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Chelating Polymers for the Haemochromatosis Treatment
Groborz, Ondřej ; Hrubý, Martin (advisor) ; Kotek, Jan (referee)
5 Chelating Polymers for the Haemochromatosis Treatment Author: Ondřej Groborz Tutor: Mgr. Martin Hrubý, Ph.D., DSc. Advisors: Ing. Kristýna Kolouchová Ing. Pavel Švec Institute of Macromolecular Chemistry, Czech Academy of Sciences Abstract Haemochromatosis is a group of hereditary diseases which are characterised by toxic accumulation of iron in parenchymal organs, leading to organ toxicity and irreversible damage. Currently, there are only a few approved medications for this disease, yet all of them possess severe side effects. Herein, we have proposed a new paradigm for treatment: insoluble polymers with negligible systemic biological availability would form stable complexes with iron ions in the gastrointestinal tract, hence decreasing biological availability of iron. The insolubility of polymers prevents them from being absorbed into the organism in the first place while having no systemic side effects or toxicity. We have prepared polymers with several covalently bound iron-chelating ligands and based on the biological data we selected the most successful chelators for possible future applications. These polymers exhibited negligible resorbability and toxicity, superior in vitro iron chelating activity and their efficacy was proven in an in vivo model. Therefore they could be used as a...
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Chelating Polymers for the Haemochromatosis Treatment
Groborz, Ondřej ; Hrubý, Martin (advisor) ; Kotek, Jan (referee)
5 Chelating Polymers for the Haemochromatosis Treatment Author: Ondřej Groborz Tutor: Mgr. Martin Hrubý, Ph.D., DSc. Advisors: Ing. Kristýna Kolouchová Ing. Pavel Švec Institute of Macromolecular Chemistry, Czech Academy of Sciences Abstract Haemochromatosis is a group of hereditary diseases which are characterised by toxic accumulation of iron in parenchymal organs, leading to organ toxicity and irreversible damage. Currently, there are only a few approved medications for this disease, yet all of them possess severe side effects. Herein, we have proposed a new paradigm for treatment: insoluble polymers with negligible systemic biological availability would form stable complexes with iron ions in the gastrointestinal tract, hence decreasing biological availability of iron. The insolubility of polymers prevents them from being absorbed into the organism in the first place while having no systemic side effects or toxicity. We have prepared polymers with several covalently bound iron-chelating ligands and based on the biological data we selected the most successful chelators for possible future applications. These polymers exhibited negligible resorbability and toxicity, superior in vitro iron chelating activity and their efficacy was proven in an in vivo model. Therefore they could be used as a...
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Determining the expression of iron transport and metabolism molecules in chosen chronic diseases.
Chmelíková, Jitka ; Kovář, Jan (advisor) ; Truksa, Jaroslav (referee)
Iron is an essential element for human organism, because it cooperates as a cofactor of enzymes in many metabolic pathways. Iron is a component of hemoglobin, and thus it is indispensable for the oxygen transport to tissues. It can exist as a ferrous or ferric form. However, ferrous iron paticipates in reactions in which highly reactive hydroxyl group can be formed. This product is harmful for the organism. Non-heme iron is taken up to the circulation through duodenal enterocyte. Iron excretion is carried out only by desquamation of the enterocytes or by bleeding. Therefore, iron intake must be strictly regulated. Iron overloading is observed in some chronic diseases (hereditary hemochromatosis, alcohol liver disease). In contrary, iron depletion can be a case of iron deficiency anemia. The aim of this master thesis is to determine the expression of iron transport molecules in duodenum in chronic diseases which originate due to disturbances of iron intake regulation. We determine the expression of molecules of iron transport (DMT1, Dcytb, ferroportin, hephaestin) on mRNA level by qPCR and on protein level by western blot. The level of serum hepcidin was determined by ELISA. Our results show an increased expression of mRNA of transporters DMT1 and ferroportin as well as ferrireductase Dcytb and ferroxidase...
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