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In vitro assesment of skin permeation of caffeine using static Franz diffusion cells
Ostrovská, Lucie ; Vopršalová, Marie (advisor) ; Mladěnka, Přemysl (referee)
This thesis aims to the assessment of methods used in in vitro analysis of dermal permeation and absorption of caffeine. Guarantee of standard processes during an experiment is essential for the rightness of results evaluation and interpretation. First part is focused on alternatives and different transport ways of substances through the skin barrier. As transdermal drug delivery offers an increasing number of advantages, the number of studies performing transdermal experiments with drug delivery grows up. On the other hand we are also able to observe or predict the risk of intoxication of individuals after exposure to different kinds of chemicals. The standard methods assessment is of great importance to obtain reproducible results. In this thesis, caffeine was chosen as a model hydrophilic compound. Skin barrier was simulated by dermatomed pig skin of two different thicknesses from ear and abdomen. Eight experimets were carried out with different types of skin using Franz cells in two types of dosing - finite and infinite. Experimental part of the thesis aims on actual determination of caffeine permeation . Measurements were taken in receptor fluid, in particular layers of the skin and on its surface. Spectrophotometry and HPLC analysis were used for the assessment. The ability of caffeine...
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Comparsion of iron reducing properties of flavonols and flavanones
Kyjovská, Veronika ; Mladěnka, Přemysl (advisor) ; Karlíčková, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Kyjovská Supervisor: P emysl Mlad nka, Ph.D. Title of Thesis: Compare iron-reducing properties of flavanols and flavanons The aim of this thesis was to compare the iron-reducing properties of flavanons and flavonols in different concentrations, at different pathophysiological pHs and in non-buffered conditions. A spectrophotometric method with ferrozin, an indicator of ferrous ions, was used. Results at pH 4.5 and in non-buffered conditions were almost comparable, while at pH 5.5 flavonoids showed almost no reduction activity. At pH 6.8 and 7.5 flavonoids did not reduce ferric ions at all. Representatives with the highest reduction activity belonged mostly to the group of flavonols (quercetin, kaempferol, morin, myricetin). Only one representative of flavanons - taxifolin showed the same reduction activity as aforementioned representatives of flavonols. This is probably due to the presence of the 3-hydroxy group in C ring. Other representatives of flavonon do not contain this group and were associated with minimal capabilities of reduction. Lower reduction activity was also observed in case of a representantive of flavonols - rutin, which has the 3-hydroxy group substituted...
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Patophysiological value of rat myocardium after acute exposition of isoprenaline.
Kostinková, Veronika ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Veronika Kostinková Supervisor: Doc. RNDr. Vladimír Semecký, CSc. Title of thesis: Patophysiological values of rat myocardium after acute exposition of isoprenaline Cardiovascular diseases remain one of the main causes of mortality despite advances in medicine. Isoprenaline (ISO) model of myocardial injury in laboratory animals is used to clarify the pathogenesis of acute myocardial infarction (AIM) and to research cardioprotective substances. The monitoring of early histopathological changes that occur in the rat myocardium at 2 hours after application of 100 mg.kg-1 s.c. ISO, was the main aim of this experiment. Histological results were completed in collaboration with the Department of Pharmacology and Toxicology which provided the data about functional parameters and biochemical markers also after 2 hours from application. Detected changes were compared against the control group to which the solvent was administered. Histopathological analysis revealed more frequent and intense changes in the subendocardial area. Some interstitial dilatation with oedema, cardiomyocytes fragmentation and presence of inflammatory infiltration were observed in the myocardium, especially in...
