You searched for subject:(Chelators)
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39 total matches.
◁ [1] [2] ▶
1.
Ferrer, Patricia.
MODULATION OF HOST IRON COMPARTMENTS CRITICAL TO THE MALARIA PARASITE DEVELOPMENT.
Degree: 2014, Johns Hopkins University
URL: http://jhir.library.jhu.edu/handle/1774.2/37885
► The overlap between of malaria and iron deficiency makes it difficult to treat both conditions since iron supplementation can increase malaria and malaria decreases iron…
(more)
▼ The overlap between of malaria and iron deficiency makes it difficult to treat both conditions since iron supplementation can increase malaria and malaria decreases iron absorption. Iron
chelators have proven antiparasitic activity. We characterized the antimalarial pharmacodynamics of the novel iron chelator FBS0701 in Plasmodium and evaluated the effect of the type and timing of iron diet on murine malaria during iron repletion. FBS0701, (S)3’’-(HO)-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator to treat transfusional iron overload. We showed that FBS0701 enter the erythrocytes and removes intracellular iron. FBS0701 reduced hepatic parasite load. FBS0701 interfered with artemisinin but was additive with chloroquine or quinine inhibition in the blood stage and with primaquine in the hepatic stage. FBS0701 killed early and late stage P. falciparum gametocytes. A single oral dose one day after infection cured P. yoelii 17XL infected mice. We
studied the importance of iron compartmentalization on hepatic malaria infection on transgenic anemic mice: mice overexpressing hepcidin with reduced iron stores in the liver and hemoglobin deficient mice with normal hepatic iron stores. We found lower parasites on mice overexpressing hepcidin compared to non-anemic control mice (with normal liver iron). Parasite loads on hemoglobin deficient mice were not significantly different to non-anemic control mice. Finally, we studied the effect of low and high iron diets on the hepatic stage of murine malaria and the interplay of hepcidin with the hepatic infection levels. We used mice that were both anemic and iron deficient as well as non-anemic mice and gave both groups low and high iron diets for 2 and 6 weeks. Our results showed that high iron diets increased liver stage parasites in non-anemic mice and that iron supplementation predominated over a negative hepcidin effect. We partially replicated in mice the human findings from the
Pemba study. In conclusion, FBS0701 could be useful as malarial prophylactic or in combination with other antimalarials. FBS0701 has the potential to be used a transmission blocking agent. Increasing liver stage may synergize with blood stage increases after iron supplementation. Therefore, iron supplementation programs in malaria endemic areas, should be accompanied of antimalarial treatment.
Advisors/Committee Members: Fairweather, DeLisa (advisor).
Subjects/Keywords: Malaria;
anemia;
iron chelators
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APA (6th Edition):
Ferrer, P. (2014). MODULATION OF HOST IRON COMPARTMENTS CRITICAL TO THE MALARIA PARASITE DEVELOPMENT. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37885
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ferrer, Patricia. “MODULATION OF HOST IRON COMPARTMENTS CRITICAL TO THE MALARIA PARASITE DEVELOPMENT.” 2014. Thesis, Johns Hopkins University. Accessed January 20, 2021.
http://jhir.library.jhu.edu/handle/1774.2/37885.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ferrer, Patricia. “MODULATION OF HOST IRON COMPARTMENTS CRITICAL TO THE MALARIA PARASITE DEVELOPMENT.” 2014. Web. 20 Jan 2021.
Vancouver:
Ferrer P. MODULATION OF HOST IRON COMPARTMENTS CRITICAL TO THE MALARIA PARASITE DEVELOPMENT. [Internet] [Thesis]. Johns Hopkins University; 2014. [cited 2021 Jan 20].
Available from: http://jhir.library.jhu.edu/handle/1774.2/37885.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ferrer P. MODULATION OF HOST IRON COMPARTMENTS CRITICAL TO THE MALARIA PARASITE DEVELOPMENT. [Thesis]. Johns Hopkins University; 2014. Available from: http://jhir.library.jhu.edu/handle/1774.2/37885
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Anna University
2.
Thalamuthu S.
Bifunctional Chelators For Metal Complexation;.
Degree: chemistry, 2013, Anna University
URL: http://shodhganga.inflibnet.ac.in/handle/10603/24485
► newlineThe most reliable and most frequently applied method of newlinelinking the metal ion to the biomolecule is by means of a bifunctional newlinechelating agent BFCA…
(more)
▼ newlineThe most reliable and most frequently
applied method of newlinelinking the metal ion to the biomolecule
is by means of a bifunctional newlinechelating agent BFCA The amino
acids are used as starting materials for newlinethe preparation of
variety of bifunctional chelators Amino acids contain free
newlinecarboxylic acid residue can be derivatized for use as BFCs
Dpenicillamine is newlinean effective chelator of copper is well
absorbed from the gastrointestinal tract newlineand promotes
urinary excretion of copper newlineThe coordination ability and
diversity of biologically important of newlinevitamin B compounds
pyridoxinePN pyridoxalPL and pyridoxamine newlinePM are important
in the field of bioinorganic chemistry Pyridoxine PN newlinethe
first isolated vitamin B6 component is essential in the diet for
the newlinemetabolism of amino acids and the maintenance of body
cells Metal newlinecomplexes of vitamin B have been reported to
inhibit the growth as well as newlinethe biosynthesis of RNA DNA
and protein of E coli B766 newlineAldehydes and ketones are used as
building blocks in the syntheses newlineof commercially important
compounds including pharmaceuticals and newlinepolymers vanillin
and hydroxy benzaldehydes are extensively used as raw
newlinematerial to synthesize pancratistatin coumarin neolignan
aromatic Cring in newlinetaxane and alibendol derivatives This
created interest towards the studies on newlineBifunctional
Chelating Agents It is the aim of present work to synthesize
newlineBifunctional Chelators of types Amino acid Chelators Vitamin
B Chelators newlineand Polyaminocarboxy Chelators and their metal
complexes newlineSynthesis acidbase equilibria Xray crystal and
experimental newlinecharge density analysis of a double
zwitterionic amino acid Schiffbase newlinecompound have been
studied in the present work The double zwitterionic newlineamino
acid Schiffbase NovanillylideneLhistidine OVHIS was
newlinesynthesized by the condensation of Lhistidine with 3methoxy
newlinesalicylaldehyde The double zwitterionic nature of the
molecule in the solid newlinestate is confirmed through an
experimental electron density distribution newlineanalysis newline
newline
Advisors/Committee Members: Neelakantan M A.
Subjects/Keywords: Bifunctional; Chelators; gastrointestinal; Metal Complexation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
S, T. (2013). Bifunctional Chelators For Metal Complexation;. (Thesis). Anna University. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/24485
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
S, Thalamuthu. “Bifunctional Chelators For Metal Complexation;.” 2013. Thesis, Anna University. Accessed January 20, 2021.
http://shodhganga.inflibnet.ac.in/handle/10603/24485.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
S, Thalamuthu. “Bifunctional Chelators For Metal Complexation;.” 2013. Web. 20 Jan 2021.
Vancouver:
S T. Bifunctional Chelators For Metal Complexation;. [Internet] [Thesis]. Anna University; 2013. [cited 2021 Jan 20].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/24485.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
S T. Bifunctional Chelators For Metal Complexation;. [Thesis]. Anna University; 2013. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/24485
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Ghana
3.
Amisigo, C.M.
Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Brucei
.
Degree: 2018, University of Ghana
URL: http://ugspace.ug.edu.gh/handle/123456789/27660
► African trypanosomiasis still remains a lethal disease to both human and livestock. The disease persists due to limited drug availability, toxicity and emergence of drug…
(more)
▼ African trypanosomiasis still remains a lethal disease to both human and livestock. The disease persists due to limited drug availability, toxicity and emergence of drug resistance, hence the need to provide alternative forms of therapy. Studies have shown that the iron chelator deferoxamine exhibited anti-trypanosomal effects by inhibiting cell growth and interfering with the activity of some iron dependent enzymes. In this study, the in vitro effects of different phenolic acids, which are known to complex iron, were assessed for their trypanocidal activities against Trypanosoma brucei brucei using the alarmaBlue assay. The cell cycle effects of the chelators were determined by flow cytometry and parasite morphological analysis was done by microscopy. Gallic acid was the most potent phenolic acid with an IC50 value of 14.2μM. The compounds showed a dose dependent effect on the cell viability and the mitochondrion membrane potential. There was also a significant loss in kinetoplast and an increase in the S phase of the cell cycle. mRNA sequencing and RT-qPCR data showed an upregulation of almost all the transcripts and a corresponding increase in the iron related genes such as the ribonucleotide reductase and cyclin 2 genes. The chelators also showed moderate toxicity against macrophages. The results throw more light on the possible mechanism of action of the chelators and provide alternative therapeutic approaches in the treatment of African trypanosomiasis which might include interfering with the iron metabolism of the parasite.
Subjects/Keywords: Iron Chelators;
Trypanosoma Brucei
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Amisigo, C. M. (2018). Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Brucei
. (Masters Thesis). University of Ghana. Retrieved from http://ugspace.ug.edu.gh/handle/123456789/27660
Chicago Manual of Style (16th Edition):
Amisigo, C M. “Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Brucei
.” 2018. Masters Thesis, University of Ghana. Accessed January 20, 2021.
http://ugspace.ug.edu.gh/handle/123456789/27660.
MLA Handbook (7th Edition):
Amisigo, C M. “Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Brucei
.” 2018. Web. 20 Jan 2021.
Vancouver:
Amisigo CM. Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Brucei
. [Internet] [Masters thesis]. University of Ghana; 2018. [cited 2021 Jan 20].
Available from: http://ugspace.ug.edu.gh/handle/123456789/27660.
Council of Science Editors:
Amisigo CM. Effects of Iron Chelators on Bloodstream Forms of Trypanosoma Brucei
. [Masters Thesis]. University of Ghana; 2018. Available from: http://ugspace.ug.edu.gh/handle/123456789/27660
4.
Akbar, Rifat.
Design synthesis and studies of some biomimetic
chelators; -.
Degree: Chemistry, 2015, INFLIBNET
URL: http://shodhganga.inflibnet.ac.in/handle/10603/48044
Abstract available
Appendix p.331-335
Advisors/Committee Members: Kanungo, B K.
Subjects/Keywords: Biomimetic; Chelators; Design; Synthesis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Akbar, R. (2015). Design synthesis and studies of some biomimetic
chelators; -. (Thesis). INFLIBNET. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/48044
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Akbar, Rifat. “Design synthesis and studies of some biomimetic
chelators; -.” 2015. Thesis, INFLIBNET. Accessed January 20, 2021.
http://shodhganga.inflibnet.ac.in/handle/10603/48044.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Akbar, Rifat. “Design synthesis and studies of some biomimetic
chelators; -.” 2015. Web. 20 Jan 2021.
Vancouver:
Akbar R. Design synthesis and studies of some biomimetic
chelators; -. [Internet] [Thesis]. INFLIBNET; 2015. [cited 2021 Jan 20].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/48044.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Akbar R. Design synthesis and studies of some biomimetic
chelators; -. [Thesis]. INFLIBNET; 2015. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/48044
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of KwaZulu-Natal
5.
Frimpong, Ebenezer Kwabena.
Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study.
