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Therapy of arterial hypertension in prehospital emergency care and at urgent admission
SYNKOVÁ, Kateřina
The bachelor thesis on the topic of Therapy of arterial hypertension in prehospital emergency care and in the emergency room is focused on dealing with states in cases of sudden escalation of patient's blood pressure. The thesis is divided into a theoretical part and a practical part. In the theoretical part, blood pressure is characterized, including the methods of its measurement, arterial hypertension and hypertensive crisis. Furthermore, there are descriptions of the basic classes of anti-hypertensives and their use in specific groups with arterial hypertension. In the practical part of the bachelor thesis, three goals were set. The first goal was to map out how arterial hypertension is treated in prehospital emergency care within the competences of paramedics and guidelines of given workplace of the emergency medical service. Second goal was to map out the way in which arterial hypertension is treated in emergency rooms of given workplaces, and the third goal was to find out what are the differences between therapy of arterial hypertension in prehospital emergency care and in the emergency room. The research study was carried out via qualitative method of data collection using semi-structured interviews. The interviews were conducted with paramedics operating within the Emergency medical services of the South Bohemia region in the districts of Písek, Tábor and Český Krumlov. In addition, selected paramedics working in the emergency department of České Budějovice Hospital also took part in the interviews. From the results of the research part of the bachelor thesis can be concluded, that the interviewed paramedics have enough experiences and knowledge in the area of treating a patient with arterial hypertension and know when it is adequate to reach out to a medical professional about possible therapy.
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Effects of Neurotransmission-Modulating Multipotent Compounds in Pharmacological Animal Models of Cognitive Deficit
Chvojková, Markéta ; Valeš, Karel (advisor) ; Kuchař, Martin (referee) ; Rudá, Jana (referee)
In preclinical research on Alzheimer's disease pharmacotherapy, attention is paid to multipotent compounds, enabling intensification of the effect by targeting multiple pathophysiological mechanisms. The aim of the thesis was to assess the effect of multipotent compounds and combination therapy in models of cognitive deficit in the rat. The mechanism of action of the tested compounds was modulation of neurotransmitter systems. The aim of the first part of the study was to compare the effect of experimental monotherapy and combination therapy with an N-methyl-D-aspartate (NMDA) receptor antagonist and a γ-aminobutyric acid type A (GABAA) receptor positive modulator in the trimethyltin-induced model. Superiority of the combination therapy was proven by histological analysis of hippocampal neurodegeneration; however, it did not reach statistical significance in the cognitive test. The other part of the thesis focused on multipotent tacrine derivatives. We demonstrated a positive effect of 6- chlorotacrine-6-nitrobenzothiazole hybrid, as well as 6-chlorotacrine-L-tryptophan hybrid, acting as acetylcholinesterase inhibitors, in the scopolamine-induced model of cognitive deficit. Besides, we demonstrated a low risk of serious side effects of other tacrine derivatives acting as NMDA receptor antagonists....
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Study on impact of selected protein kinase inhibitors on drug resistance mediated by cytochromes P450
Janoušková, Adéla ; Hofman, Jakub (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Adéla Janoušková Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on impact of selected protein kinase inhibitors on drug resistance mediated by cytochromes P450 Pharmacokinetic drug resistance often leads to failure of an anticancer therapy. One of the mechanisms is increased efflux of drugs from tumour cells, whereas some studies suggest that increased drug conversion to an inactive metabolite might be another contributing mechanism. The aim of this work was to define the possible role of CYP3A4 and CYP2C8 enzymes in the phenomenon of pharmacokinetic resistance and to investigate the possibility of its modulation by new targeted drugs. In the first part, we used the MTT proliferation method together with HepG2 cells stably transduced with particular human enzymes and demonstrated significant involvement of CYP3A4 in docetaxel resistance. In the following part, we examined the inhibitory effects of four selected tyrosine kinase inhibitors on the CYP3A4 activity in intact cells using a commercial kit. Cobimetinib and dabrafenib showed significant inhibitory activity, while osimertinib and brivanib did not. In the final part, we demonstrated the ability of the first two...
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Advanced antibacterial activity testing of candidate newly synthesized compounds
Novotná, Simona ; Konečná, Klára (advisor) ; Kučerová, Marta (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Pharmacy Author: Simona Novotná Supervisor: RNDr. Klára Konečná, Ph.D. Title of diploma thesis: Advanced antibacterial activity testing of candidate newly synthesized compounds Background: The aim of this thesis was to perform an extended study of the antibacterial activity of selected newly synthesized rhodanine derivatives. In this study, activity against clinical isolates of bacterial strains of the genus Staphylococcus and Enterococcus was evaluated. The main part of the work also includes the evaluation of the antibacterial activity of one selected substance in combination with commercially available antibiotics using the checkerboard method. Methods: Evaluation of the antibacterial activity of tested substances was performed using the broth microdilution method according to EUCAST guidelines (with minor modifications). The activity of these substances was evaluated against clinical isolates of bacteria of the genera Staphylococcus and Enterococcus and one Staphylococcus aureus MRSA reference strain (ATCC 43300, CCM 4750). For a selected compound with a demonstrably promising antistaphylococcal effect, the combined effect of this substance was tested with three...
