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Prospective study of long-term neurological sequelae of acute methanol poisoning
Kotíková, Kateřina ; Zacharov, Sergej (advisor) ; Pohanka, Miroslav (referee) ; Ehler, Edvard (referee)
Background: Methanol is widely industrially used alcohol with known neurotoxic properties. Bilateral necrosis of basal ganglia is a typical finding detected on MRI or CT scan of the brain in acute methanol poisoning. The impact of methanol exposure on peripheral nervous system is unknown. Aim: To study the prevalence and predisposing factors of haemorrhagic and non-haemorrhagic brain lesions in survivors of acute methanol poisoning; to investigate whether 123 I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning; to investigate the role of acute methanol exposure in the development of peripheral polyneuropathy (PNP) during the years following discharge from the hospital. Methods: A six year prospective, single-centre, cohort study of patients with confirmed methanol poisoning was conducted. The examination protocol consisted of neurological examination, including magnetic resonance imaging (MRI) of the brain, DaT SPECT and electromyographic examination, further, visual evoked potentials, ocular examination with retinal nerve fiber layer thickness measurement, series of biochemical and toxicological tests. In 46 patients, follow-up examinations including brain MRI were performed 3-8 and 24-28 months after discharge from the hospital, in 42...
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Testing of new potencial substances for the treatment of Alzheimer's Disease
Drtinová, Lucie ; Pohanka, Miroslav (advisor) ; Patočka, Jiří (referee) ; Mokrý, Milan (referee)
University of Defence in Brno Faculty of Military Health Sciences in Hradec Králové Department of Toxikology and Centre of Advanced Studies Student: Mgr. Lucie Drtinová Supervisor: pplk. doc. RNDr. Miroslav Pohanka, Ph. D., DSc Title of Disertation: Testing of new potencial substances for the treatment of Alzheimer's Disease Alzheimer's disease (AD) is the most common form of dementia which is manifested especially by loss of short-term memory, spatial disorientation, progressive loss of cognitive function and progressive deterioration of intellect. It is estimated about 36 million (mostly AD) people worldwide suffer from dementia and this number continues to grow. AD is unpredictable, multifactorial disease of unknown origin and casual therapy. In most post- mortem investigated brains, loss of nerve tissue, oxidative damage induced by inflammation and neuronal decay, extracellular aggregated amyloid beta in amyloid plaque and hyperphosphorylated tau protein tangles were discovered. This disease always ends lethally after 2-10 years from diagnosis. At present, the only available drugs for AD are for symptomatic treatment and most treated patients build a tolerance to them over time. The effect of drugs used in the treatment of AD is based on inhibition of acetylcholinesterase (AChE) (donepezil,...
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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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Prospective study of the role of oxidative stress in acute methanol poisonings.
Hlušička, Jiří ; Zacharov, Sergej (advisor) ; Lambert, Lukáš (referee) ; Pohanka, Miroslav (referee)
5 SUMMARY Context: Acute methanol poisoning is a life-threatening condition. Methanol is metabolized in the organism to formaldehyde and than to formic acid, which inhibits cytochrome c oxidase in mitochondria and thus contributes to the development of oxidative stress. Aim: To study the role of oxidative stress in the pathogenesis of acute neuronal damage to the central nervous system (CNS), in the development of long-term sequelae of methanol poisoning and chronic neurodegenerative processes in the years following acute methanol exposure. Material and Methods: Methanol intoxication was confirmed analytically in 55 patients included in he d ; hei age a he ime f i ning a 46.7 3.6 ea (9 female and 46 male ). All a ien , together with 41 control subjects, were examined in a prospective longitudinal cohort study. At admission, during hospitalisation, and at regular intervals after discharge during the follow-up, the patients were sampled for serum concentrations of lipid oxidative damage markers 4-hydroxy-trans-2- hexenal (HHE), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and 8-isoprostane, for nucleic acids oxidative damage markers 8-hydroxy-2 -deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8- OHG), 5- (hydroxymethyl) uracil (5-OHMU), for proteins oxidative damage markers ortho-tyrosine (o- Tyr),...