Degree: 2016, University of KwaZulu-Natal
URL: https://researchspace.ukzn.ac.za/handle/10413/18516
► Organometallic chelators can be potentially used for radiometal-based pharmaceuticals. The bifunctional chelator, which is covalently bound to a lead compound, forms a stable chelator―ion complex…
(more)
▼ Organometallic
chelators can be potentially used for radiometal-based pharmaceuticals. The bifunctional chelator, which is covalently bound to a lead compound, forms a stable chelator―ion complex to deliver an isotope, as a labelling agent, towards a specific in vivo target. The quest to find the optimal match between
chelators and radiometal ions is of interest in the field of radio pharmaceuticals. A loss of radiometal ion from a chelator without reaching to its specific target organ in vivo could be disastrous to the body. The present project is focused on the complexation of 1, 4, 7, 10-tetraazacyclododecane-1, 4, and 7, 10-tetraacetic acid (DOTA) with alkali metals and radiometal ions. Herein, we investigated DOTA―alkali metal ions complexes with density functional theory using B3LYP and ωB97XD functionals and the 6-311+G(2d,2p) basis set for Li+, Na+ and K+ and Def2-TZVPD for Rb+. Conformational possibilities, starting from x-ray crystal structures and considering a different number of arms (2, 3 and 4) interacting with the ions were explored. Interaction and relaxation energies, thermochemical parameters, HOMO/LUMO energies, ΔEHOMO-LUMO and chemical hardness indicate the decrease in the stability of DOTA―ions down the alkali metal series. Natural bond orbital analysis reveals charge transfer between DOTA and alkali metals. Regarding radiometal ions, the geometries for the various complexes were consistent with experimentally reported binding constants. NBO analysis indicates charge transfer from the chelator to the radio metals resulting in reduced positive atomic charge values for all the ions. DOTA―Ga3+, DOTA―In3+ and DOTA―Sc3+ complexes recorded higher ΔELUMO-HOMO energies and chemical hardness values. The DOTA―Cu2+ complex was the least stable among the selected complexes. This study serves as a guide to researchers in the field of organometallic
chelators, particularly; radio-pharmaceuticals in finding the efficient optimal match between
chelators and different metal ions.
Advisors/Committee Members: Honarparvar, Bahareh. (advisor), Skelton, Adam Arnold. (advisor).
Subjects/Keywords: Radio -pharmaceutical applications.; Radiometal ions.; DOTA.; Organometallic chelators.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Frimpong, E. K. (2016). Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study. (Thesis). University of KwaZulu-Natal. Retrieved from https://researchspace.ukzn.ac.za/handle/10413/18516
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Frimpong, Ebenezer Kwabena. “Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study.” 2016. Thesis, University of KwaZulu-Natal. Accessed January 20, 2021.
https://researchspace.ukzn.ac.za/handle/10413/18516.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Frimpong, Ebenezer Kwabena. “Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study.” 2016. Web. 20 Jan 2021.
Vancouver:
Frimpong EK. Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study. [Internet] [Thesis]. University of KwaZulu-Natal; 2016. [cited 2021 Jan 20].
Available from: https://researchspace.ukzn.ac.za/handle/10413/18516.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Frimpong EK. Matching a chelator (DOTA) with ions for radio-pharmaceutical applications using DFT study. [Thesis]. University of KwaZulu-Natal; 2016. Available from: https://researchspace.ukzn.ac.za/handle/10413/18516
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne
6.
Rudd, Stacey Erin.
Zirconium and copper immunoPET imaging agents for the diagnosis of cancer.
Degree: 2018, University of Melbourne
URL: http://hdl.handle.net/11343/219461
► Positron emission tomography (PET) is a medical diagnostic imaging technique that is particularly useful in cancer diagnostics. In addition to tumour burden assessment, the technology…
(more)
▼ Positron emission tomography (PET) is a medical diagnostic imaging technique that is particularly useful in cancer diagnostics. In addition to tumour burden assessment, the technology can also provide molecular information, such as specific receptor expression profiles of cancer cells.
The technique requires administration of an imaging agent to a patient, and the imaging agent must incorporate a positron emitting radionuclude. The positron-emitting radionuclide may be tethered to a targeting motif for accumulation at disease-afflicted tissues in the patient. Tight control over the biodistribution of the radionuclide is essential for both patient safety and image quality, and the extremely high affinity and specificity of monoclonal antibodies (mAbs) for their target antigen makes them an excellent candidate for delivering a radioisotope to a site of interest in vivo. The long pharmacokinetic half-life of antibodies, however, necessitates the use of a long-lived radionuclide such as 89Zr (t1/2 79 h) or 64Cu (t1/2 12.7 h).
This thesis presents the development of novel PET imaging agents using 89Zr and 64Cu. Bifunctional chelators that can be used to attach these metal-based radionuclides to antibodies are described. The synthesis, bioconjugation, radiolabelling and preclinical imaging of various 89Zr immunoPET imaging agents using desferrioxamine (DFO) squaramide are presented. Our DFO-squaramide-based imaging agents outmatched the commercially-available isothiocyanate analogue. A DFO squaramide derivative suitable for use in enzyme-assisted, site-specific bioconjugations was developed, and successfully employed in the modification of antibody fragments using the bacterial transpeptidase Sortase A. The various forms of desferrioxamine squaramide conjugates were then assessed for suitability with various targeting agents, including mAbs and antibody fragments. These conjugates were evaluated as imaging agents in mice models of various cancer types that exhibit overexpression of the human epidermal growth factor receptors.
The sarcophagine MeCOSar was also evaluated for [64Cu]Cu2+ labelling of antibodies and fragments. The bioconjugation of the ligand was performed using both an activated ester derivative and a Sortase A mediated coupling. The ligand was assessed in mice models of cancer using various antibodies and fragments as each conjugate exhibited unique biodistribution profiles. The most effective immunoPET agent for imaging of HER2-positive tumours was based on a full IgG construct with trastuzumab, although in a clinical setting the practical and logistical benefits of the F(ab’)2 imaging agent may outweigh its comparatively reduced uptake in tumour tissue.
Subjects/Keywords: positron emission tomography; immunoPET; PET; zirconium; copper; bifunctional chelators
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Rudd, S. E. (2018). Zirconium and copper immunoPET imaging agents for the diagnosis of cancer. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/219461
Chicago Manual of Style (16th Edition):
Rudd, Stacey Erin. “Zirconium and copper immunoPET imaging agents for the diagnosis of cancer.” 2018. Doctoral Dissertation, University of Melbourne. Accessed January 20, 2021.
http://hdl.handle.net/11343/219461.
MLA Handbook (7th Edition):
Rudd, Stacey Erin. “Zirconium and copper immunoPET imaging agents for the diagnosis of cancer.” 2018. Web. 20 Jan 2021.
Vancouver:
Rudd SE. Zirconium and copper immunoPET imaging agents for the diagnosis of cancer. [Internet] [Doctoral dissertation]. University of Melbourne; 2018. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/11343/219461.
Council of Science Editors:
Rudd SE. Zirconium and copper immunoPET imaging agents for the diagnosis of cancer. [Doctoral Dissertation]. University of Melbourne; 2018. Available from: http://hdl.handle.net/11343/219461

Duke University
7.
Hyman, Lynne.
Development of Fluorescent Iron and Copper Sensors Activated by Hydrogen Peroxide or Ultraviolet Light
.
Degree: 2011, Duke University
URL: http://hdl.handle.net/10161/3884
► Fluorescent sensors provide a powerful analytical tool for the intracellular detection of metal cations. In some cases, these fluorescent metal-chelating sensors have helped elucidate…
(more)
▼ Fluorescent sensors provide a powerful analytical tool for the intracellular detection of metal cations. In some cases, these fluorescent metal-chelating sensors have helped elucidate the function of metal cations within complicated cellular systems. However, most measure or sense changes in the bulk concentration of a metal species and do not respond to those involved in a specific cellular event. For instance, misregulated copper and iron are implicated in neurodegenerative disease and cancer because of their ability to catalytically propagate the formation of the hydroxyl radical through reaction with hydrogen peroxide. A fluorescent sensor that is unresponsive to metal binding until activation by intracellular hydrogen peroxide could potentially pinpoint the location of this oxidative reaction and provide an understanding of the relationship between copper/iron and hydrogen peroxide. Described here is the development of two fluorescent prochelators that show a selective fluorescence response to iron or copper only in the presence of hydrogen peroxide. A boronic ester masked spirolactam-based prochelator displays a copper-selective turn-on response after oxidation with hydrogen peroxide in organic solvents as determined by absorbance and fluorescence spectroscopy. However, a competing mechanism occurs in aqueous solution due to hydrolytic instability of the masked prochelator and results in a separate copper-dependent turn-on response as verified by liquid chromatography-mass spectroscopy. A second fluorescent prochelator design relies on metal-dependent fluorescence quenching after oxidation of a self-immolative boronic ester in both organic and aqueous solvents. Cellular microscopy studies show that the sensor's fluorescence intensity is unchanged until incubation with exogenous hydrogen peroxide, which resulted in a decreased fluorescent signal that is restored upon competitive chelation. Both of these prochelators provide a template for future applications and designs with improved properties. Two additional chapters describe the development of a UV-activated iron prochelator and a new fluorescently tagged metal chelator. The UV-activated prochelator is protected with two nitrophenyl groups that are photolyzed with 350 nm light within 10 minutes to reveal a high affinity iron triazole-base chelator. A chelator of this nature may provide protection from UV-induced iron liberation and oxidative stress. A second triazole-based chelator with an embedded coumarin fluorophore was prepared as a potential metal sensor. However, this design showed off-target fluorescence responses, thus it cannot be utilized in its current form for metal detection.
Advisors/Committee Members: Franz, Katherine J (advisor).
Subjects/Keywords: Chemistry;
chelators;
copper;
fluorescent sensors;
iron;
oxidative stress
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hyman, L. (2011). Development of Fluorescent Iron and Copper Sensors Activated by Hydrogen Peroxide or Ultraviolet Light
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/3884
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hyman, Lynne. “Development of Fluorescent Iron and Copper Sensors Activated by Hydrogen Peroxide or Ultraviolet Light
.” 2011. Thesis, Duke University. Accessed January 20, 2021.
http://hdl.handle.net/10161/3884.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hyman, Lynne. “Development of Fluorescent Iron and Copper Sensors Activated by Hydrogen Peroxide or Ultraviolet Light
.” 2011. Web. 20 Jan 2021.
Vancouver:
Hyman L. Development of Fluorescent Iron and Copper Sensors Activated by Hydrogen Peroxide or Ultraviolet Light
. [Internet] [Thesis]. Duke University; 2011. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10161/3884.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hyman L. Development of Fluorescent Iron and Copper Sensors Activated by Hydrogen Peroxide or Ultraviolet Light
. [Thesis]. Duke University; 2011. Available from: http://hdl.handle.net/10161/3884
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Floresta, Giuseppe.
Design and synthesis of novel compounds as fatty acids binding protein inhibitors and as gallium-68 chelators for positron emission tomography.
Degree: 2018, Università degli Studi di Catania
URL: http://hdl.handle.net/10761/4168
► Finding new small molecules targets as well as improving the diagnosis methodologies are two of the most important areas in which the researchers are spending…
(more)
▼ Finding new small molecules targets as well as improving the diagnosis methodologies are two of the most important areas in which the researchers are spending efforts to improve our arsenal to fight cancer and other diseases. In this thesis, two different chapters are discussed. In the first one, the design of new Fatty acid binding protein 4 inhibitors is discussed. In the second one, the design of two targeting peptide bioconjugates for the detection of cancers is reported.
Fatty acid binding proteins are a class of proteins involved particularly in the transport of fatty acids in human. Recently it comes out that the Fatty acid binding proteins are an interesting molecular target for the treatment of type 2 diabetes, other metabolic diseases and some type of cancers. In this chapter (first), three new molecules inhibitors of the Fatty acid binding protein 4 are designed, using computer-aided drug design methodologies, and synthesized. The three molecules, AST_1 3, were synthesized and tested against the target protein and showed an IC50 between 3.70 and 5.59 uM. Moreover, a huge number of different other molecules were theorized to be as effective as the three synthesized. Among them, some are derived from a virtual screening of an FDA approved drugs database and some from the bioisosteric scaffold-hopping analysis of a note inhibitor of the fatty acid binding protein 4 (BMS309403).
In the second chapter, two different targeting peptides, against two proteins involved in particular types of cancer (c-Met and GLP-1), were synthesized and then conjugated to a small molecule able to chelate gallium, for their potential applicability as PET tracers. The two compounds were then evaluated as effective 68-gallium chelating compounds and the result showed their capability in the binding of the 68Ga.
Subjects/Keywords: Area 03 - Scienze chimiche; FABP4 inhibitors, gallium-68 chelators, cancer
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Floresta, G. (2018). Design and synthesis of novel compounds as fatty acids binding protein inhibitors and as gallium-68 chelators for positron emission tomography. (Thesis). Università degli Studi di Catania. Retrieved from http://hdl.handle.net/10761/4168
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Floresta, Giuseppe. “Design and synthesis of novel compounds as fatty acids binding protein inhibitors and as gallium-68 chelators for positron emission tomography.” 2018. Thesis, Università degli Studi di Catania. Accessed January 20, 2021.
http://hdl.handle.net/10761/4168.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Floresta, Giuseppe. “Design and synthesis of novel compounds as fatty acids binding protein inhibitors and as gallium-68 chelators for positron emission tomography.” 2018. Web. 20 Jan 2021.
