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Anthelmintics in the environment: circulation, metabolism and effects
Navrátilová, Martina ; Matoušková, Petra (advisor) ; Pohanka, Miroslav (referee) ; Česlová, Lenka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Biochemical Sciences Doctoral Degree Program Xenobiochemistry and Pathobiochemistry Candidate Mgr. Martina Navrátilová Supervisor Assoc. Prof. Ing. Petra Matoušková, Ph.D. Advisor PharmDr. Ivan Vokřál, Ph.D. Title of Doctoral Thesis Anthelmintics in the environment: circulation, metabolism and effects This dissertation investigates the environmental impact of anthelmintics, specifically focusing on their circulation, metabolism, and effects in the environment. The primary objective was to explore the extent to which anthelmintics, particularly albendazole, affect plants under laboratory and field conditions and the potential for these effects to contribute to drug resistance in parasites. The study used an analytical technique, UHPLC-MS/MS, to monitor the uptake and biotransformation of albendazole and biochemical assays to asses phytotoxicity in plants like alfalfa and clover. Field experiments demonstrated the circulation of albendazole and its metabolites from sheep dung to plants and back to the sheep, indicating continuous environmental exposure. Furthermore, the investigation into the parasitic nematode Haemonchus contortus revealed changes in the expression of drug-metabolizing enzymes and the...
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COLORIMETRIC ANALYSIS OF BIOCHEMICAL MARKERS USING PHOTOGRAPHY
Mackurová, Kateřina ; Pohanka, Miroslav (advisor) ; Vlček, Vítězslav (referee)
University of Pardubice Faculty of Chemical Technology in Pardubice Performed at: University of defence in Brno, Fakulty of Military Health Sciences in Hradec Králové, Department of Molecular Pathology and Biology Student: Kateřina Mackurová Leader of diploma thesis: pplk. prof. RNDr. Miroslav Pohanka, Ph.D., DSc. Consultant: Mgr. Šárka Štěpánková, Ph.D. Title of diploma thesis: Colorimetric Analysis Of Biochemical Markers Using Photography Keywords: colorimetry, acetylcholinesterase, tacrine, photometric method Acetylcholine, which is responsible for synaptic transmission, is nowadays considered to be the main neurotransmitter in the brain. It is degraded into choline and acetate by two enzymes - acetylcholinesterase (AChE) (EC 3.1.1.7) and butyrylcholinesterase (BChE) (EC 3.1.1.8) AChE inhibitors represent an interesting subject of current scientific research since they belong to the main treatments for Alzheimer's disease or myasthenia gravis. The aim of the thesis was to verify the photometric equipment while determining the reaction of AChE with the substrate on pH papers, to determine the kinetic parameters AChE, and to optimize the method for the determination of the takrin inhibitor. Furthermore, the goal was to determine the influence of selected matrices on AChE using the photometric...
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Application of liquid chromatography in the analysis of biological material for clinical research
Turoňová, Dorota ; Kujovská Krčmová, Lenka (advisor) ; Pohanka, Miroslav (referee) ; Solichová, Dagmar (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Mgr. Dorota Turoňová Supervisor: Assoc.prof. RNDr. Lenka Kujovská Krčmová, Ph.D. Title of doctoral thesis: Application of liquid chromatography in the analysis of biological material for clinical research The dissertation focuses on the use of liquid chromatography for clinical research. It is divided into two main sections, Theoretical part and Commentary on selected published articles. The theoretical part describes the application of high-performance liquid chromatography in practice. Key parameters for the development of LC methods and trends in current bioanalytical practice are discussed. Furthermore, the sample collection and preparation of different biological matrices is explained, including all the obstacles and pitfalls that need to be taken into account. Modern trends are also briefly mentioned. The chapter on sample preparation also includes a section on derivatization and its use in the analysis of platinum derivatives, which is related to the commentary on the published work. The main part of the thesis deals with commentary on four published articles. The first presents a review article dealing with the use of microextraction in pipette tips in clinical and forensic toxicology....
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Application of liquid chromatography in the analysis of biological material for clinical research
Turoňová, Dorota ; Kujovská Krčmová, Lenka (advisor) ; Pohanka, Miroslav (referee) ; Solichová, Dagmar (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Mgr. Dorota Turoňová Supervisor: Assoc.prof. RNDr. Lenka Kujovská Krčmová, Ph.D. Title of doctoral thesis: Application of liquid chromatography in the analysis of biological material for clinical research The dissertation focuses on the use of liquid chromatography for clinical research. It is divided into two main sections, Theoretical part and Commentary on selected published articles. The theoretical part describes the application of high-performance liquid chromatography in practice. Key parameters for the development of LC methods and trends in current bioanalytical practice are discussed. Furthermore, the sample collection and preparation of different biological matrices is explained, including all the obstacles and pitfalls that need to be taken into account. Modern trends are also briefly mentioned. The chapter on sample preparation also includes a section on derivatization and its use in the analysis of platinum derivatives, which is related to the commentary on the published work. The main part of the thesis deals with commentary on four published articles. The first presents a review article dealing with the use of microextraction in pipette tips in clinical and forensic toxicology....