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Assesment of Iron Chelation by 4-Acyl-5-Pyrazolones by Direct Spectrophotometry
Jarkovská, Stanislava ; Mladěnka, Přemysl (advisor) ; Chocholouš, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Stanislava Jarkovská, MSc. Consultant: Přemysl Mladěnka, Ph.D. Title of Thesis: Assessment of iron chelation by 4-acyl-5-pyrazolones by direct spectrophotometry. Iron chelators are used to treat a variety of acquired or inherited hematological disorders and diseases, in which the human body is overloaded by dangerous iron. This pathological deviation is observed mostly in patients with anemias treated with regular blood transfusions. Iron accumulation leads significantly to increased morbidity and mortality if untreated. At present, other potential indications of iron chelators are intensively studied, especially the treatment of acute myocardial infarction, certain types of cancer or malaria. In the first two tested indications, pH drop plays an important role. The subject of this thesis is to verify the iron-chelating properties of selected chelators from 4-acyl-5-pyrazolone group by use of direct spectrophotometry at different pathophysiologically important pHs. Two substances were chosen from this chemical group - phenyl- and thienylderivatives of the basic structure, whose chelating properties had been successfully verified using ferrozine screening method. Both of the tested...
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Comparison of Iron-chelating Effects of Clinically Used Peroral Iron Chelators and 8-hydroxyquinolines
Zárubová, Pavla ; Mladěnka, Přemysl (advisor) ; Pávek, Petr (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Pavla Zárubová Consultant: Přemysl Mladěnka, Ph.D. Name of thesis: Comparison of iron-chelating effects of clinically used peroral iron chelators and 8-hydroxyquinolines Iron is an essentials element, which takes part in many vital processes. However, excessive iron can be toxic for the organism by catalyzing production of free radicals. Long-term administration of blood transfusions in the therapy of various anaemias is the most common cause of iron overload. Each transfuzion represents an intake of 200-250 mg iron in the organism, which due to low daily elimination (only 1-2 mg) leads to iron overload. As a result, complications like cardiovascular impairment or liver fibrosis can emerge. The risk of these severe complications can be reduced by administration of iron chelators. Deferoxamine has been traditionally used for the chelation therapy of chronic iron overload, but to his disadvantages belong frequent parenteral applications. In these days we can also use modern orally acive chelators (deferipron, deferoxamin). Furthermore, there is a wide range of potentially new indications (inflammation, tumor, cardiovascular and neurodegenerative diseases). In all these...
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Influence of selected substances with cardioprotective potential on iso-prenaline induced myocardial damage in a rat model.
Koulová, Jana ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Jana Koulová Supervisor: Doc. RNDr. Vladimír Semecký, CSc. Title of thesis: Influence of selected substances with cardioprotective potential on iso- prenaline induced myocardial damage in a rat model. Cardiovascular diseases are one of the major cause of mortality. To clarify the pathogenesis of acute myocardial infarction (AMI) and to research cardioprotective substances, an iso- prenaline (ISO) model of rat myocardial damage is used. This study assessed the cardiopro- tective potential of intravenously administered rutin in a single dose 11.5 mg / kg in the rat myocardium, which was later given a single subcutaneous dose of ISO (100 mg / kg). The aim of the experiment was to study the functional, biochemical and histological changes occurring in the rat myocardium after 2 hours from application of ISO and rutin with ISO. Observed changes were compared among themselves and also compared to the control group, which was applied intravenously with solvent NaHCO3 in a single dose of 4.6 ml / kg. Functional parameters as heart rate and blood pressure after 2 hours from the application were consistent with the expected development presented in studies with ISO that have been made...
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Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II
Břečková, Anna ; Mladěnka, Přemysl (advisor) ; Hašková, Pavlína (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Anna Břečková Supervisor: Přemysl Mladěnka, Ph.D. Title of Thesis: Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II Iron deficiency and iron overload play important roles in the pathophysiology of certain human diseases. Administration of iron chelators is a suitable therapy in iron overload conditions, especially in cases of hematological diseases treated with blood transfusions. Iron- chelating therapy appears as well as a promising tool for other diseases (acute myocardial infarction, tumor, etc.). Several factors should be considered according to expected indications: 1) oral efficiency, 2) activity in acidic environment, 3) ability to reduce ferric ions to ferrous ions (risk of pro-oxidation). The aim of this thesis was to verify the iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group by use of UV-VIS spectrophotometric methods. From this group, p-terc.butyl- and p-nitroderivatives of the basic structure and the derivatives marked as H2Q3Q and H2QPy, which are double molecules of the basic structure, were chosen. All of the tested substances had some potential to chelate ferrous ions and were also devoid of...