Vancouver:
Floresta G. Design and synthesis of novel compounds as fatty acids binding protein inhibitors and as gallium-68 chelators for positron emission tomography. [Internet] [Thesis]. Università degli Studi di Catania; 2018. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10761/4168.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Floresta G. Design and synthesis of novel compounds as fatty acids binding protein inhibitors and as gallium-68 chelators for positron emission tomography. [Thesis]. Università degli Studi di Catania; 2018. Available from: http://hdl.handle.net/10761/4168
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Tennessee – Knoxville
9.
Choi, Inseob.
Reducing skim milk powder dispersion turbidity by dissociation of casein micelles at acidic and neutral pH: Physicochemical properties and possible mechanisms.
Degree: MS, Food Science, 2019, University of Tennessee – Knoxville
URL: https://trace.tennessee.edu/utk_gradthes/5407
► Casein micelles comprise 80% of dairy proteins. However, casein micelles as the source for protein fortification in beverages are limited due to its contribution to…
(more)
▼ Casein micelles comprise 80% of dairy proteins. However, casein micelles as the source for protein fortification in beverages are limited due to its contribution to dispersion turbidity. On the other hand, protein beverages are experiencing substantial market growth and what follows is the demand for new protein ingredients. At acidic conditions, like those commonly found in lots of beverages, dispersions of skim milk powder (SMP) have high turbidity and readily precipitate. In order to circumvent these problems, the dissociation of casein micelles is required to reduce turbidity and improve dispersion stability during storage. Additionally, beverages with neutral pH are preferred to consumers suffering dental problems such as tooth erosion. The objectives of the present study were 1) to reduce turbidity of SMP dispersions and 2) characterize their physicochemical properties after treatment at acidic and neutral pH. To acidify SMP dispersions to pH 2.4-3.0, citric acid or glucono delta-lactone was added, followed by subsequent heating at 60, 70, 80, or 90 °C for 2, 5, 10, 30, or 60 min. A lower pH (i.e., pH 2.4) was more effective than pH 3.0 to reduce the dispersion turbidity (e.g., 223 vs 861 NTU) and the hydrodynamic diameter (e.g., 115 vs 265 nm) after heating at 90 °C for 10 min. At neutral pH, translucent dispersions were obtained with the addition of calcium
chelators; sodium tripolyphosphate, trisodium citrate, or sodium hexametaphosphate. Higher concentrations of calcium
chelators in SMP dispersions resulted in significant reduction in turbidity values compared to the control (e.g., 230 NTU vs >4000). The amount of dissolved calcium in the SMP serum phase apart from the casein micelles increased from ~150 to more than 500 mg/L after treatments at both acidic and neutral pH, indicating the dissociation of casein micelles due to the disruption of colloidal calcium phosphate. The SMP dispersions with modified casein structures can be utilized to produce novel types of beverages.
Advisors/Committee Members: Qixin Zhong, Vermont P. Dia, Tao Wu.
Subjects/Keywords: Casein micelle; Milk; calcium chelators; colloidal calcium phosphate (CCP); hydrophobic interactions
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Choi, I. (2019). Reducing skim milk powder dispersion turbidity by dissociation of casein micelles at acidic and neutral pH: Physicochemical properties and possible mechanisms. (Thesis). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_gradthes/5407
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Choi, Inseob. “Reducing skim milk powder dispersion turbidity by dissociation of casein micelles at acidic and neutral pH: Physicochemical properties and possible mechanisms.” 2019. Thesis, University of Tennessee – Knoxville. Accessed January 20, 2021.
https://trace.tennessee.edu/utk_gradthes/5407.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Choi, Inseob. “Reducing skim milk powder dispersion turbidity by dissociation of casein micelles at acidic and neutral pH: Physicochemical properties and possible mechanisms.” 2019. Web. 20 Jan 2021.
Vancouver:
Choi I. Reducing skim milk powder dispersion turbidity by dissociation of casein micelles at acidic and neutral pH: Physicochemical properties and possible mechanisms. [Internet] [Thesis]. University of Tennessee – Knoxville; 2019. [cited 2021 Jan 20].
Available from: https://trace.tennessee.edu/utk_gradthes/5407.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Choi I. Reducing skim milk powder dispersion turbidity by dissociation of casein micelles at acidic and neutral pH: Physicochemical properties and possible mechanisms. [Thesis]. University of Tennessee – Knoxville; 2019. Available from: https://trace.tennessee.edu/utk_gradthes/5407
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Tennessee – Knoxville
10.
Goan, Eric Calvin.
Quality of Applesauce and Raspberry Puree Applesauce as Affected by Type of Ascorbic Acid, Calcium Salts and Chelators under Stress Storage Conditions.
Degree: MS, Food Science and Technology, 2011, University of Tennessee – Knoxville
URL: https://trace.tennessee.edu/utk_gradthes/873
► Applesauce prepared for the US military is processed as MRE (meals-ready-to-eat) in several forms including Type VI - Applesauce with raspberry puree, and Type…
(more)
▼ Applesauce prepared for the US military is processed as MRE (meals-ready-to-eat) in several forms including Type VI - Applesauce with raspberry puree, and Type VII - Carbohydrate enriched applesauce. Production of MRE applesauce starts with commercially prepared and thermally processed applesauce that is further processed by a military contractor. The further processing includes adjusting pH, ºBrix, and ascorbic acid level, packaging into pouches, and again thermally processing. Both types of the MRE applesauce are very much liked by troops, but under stress storage applesauce darkens and its consumption is drastically reduced. The overall goal of this project was to identify additives to be used during further processing in order to slow darkening when exposed to elevated temperatures during shipping and storage. The specific objective was to determine whether different types of ascorbic acid, calcium salts, or addition of
chelators can reduce deterioration under stress storage. Applesauce (AS), applesauce with raspberry puree (RPAS), MRE AS (Type VII) and MRE RPAS (Type VI) for all experiments were provided by Sopakco, Bennettsville S.C. The research was carried out in three phases. From the Phase 1, we learned that Type VII and Type VI darkened at faster rates at the beginning of the storage, but the effects of storage at 50°C for more than 2 weeks overcame any differences caused by further processing. Phase 2 helped us determine the formulations for the processing on the industrial scale. The formulations were: 0.15% L-ascorbic-acid (AA), and 0.15% AA with 300 ppm EDTA for both AS and RPAS, with 0.83% calcium lactate gluconate (CLG) for AS, and 0.15% ascorbyl-palmitate for RPAS. The results from the Phase 3 indicated that AS with addition of CLG and RPAS with total of 0.18% AA had the least total color change. In all samples, accumulation of HMF was related to amount of ascorbic acid with exception of samples with Pal which had the lowest HMF content. Our results indicate that current MRE Types VI and VII may have better stability at stress storage if the level of AA is limited to 0.18% and 0.83% CLG is added to the AS formulation.
Advisors/Committee Members: Svetlana Zivanovic, John Mount, Carl Sams.
Subjects/Keywords: Applesauce; Ascorbic acid; Chelators; Calcium salts; Food Chemistry; Food Processing
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Goan, E. C. (2011). Quality of Applesauce and Raspberry Puree Applesauce as Affected by Type of Ascorbic Acid, Calcium Salts and Chelators under Stress Storage Conditions. (Thesis). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_gradthes/873
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Goan, Eric Calvin. “Quality of Applesauce and Raspberry Puree Applesauce as Affected by Type of Ascorbic Acid, Calcium Salts and Chelators under Stress Storage Conditions.” 2011. Thesis, University of Tennessee – Knoxville. Accessed January 20, 2021.
https://trace.tennessee.edu/utk_gradthes/873.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Goan, Eric Calvin. “Quality of Applesauce and Raspberry Puree Applesauce as Affected by Type of Ascorbic Acid, Calcium Salts and Chelators under Stress Storage Conditions.” 2011. Web. 20 Jan 2021.
Vancouver:
Goan EC. Quality of Applesauce and Raspberry Puree Applesauce as Affected by Type of Ascorbic Acid, Calcium Salts and Chelators under Stress Storage Conditions. [Internet] [Thesis]. University of Tennessee – Knoxville; 2011. [cited 2021 Jan 20].
Available from: https://trace.tennessee.edu/utk_gradthes/873.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Goan EC. Quality of Applesauce and Raspberry Puree Applesauce as Affected by Type of Ascorbic Acid, Calcium Salts and Chelators under Stress Storage Conditions. [Thesis]. University of Tennessee – Knoxville; 2011. Available from: https://trace.tennessee.edu/utk_gradthes/873
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Sydney
11.
Lai, Yu-Wen.
Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies
.
Degree: 2016, University of Sydney
URL: http://hdl.handle.net/2123/17064
► There is an urgent need to improve the efficacy and range of antifungal drugs due to a global increase in invasive fungal infections, which are…
(more)
▼ There is an urgent need to improve the efficacy and range of antifungal drugs due to a global increase in invasive fungal infections, which are difficult to treat and are associated with high rates of mortality. Developing new drugs is expensive and time consuming and synergistic therapies that enhance the efficacy of current drugs are an alternative approach. Iron chelators have been used as antifungal synergents in salvage therapy, however, how these cause synergy are unknown. This thesis aims to use a transcriptomic approach to understand the mechanistic detail of antifungal-chelator synergy in the pathogen Cryptococcus to find potential antifungal targets. It focuses on amphotericin B (AMB) and lactoferrin (LF) synergy and voriconazole (VRC) and EDTA antagonism upon screening the interactions of various antifungal - chelator combinations in Cryptococcus. LF was found to enhance the antifungal effect of AMB in two ways: via the dysregulation of stress responses and metal homeostasis that disrupted the cell’s ability to mount an appropriate stress response, and by overwhelming the cell’s stress response via the cumulative strain from ER stress, disruption of transmembrane transport processes and increased metal dysregulation. Metal homeostasis was vital to both processes and the direct disruption of metal homeostasis, via deletion of iron (Aft1, Cir1 and HapX) and zinc (Zap1 and Zap104) regulating transcription factors, resulted in increased AMB susceptibility. Analysis of drug-binding domains in Zap1 and Zap104 found these to contain druggable sites and be potential antifungal drug targets. EDTA in the presence of VRC was found to disrupt mitochondrial functions along with an up-regulation of drug efflux genes, suggesting a potential mechanism of antagonism by mediating the efflux of intracellular VRC. Overall, metal regulation is important for resisting antifungal stress and is a potential antifungal strategy, where Zap1 is a potential antifungal drug target.
Subjects/Keywords: Cryptococcus;
Transcriptomics;
Drug Synergy;
Iron Chelators;
Drug Antagonism;
Antifungal Drugs
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lai, Y. (2016). Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/17064
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lai, Yu-Wen. “Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies
.” 2016. Thesis, University of Sydney. Accessed January 20, 2021.
http://hdl.handle.net/2123/17064.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lai, Yu-Wen. “Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies
.” 2016. Web. 20 Jan 2021.
Vancouver:
Lai Y. Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies
. [Internet] [Thesis]. University of Sydney; 2016. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2123/17064.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lai Y. Transcriptomic analysis of synergy between antifungal drugs and iron chelators for alternative antifungal therapies
. [Thesis]. University of Sydney; 2016. Available from: http://hdl.handle.net/2123/17064
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales
12.
Nguyen, Hong Loi.
The effects of hypoxic postconditioning and prolyl hydroxylase inhibitors on brain repair after stroke.