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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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Prospective study of long-term visual sequelae of acute methanol poisonings
Nurieva, Olga ; Zacharov, Sergej (advisor) ; Lišková, Petra (referee) ; Pohanka, Miroslav (referee)
Background: Methanol poisoning is a life-threatening condition which induces acute toxic optic neuropathy with possible long-term visual sequelae in survivors. Aim: To study the prevalence, character, dynamics, and key determinants of chronic morphological and functional visual pathway changes during 4 years after methanol-induced optic neuropathy. Methods: A total of 55 patients with confirmed methanol poisoning with mean age 46.7 ± 3.6 years (46 males and 9 females), and 41 controls were included in this prospective longitudinal cohort study. The patients were examined 4.9 ± 0.6, 25.0 ± 0.6, and 49.9 ± 0.5 months after discharge. The following tests were performed: visual evoked potential (VEP), optical coherence tomography with retinal nerve fiber layer (RNFL) measurement, brain magnetic resonance imaging (MRI), complete ocular examination, biochemical tests, and apolipoprotein E (ApoE) genotyping. Results: Of 42/55 patients with all three consecutive examinations, abnormal RNFL thickness was registered in 13 (31%) and chronic axonal loss during the observation period was found in 10 (24%) patients. The risk estimate of chronic global RNFL loss for arterial blood pH<7.3 at admission was: 11.65 (1.91-71.12; 95% CI) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated...
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Testing of new potencial substances for the treatment of Alzheimer's Disease
Drtinová, Lucie ; Pohanka, Miroslav (advisor) ; Patočka, Jiří (referee) ; Mokrý, Milan (referee)
University of Defence in Brno Faculty of Military Health Sciences in Hradec Králové Department of Toxikology and Centre of Advanced Studies Student: Mgr. Lucie Drtinová Supervisor: pplk. doc. RNDr. Miroslav Pohanka, Ph. D., DSc Title of Disertation: Testing of new potencial substances for the treatment of Alzheimer's Disease Alzheimer's disease (AD) is the most common form of dementia which is manifested especially by loss of short-term memory, spatial disorientation, progressive loss of cognitive function and progressive deterioration of intellect. It is estimated about 36 million (mostly AD) people worldwide suffer from dementia and this number continues to grow. AD is unpredictable, multifactorial disease of unknown origin and casual therapy. In most post- mortem investigated brains, loss of nerve tissue, oxidative damage induced by inflammation and neuronal decay, extracellular aggregated amyloid beta in amyloid plaque and hyperphosphorylated tau protein tangles were discovered. This disease always ends lethally after 2-10 years from diagnosis. At present, the only available drugs for AD are for symptomatic treatment and most treated patients build a tolerance to them over time. The effect of drugs used in the treatment of AD is based on inhibition of acetylcholinesterase (AChE) (donepezil,...
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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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Study of new acetylcholinesterase modulators
Račáková, Veronika ; Opletalová, Veronika (advisor) ; Pohanka, Miroslav (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Veronika Račáková Consultant: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Thesis: Study of new acetylcholinesterase modulators. Organophosphorus compounds are chemically organophosphates or organophosphonates. They have been widely used as a pesticides but because of their high toxicity and relatively cheap and easy synthesis they can be easily misused as chemical weapons - nerve paralytic compounds. Toxic effect of these compounds is based on irreversible inhibition of the enzyme acetylcholinesterase (AChE). In case of intoxication by these compounds anticholinergic drugs (atropin) and reactivators of AChE are usually used as antidots. The effect of the reactivators is based on splitting the complex enzyme-inhibitor. Pralidoxim, trimedoxim, obidoxim and asoxim (HI-6) are still the most often used reactivators all over the world. They are the compounds which contain oxime group and one or two quarternary nitrogens in their molecule, what ensures that their affinity to AChE will be strong enough. Screening and synthesis of new more effective broad-spectrum reactivators of AChE with lower side effects is still very actual and discussed theme. Strategy...
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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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