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Advanced antibacterial activity testing of candidate newly synthesized compounds
Novotná, Simona ; Konečná, Klára (advisor) ; Kučerová, Marta (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Pharmacy Author: Simona Novotná Supervisor: RNDr. Klára Konečná, Ph.D. Title of diploma thesis: Advanced antibacterial activity testing of candidate newly synthesized compounds Background: The aim of this thesis was to perform an extended study of the antibacterial activity of selected newly synthesized rhodanine derivatives. In this study, activity against clinical isolates of bacterial strains of the genus Staphylococcus and Enterococcus was evaluated. The main part of the work also includes the evaluation of the antibacterial activity of one selected substance in combination with commercially available antibiotics using the checkerboard method. Methods: Evaluation of the antibacterial activity of tested substances was performed using the broth microdilution method according to EUCAST guidelines (with minor modifications). The activity of these substances was evaluated against clinical isolates of bacteria of the genera Staphylococcus and Enterococcus and one Staphylococcus aureus MRSA reference strain (ATCC 43300, CCM 4750). For a selected compound with a demonstrably promising antistaphylococcal effect, the combined effect of this substance was tested with three...
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Study on impact of selected tyrosine kinase inhibitors on multidrug resistance mediated by ABC drug efflux transporters
Sýkorová, Martina ; Hofman, Jakub (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martina Sýkorová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on impact of selected tyrosine kinase inhibitors on multidrug resistance mediated by ABC drug efflux transporters Tyrosine kinases are an important class of enzymes controlling cell proliferation, carcinogenesis, apoptosis and cell differentiation. Deregulation of these enzymes can transform normal cell into a cancerous one. Blocking their function by tyrosine kinase inhibitors (TKi) is considered a promising treatment for various types of cancer. ATP-binding cassette (ABC) transporters form a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes via ATP-dependent drug efflux pumps. They modulate drug pharmacokinetics, but on the other hand, lead to therapy failure due to overexpression in cancer cells. In our previous study, we evaluated inhibition properties of two selected TKi (alectinib, brivanib) in MDCKII cell lines (parent one and those transduced with human ABCB1, ABCC1 and ABCG2). Alectinib significantly inhibited ABCB1, ABCG2 but not ABCC1 transporter. Brivanib showed triple inhibition of all studied transporters. In the present work, we...
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Study on impact of selected protein kinase inhibitors on drug resistance mediated by cytochromes P450
Janoušková, Adéla ; Hofman, Jakub (advisor) ; Novotná, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Adéla Janoušková Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on impact of selected protein kinase inhibitors on drug resistance mediated by cytochromes P450 Pharmacokinetic drug resistance often leads to failure of an anticancer therapy. One of the mechanisms is increased efflux of drugs from tumour cells, whereas some studies suggest that increased drug conversion to an inactive metabolite might be another contributing mechanism. The aim of this work was to define the possible role of CYP3A4 and CYP2C8 enzymes in the phenomenon of pharmacokinetic resistance and to investigate the possibility of its modulation by new targeted drugs. In the first part, we used the MTT proliferation method together with HepG2 cells stably transduced with particular human enzymes and demonstrated significant involvement of CYP3A4 in docetaxel resistance. In the following part, we examined the inhibitory effects of four selected tyrosine kinase inhibitors on the CYP3A4 activity in intact cells using a commercial kit. Cobimetinib and dabrafenib showed significant inhibitory activity, while osimertinib and brivanib did not. In the final part, we demonstrated the ability of the first two...
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Study on impact of selected tyrosine kinase inhibitors on multidrug resistance mediated by ABC drug efflux transporters
Sýkorová, Martina ; Hofman, Jakub (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martina Sýkorová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on impact of selected tyrosine kinase inhibitors on multidrug resistance mediated by ABC drug efflux transporters Tyrosine kinases are an important class of enzymes controlling cell proliferation, carcinogenesis, apoptosis and cell differentiation. Deregulation of these enzymes can transform normal cell into a cancerous one. Blocking their function by tyrosine kinase inhibitors (TKi) is considered a promising treatment for various types of cancer. ATP-binding cassette (ABC) transporters form a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes via ATP-dependent drug efflux pumps. They modulate drug pharmacokinetics, but on the other hand, lead to therapy failure due to overexpression in cancer cells. In our previous study, we evaluated inhibition properties of two selected TKi (alectinib, brivanib) in MDCKII cell lines (parent one and those transduced with human ABCB1, ABCC1 and ABCG2). Alectinib significantly inhibited ABCB1, ABCG2 but not ABCC1 transporter. Brivanib showed triple inhibition of all studied transporters. In the present work, we...
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