thiaquinazoline derivate 2 (Pe= 3,79×10-6 cm/s) had uncertain permeability and tacrine-thiaquinazoline derivate 5 (Pe= 2,0×10-6 cm/s) was not permeable. In the pre-clinical evaluation of...
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Hispanoamerican Literary Tradition as Reflected in the Jorge Luis Borges' Works
Krátká, Tereza ; Poláková, Dora (advisor) ; Housková, Anna (referee)
The aim of the work is to present Argentinian literary tradition as reflected in the Jorge Luis Borges' essays and collections of poems from his early creative period (twentieth and thirtieth of 20th century). The corpus of the analyzed works is created by three collections of poems - Passion for Buenos Aires, Moon across the Way, San Martin Copybook and three books of essays - Evaristo Carriego, The Size of My Hope and The language of the Argentines. At the beginning, the text is focused on Argentinian (respectively on Hispanoamerican) cultural context at the turn of the 19th and 20th centuries. Then, the text continues by analysis of six Borges' books mentioned above reflecting five most important Argentinian motives - pampa, gaucho, compadrito, Buenos Aires and its suburbs and dictator. The author notices different attitudes to Argentinian topic and concludes that Argentina symbolizes very important theme, which is influenced also by Borges' predecessors (e. g. Sarmiento, Hernández or Lugones). Key words: Jorge Luis Borges, Argentinian literary tradition, cultural identity, textual analyse, Buenos Aires, suburb, pampa, compadrito, dictator.
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