Degree: Medical Sciences, 2017, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/59072
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48393/SOURCE02?view=true
► Ischaemic stroke remains a major cause of death and adult disability in the world. Post stroke treatment with mild hypoxic postconditioning (HPC) and prolyl hydroxylase…
(more)
▼ Ischaemic stroke remains a major cause of death and adult disability in the world. Post stroke treatment with mild hypoxic postconditioning (HPC) and prolyl hydroxylase (PHD) inhibitors, which are compounds that mimic the effects of hypoxia, have shown to be neuroprotective in adult rats. However, there are limited studies showing functional improvements following these treatments. The effects of HPC and PHD inhibitors, ethy-3, 4-dihydroxybenzoate (EDHB) and deferoxamine (DFX), on functional recovery and brain histology were examined using an endothelin-1-stroke model in adult rats. Stroke was induced in conscious rats by delivery of endothelin-1 onto the middle cerebral artery via intracranial injection. Animals were exposed to HPC, starting 24h after stroke in a hypoxic chamber (8% O2, 1h/d for 5d) or treated with EDHB (200mg/kg daily, for 3 day, i.p) or DFX (200mg/kg single dose, i.p) 6h after stroke. Sham animals were exposed to room air or injection with saline. Motor and sensory function tests were conducted and brains were collected at the end of each experiment for histological analyses. Stroke resulted in contralateral motor and sensory deficits with accompanying ipsilateral brain injury. HPC after stroke reversed some of the contralateral motor and sensory deficits in addition to reduced ipsilateral brain injury 6d after stroke. HPC also enhanced the astrocyte response and reduced neuronal injury in the cortex following stroke. Post-stroke treatment with DFX or EDHB reduced contralateral motor and sensory deficits up to 2 and 3 weeks respectively and reduced ipsilateral brain damage. This demonstrates that induction of hypoxia-induced adaptions by HPC, DFX or EDHB after stroke can promote brain repair. Further investigations of DFX-induced neuroprotection in hippocampal cultures revealed that protection is partially dependent on hypoxia inducible factor-1 and reduction of oxidative stress is also likely to be involved. HPC and PHD inhibitors have the potential to be a novel therapeutic approach that can enhance endogenous repair of the brain after stroke.
Advisors/Committee Members: Fath, Thomas, Medical Sciences, Faculty of Medicine, UNSW, Jones, Nicole, Medical Sciences, Faculty of Medicine, UNSW.
Subjects/Keywords: Brain repair; Stroke; Hypoxia; Hypoxia postconditioing; prolyl hydroxylase inhibitors; Iron chelators
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Nguyen, H. L. (2017). The effects of hypoxic postconditioning and prolyl hydroxylase inhibitors on brain repair after stroke. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/59072 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48393/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Nguyen, Hong Loi. “The effects of hypoxic postconditioning and prolyl hydroxylase inhibitors on brain repair after stroke.” 2017. Doctoral Dissertation, University of New South Wales. Accessed January 20, 2021.
http://handle.unsw.edu.au/1959.4/59072 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48393/SOURCE02?view=true.
MLA Handbook (7th Edition):
Nguyen, Hong Loi. “The effects of hypoxic postconditioning and prolyl hydroxylase inhibitors on brain repair after stroke.” 2017. Web. 20 Jan 2021.
Vancouver:
Nguyen HL. The effects of hypoxic postconditioning and prolyl hydroxylase inhibitors on brain repair after stroke. [Internet] [Doctoral dissertation]. University of New South Wales; 2017. [cited 2021 Jan 20].
Available from: http://handle.unsw.edu.au/1959.4/59072 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48393/SOURCE02?view=true.
Council of Science Editors:
Nguyen HL. The effects of hypoxic postconditioning and prolyl hydroxylase inhibitors on brain repair after stroke. [Doctoral Dissertation]. University of New South Wales; 2017. Available from: http://handle.unsw.edu.au/1959.4/59072 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:48393/SOURCE02?view=true

University of British Columbia
13.
Ng-Muk-Yuen, Jennifer Diane.
Prevention of bacterial growth in platelet products via inclusion of iron chelators.
Degree: MS- MSc, Pathology, 2008, University of British Columbia
URL: http://hdl.handle.net/2429/1338
► Bacterial infection is a leading cause of morbidity and mortality arising from platelet transfusions (1, 2). Storage of platelet products at room temperature (20 to…
(more)
▼ Bacterial infection is a leading cause of morbidity and mortality arising from platelet transfusions (1, 2). Storage of platelet products at room temperature (20 to 24ºC) provides ideal conditions for bacterial proliferation (1, 3-6). Furthermore, platelets are stored in plasma containing bioavailable iron that bacteria require to survive (7). Thus we hypothesize that the inclusion of iron chelators will bind and remove iron, thereby inhibiting bacterial growth in both culture medium and platelet concentrates. Additionally, we hypothesize that residual red blood cells (RBCs) in platelet units may contribute bioavailable iron that promotes bacterial growth.
To test these hypotheses, we first assessed growth of Staphylococcus epidermidis in culture medium after treatment with the iron chelators deferoxamine (DFO) or phytic acid. DFO significantly inhibited bacterial growth in a dose dependent manner (p < 0.009). Conversely, phytate only inhibited bacterial growth at concentrations ≥ 100 mM (p < 0.001); at ≤ 5 mM, phytate supplied S. epidermidis with additional nutrients and significantly promoted growth (p < 0.001). Subsequently, we monitored the change in RBCs over time. Hemolysis, methemoglobin, and iron levels all significantly increased over the 7-day storage period (p < 0.001) releasing bioavailable iron. Indeed, we found that S. epidermidis growth in iron-poor medium drastically increased with the addition of RBCs, thus supporting our second hypothesis. Surprisingly, the inclusion of DFO in minimal medium did not demonstrate a bacteriostatic effect in the presence of RBCs. The inhibitory effect of DFO was likely overcome by iron released from the elevated methemoglobin levels arising from the direct interaction of DFO with hemoglobin. Previous studies demonstrate that methemoglobin releases iron more quickly than normal hemoglobin (8).
Lastly, we evaluated the effect of DFO on microbial growth in platelet concentrates using the BacT/ALERT system. The presence of DFO significantly inhibited S. epidermidis growth in buffy coat platelets in a dose dependent manner (p < 0.001). With these findings, the inclusion of iron chelators is a promising approach to preventing transfusion-transmitted bacterial infection and providing patients with a safer platelet product.
Subjects/Keywords: Platelets; Iron chelators; Bacteria
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ng-Muk-Yuen, J. D. (2008). Prevention of bacterial growth in platelet products via inclusion of iron chelators. (Masters Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/1338
Chicago Manual of Style (16th Edition):
Ng-Muk-Yuen, Jennifer Diane. “Prevention of bacterial growth in platelet products via inclusion of iron chelators.” 2008. Masters Thesis, University of British Columbia. Accessed January 20, 2021.
http://hdl.handle.net/2429/1338.
MLA Handbook (7th Edition):
Ng-Muk-Yuen, Jennifer Diane. “Prevention of bacterial growth in platelet products via inclusion of iron chelators.” 2008. Web. 20 Jan 2021.
Vancouver:
Ng-Muk-Yuen JD. Prevention of bacterial growth in platelet products via inclusion of iron chelators. [Internet] [Masters thesis]. University of British Columbia; 2008. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2429/1338.
Council of Science Editors:
Ng-Muk-Yuen JD. Prevention of bacterial growth in platelet products via inclusion of iron chelators. [Masters Thesis]. University of British Columbia; 2008. Available from: http://hdl.handle.net/2429/1338
14.
Klaber, Nica.
A Phytoremediation Study on the Effects of Soil Amendments on the Uptake of Arsenic by Two Perennial Grasses.
Degree: MS(M.S.), Plant & Soil Sciences, 2009, U of Massachusetts : Masters
URL: http://scholarworks.umass.edu/theses/368
► The effects of varying concentrations of two chelators: EDTA, citric acid (CA), and phosphorus on the accumulation of arsenic in soil by two perennial grasses,…
(more)
▼ The effects of varying concentrations of two
chelators: EDTA, citric acid (CA), and phosphorus on the accumulation of arsenic in soil by two perennial grasses, Leersia oryzoides and (rice cut-grass) Festuca arundinacea (tall fescue). Each experiment was run for eight weeks, after which plants were harvested, oven-dried, digested in acid and analyzed using an ICP-OES. Phosphorus soil amendments were applied as 0, 15, 30, 60, 120 mg P/kg soil. For the first chelator experiment, CA and EDTA concentrations of 0, 2.5, and 5.0 mmol/kg soil were added in pulse form to the soil. In the second chelator experiment, concentrations of CA were added in 0, 2.0, 4.0 mmol/kg soil and EDTA was added as 0, 0.25, 0.50 mmol/kg soil. Both plant species accumulated enough arsenic in the root and shoot tissues to be considered at hyperaccumulator species. Citric acid produced comparable results with EDTA, and is considerable much safer for the environment than any synthetic chelator. Certain soil amendments (citric acid and phosphorus) and hyperaccumulator species used in this study warrant further research in the field.
Advisors/Committee Members: Allen Barker, Baoshan Xing.
Subjects/Keywords: phytoremediation; arsenic; perennial grasses; soil; chelators; citric acid; EDTA; Other Environmental Sciences
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Klaber, N. (2009). A Phytoremediation Study on the Effects of Soil Amendments on the Uptake of Arsenic by Two Perennial Grasses. (Masters Thesis). U of Massachusetts : Masters. Retrieved from http://scholarworks.umass.edu/theses/368
Chicago Manual of Style (16th Edition):
Klaber, Nica. “A Phytoremediation Study on the Effects of Soil Amendments on the Uptake of Arsenic by Two Perennial Grasses.” 2009. Masters Thesis, U of Massachusetts : Masters. Accessed January 20, 2021.
http://scholarworks.umass.edu/theses/368.
MLA Handbook (7th Edition):
Klaber, Nica. “A Phytoremediation Study on the Effects of Soil Amendments on the Uptake of Arsenic by Two Perennial Grasses.” 2009. Web. 20 Jan 2021.
Vancouver:
Klaber N. A Phytoremediation Study on the Effects of Soil Amendments on the Uptake of Arsenic by Two Perennial Grasses. [Internet] [Masters thesis]. U of Massachusetts : Masters; 2009. [cited 2021 Jan 20].
Available from: http://scholarworks.umass.edu/theses/368.
Council of Science Editors:
Klaber N. A Phytoremediation Study on the Effects of Soil Amendments on the Uptake of Arsenic by Two Perennial Grasses. [Masters Thesis]. U of Massachusetts : Masters; 2009. Available from: http://scholarworks.umass.edu/theses/368
15.
Paixão, João Carlos Rodrigues.
Considerações sobre o papel da química bioinorgânica na saúde.
Degree: 2013, Universidade Fernando Pessoa
URL: https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/4480
► Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
Uma das características dos…
(more)
▼ Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
Uma das características dos metais que os torna tão importantes como componentes dos seres vivos é o facto de serem solúveis nos fluidos biológicos, o que promove a sua interação com as moléculas biológicas, explicando, assim, a razão pela qual muitos dos processos vitais exigirem a presença de iões metálicos. Respiração, fixação de azoto, contração muscular e muitas reações metabólicas, designadamente de desenvolvimento, crescimento, transdução de sinal e proteção face a agentes mutagénicos, são alguns exemplos desses processos. Deste modo, a utilização de metais como forma de tratamento é de extrema utilidade e, por isso, ao longo das últimas décadas, a Química Bioinorgânica tem sido responsável por grandes contribuições para a saúde humana e Ciência Médica. A caracterização das principais atividades dos metais para uso terapêutico e a sua importância são temas pertinentes nos dias de hoje, uma vez que a incorporação de metais em moléculas orgânicas está em crescimento exponencial, sendo de grande interesse conhecer o papel dos iões metálicos nas patogenias, as interações metal-fármaco e os metais presentes em fármacos. Estes metalofármacos podem ser usados, entre outros exemplos, como antineoplásicos, antibacterianos, antiartríticos ou antidepressivos. Os metais, apesar de serem farmacologicamente muito úteis, podem exibir, também, elevados níveis de toxicidade quando se encontram em excesso no organismo. A toxicidade pode ser responsável por doenças graves e, em casos extremos, a morte. A quelatoterapia é um método utilizado para a remoção de metais presentes no organismo, sendo há muito tempo utilizado em intoxicações por metais. One of the characteristics that make metals such important components of the living beings is the fact that they are soluble in biological fluids, which promotes their interaction with biological molecules, therefore explaining why many of the vital processes demand the presence of metal ions. Breathing, nitrogen fixation, muscular contraction and many metabolic reactions including development, growth, signalling transduction and protection against mutagenic agents, are some of the examples of these processes. Thus, the use of metals as a form of treatment is extremely useful and therefore, for the past decades, Bioinorganic Chemistry has been responsible for major contributions to the Human Health and Medical Science. The characterization of the main activities of metals for therapeutic use and their importance are pertinent topics today, because the incorporation of metals in organic molecules is in exponential growth, being extremely essential to understand the role of metal ions in pathogenesis, the metal-drug interactions and the metals that are present in drugs. These metallodrugs can be used, among other examples, as antineoplastic, antibacterial, antiarrhythmic or…
Advisors/Committee Members: Moutinho, Carla, Balcão, Victor M..
