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1
Slámová, Jitka. "Studium sterilizačních účinků dielektrického bariérového výboje." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2013. http://www.nusl.cz/ntk/nusl-233367.
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The overall goal of the presented dissertation thesis was to study the sterilization efficiency of dielectric barrier discharge operated at atmospheric pressure. The fungi Aspergillus niger, gram-positive bacteria Bacillus subtilis and in some experiments also gram-negative bacteria Escherichia coli were used as a bio-indicator enabling to evaluate the effect of plasma assisted microbial inactivation. The samples of microorganism were placed on paper Whatman 1 or PET foil and exposed to plasma. The plasma was generated in argon, nitrogen, synthetic dry/humid air with frequency up to 10 kHz and plasma power density in the range of 1,2-2,9 W/cm3 (according to the process gas). The influence of process gas, plasma power density, plasma exposition time, type of microorganism and material of the substrate on the sterilization effect of dielectric barrier discharge was evaluated. Furthermore the contribution of each single mechanism (UV radiation, temperature and reactive species) to the sterilization effect of plasma and influence of gas humidity was evaluated. The DBD was analysed by means of optical emission spectroscopy, thermocouple was used to measure temperature during a sterilization process. In order to verify the mechanical damage of the microbial cell or the substrates during the plasma process the samples were studied by scanning electron microscopy. Generally, on the basis of experimental results, at increasing treatment times, the remaining number of spores (CFU) decreased. Similarly at increasing the plasma power input, the sterilization rate increased. When sterilising the spores of A. niger in plasma using different process gasses, the efficiency of plasma sterilization decreased as follows: argon, humid synthetic air, nitrogen and dry synthetic air. The results observed in argon plasma using different microorganism demonstrated that the sensitivity of vegetative cells resp. spores to DBD decreased as follows: A. niger spores, B. subtilis vegetative cells, E. coli vegetative cells and B. subtilis spores. Simultaneously results observed for sterilization of spores and vegetative cells of B. subtilis and A. niger demonstrated that the spores are generally more resistant to plasma than are the corresponding vegetative cells. Combining the results of contribution of each single mechanism, optical emission spectroscopy and inactivation characteristic it was found out that the reactive species significantly contribute to the plasma sterilization in all process gasses. Furthermore the inactivation process can be partly assisted by UV radiation and also the temperature can contribute in limited extent to inactivation process in some gasses. The contribution of UV radiation to the plasma sterilization decreased as follows: nitrogen, argon, dry syntetic air and humid syntetic air. Moreover it was found out that the contribution of each single mechanism can be species dependent, this is due to the different response of microorganism to the unfavorable external conditions. SEM analysis of the substrates prooved the etching actions of the plasma generated in all process gasses on the surface of the PET foil. The several minute plasma exposition of the PET foil resulted in the occurence of the „hole corrosion“ on the PET surface. Contrary to these there were no visible changes observed in the paper structure.
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Drábková, Markéta. "Donepezil-mechanismus účinku a hodnocení účinnosti." Master's thesis, 2009. http://www.nusl.cz/ntk/nusl-279552.
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1 Summary Title: Donepezil - biological activity and evaluation of its efficiency Author: Markéta Drábková Supervisor: Doc. MUDr. Josef Herink, DrSc. Department: Department of biological and medicinal sciences Cognitive enhancers are drugs which preferentially affect cholinergic transmission in the central nervous system. The cholinergic system in the brain is the most seriously damaged neurotransmitter system in Alzheimer, s disease and dementia with Lewy bodies. Donepezil is a new cognitive enhancer whose mechanism of action consists of reversible specific inhibition of acetylcholinesterase activity. Donepezil increases the amount of acetylcholine available for neuron-to-neuron communication, which may relieve some memory impairment and thus prolonging of patients' self-support. Present thesis classifies cognitive enhancers, it especially describes the mechanism of action and effect of donepezil and its therapeutical usage. The principal aim of my work was to assess and evaluate the efficacy and adverse effects of donepezil from chosen clinical studies in the years 2003- 2009. The results support the conclusion that donepezil is safe and effective for long-term treatment of patients with mild or moderate Alzheimer's dementia, vascular dementia, mild cognitive impairment and multiple sclerosis. In...