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The different extraction techniques using for HPLC evaluation of some drugs
Kračmarová, Alžběta ; Mokrý, Milan (advisor) ; Pohanka, Miroslav (referee)
In this study the reversed-phased HPLC method for determination of an atypical antipsychotic drug amisulpride in a rabbit plasma was developed. The amisulpride is a benzamide derivative, which antagonizes human dopamine D2/D3 receptors. The main clinical efficacy of this drug is the therapy of both negative and positive symptoms of schizophrenia and low propensity to produce extrapyramidal sight effects. A Separon SGX C18 (size of particles 7 μm) as a stationary phase, a mixture of an acetonitrile - 0,1M amonium acetate (pH 5,6) 40:60 (v/v) as a mobile phase and an ambroxol as an internal standard were used for the analysis. Before the determination a solid-phase extraction was made. The method is linear in concentrations between 200 and 800 ng/ml (y=0,0065x-0,0695, r2 =0,9930), selective and robust. The analysis time was 11 min. A teoretical part of this study is approached to methods of an extraction, which is a very important step in an analysis of a biological material.
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The relationship between structure and activity of potential reactivators of acetylcholinesterase I.
Holas, Ondřej ; Opletalová, Veronika (advisor) ; Pohanka, Miroslav (referee)
The realtionship between structure and activity of potencial reactivators of acetylcholinesterase Organophosphorus compounds (OPC) are used as agricultural pesticides and in industry as fire retardants or plastificators. For military use there have been developed nerv agents (NA, e.g. tabun, sarin, somna, VX). The toxicity of these compounds is based upon phosphorylation or phosphonylation at the serine hydroxy group (Ser200) of the active site of the acetylcholinesterase. The current standard treatment consists of administration oxime reactivators in combination with anticholinergic drug (preferably atropin). Unfortunately, none from the currently used oximes is sufficiently effective against all types of the OPCs. The aim of this study is determination of the relationship between structure and activity of new reactivators against paraoxon inhibited AChE in vitro and comparison with currently available substances. For evaluation of reactivation activity has been chosen standard in vitro test using rat brain homogenate
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Development of bioanalytical methods for the determination of diagnostic markers and drugs using chromatographic techniques
Javorská, Lenka ; Solich, Petr (advisor) ; Pohanka, Miroslav (referee) ; Šatínský, Dalibor (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Analytical Chemistry Candidate: Mgr. Lenka Javorská Supervisor: prof. RNDr. Petr Solich, CSc. Consultant: assoc. prof. RNDr. Lenka Kujovská Krčmová, Ph.D. Title of dissertation thesis: Development of bioanalytical methods for the determination of diagnostic markers and drugs using chromatographic techniques The presented dissertation is focused on the development and validation of chromatographic method for the determination of glycopeptide antibiotic vancomycin, and L-arginine and its pathway related substances in biofluids. Furthermore, the potential of neopterin, kynurenine and tryptophan as biomarkers of immune response to surgical procedure and prediction of postoperative complications is investigated in connection with oncological diseases. In the theoretical part trends in instrumentation, stationary phases and extraction techniques are described. The issues of separation and retention of polar compounds and biological matrix pretreatment before analysis are also discussed there. Next part deals with selected analytes and their application to the clinical purpose for which the chromatographic methods are developed. It also provides an overview of published methods for their determination using liquid...
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Development of bioanalytical methods for the determination of diagnostic markers and drugs using chromatographic techniques
Javorská, Lenka ; Solich, Petr (advisor) ; Pohanka, Miroslav (referee) ; Šatínský, Dalibor (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Analytical Chemistry Candidate: Mgr. Lenka Javorská Supervisor: prof. RNDr. Petr Solich, CSc. Consultant: assoc. prof. RNDr. Lenka Kujovská Krčmová, Ph.D. Title of dissertation thesis: Development of bioanalytical methods for the determination of diagnostic markers and drugs using chromatographic techniques The presented dissertation is focused on the development and validation of chromatographic method for the determination of glycopeptide antibiotic vancomycin, and L-arginine and its pathway related substances in biofluids. Furthermore, the potential of neopterin, kynurenine and tryptophan as biomarkers of immune response to surgical procedure and prediction of postoperative complications is investigated in connection with oncological diseases. In the theoretical part trends in instrumentation, stationary phases and extraction techniques are described. The issues of separation and retention of polar compounds and biological matrix pretreatment before analysis are also discussed there. Next part deals with selected analytes and their application to the clinical purpose for which the chromatographic methods are developed. It also provides an overview of published methods for their determination using liquid...
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Antiproliferative activity of novel dexrazoxane analogues and their effect on antitumor effectiveness of anthracyclines
Martinková, Pavla ; Jirkovská, Anna (advisor) ; Pohanka, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Pavla Martinková Supervisor: PharmDr. Anna Jirkovská, PhD. Title of diploma thesis: Antiproliferative activity of novel dexrazoxane analogues and their effect on antitumor effectiveness of anthracyclines Athracycline antibiotics (such as daunorubicin, doxorubicin or epirubicin) belong to the most common terapeutics of both solid tumors and hematological malignities. Unfortunately the serious and life-threatening adverse effect cardiotoxicity compromises their clinical usefulness. The only approved protection against anthracycline cardiotoxicity so far is dexrazoxane. Despite the outstanding cardioprotective ability, dexrazoxane use is very limited mainly due to its possible side effects. So we were directed towards synthesis of dexrazoxane analogues with better pharmacological properties. The aim of this diploma thesis was to assess the antiproliferative activity of novel analogues of both dexrazoxane (MK-15 and ES-5) and ADR-925 (JR-159 and KH- TA4) and their influence on the antiproliferative effectiveness of anthracyclines. Moreover, we aimed to study their chelating properties and their inhibition of the topoisomerase II in solution. We tested the antiproliferative activity of...
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