Subjects/Keywords: Química Bioinorgânica; Metais; Toxicidade; Homeostase; Quelantes; Bioinorganic Chemistry; Metals; Toxicity; Homeostasis; Chelators
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Paixão, J. C. R. (2013). Considerações sobre o papel da química bioinorgânica na saúde. (Thesis). Universidade Fernando Pessoa. Retrieved from https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/4480
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Paixão, João Carlos Rodrigues. “Considerações sobre o papel da química bioinorgânica na saúde.” 2013. Thesis, Universidade Fernando Pessoa. Accessed January 20, 2021.
https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/4480.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Paixão, João Carlos Rodrigues. “Considerações sobre o papel da química bioinorgânica na saúde.” 2013. Web. 20 Jan 2021.
Vancouver:
Paixão JCR. Considerações sobre o papel da química bioinorgânica na saúde. [Internet] [Thesis]. Universidade Fernando Pessoa; 2013. [cited 2021 Jan 20].
Available from: https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/4480.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Paixão JCR. Considerações sobre o papel da química bioinorgânica na saúde. [Thesis]. Universidade Fernando Pessoa; 2013. Available from: https://www.rcaap.pt/detail.jsp?id=oai:bdigital.ufp.pt:10284/4480
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Otago
16.
Ariffin, Mimi.
Crosstalk Between Iron Homeostasis And Nitric Oxide Signalling: Impact On Cancer Cell Viability
.
Degree: 2012, University of Otago
URL: http://hdl.handle.net/10523/2282
► The element iron (Fe) is essential for mammals since many enzymes require Fe as a cofactor for metabolic processes. Fe regulation is extremely important to…
(more)
▼ The element iron (Fe) is essential for mammals since many enzymes require Fe as a cofactor for metabolic processes. Fe regulation is extremely important to maintain Fe homeostasis as Fe overload and Fe deprivation are cytotoxic. Fe overload can cause oxidative damage via excessive production of reactive oxygen species (ROS). On the other hand, Fe deprivation can inhibit cellular growth and lead to apoptosis. Iron regulatory proteins (IRPs) are important for maintaining cellular Fe homeostasis. Regulation of these proteins involves the redox status of the iron-sulphur (Fe-S) clusters of the enzyme aconitase. IRPs are very sensitive to oxidative stress. Excessive exposure of these regulatory proteins to ROS will disrupt cellular Fe regulation by inducing Fe trafficking in cells. The major cellular systems (e.g. mitochondrial respiratory chain) are dependent on Fe for their functionality. With a lack of Fe, these systems will be affected. The susceptibility of cells to oxidative damage will increase under Fe deprivation conditions. Therefore, potentially both Fe overload and Fe deprivation are beneficial for cancer therapy if they could be selectively induced within a tumour. In the present study, nitric oxide (•NO) released by a novel photoactive agent, tDSNO, was studied as a means of selectively impairing Fe homeostasis and exacerbating the effect of Fe deprivation. The exposure to •NO was hypothesised to cause toxicity to cancer cells by exaggerating the stress conditions, which is the characteristic of both Fe overload and Fe deprivation pathways. Results showed that the exposure of breast cancer cells (MDA-MB-231) and lung cancer cells (A549) to •NO under normal Fe homeostasis conditions was unable to promote Fe overload as the intracellular Fe content did not significantly increase relative to control (p>0.05). However, the efficacy of tDSNO was potentiated under conditions of Fe deprivation. A maximum cellular death of 59.1 ± 1.2% was observed after 24 h of exposure to 40 µM of tDSNO at 37 °C (p<0.05), while under these conditions, the drug tDSNO displayed a low toxicity in cells with normal Fe homeostasis. Therefore, the toxic effect of tDSNO in cancer cells was substantially enhanced under Fe deprivation conditions. It was then concluded that this novel drug could be more effective if used in combination with Fe chelation therapy.
Advisors/Committee Members: Giles, Gregory (advisor).
Subjects/Keywords: Nitric oxide;
Iron homeostasis;
Nitric oxide donors;
Iron chelators;
Breast cancer;
Lung cancer
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ariffin, M. (2012). Crosstalk Between Iron Homeostasis And Nitric Oxide Signalling: Impact On Cancer Cell Viability
. (Masters Thesis). University of Otago. Retrieved from http://hdl.handle.net/10523/2282
Chicago Manual of Style (16th Edition):
Ariffin, Mimi. “Crosstalk Between Iron Homeostasis And Nitric Oxide Signalling: Impact On Cancer Cell Viability
.” 2012. Masters Thesis, University of Otago. Accessed January 20, 2021.
http://hdl.handle.net/10523/2282.
MLA Handbook (7th Edition):
Ariffin, Mimi. “Crosstalk Between Iron Homeostasis And Nitric Oxide Signalling: Impact On Cancer Cell Viability
.” 2012. Web. 20 Jan 2021.
Vancouver:
Ariffin M. Crosstalk Between Iron Homeostasis And Nitric Oxide Signalling: Impact On Cancer Cell Viability
. [Internet] [Masters thesis]. University of Otago; 2012. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10523/2282.
Council of Science Editors:
Ariffin M. Crosstalk Between Iron Homeostasis And Nitric Oxide Signalling: Impact On Cancer Cell Viability
. [Masters Thesis]. University of Otago; 2012. Available from: http://hdl.handle.net/10523/2282
17.
Tury, Sandrine.
Intérêt thérapeutique de la privation en fer dans les cancers du sein : Iron deprivation for breast cancer treatment.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2017, Paris Sciences et Lettres (ComUE)
URL: http://www.theses.fr/2017PSLET014
► La dérégulation du métabolisme des cellules tumorales est un hallmark du cancer clairement établi. Pour assurer leur taux de proliferation élevé, les cellules cancéreuses adaptent…
(more)
▼ La dérégulation du métabolisme des cellules tumorales est un hallmark du cancer clairement établi. Pour assurer leur taux de proliferation élevé, les cellules cancéreuses adaptent leur métabolisme, ce qui leur permet de répondre à leurs nouveaux besoins énergétiques. Dans ce contexte, les cellules tumorales présentent des besoins en fer augmentés ainsi que de multiples perturbations du métabolisme du fer, ce qui les rend plus sensibles à la privation en fer. Cette vulnérabilité pourrait ainsi faire l’objet d’un ciblage thérapeutique. Dans les cancers du sein, de nouvelles approches thérapeutiques sont très attendues en particulier pour les cancers triple-négatifs qui développent fréquemment des résistances à la chimiothérapie et qui souffrent d'un manque de cibles thérapeutiques spécifiques. L’activité antitumorale des chélateurs de fer tels que le déférasirox (DFX) évalués en monothérapie a déjà été démontrée dans différents types de cancers mais ne semble pas être suffisamment efficace pour éradiquer les tumeurs. Dans cette étude, nous avons démontré que le DFX agit en synergie avec des molécules de chimiothérapies conventionnelles telles que la doxorubicine, le cisplatine et le carboplatine pour inhiber la prolifération cellulaire et induire l’apoptose et l’autophagie de lignées cellulaires mammaires de sous-type triple-négatif. De plus, la combinaison du DFX avec la doxorubicine et le cyclophosphamide permet de retarder voire d’éviter les récidives dans des xénogreffes de tumeurs mammaires triple-négatives (PDX) sans augmenter les effets secondaires de la chimiothérapie seule ni impacter les réserves en fer globales des souris. Au niveau moléculaire, nous avons montré que la synergie antitumorale du DFX et de la doxorubicine implique une inhibition des voies PI3K et NF-κB. Par ailleurs, étant donné que les patients présentant un cancer triple-négatif avec de faibles réserves en fer tumorales présentent un bon pronostic, nous pensons que la privation en fer au moyen de chélateurs de fer pourrait constituer une approche d’autant plus efficace pour augmenter l’efficacité des chimiothérapies conventionnelles dans le traitement de ces cancers.
Deregulation of tumor cell metabolism is a clearly established cancer hallmark. To ensure their high proliferation rate, cancer cells adapt their metabolism to meet their new energy needs. In this context, tumor cells display increased iron needs as well as multiple disturbances in their iron metabolism, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple negative tumors (TNBC) which frequently develop chemotherapies resistance and suffer from a lack of targeted therapies. The anticancer activity of iron chelators such as deferasirox (DFX) assessed in monotherapy has been demonstrated in different types of cancers. However, iron chelators do not appear to be effective enough to eradicate cancer. In this work, we…
Advisors/Committee Members: Callens, Céline (thesis director), Bièche, Ivan (thesis director).
Subjects/Keywords: Cancers du sein; Chélateurs de fer; Chimiothérapie; Breast cancers; Iron chelators; Chemotherapy; 570
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tury, S. (2017). Intérêt thérapeutique de la privation en fer dans les cancers du sein : Iron deprivation for breast cancer treatment. (Doctoral Dissertation). Paris Sciences et Lettres (ComUE). Retrieved from http://www.theses.fr/2017PSLET014
Chicago Manual of Style (16th Edition):
Tury, Sandrine. “Intérêt thérapeutique de la privation en fer dans les cancers du sein : Iron deprivation for breast cancer treatment.” 2017. Doctoral Dissertation, Paris Sciences et Lettres (ComUE). Accessed January 20, 2021.
http://www.theses.fr/2017PSLET014.
MLA Handbook (7th Edition):
Tury, Sandrine. “Intérêt thérapeutique de la privation en fer dans les cancers du sein : Iron deprivation for breast cancer treatment.” 2017. Web. 20 Jan 2021.
Vancouver:
Tury S. Intérêt thérapeutique de la privation en fer dans les cancers du sein : Iron deprivation for breast cancer treatment. [Internet] [Doctoral dissertation]. Paris Sciences et Lettres (ComUE); 2017. [cited 2021 Jan 20].
Available from: http://www.theses.fr/2017PSLET014.
Council of Science Editors:
Tury S. Intérêt thérapeutique de la privation en fer dans les cancers du sein : Iron deprivation for breast cancer treatment. [Doctoral Dissertation]. Paris Sciences et Lettres (ComUE); 2017. Available from: http://www.theses.fr/2017PSLET014

University of South Florida
18.
Woodroffe, Josanne-Dee.
Design and Synthesis of CpG-Lytic Peptide Conjugate, Brachytherapy Beads and a Combinatorial Library of Primary Amines used as Potential Therapeutics in the Treatment of Cancers.
Degree: 2017, University of South Florida
URL: https://scholarcommons.usf.edu/etd/7453
► Cancer remains one of the most feared diseases affecting the modern world. Second to heart disease, it is the largest cause of deaths, affecting one…
(more)
▼ Cancer remains one of the most feared diseases affecting the modern world. Second to heart disease, it is the largest cause of deaths, affecting one in three persons. Cancer cells are formed when normal, healthy cells become damage, losing their normal regulatory mechanism that control cell growth. There are many different types and progression of these cancer cells that determine the type of treatment a patient receives. The primary focus of this dissertation is to propose three studies of anticancer agents. In Chapter one, a CpG-lytic peptide conjugate was designed to target receptors on the cell membrane to concentrate the lytic peptide around the cells to cause triggered cell death, in the treatment of Myelodysplastic Syndromes (MDS). This conjugate act like monoclonal antibodies in that the molecular size is too large to enter the cell, therefore it targets the TLR9 receptors expressed extracellularly in precancer cells in MDS. Chapter two, focuses on the screening of anticancer agents used in targeted therapy. It provides a general scheme applied to the synthesis of a combinatorial library of primary amines used as small-molecule drugs coupled unto a solid support bead (Positional Scanning Library Method) to screen for biological effects on various types of cancers. Chapter three address the issue of radiotherapy treatments, one of the most widely used treatment of cancer. To improve the efficacy of conventional radiation therapy and reduce the cytotoxicity of healthy tissue, High-Dose Rate brachytherapy (HDR) may be used as a stand-alone treatment or after surgery to prevent the recurrence of cancer cells. To design and provide studies of these brachytherapy beads, a model was developed by coupling a chelating agent DOTA onto the surface of macrobeads that coordinated to Europium (III) in efforts to mimic the radiolabeling with a radioactive metal. These brachytherapy beads will be used to conduct in vitro studies in the treatment of local cancers with massive concentrations of radiation without damaging surrounding healthy tissue.