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Heřmanová, Ivana. "Mechanismus účinku L-asparaginázy u dětské akutní lymfoblastické leukemie." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-350099.
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Acute lymphoblastic leukemia (ALL) is the most frequent type of childhood cancer. The key component in the therapy, L-asparaginase (ASNase), hydrolyzes plasma asparagine and glutamine. Leukemic cells are sensitive to the depletion due to low activity of asparagine synthetase. Although the treatment is very effective, resistance and side effects remain a serious problem in some cases and its mechanism of action is not well understood. In this study, we wanted to elucidate the effect of ASNS expression level on the sensitivity of ALL cells to ASNase treatment. Our aim was also to clarify the intracellular consequences of the amino acid depletion to define the reason of different patients' response. We used four ALL cell lines (NALM-6, RS4;11, REH, and UOCB-6) and 30 diagnostic bone marrow samples of ALL patients to study the relationship between ASNS expression and sensitivity to ASNase using MTS proliferation assay. RNA interference was used to study the effect of a range of ASNS levels on the response to ASNase treatment. Using a cell line model with a gradually knocked-down ASNS gene, we defined a cutoff level below which ASNS gene expression does not correlate with sensitivity to ASNase. Importantly, ASNS gene expression in patients' ALL blasts is below this level. We confirmed that there was no...
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Hofmannová, Jana. "Molekulárně-buněčný mechanismus účinku ancymidolu na buněčné unie tabáku." Master's thesis, 2006. http://www.nusl.cz/ntk/nusl-370169.
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Vranová, Iveta. "Mechanismus působení protinádorového léčiva ellipticinu v cílových tkáních jeho účinku." Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-305429.
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Ellipticine is an alkaloid isolated from Apocynaceae plants exhibiting significant antitumor and anti-HIV activities. Cytochromes P450 (CYP) and peroxidases are the enzymes participating in metabolism of ellipticine. This process provides activation and detoxication metabolites of ellipticine. The CYP enzymes, which participate in oxidation of ellipticine in different tissues (liver, lung and kidney) of rat, a model organism simulating the fate of ellipticine in humans have already been identified. In this work, the effects of ellipticine on contents and catalytic activities of CYPs and other components of the mixed-function oxidase (MFO) system in this animal system were studied. For detection of contents of CYPs and other components of the MFO system, spectroscopic and electrochemical methods were used. To determine catalytic activities of CYPs and NADPH:cytochrome P450 reductase, reactions with specific substrates of these enzymes were utilized. The results found in this study demonstrate that expression and catalytic activity of CYP1A is induced by ellipticine in all of the tested organs (liver, kidney and lung) of rats treated with the drug. Moreover in liver, the cytochrome b5 expression is also induced. In addition, in this organ, expression and catalytic activity of CYP3A was increased by...
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STEINBAUEROVÁ, Veronika. "Mechanismus toxického účinku adenosinu na buňky imaginálních terčků \kur{Drosophila melanogaster}." Master's thesis, 2005. http://www.nusl.cz/ntk/nusl-43017.
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Pokorná, Jana. "Modulace aktivity HIV-1 proteasy." Doctoral thesis, 2013. http://www.nusl.cz/ntk/nusl-322613.
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HIV-1 protease plays a crucial role in the late state of the life cycle of HIV virus when it cleaves the viral polyprotein precursors into the structural and functional proteins. If it is effectively inhibited, HIV particles remain immature and noninfectious. The application of highly active antiretroviral therapy (HAART) including protease inhibitors can reduce plasma HIV-1 levels below the detection limit in adherent patients and thus dramatically change their life expectancy. The clinical utility of the first inhibitors was limited by severe side effects, low bioavailability, high pill burdens, and rapid development of viral resistance under the selection pressure of HIV antiretrovirals. To overcome these difficulties, second-generation inhibitors were developed. Despite an indisputable improvement they brought to antiretroviral therapy, the development of new highly active HIV-1 protease inhibitors with optimal pharmacokinetic properties, higher metabolic stability, little off-target activity, and particularly, more favorable resistance profiles is still of high importance. This thesis provides an overview of anti-HIV- drugs including development of substituted metallacarboranes, a new class of potent, unusual, nonpeptidic HIV protease inhibitors with therapeutic potential. Next, the impact of...
