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Biological characteristics of polysccharide based contrast agents for cancer diagnostics
Křivánková, Markéta
Despite all the progress made in the treatment of cancer in recent years, it is still necessary to continue with the research of more effective and specific drugs. In recent years, there has been a growing interest in personalized medicine and its application through drug delivery systems, which could help increase the specificity of cancer treatment and subsequently its effectiveness. Drug delivery systems can use different platforms for their design, whether they are liposomes, micelles, nano crystals or others. A very interesting platform for the construction of drug delivery systems are polysaccharides, which were, as carriers of contrast agents in order to effectively display tumours, characterized in this doctoral thesis. But polysaccharides are interesting for more reasons. Both by its availability, and by its biocompatibility and non-toxic character. In this doctoral thesis we deal with two types of polysaccharides conjugates with linked contrast agents for magnetic resonance and fluorescent imaging. The first type of polysaccharide is glycogen, the second is mannan. Both constructs - glycogen and mannan based, were synthesized in a version with and without polymethyloxazolin, which should prolong their circulation in the organism. Both types of polysaccharide conjugates used passive...
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Biological characteristics of polysccharide based contrast agents for cancer diagnostics
Křivánková, Markéta ; Jirák, Daniel (advisor) ; Shapoval, Oleksandr (referee) ; Vannucci, Luca Ernesto (referee)
Despite all the progress made in the treatment of cancer in recent years, it is still necessary to continue with the research of more effective and specific drugs. In recent years, there has been a growing interest in personalized medicine and its application through drug delivery systems, which could help increase the specificity of cancer treatment and subsequently its effectiveness. Drug delivery systems can use different platforms for their design, whether they are liposomes, micelles, nano crystals or others. A very interesting platform for the construction of drug delivery systems are polysaccharides, which were, as carriers of contrast agents in order to effectively display tumours, characterized in this doctoral thesis. But polysaccharides are interesting for more reasons. Both by its availability, and by its biocompatibility and non-toxic character. In this doctoral thesis we deal with two types of polysaccharides conjugates with linked contrast agents for magnetic resonance and fluorescent imaging. The first type of polysaccharide is glycogen, the second is mannan. Both constructs - glycogen and mannan based, were synthesized in a version with and without polymethyloxazolin, which should prolong their circulation in the organism. Both types of polysaccharide conjugates used passive...
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Metabolism of new polysacharidic nanomaterials for biomedicinal applications
Jirátová, Markéta ; Hrubý, Martin (advisor) ; Jirák, Daniel (referee)
Cancer is one of the leading cause of death in modern world, so there is an emerging demand for better diagnostic tools and more specific less toxique therapeutics. Nanoparticles offers characteristics that could fullfill such perspectives. They can easily target tumor by ehanced permeation and retention effect (EPR). Nanoparticles can combine more than one imaging properties, so we can say that they are multimodal, some of them could combine diagnostic and therapeutic molecules in one nanoparticle, which is now highly popular topic of nanoparticles for theranostics . The aim of this thesis was to characterize new multimodal glycogen-based nanoparticle. Glycogen is an ideal structure for nanoparticle design. Glycogen is part of natural dendrimers group which are easily to modify. Glycogen's size is suitable for EPR effect. We have evaluated biological characteristics of five different types of modified glycogen. The in vitro experiments were carried on HepG2 cells. We have set time curve of cellular uptake of this glycogen probes, evaluated cytoplasmatic localization and for the first time we have carried MTT assay. Biodistribution studies on CD1-Nude mice were performed by using non-invasive method for measuring in vivo fluorescence. In conlusion we've provided some of the biological characteristics of new...
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Pharmacological modifications of potential signal systems regulating metabolism of adipocytes and hepatocytes and their influence on obesity
Hodis, Jiří ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Otová, Berta (referee)
v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...