Subjects/Keywords: Myelodysplastic Syndromes; Oligonucleotides; Positional Scanning Libraries; DOTA Chelators; Internal Radiation; Biochemistry; Organic Chemistry
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Woodroffe, J. (2017). Design and Synthesis of CpG-Lytic Peptide Conjugate, Brachytherapy Beads and a Combinatorial Library of Primary Amines used as Potential Therapeutics in the Treatment of Cancers. (Thesis). University of South Florida. Retrieved from https://scholarcommons.usf.edu/etd/7453
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Woodroffe, Josanne-Dee. “Design and Synthesis of CpG-Lytic Peptide Conjugate, Brachytherapy Beads and a Combinatorial Library of Primary Amines used as Potential Therapeutics in the Treatment of Cancers.” 2017. Thesis, University of South Florida. Accessed January 20, 2021.
https://scholarcommons.usf.edu/etd/7453.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Woodroffe, Josanne-Dee. “Design and Synthesis of CpG-Lytic Peptide Conjugate, Brachytherapy Beads and a Combinatorial Library of Primary Amines used as Potential Therapeutics in the Treatment of Cancers.” 2017. Web. 20 Jan 2021.
Vancouver:
Woodroffe J. Design and Synthesis of CpG-Lytic Peptide Conjugate, Brachytherapy Beads and a Combinatorial Library of Primary Amines used as Potential Therapeutics in the Treatment of Cancers. [Internet] [Thesis]. University of South Florida; 2017. [cited 2021 Jan 20].
Available from: https://scholarcommons.usf.edu/etd/7453.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Woodroffe J. Design and Synthesis of CpG-Lytic Peptide Conjugate, Brachytherapy Beads and a Combinatorial Library of Primary Amines used as Potential Therapeutics in the Treatment of Cancers. [Thesis]. University of South Florida; 2017. Available from: https://scholarcommons.usf.edu/etd/7453
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
19.
Portier, Emilie.
Rôle du fer sur Legionella pneumophila et sur sa persistance dans les biofilms naturels : Role of iron on Legionella pneumophila and on its persistence in complex biofilms.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2014, Poitiers
URL: http://www.theses.fr/2014POIT2287
► L. pneumophila est une bactérie ubiquitaire des environnements aquatiques, responsable de la légionellose. Elle est principalement retrouvée au sein de protozoaires, mais aussi dans les…
(more)
▼ L. pneumophila est une bactérie ubiquitaire des environnements aquatiques, responsable de la légionellose. Elle est principalement retrouvée au sein de protozoaires, mais aussi dans les biofilms. Il est admit que le fer est l'un des éléments indispensable à la croissance de ce pathogène. En 2008, une étude a été réalisée au sein de notre équipe montrant une modulation de l'expression des gènes entre L. pneumophila à l'état planctonique, et à l'état de biofilm. Dans cette même étude, l'ajout de forte concentration en fer (1,25 g/l), dans le milieu de culture des biofilms, a révélé une inhibition de leur développement. Le fer présente donc un rôle dans l'établissement de biofilms mono espèces de L. pneumophila. Nous avons développé un modèle de biofilms naturels, formés à partir d'eau de rivière, afin de tester l'établissement de L. pneumophila, dans des conditions où l'eau de rivière est supplémentée en fer ou au contraire appauvrit, par l'ajout de chélateurs, le deferoxamine mesylate (DFX) ou le dipyridyl (DIP). Les ajouts de fer et de DFX n'ont eu aucun impact sur l'établissement de L. pneumophila contrairement au DIP, qui a induit une augmentation de l'implantation de ces bactéries.Par ailleurs, nous avons effectué une analyse transcriptomique sur L. pneumophila cultivées en milieu liquide supplémenté en DFX. L'ajout du chélateur a entrainé une induction de l'expression de 113 gènes et la répression de 246 gènes. Parmi les gènes induits, certains sont déjà connus comme étant impliqués dans le métabolisme du fer ou contrôlés par le fer. Parmi eux, un gène a été surexprimé, il n'a jamais été associé au fer et sa fonction est encore inconnue à ce jour. Il s'agit du gène lpp2867. Des investigations ont été réalisées afin de caractériser et de comprendre le rôle de la protéine pour laquelle il code. Elle est notamment impliquée dans l'infection des amibes et des macrophages. Son rôle dans le transport du fer ferreux a également été mis en avant. Cette protéine a été nommée IroT pour « iron transporter ».
L. pneumophila is a ubiquitous bacterium found in aquatic environments, and responsible for legionellosis. It is mainly found into both protozoa and biofilms. Iron is a key nutrient for an optimal growth of this pathogen. In 2008, a transcriptomic analysis was carried out within our team, revealing a differential expression of genes involved in iron metabolism between sessile and planktonic bacteria. Also, this study showed that, for high iron concentrations (1.25 g/l), biofilm formation by L. pneumophila was inhibited. It suggested that iron is important for biofilm formation by L. pneumophila. To extend these observations in more natural conditions, a model of biofilm formation, using natural river water, was developed. Water was spiked with L. pneumophila and supplemented with iron or iron chelator, deferoxamine mesylate (DFX) or dipyridyl (DIP). Addition of iron and DFX did not have any effect on L. pneumophila establishment unlike the DIP which induced an increase of L. pneumophila concentration into the…
Advisors/Committee Members: Héchard, Yann (thesis director), Labanowski, Jérôme (thesis director).
Subjects/Keywords: Legionella; Biofilms complexes; Fer; Chélateurs; Transport; Effecteurs; Virulence; Legionella; Complex biofilms; Iron; Chelators; Transport; Effectors; Virulence; 579.33
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Portier, E. (2014). Rôle du fer sur Legionella pneumophila et sur sa persistance dans les biofilms naturels : Role of iron on Legionella pneumophila and on its persistence in complex biofilms. (Doctoral Dissertation). Poitiers. Retrieved from http://www.theses.fr/2014POIT2287
Chicago Manual of Style (16th Edition):
Portier, Emilie. “Rôle du fer sur Legionella pneumophila et sur sa persistance dans les biofilms naturels : Role of iron on Legionella pneumophila and on its persistence in complex biofilms.” 2014. Doctoral Dissertation, Poitiers. Accessed January 20, 2021.
http://www.theses.fr/2014POIT2287.
MLA Handbook (7th Edition):
Portier, Emilie. “Rôle du fer sur Legionella pneumophila et sur sa persistance dans les biofilms naturels : Role of iron on Legionella pneumophila and on its persistence in complex biofilms.” 2014. Web. 20 Jan 2021.
Vancouver:
Portier E. Rôle du fer sur Legionella pneumophila et sur sa persistance dans les biofilms naturels : Role of iron on Legionella pneumophila and on its persistence in complex biofilms. [Internet] [Doctoral dissertation]. Poitiers; 2014. [cited 2021 Jan 20].
Available from: http://www.theses.fr/2014POIT2287.
Council of Science Editors:
Portier E. Rôle du fer sur Legionella pneumophila et sur sa persistance dans les biofilms naturels : Role of iron on Legionella pneumophila and on its persistence in complex biofilms. [Doctoral Dissertation]. Poitiers; 2014. Available from: http://www.theses.fr/2014POIT2287
20.
Cui, H.
The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer.
Degree: 2018, University of Tasmania
URL: https://eprints.utas.edu.au/28657/1/Cui_whole_thesis_ex_pub_mat.pdf
;
https://eprints.utas.edu.au/28657/2/Cui_whole_thesis.pdf
;
Cui,
H
ORCID:
0000-0002-9009-7330
<https://orcid.org/0000-0002-9009-7330>
2018
,
'The
role
of
copper
transporters
in
in
vitro
cytotoxicity
of
oxaliplatin
and
their
expression
in
colorectal
cancer',
PhD
thesis,
University
of
Tasmania.
► Colorectal cancer (CRC) is a major health problem and cause of morbidity and mortality worldwide. The clinical efficacy of oxaliplatin (OXL), a commonly used chemotherapy…
(more)
▼ Colorectal cancer (CRC) is a major health problem and cause of morbidity and mortality worldwide. The clinical efficacy of oxaliplatin (OXL), a commonly used chemotherapy agent, is limited by tumor resistance largely due to reduced drug accumulation. The role of copper (Cu) transporters in the transport and pharmacology of OXL is unclear, including Cu uptake transporter 1 (CTR1), and efflux transporter Cu+-transporting P-type ATPase ATP7A and ATP7B. The project aimed to investigate the contribution of Cu transporters to the uptake and cytotoxicity of OXL, and their expression in CRC.
CRC cells were engineered to overexpress hCTR1 gene (hCTR1/DLD-1 cells) or the empty vector as mock control cells to study the uptake and cytotoxicity of OXL. A fluorescent probe FDCPt1 was used to visualize the cellular uptake of OXL-derived monofunctional platinum bio-transformed products. The expression profile of Cu transporters was characterized in colorectal cancer cell lines before evaluating the synergism between Cu chelators and OXL in colorectal cancer cells based on their regulation on hCTR1 protein. The expression of copper transporters was also investigated in paired patient tumor biopsies. In addition, a colitis model of Winnie mouse carrying point mutation of Muc2 gene and a dextran sodium sulphate (DSS)-induced colonic dysplasia model were used to determine the correlation of Cu transporters with these precancerous conditions.
Overexpression of hCTR1 contributes to OXL cytotoxicity and uptake in recombinant colorectal cancer DLD-1 cells, with increased sensitivity and stronger FDCPt1-derived fluorescent signals than mock cells.
The mRNA of Cu transporters was detected at constantly high levels in colorectal cancer cell lines with different origins. hCTR1 protein was expressed abundantly with the expression intensity higher than ATP7A or ATP7B across cell lines. Cu chelators, ammonium tetrathiomolybdate, and D-penicillamine, and bathocuprione disulphonate up regulated hCTR1 protein levels and enhanced the cell-killing capacity of OXL in some of CRC cells.
Human colonic tissues were stained positive for Cu transporters with varying percentage of staining between individual patients. Semi-quantitative analysis using de-convolution method shows hCTR1 staining seems to be similar between tumor and the matched normal tissues. ATP7B expression exhibits a trend towards up regulation in tumor tissues compared to that of normal tissues, suggesting this protein may be involved in the development of colonic malignancy.
Chronic intestinal colitis and dysplasia were confirmed histologically in colonic tissues of Winnie mice, and DSS-treated Winnie mice, respectively. Mouse Cu transporter 1 (mCTR1) was detected in colonic tissues of these animals, but with varying localization and intensity. The percentage of mCTR1 staining increased in colonic tissues of Winnie mice, but decreased in tissues of dysplasia model compared to that of the normal colon tissues. ATP7A and ATP7B expression did not change in colitis tissues but decreased…
Subjects/Keywords: Copper transporters; oxaliplatin; colorectal cancer; chelators; cytotoxicity
…28
1.3.2 Effect of Cu chelators on the expression of hCTR1… …34
1.3.3 Effect of Cu chelators on copper efflux transporters… …76
Chapter 4 Effects of Cu Chelators and Cu chloride on Oxaliplatin Cytotoxicity in… …82
4.2.4 Studies on the effect of copper chelators, copper chloride and oxaliplatin on the… …4.2.5 Toxicity assays of DLD-1 and SW620 cells in the presence of copper chelators or
copper…
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cui, H. (2018). The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/28657/1/Cui_whole_thesis_ex_pub_mat.pdf ; https://eprints.utas.edu.au/28657/2/Cui_whole_thesis.pdf ; Cui, H ORCID: 0000-0002-9009-7330 <https://orcid.org/0000-0002-9009-7330> 2018 , 'The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer', PhD thesis, University of Tasmania.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Cui, H. “The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer.” 2018. Thesis, University of Tasmania. Accessed January 20, 2021.
https://eprints.utas.edu.au/28657/1/Cui_whole_thesis_ex_pub_mat.pdf ; https://eprints.utas.edu.au/28657/2/Cui_whole_thesis.pdf ; Cui, H ORCID: 0000-0002-9009-7330 <https://orcid.org/0000-0002-9009-7330> 2018 , 'The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer', PhD thesis, University of Tasmania..