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Riedlbauchová, Lucie. "Mechanismus účinku biventrikulární kardiostimulace v porovnání se stimulací levé komory a bifokální stimulací pravé komory u nemocných s chronickým srdečním selháním." Doctoral thesis, 2007. http://www.nusl.cz/ntk/nusl-288086.
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Cardiac resynchronization therapy (CRT) represents an accepted treatment modality in patients with advance chronic heart failure, acute and long-term benefit of which was confirmed in several clinical trials. Recently, reduced mortality and rate of hospitalization for heart failure were also demonstrated. However, response to CRT is interindividually highly variable with a substantial proportion of CRT recipients who do not respond to this therapy. Although the identification of suitable candidates is probably the most important factor in the reduction of the rate of non-responders, some other determinants, peri- and post-implant, may substantially affect the final effect of CRT. The present PhD focused on some of these variables: 1/ First of them is a selection of the appropriate pacing mode. This PhD evaluated effect of 3 pacing modalities that have been proposed as alternatives of CRT - biventricular pacing (BiV), single-site left-ventricular pacing (LVP) and rightventricular bifocal pacing (Bif). It was clearly shown that the first two pacing strategies, BiV (it is simultaneous pacing of both ventricles) and LVP, cause comparable acute hemodynamic improvement at rest. Study No.2 of this PhD confirms that the comparable effect of BiV and LVP is preserved also during the exercise. In addition, study No.1...
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Butorová, Lucie. "Mechanismy účinku moderních antiepileptik (hodnocení nežádoucích účinků)." Master's thesis, 2008. http://www.nusl.cz/ntk/nusl-292573.
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1 Summary Title: Mechanisms of effect of new antiepileptic drugs (An evaluation of adverse effects) Author: Lucie Butorová Supervisor: Doc. MUDr. Josef Herink, DrSc. Department: Department of biological and medicinal sciences Epilepsy is frequent neurological disease. It is characterised by spontaneously repeated epileptic seizures, which are caused by abnormalities of neuronal activity of the brain. Therapy of epilepsy consists in prophylaxis of epileptic seizures, and that is why it is necessary to use the antiepileptic drugs for a long time. This administration is accompanied by the increased risk of adverse effects. Present thesis classifies particular epileptic seizures, describes pathophysiology of epilepsy and the principles of therapy with antiepileptic drugs. The principal aim of my work was to find out and evaluate side effects of antiepileptic drugs by the help of the questionnaire. The results proved higher efficacy and fewer adverse effects of monotherapy in a comparison with combined therapy and also 3rd generation antiepileptic drugs in a comparison with the 1st generation of antiepileptic drugs. In conclusion of my work I aimed to compare efficacy and the occurrence of adverse effects concerning antiepileptic drugs used and hereafter compare these results with published data concerning...
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Koutníková, Jitka. "LAKTOFERIN - mechanismy biologického účinku." Master's thesis, 2006. http://www.nusl.cz/ntk/nusl-268417.
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Černá, Tereza. "Studium mechanismu účinku protinádorových léčiv na neuroblastomy." Doctoral thesis, 2018. http://www.nusl.cz/ntk/nusl-389781.
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Despite advances in cancer diagnosis and therapy, cancer is the second leading cause of death globally. The improvements of cancer treatment are the major challenge in this research. The aim of the thesis was studying of effects of two anticancer drugs ellipticine (Elli) and doxorubicin (DOX) on some cancer and healthy cell lines. Specific consideration was given to expand current knowledge about the metabolism and cytostatic effects of Elli in neuroblastoma cell lines. Another part of this study was focused on mechanisms contributing to the development of ellipticine-resistance in cancer cells and influence of histone deacetylase inhibitors on anticancer therapy was investigated. Moreover, the aim was to develop apoferritin (Apo) nanocarrier suitable for the active transport of cytostatics to cancer cells. Several essential data were found in this doctoral thesis. Anticancer efficiency of Elli depends on the CYP3A4-mediated metabolism in cancer. The CYP3A4 enzyme encapsulated into two nanoparticle forms, liposomes and SupersomesTM , was tested to activate ellipticine to its reactive species forming covalent DNA adducts. The formation of adducts seems to be dependent on concentrations of CYP3A4 in nanoparticle systems. A higher effectiveness of CYP3A4 in SupersomesTM than in liposomes to form...