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Metabolism of new polysacharidic nanomaterials for biomedicinal applications
Jirátová, Markéta ; Hrubý, Martin (advisor) ; Jirák, Daniel (referee)
Cancer is one of the leading cause of death in modern world, so there is an emerging demand for better diagnostic tools and more specific less toxique therapeutics. Nanoparticles offers characteristics that could fullfill such perspectives. They can easily target tumor by ehanced permeation and retention effect (EPR). Nanoparticles can combine more than one imaging properties, so we can say that they are multimodal, some of them could combine diagnostic and therapeutic molecules in one nanoparticle, which is now highly popular topic of nanoparticles for theranostics . The aim of this thesis was to characterize new multimodal glycogen-based nanoparticle. Glycogen is an ideal structure for nanoparticle design. Glycogen is part of natural dendrimers group which are easily to modify. Glycogen's size is suitable for EPR effect. We have evaluated biological characteristics of five different types of modified glycogen. The in vitro experiments were carried on HepG2 cells. We have set time curve of cellular uptake of this glycogen probes, evaluated cytoplasmatic localization and for the first time we have carried MTT assay. Biodistribution studies on CD1-Nude mice were performed by using non-invasive method for measuring in vivo fluorescence. In conlusion we've provided some of the biological characteristics of new...
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Pharmacological modifications of potential signal systems regulating metabolism of adipocytes and hepatocytes and their influence on obesity
Hodis, Jiří ; Farghali, Hassan (advisor) ; Kršiak, Miloslav (referee) ; Otová, Berta (referee)
v anglickém jazyce: Thesis abstract: Background and aims: Both obesity and metabolic syndrome form severe health problems in the whole world. Nevertheless the armament of pharmacotherapy for both diseases remains unsatisfactory. We aimed our work to main organs in risk of the mentioned diseases -liver and visceral fat using hepatocytes and visceral adipocytes as model. We detected 3 main metabolic and signalization activities- glycogenolysis, Nitric oxide (NO) production and transcription of inducible NO synthase (iNOS) in hepatocytes, lipolysis, NO production and iNOS transcription rate in adipocytes. We directed our interest to combination of peroxisome proliferation activator receptor γ (PPARγ) agonist, antagonist and β3 adrenergic agonist in the culture of epididymal rat adipocytes in the first part of our work. While in the second part we investigated the influence of β and α adrenergic mimetics, adrenergic blockers in the culture of rat high glycogen content hepatocytes. Methods: NO production was detected under the active agents treatments by detection of NO oxidative products NO2 and NO3 in media. Glycogenolysis was measured as free glucose rise released by hepatocytes into the media. NOS transcription level was extrapolated after comparative polymerase chain reaction with reverse...
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Vitellogenesis in caryophyllidean cestodes.
DROBNÍKOVÁ, Petra
Vitellogenesis in two caryophyllidean cestodes Caryophyllaeus laticeps and Khawia sinensis, parasitizing cyprinid fishes, were examined using light(LM)and transmission electron microscopy(TEM)and cytochemical staining for glycogen. Mature vitelline folicles consist of vitelline cells at various stages of development and an interstitial tissue. Maturing and mature vitellocytes contain vitelline material in the form of single small shell globules, which fuse and give rise to the large shell globule clusters.Glycogen was present in the cytoplasm and in the nucleus of the mature vitellocytes. Small lipid droplets were found in the cytoplasm of C. laticeps. "Lamellar granules" were observed in the cytoplasm of the mature vitellocytes in K. sinensis.
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Cold hardiness of larvae of the fruit fly, \kur{Drosophila melanogaster} (Diptera: Drosophilidae)
KORBELOVÁ, Jaroslava
We assessed survival of larvae of the fruit fly, Drosophila melanogaster at low temperatures (0°C and 5°C) after rearing them under seven different acclimation regimes. Larvae that have developed in a standard diet at 25°C showed 50% mortality after 12,6 min of the exposure to 0°C (Lt50 = 0.21 h). In contrast, larvae that have developed in a diet enriched with glycerol at 15°C, and were cold acclimated at 5°C during last two days of their development, had Lt50 = 38.6 h. It means that it was possible to increase the Lt50 at 0°C more than 180-fold using simple manipulations with rearing temperatures and diet composition. The physiological differences in duration of larval development, fresh mass, dry mass, hydration and total contents of proteins, lipids and glycogen between the larvae belonging to different acclimation variants are described. The samples for future detailed metabolomic analysis were prepared.
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