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Effects of chronic growth hormone and melatonin administration on EEG delta power in old rats
Hlubuček, Petr ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Petr Hlubuček Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Effects of chronic growth hormone and melatonin administration on EEG delta power in old rats. Slow wave sleep (SWS), characterized by an increase in delta power (typically 0.1-4 Hz) of EEG spectral analysis is considered to be a core component of deep sleep and is associated with sleep's anabolic restorative properties necessary for good mental and physical health. The reduction of delta power represents one of the hallmarks of sleep alterations with age. In order to study effects of chronic growth hormone (GH) and melatonin administration on sleep EEG power spectra, young (3-4 months) and old (22-23 months) male Wistar rats were implanted with EEG and EMG electrodes. During one month a group of old animals was treated with GH administered intraperitonealy (i.p.), second group of old animals was treated with melatonin diluted in drinking water. Additional two groups of young and old rats with no treatment served as controls. After the treatment, EEG and EMG were recorded and analyzed. Then Fast Fourier transform was used to compute spectral power of REM and NREM sleep. Our results show rapid...
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Determination of the Stoichiometric Ratio of Iron Chelators by Job's Method
Staňová, Zuzana ; Mladěnka, Přemysl (advisor) ; Hašková, Pavlína (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Zuzana Staňová, MSc. Consultanat: Přemysl Mladěnka, Ph.D. Title of Thesis: : Determination of the stoichiometric ratio of iron chelators by Job's method Iron is an important biogenic element affecting many biochemical reactions in the body. Its deficiency and excess cause pathophysiological changes in the organism. Excess of iron is very often the result of frequent blood transfusions in the treatment of hematologic diseases. It may also occur in iron metabolism disorders (chronic intoxication). Acute intoxication after ingestion of excessive amounts of iron is life threatening especially in children. Chelators are used to remove excess iron from the body. It is a heterogeneous group of substances capable of binding iron. Standard drug of this group is parenterally administered deferoxamine. Oral chelators (deferiprone, deferasirox) are also currently used. Other indications of these substances are now the subject of research, which investigates their potential benefits in cancer therapy and acute myocardial infarction. The pH changes play an important role in the pathogenesis of both mentioned conditions. In this work, the stoichiometric ratios of complexes of selected...
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Comparison of Iron Chelating Activity of 8-hydroxyquinolines by Direct Spectrophotometry
Šulcová, Monika ; Mladěnka, Přemysl (advisor) ; Karlíčková, Jana (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of pharmacology and toxicology Candidate: Monika Šulcová MSc. Consultant: Dr. Přemysl Mladěnka, Ph.D. Name of thesis: Comparison of iron chelating activity of 8-hydroxyquinolines by direct spectrophotometry Iron is a biogenic element needed for cell life. Excess iron can be very dangerous for the organism. Thus iron fate in the organism is meticulously regulated. The iron overload arises mainly as the result of frequent blood transfusion or some hematologic diseases. Toxicity of iron is based on the ability to catalyze the formation of reactive oxygen species. The risk can be reduced by the treatment with iron chelators. Iron chelators are compounds with different structures that are therapeutically used for iron intoxication, but are also examined in the treatment of neurodegenerative diseases, acute myocardial infarction and cancer. The ability to bind iron chelator depends not only on its structure, but also on pH. The aim of this work was to compare iron-chelating activity of 8- hydroxyquinolines (basic substance and its derivatives - 5,7-dichloro derivative cloroxin and 5-chlor-7-iod derivative clioquinol) by direct spectrophotometry and to find out the stoichiometry of their complexes with ferrous/ferric...
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