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Svoboda, Michal. "Studium mechanismu účinku metallakarboranových inhibitorů HIV proteasy." Master's thesis, 2011. http://www.nusl.cz/ntk/nusl-313248.
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English Abstract Shortly after the identification of HIV as a causative agent of AIDS, an aspartic protease was identified in the viral genetic information. The very same time protease has become one of the dominant therapeutical targets in AIDS therapy. The introduction of protease inhibitors into the antiretroviral therapy has led to a significant improvement in the quality and length of life of HIV patients. However, the virus is still able to effectively prevent the impact of an inhibitor via generating inhibitor-resistant mutated protease variants. Thus, there is a constant need for novel types of inhibitors that would be capable of effectively blocking these resistant variants and simultaneously not supporting the development of novel resistant viral strains. One way to identify such inhibitors could be searching for compounds interacting with the enzyme at different sites than the active cavity, via the mechanisms of noncompetitive or uncompetitive inhibition. The group of compounds called metallacarboranes - inorganic compounds consisting of carbon, boron, hydrogen and metall ion - were shown to exhibit such an activity against HIV-1 protease. However, for further optimization of these inhibitors, detailed biophysical investigation of the enzyme-inhibitor complex is needed. This work focuses on the...
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Švecová, Milena. "Studium molekulárních mechanismů účinku kyseliny nikotinové v léčbě aterosklerózy." Master's thesis, 2009. http://www.nusl.cz/ntk/nusl-282980.
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To investigate molecular mechanism of action of nicotinic acid in the treatment of atherosclerosis, we have used genetically modified mice, LDLR k.o. mice and PumaG double deficient mice. Mice were fed high fat diet for sixteen weeks and treated with or without 0.3% nicotinic acid in drinking water. Afterwards mice were sacrificed and the hearts were used for determination of the atherosclerotic lesions by defining the plaque area and areas immunostained for macrophages. Further we aimed at clearing the mechanism of action of nicotinic acid. By using fluorescence microscopy we found area with expression of gene GPR109A in peritoneal exudates cells. Next, by setting the limit of intracellular calcium I was measuring the response of peritoneal cells to the nicotinic acid with subsequent addition of chemokines - mcp-1, rantes, il- 8, mip-1- α. The goal was to lower the level of chemokines and thus to reduce the inflammation.
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Ballóková, Anna. "Obranné mechanismy motolice kopinaté před účinky anthelmintik." Master's thesis, 2010. http://www.nusl.cz/ntk/nusl-282944.
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Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Anna Ballóková Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Defence mechanisms of lancet fluke against effects of anthelmintics Dicroceliosis, helminthosis caused by Dicrocoelium dendriticum (lancet fluke), is worldwide spread infection of small ruminants. The only way of effective control of this parasitosis is in administration of anthelmintics. In lancet fluke, benzimidazole anthelmintic albendazole metabolism via enzymatic sulfoxidation was found but no information about albendazole oxidases is available. The aim of this work was to identify enzymes involved in the metabolism of albendazole in Dicrocoelium dendriticum isolated from naturally infected mouflons (Ovis musimon). To determinate the involved enzymes some of the specific inhibitors were used. The only effective inhibitors used in this work were α-nafthylthiourea and methimazole, specific inhibitors of flavin-containing monooxygenases. Indole-3-carbinole, used as the specific inhibitor of the same enzymatic system, was without any effect. Other inhibitors were used: 3-amino-1,2,4-triazole for catalase, diethyldithiocarbamate and octylamine for cytochrome P450 and salicylohydroxamic acid and...
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Čujová, Sabína. "Nové antimikrobiální peptidy izolované z jedu včel a studium mechanismu jejich účinku." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-334586.