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Cui, H. “The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer.” 2018. Web. 20 Jan 2021.
Vancouver:
Cui H. The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer. [Internet] [Thesis]. University of Tasmania; 2018. [cited 2021 Jan 20].
Available from: https://eprints.utas.edu.au/28657/1/Cui_whole_thesis_ex_pub_mat.pdf ; https://eprints.utas.edu.au/28657/2/Cui_whole_thesis.pdf ; Cui, H ORCID: 0000-0002-9009-7330 <https://orcid.org/0000-0002-9009-7330> 2018 , 'The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer', PhD thesis, University of Tasmania..
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Cui H. The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer. [Thesis]. University of Tasmania; 2018. Available from: https://eprints.utas.edu.au/28657/1/Cui_whole_thesis_ex_pub_mat.pdf ; https://eprints.utas.edu.au/28657/2/Cui_whole_thesis.pdf ; Cui, H ORCID: 0000-0002-9009-7330 <https://orcid.org/0000-0002-9009-7330> 2018 , 'The role of copper transporters in in vitro cytotoxicity of oxaliplatin and their expression in colorectal cancer', PhD thesis, University of Tasmania.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
21.
Randazzo, Paola.
Study of the regulatory network linked to metal ion homeostasis in Bacillus subtilis : Investigation sur le réseau de régulation de l'homéostasie des ions métalliques dans Bacillus subtilis.
Degree: Docteur es, Sciences de la vie et de la santé, 2016, Université Paris-Saclay (ComUE)
URL: http://www.theses.fr/2016SACLS387
► Le projet de thèse concerne l’étude des réseaux de régulation en lien avec l’homéostasie des ions métalliques chez la bactérie à Gram-positif Bacillus subtilis. Les…
(more)
▼ Le projet de thèse concerne l’étude des réseaux de régulation en lien avec l’homéostasie des ions métalliques chez la bactérie à Gram-positif Bacillus subtilis. Les ions métalliques tels que Fe(II), Mn(II) et Zn(II) sont essentiels dans un grand nombre de processus cellulaires entant que cofacteur d’enzymes ou en tant qu’élément structural dans les protéines. Cependant, à trop hautes concentrations, ils peuvent avoir des effets toxiques en endommageant la membrane cellulaire et l’ADN ainsi qu’en inactivant la fonction de certaines protéines. De plus, en condition aérobie, B. subtilis produit du peroxyde d’hydrogène H₂O₂ qui réagit avec les ions Fe(II) pour produire des radicaux libres hautement toxiques pour la cellule. La régulation de l’homéostasie des ions métalliques doit donc être parfaitement régulée et coordonnée avec les autres processus cellulaires. J’essaie de comprendre de façon globale, via des approches expérimentales à grande échelle, les interconnexions entre les régulateurs de l’homéostasie des ions métalliques et autres voies métabolique dans Bacillus subtilis.
The present doctoral thesis concerns the study of the regulatory network linked tometal ions homeostasis in the Gram+ Bacillus subtilis. Metal ions such as Fe(II), Mn(II) andZn(II) are essential for many metabolic processes, since they function as enzyme cofactors andstructural ligands of proteins. Changes in ions availability can alter activity of enzymes of thecarbon metabolism and lead to changes in gene expression. In addition, the modulation of metalion homeostasis is intimately linked with the oxidative stress response: during aerobic growth,hydrogen peroxide is generated and it rapidly reacts with ferrous iron to form ROS molecules.Hence, regulation of metal ions uptake/efflux has to be finely regulated and coordinated with othercellular processes. With the present project, I aim to understand at system’s level how Bacillussubtilis integrates the control of metal ions homeostasis with other metabolic processes.
Advisors/Committee Members: Auger, Sandrine (thesis director).
Subjects/Keywords: Bacillus; Manganèse; Stress oxydant; Protéomique; Chelateurs des metaux; Transcriptomique; Bacillus; Manganese; Oxidative stress; Proteomic; Metal chelators; Transcriptomic
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Randazzo, P. (2016). Study of the regulatory network linked to metal ion homeostasis in Bacillus subtilis : Investigation sur le réseau de régulation de l'homéostasie des ions métalliques dans Bacillus subtilis. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2016SACLS387
Chicago Manual of Style (16th Edition):
Randazzo, Paola. “Study of the regulatory network linked to metal ion homeostasis in Bacillus subtilis : Investigation sur le réseau de régulation de l'homéostasie des ions métalliques dans Bacillus subtilis.” 2016. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 20, 2021.
http://www.theses.fr/2016SACLS387.
MLA Handbook (7th Edition):
Randazzo, Paola. “Study of the regulatory network linked to metal ion homeostasis in Bacillus subtilis : Investigation sur le réseau de régulation de l'homéostasie des ions métalliques dans Bacillus subtilis.” 2016. Web. 20 Jan 2021.
Vancouver:
Randazzo P. Study of the regulatory network linked to metal ion homeostasis in Bacillus subtilis : Investigation sur le réseau de régulation de l'homéostasie des ions métalliques dans Bacillus subtilis. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2016. [cited 2021 Jan 20].
Available from: http://www.theses.fr/2016SACLS387.
Council of Science Editors:
Randazzo P. Study of the regulatory network linked to metal ion homeostasis in Bacillus subtilis : Investigation sur le réseau de régulation de l'homéostasie des ions métalliques dans Bacillus subtilis. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2016. Available from: http://www.theses.fr/2016SACLS387
22.
Tian, Yue.
Traitement électrocinétique des sédiments de dragage multi-contaminés et évolution de leur toxicité : Electro-remediation of dredged multi-contaminated sediments and the evolution of their toxicity.
Degree: Docteur es, Génie civil, 2017, Normandie
URL: http://www.theses.fr/2017NORMLH24
► Les travaux de cette thèse sont consacrés principalement à l'optimisation d'une méthode de remédiation électrocinétique (EK) comme une technologie appropriée pour le traitement de sédiments…
(more)
▼ Les travaux de cette thèse sont consacrés principalement à l'optimisation d'une méthode de remédiation électrocinétique (EK) comme une technologie appropriée pour le traitement de sédiments de dragage de faible perméabilité hydraulique et multi-contaminés (en éléments traces (ET), hydrocarbures aromatiques polycycliques (HAP) et polychlorobiphényles (PCB)). Cette étude porte également sur l’effet du traitement EK sur l’évolution de la toxicité des sédiments. Après une revue bibliographique, une seconde partie a été dédiée aux méthodes d’analyse des contaminants, avec un focus sur leur extraction de la matrice sédimentaire ; ainsi, une nouvelle méthode d’extraction par dispersion de la matrice solide (MSPD) a été développée, pour une extraction rapide et simultanée des HAP et de PCB et une purification de l’échantillon, qui s’est avérée plus efficace que la méthode d’extraction assistée par micro-ondes (MAE). Plusieurs études expérimentales (à différentes échelles) de remédiation électrocinétique ont été décrites dans une troisième partie ; ces études ont été menées sur un sédiment reconstitué ou des sédiments de dragage portuaire. De nombreuses combinaisons de tensioactifs et d’agents chélatants ont été testées comme agents d’amélioration pour abaisser simultanément la concentration en métaux (Cd, Cr, Cu, Pb, Zn) et des HAP/PCB. Le choix a été effectué en raison notamment de leur faible toxicité potentielle, en vue de pouvoir les appliquer ultérieurement pour une restauration sur site : (bio)surfactants (Rhamnolipides, Saponine et Tween 20) combinés avec des agents chélatants (acide citrique (CA) et EDDS). Les résultats obtenus montrent que les métaux (à l'exception de Cr) sont difficiles à extraire de ces sédiments de dragage portuaire à caractère réducteur, qui présentent une capacité tampon élevée, une perméabilité hydraulique très faible et une teneur en matière organique élevée. En revanche, les HAP et les PCB fournissent de meilleurs taux d'abattement (29,2% et 50,2%, respectivement). Dans une quatrième partie, l'efficacité du procédé EK a également été évaluée à travers l’évolution de la toxicité aiguë des sédiments traités sur les copépodes E. affinis exposés aux élutriats de sédiments. Les résultats ont montré que l'utilisation de CA,des biosurfactants et du Tween 20 n'a pas eu d'impact significatif sur la toxicité des sédiments traités. Cependant, les copépodes E. affinis étaient sensibles aux faibles valeurs de pH et aux conditions très oxydantes, ainsi qu’à la présence de Cu et, dans une moindre mesure, de Pb, à condition toutefois qu’ils soient rendus plus mobiles et biodisponibles. En revanche, la toxicité a été peu et même négativement corrélée aux concentrations des HAP et des PCB après le traitement EK, probablement en raison de la production de métabolites oxydés des HAP et des PCB, plus toxiques que les composés natifs.
This thesis research is mainly devoted to the optimization of an electrokinetic (EK) remediation process as a promising technology for treating multi-contaminated (trace metals,…
Advisors/Committee Members: Benamar, Ahmed (thesis director), Portet-Koltalo, Florence (thesis director).
Subjects/Keywords: Electroremédiation; Agents chélatants; Electrokinetic remediation; Sediments; Trace metals; PAHs; PCBs; Biosurfactants; Chelators; E. affinis; Acute toxicity; Principal component analysis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Tian, Y. (2017). Traitement électrocinétique des sédiments de dragage multi-contaminés et évolution de leur toxicité : Electro-remediation of dredged multi-contaminated sediments and the evolution of their toxicity. (Doctoral Dissertation). Normandie. Retrieved from http://www.theses.fr/2017NORMLH24
Chicago Manual of Style (16th Edition):
Tian, Yue. “Traitement électrocinétique des sédiments de dragage multi-contaminés et évolution de leur toxicité : Electro-remediation of dredged multi-contaminated sediments and the evolution of their toxicity.” 2017. Doctoral Dissertation, Normandie. Accessed January 20, 2021.
http://www.theses.fr/2017NORMLH24.
MLA Handbook (7th Edition):
Tian, Yue. “Traitement électrocinétique des sédiments de dragage multi-contaminés et évolution de leur toxicité : Electro-remediation of dredged multi-contaminated sediments and the evolution of their toxicity.” 2017. Web. 20 Jan 2021.
Vancouver:
Tian Y. Traitement électrocinétique des sédiments de dragage multi-contaminés et évolution de leur toxicité : Electro-remediation of dredged multi-contaminated sediments and the evolution of their toxicity. [Internet] [Doctoral dissertation]. Normandie; 2017. [cited 2021 Jan 20].
Available from: http://www.theses.fr/2017NORMLH24.
Council of Science Editors:
Tian Y. Traitement électrocinétique des sédiments de dragage multi-contaminés et évolution de leur toxicité : Electro-remediation of dredged multi-contaminated sediments and the evolution of their toxicity. [Doctoral Dissertation]. Normandie; 2017. Available from: http://www.theses.fr/2017NORMLH24

University of Melbourne
23.
Betrie, Ashenafi Haileyesus.
Investigation of transition metal pharmacology in the cardiovascular system.
Degree: 2017, University of Melbourne
URL: http://hdl.handle.net/11343/212122
► Understanding transition metal dys/homeostasis holds potential for the discovery of new treatments to curb the increasing burden of cardio- and cerebrovascular diseases. However, their pharmacology…
(more)
▼ Understanding transition metal dys/homeostasis holds potential for the discovery of new treatments to curb the increasing burden of cardio- and cerebrovascular diseases. However, their pharmacology and roles in the cardiovascular system have been underexplored. This thesis investigated examples of transition metal pharmacology in the cardiovascular system by (1) using genetically-modified mice susceptible to iron accumulation and (2) pharmacologically elevating the levels of zinc in isolated arteries to probe its roles.
