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Evaluation of cytotoxicity of newly synthesized phenoxytacrine derivatives as potential therapeutics of Alzheimer's dementia
Koperová, Erika ; Macháček, Miloslav (advisor) ; Múčková, Ľubica (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Erika Koperová Supervisor: RNDr. Miloslav Macháček, Ph.D. Supervisor-consultant: RNDr. Tereza Kobrlová, Ph.D. Title of diploma thesis: Evaluation of cytotoxicity of newly synthesized phenoxytacrine derivatives as potential therapeutics of Alzheimer's dementia. The increasing prevalence of Alzheimer's disease and the availability of mainly symptomatic treatment as opposed to causal therapy require the development of new drugs that affect the complex pathogenesis of this condition. Recently, the prevailing effort to create compounds with a multimodal effect and lower toxicity compared to Tacrine has led to the synthesis of phenoxytacrine and its derivatives. These substances, due to their targeting of multiple targets simultaneously, appear to be suitable candidates for the treatment of Alzheimer's disease. The subject of this thesis is the determination of the cytotoxicity of phenoxytacrine derivatives and the evaluation of its relationship to the structure of the studied compounds. Cytotoxicity studies are an important aspect of drug development, determining the effect of a specific chemical compound on living cells. This type of study is crucial for understanding the potential toxicity of new...
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Laboratory diagnostics of kidney injury in patients with diabates mellitus I and II.
Múčková, Ľubica ; Dršata, Jaroslav (advisor) ; Tichý, Aleš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Ľubica Múčková Supervisor: Prof. MUDr. Jaroslav Dršata, CSc. Consultant: Ing. Jana Netriová, PhD. Title of diploma thesis: Laboratory diagnostics of kidney injury in patients with diabetes mellitus I and II Diabetes mellitus is a chronic metabolic disease. This disease leads to develompement of both microvascular and macrovascular complications. In this work we examined a microvascular complication - diabetic nephropathy - and its laboratory diagnostics. We focussed on parameters cystatin C and creatinine. We estimated a glomerular filtration with Grubb, Stevens and MDRD equations. The Grubb and Stevens equations use cystatin C to determine the glomerular fitrlation rate (GFR), MDRD equations use creatinine, albumin and urea. For the asessment of kidney function we evaluated albumin and total protein waste in urine samples collected for 24 hours. The parameters were measured in file of 183 patients. Number of pacients with diabetes I.type was 49 and with diabetes II.type was 134. The main intention of this work was to evaluate equations used for determination of GFR, to compare their pros and cons and put them in contrast with albumin and total proteins waste. In case of the patients...
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ln vitro characterization of acetylcholinesterase modulators
Múčková, Ľubica ; Jun, Daniel (advisor) ; Boušová, Iva (referee) ; Štětina, Rudolf (referee)
Various in vitro approaches are available to evaluate the toxicity of substances as well as their mechanism of toxicity in the early stages of the process of developing new chemical entities. These systems are mainly used for screening and allow the creation of more complex toxicological profiles. The present work focuses on in vitro evaluation of substances modulating acetylcholinesterase activity. The enzyme plays a crucial role in the nervous system and occurs mainly in cholinergic synapses and neuromuscular junctions. The primary biological function of this enzyme is the termination of the nerve impulse at these synapses by the rapid hydrolysis of the neurotransmitter acetylcholine to choline and acetate. Acetylcholinesterase is a target enzyme for many drugs, e.g., for Alzheimer's disease or other neurodegenerative diseases. The most often used are reversible and pseudoreversible inhibitors. It also plays a role in poisoning by chemical warfare agents, namely nerve agents and organophosphorus pesticides. Acetylcholinesterase reactivators are used as antidotes for these poisons. Reactivators (asoxime, pralidoxime, obidoxime, trimedoxime, methoxime and oximes K027, K048, K074, K075, and K203) and inhibitors (pyridostigmine, galantamine, rivastigmine, donepezil, tacrine, 7-methoxytacrine, and...
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Laboratory diagnostics of kidney injury in patients with diabates mellitus I and II.
Múčková, Ľubica ; Dršata, Jaroslav (advisor) ; Tichý, Aleš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Ľubica Múčková Supervisor: Prof. MUDr. Jaroslav Dršata, CSc. Consultant: Ing. Jana Netriová, PhD. Title of diploma thesis: Laboratory diagnostics of kidney injury in patients with diabetes mellitus I and II Diabetes mellitus is a chronic metabolic disease. This disease leads to develompement of both microvascular and macrovascular complications. In this work we examined a microvascular complication - diabetic nephropathy - and its laboratory diagnostics. We focussed on parameters cystatin C and creatinine. We estimated a glomerular filtration with Grubb, Stevens and MDRD equations. The Grubb and Stevens equations use cystatin C to determine the glomerular fitrlation rate (GFR), MDRD equations use creatinine, albumin and urea. For the asessment of kidney function we evaluated albumin and total protein waste in urine samples collected for 24 hours. The parameters were measured in file of 183 patients. Number of pacients with diabetes I.type was 49 and with diabetes II.type was 134. The main intention of this work was to evaluate equations used for determination of GFR, to compare their pros and cons and put them in contrast with albumin and total proteins waste. In case of the patients...
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