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EN The growing emergence of bacteria resistant to conventional antibiotics is very alarming. This has prompted an intensive search for alternative antimicrobial agents which kill bacteria with different modes of action than do traditional antibiotics and do not develop drug resistance. Among these, antimicrobial peptides (AMPs) are considered as promising compounds against resistant pathogens. These positively charged peptides permeabilize or disrupt bacterial cell envelope which leads to leakage of cytoplasmic components and cell death. The aim of my dissertation thesis was the study of the action mechanism of novel antimicrobial peptides which I have isolated from the venom of different wild bees. I identified six novel AMPs which were named panurgines (PNG), codesane (COD) and antapines (ANTPs). These peptides were isolated from the venom of three different bee species (Panurgus calcaratus, Collete daviesanus and Anthophora plumipes). I was also involved in the structural studies of lasiocepsin (Las), the antimicrobial peptide identified in the venom earlier in our laboratory. All studied peptides possess activity against various strains of bacteria and low or moderate hemolytic activity. We prepared series of PNG, COD and ANTP analogs in order to study the effect of physicochemical properties...
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Podzimek, Štěpán. "Studium kompenzačních mechanismů nežádoucích účinků kovů na lidský organismus." Doctoral thesis, 2006. http://www.nusl.cz/ntk/nusl-269691.
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Hrabáková, Rita. "Proteomová analýza účinků protinádorových léčiv a charakterizace mechanismů nádorové rezistence." Doctoral thesis, 2013. http://www.nusl.cz/ntk/nusl-328676.
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Despite significant progress in the development of anti-cancer drugs, there is still a need for novel therapeutic strategies that would improve the outcome of cancer patients. Using proteomic technologies and cell lines with different phenotype of p53 tumour suppressor, we monitored cancer cell response to anti-cancer treatment with focus on the development of drug resistance. The different levels of metabolic proteins were identified in our study which may help to explain different anti-cancer activity of drugs with only a subtle difference in structure. More importantly, proteins associated with the development of drug resistance were identified and such expression changes have become a focus of interest. Our findings demonstrate a higher protein level of serine hydroxymethyltransferase, serpin B5 and calretinin in cancer cells resistant to Aurora kinase inhibitors. Such proteins promote the tumour growth with no apparent impact of p53 phenotype whilst voltage-dependent anion-selective channel protein 2 contributes to the development of resistance only in cells with functional p53 which is accompanied by the decreased level of elongation factor 2. On the other hand, cancer cells with loss of p53 appear to amplify alternative mechanisms such as protection against oxidative stress. The results...
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Klimentová, Jana. "Strukturní obměny transkarbamů - syntéza a sledování vlastností a biologické aktivity se zaměřením na objasnění mechanismu účinku." Doctoral thesis, 2006. http://www.nusl.cz/ntk/nusl-269944.
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One of the subjects studied in the Department of Inorganic and Organic Chemistry of the Faculty of Pharmacy focuses on the synthesis and biological evaluation of potential transdermal permeation enhancers. Over the past few years, series of esters of 6-aminohexanoic acid of high enhancing activity and their analogues have been prepared. Presently, the structure-activity relationships are being studied. This work contributes to this problem by searching for the mechanism of action of one of the most active compounds, transkarbam 12 (T12). Transdermal permeation enhancers facilitate drug absorption through the skin. Generally, their mechanisms of action include the disturbance of highly ordered structure of stratum corneum, promotion of drug solubility in the vehicle or enhancing the partitioning of drug from the vehicle into stratum corneum. Nevertheless, the exact mechanism is usually unclear. T12 is a carbamic acid salt derived from two molecules of 6-aminohexanoic acid dodecyl ester. In slightly acidic environment (as in stratum corneum, its target place) it decomposes easily releasing a molecule of CO2 and free amino ester. To find out whether this ability contributes to its high activity, a series of T12 analogues with CO2 covalently bound in the polar head was prepared (esters of carbonic,...
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Hergeselová, Tereza. "In vitro studie molekulárních mechanismů antiproliferativního účinku extraktu z plodu jalovce v buňkách kolorektálního karcinomu." Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-346962.
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Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences University of Helsinki Faculty of Pharmacy Division of Pharmacology and Pharmacotherapy and Faculty of Agriculture and Forestry Department of Food and Environmental Sciences Candidate: Tereza Hergeselová Supervisors: Doc. Atso Raasmaja Doc. Anne-Maria Pajari, Ph.D Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: In vitro study of molecular mechanisms of antiproliferative activity of extract from juniper berry in colorectal cancer cells Colorectal cancer is one of the most diagnosed cancers and one of the leading causes of cancer-related death in developed countries. Its development is strongly influenced by environmental factors, particularly by diet that could provide cancer prevention and treatment with plant-derived substances possessing chemopreventive and/or antiproliferative ability with minimum of the undesirable side-effects, often seen with synthetic medicines. Phenolic compounds contained especially in various berries have displayed health-promoting properties including the anticarcinogenic effect. In this study, the cytotoxic effects of juniper berry extract and the mechanisms of its antiproliferative activity were evaluated in vitro. Two colorectal cancer cell lines - HCA-7...
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Kutová, Martina. "Role serotoninových 5-HT1 a 5-HT2 receptorů v mechanismu účinku syntetické drogy 2C-B: behaviorální studie na potkanech." Master's thesis, 2008. http://www.nusl.cz/ntk/nusl-272688.
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VÁCOVÁ, Nikol. "Použití agonistů fagocytárních receptorů pro terapii nádorových onemocnění a studium možnosti zesílení jejich účinků současnou stimulací TLR receptorů." Master's thesis, 2015. http://www.nusl.cz/ntk/nusl-187646.
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Binding of agonist of phagocytic receptors on surface of tumor cells caused significant reduction of tumor growth. This reduction was enhanced by stimulation of TLR receptors. This immunotherapy combines ligation of phagocytic receptors and signaling receptors to achieve anti-tumor effect. The next part of this thesis was focused on the study of mechanism of the anti-tumor activity of neutrophils.
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Škodová, Adriana. "Gemmoterapie a její využití v praxi." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-367738.
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GEMMOTHERAPY AND ITS USE IN PRACTISE Student: Škodová Adriana Tutor: PharmDr. Jitka Pokladníková, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Czech Republic Introduction: Gemmotherapy or budding medicine is an herbal healing method, whose roots go back to the Middle Ages and folk healing. It uses germ-shaped parts of plants (especially buds) for the production of liqueur glycerin macerates, which are proven to contain larger quantities of some important substances with healing properties than adult parts of plants. Objectives: The aim of this work was to summarize basic information about gemmotherapy from available literature; to summarize the description of the traditional use of selected plants and gemmotherapeutics prepared therefrom; to provide a summary of studies based on evidence-based literature, especially with regard to content and confirmatory medicinal properties, adverse effects, drug interactions and contraindications. Methods: General information about gemmotherapy was mainly drawn from books available in the Czech language. Data collection took place from October 2016 to August 2017, and researches based on literature were mainly based on the electronic databases PubMed, Web of Science, Wiley Online Library,...
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Horáková, Kateřina. "Retrográdní studie efektu terapie rázovou vlnou u funkčních poruch muskuloskeletálního systému." Master's thesis, 2013. http://www.nusl.cz/ntk/nusl-341914.
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This thesis assesses the effectiveness of shock wave therapy for dysfunctional disorders of the musculoskeletal system. While we are well aware of the physical principles and history of shock wave generators, opinion differs on the treatment effectiveness mechanisms. The theoretical part of this work explains the effects of shock waves on various types of tissue, the differentiation of the cells, and the analgetic effect of therapy. It summarizes the indications, side effects and contraindications of shock wave therapy. The research part of this thesis deals with the effectiveness of shock wave therapy at the Department of Rehabilitation and Sports Medicine at the Motol University Hospital, which specialises in various musculoskeletal disorders. This thesis evaluates the correlation between the effectiveness of shock wave therapy and length of time the patient has experienced difficulties before undergoing treatment. This thesis also reviews whether the number of treatment applications has the capability to influence the outcome of therapy. The study is controlled by a control group of 22 patients. The total effectiveness of shock wave therapy is p = 1,12*10-10 . The shock wave therapy effectiveness of patients with heel spur is p = 0,00176. The shock wave therapy effectiveness of patients with...