To understand the role of iron, two age groups of mice (13 mo and 23 mo) deficient in the microtubule-associated protein tau (MAPT, whose role in iron homeostasis of the brain was recently established) and their wild type counterparts were used. Loss of tau protein presented an accelerated age-dependent cardiomyopathy phenotype accompanied by cardiac iron accumulation. Increased systolic blood pressure, cardiac hypertrophy and lower basal right atrial rate were seen as early as 13 mo and were further aggravated by 23 mo. Notably, 23 mo wild type mice also showed a similar phenotype with a significant iron, zinc and copper accumulation together with an altered sensitivity of isolated mesenteric arteries to contractile agonists. More importantly, chronic treatment of the middle-aged tau KO mice with clioquinol prevented the increase in systolic blood pressure, cardiac hypertrophy and lowering of the basal right atrial rate.
Clioquinol is a moderate Fe2+ chelator and a Zn2+ ionophore. Thus, by using compounds with similar properties (ionophores that deliver metals across membrane and chelators that remove them), the role of zinc in vascular tone was explored in rat isolated small resistance arteries. Four different zinc ionophores from structurally-distinct chemical classes all caused a concentration-dependent relaxation of mesenteric arteries pre-contracted by a range of agonists. The potency and efficacy were comparable to the established vasodilator drugs, sodium nitroprusside and acetylcholine. The effects were also observed in middle cerebral, basilar, coronary, saphenous and pulmonary arteries. The archetypal ionophore Zn(DTSM) also showed a depressor effect in vivo. Importantly, removal of the endogenous zinc from resting cerebral and coronary arteries with basal tone, but not the others, caused an active contraction suggesting a crucial role of zinc in maintaining resting vascular tone.
In isolated small mesenteric arteries, the mechanism of zinc ionophore-induced vasorelaxation was then investigated. Vasorelaxation by zinc ionophores involved a combination of non-competitive inhibition of voltage-operated Ca2+ channels (common to all the four classes) and a competitive α1-adrenoceptor antagonism (clioquinol). The release of vasodilatory mediators from the endothelium or perivascular nerves, antagonising the actions of endothelin, arginine vasopressin and thromboxane A2 receptors, activating potassium channels (voltage-operated, ATP-sensitive and calcium-activated) were all not involved…
Subjects/Keywords: pharmacology; cardiovascular; vascular tone; heart; mesenteric arteries; cerebral arteries; coronary arteries; Tau protein; iron; zinc; ionophores; chelators
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Betrie, A. H. (2017). Investigation of transition metal pharmacology in the cardiovascular system. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/212122
Chicago Manual of Style (16th Edition):
Betrie, Ashenafi Haileyesus. “Investigation of transition metal pharmacology in the cardiovascular system.” 2017. Doctoral Dissertation, University of Melbourne. Accessed January 20, 2021.
http://hdl.handle.net/11343/212122.
MLA Handbook (7th Edition):
Betrie, Ashenafi Haileyesus. “Investigation of transition metal pharmacology in the cardiovascular system.” 2017. Web. 20 Jan 2021.
Vancouver:
Betrie AH. Investigation of transition metal pharmacology in the cardiovascular system. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/11343/212122.
Council of Science Editors:
Betrie AH. Investigation of transition metal pharmacology in the cardiovascular system. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/212122
24.
Spampinato, Giorgia.
Genomic analysis in human solid tumours: Copper Homeostasis Genes in Colorectal cancer.
Degree: 2016, Università degli Studi di Catania
URL: http://hdl.handle.net/10761/4059
► 1. The public database: Cancer Genome Atlas Network has been consulted in order to reveal the presence of somatic mutations in copper homeostasis genes (CHGs)…
(more)
▼ 1. The public database: Cancer Genome Atlas Network has been consulted in order to reveal the presence of somatic mutations in copper homeostasis genes (CHGs) in colorectal cancer, and such analysis, performed on 228 colorectal tumor samples, has revealed that inactivating mutations are extremely rare in CHGs.
2. The collection of whole transcriptome profiles by oligonucleotide microarrays represents the second aim of the thesis. CHGs mRNA levels have been measured in 37 colorectal carcinoma samples in comparison to matched normal colonic mucosae. The transcriptome analysis has been perfomed using the last Human Transcriptome Array (HTA 2.0, Affymetrix) which allows to analyze simultaneously 40.000 coding transcripts and 20.000 non-coding transcripts and to reveal variations of mRNA levels between in colorectal cancer samples respect to normal colonic mucosae. The gene expression analysis has showed an up-regulation of several transcripts involved in copper homeostasis pathway (such as SLC31A1, SLC31A2, COX11, SCO1, SOD1) in two different conditions. On the contrary, some genes did not show variations of expression between two tested conditions suggesting the idea that these genes, if experimental altered in their expression, could represent the good targets for specific drug treatments. The transcriptome analysis by the last generation on oligonucleotide microarrays gives a possibility to analyse gene expression levels and single exon expression levels. In the 37 human colorectal samples, the exon-level expression analysis has been revealed the presence of alternative transcripts prevalent in a condition respect to other.
3. In this part of thesis the experimental down-regulation, by short interfering, of a copper chaperone ATOX1, significantly reduced the tumor growth in a Caco2 colorectal cell line. It has been demonstrated that the copper addition increase the toxic effects of some copper binding compounds, in particular, the ionophore copper-ionophore 5-chloro-8-hydroxyquinoline (ClHQ) and the copper chelator (N,N,N'N',-tetrakis (2- pyridylmethyl)ethylenediamine (TPEN) in two human colorectal cancer cell lines (Caco-2 and HT29). Moreover, the Atox1 silencing has enhanced the toxic effects of copper-ClHQ complexes and TPEN in Caco-2 cells confirming that the inhibition of copper chaperone Atox1 could be a good strategy to attenuate the cancer cell proliferation and to increase the anticancer effects of some copper binding drugs.
Subjects/Keywords: Area 05 - Scienze biologiche; Copper Homeostasis Genes, Colorectal Cancer, Global expression analysis, cell cultures, RNA interference, Ionophores and chelators
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Spampinato, G. (2016). Genomic analysis in human solid tumours: Copper Homeostasis Genes in Colorectal cancer. (Thesis). Università degli Studi di Catania. Retrieved from http://hdl.handle.net/10761/4059
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Spampinato, Giorgia. “Genomic analysis in human solid tumours: Copper Homeostasis Genes in Colorectal cancer.” 2016. Thesis, Università degli Studi di Catania. Accessed January 20, 2021.
http://hdl.handle.net/10761/4059.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Spampinato, Giorgia. “Genomic analysis in human solid tumours: Copper Homeostasis Genes in Colorectal cancer.” 2016. Web. 20 Jan 2021.
Vancouver:
Spampinato G. Genomic analysis in human solid tumours: Copper Homeostasis Genes in Colorectal cancer. [Internet] [Thesis]. Università degli Studi di Catania; 2016. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10761/4059.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Spampinato G. Genomic analysis in human solid tumours: Copper Homeostasis Genes in Colorectal cancer. [Thesis]. Università degli Studi di Catania; 2016. Available from: http://hdl.handle.net/10761/4059
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Vienna
25.
Priester, Elisabeth.
Penetration of Hydroxypyridinones through the Blood-Brain Barrier based on a cell monolayer system.
Degree: 2010, University of Vienna
URL: http://othes.univie.ac.at/10319/
► Die Blut-Hirn Schranke (BHS) stellt eine wichtige Teilung zwischen Blutzirkulation und Gehirn dar. Sie sorgt dafür, dass unerwünschte Stoffe nicht ins Gehirn kommen, Substrate jedoch…
(more)
▼ Die Blut-Hirn Schranke (BHS) stellt eine wichtige Teilung zwischen Blutzirkulation und Gehirn dar. Sie sorgt dafür, dass unerwünschte Stoffe nicht ins Gehirn kommen, Substrate jedoch zur Genüge geliefert werden. Für manche Medikamente ist es, wegen möglicher Nebenwirkungen wichtig, dass sie nicht ins Gehirn gelangen. Für andere ist der Zutritt zum Gehirn essentiell um den gewünschten Effekt zu erreichen, z.B. Pharmazeutika, zur Therapie von neurodegenerativen Krankheiten.
Zur Erforschung der BHS wurden verschiedene Systeme entwickelt. Im Bereich der in vitro Kulturen wurde eine immortalisierte, menschliche Zelllinie von mikrovaskulären Endothelzellen der BHS entwickelt, die in dieser Studie verwendet wurden.
Deferipron (CP20), ein weitgehend verwendeter Eisenchelator wurde untersucht. Neuere Studien belegen, dass übermäßiges Eisen im Gehirn bei der Entstehung von neurodegenerativen Krankheiten beteiligt sein kann.
Während der Experimente wurden einige Probleme bezüglich der Analyse des Stoffes herausgefunden. Daher wurde versucht, das zur Lyse verwendete Detergens Triton auszutauschen, da es CP20 im HPLC-Chromatogramm überlagerte. Daraufhin wurde destilliertes Wasser genutzt, das ebenfalls nicht das gewünschte Ergebnis brachte.
Um die Experimente zu ändern und Hindernisse zu überbrücken, wurde Proteinfällung oder Vereinigung mehrerer Proben versucht. Jedoch konnte CP20 auch in diesen Versuchen nicht detektiert werden.
Ein weiteres Experiment, der genaueren Untersuchung würdig, ist das der 24-Stunden-Aufnahme, das eine verringerte Saccharose-Konzentration bei erhöhter CP20-Konzentration aufwies.
Unter diesen Umständen war es nicht möglich war eine Aussage über die Fähigkeit von CP20 die BHS zu übertreten, zu treffen. Änderungen in den Experimenten könnten aber neue Erkenntnisse diesbezüglich und folglich auch in der Therapie von neurodegenerativen Erkrankungen bringen.
The Blood-Brain Barrier (BBB) is an important partition of the blood circulation and the brain environment. It makes sure unwanted agents cannot enter the brain whereas substrates are supplied sufficiently. Some drugs should not enter the brain because of sideeffects, others penetration into the brain is essential for the effect, e.g. therapeutics treating neurodegenerative diseases.
In order to obtain insight in the mechanisms of the BBB, various systems have been developed. In vitro cultures, e.g. an immortalized human cell line of microvascular endothelial cells appearing at the BBB were created, which were used in this study.
The compound analysed was deferiprone (or CP20), an iron chelator widely used. Recent studies showed that iron overload in the brain is participating in neurodegenerative diseases.
During the experiments it was discovered that the system had some problems with the analysis of the compound. It was attempted to change the detergent, Triton, as it was interfering with CP20 in the HPLC chromatogram. Distilled water was chosen as a replacement but did not show more promising results.
To vary the experimental setting…
Subjects/Keywords: 30.99 Naturwissenschaften allgemein: Sonstiges; 44.38 Pharmakologie; Blut-Hirn Schranke / Eisenchelatoren / hCMEC/D3 / Neurotherapeutika / Zellkultur / neurodegenerative Krankheiten; Blood-Brain Barrier / iron chelators / hCMEC/D3 / neurotherapeutics / cell culture / neurodegenerative diseases
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Priester, E. (2010). Penetration of Hydroxypyridinones through the Blood-Brain Barrier based on a cell monolayer system. (Thesis). University of Vienna. Retrieved from http://othes.univie.ac.at/10319/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Priester, Elisabeth. “Penetration of Hydroxypyridinones through the Blood-Brain Barrier based on a cell monolayer system.” 2010. Thesis, University of Vienna. Accessed January 20, 2021.
http://othes.univie.ac.at/10319/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Priester, Elisabeth. “Penetration of Hydroxypyridinones through the Blood-Brain Barrier based on a cell monolayer system.” 2010. Web. 20 Jan 2021.
Vancouver:
Priester E. Penetration of Hydroxypyridinones through the Blood-Brain Barrier based on a cell monolayer system. [Internet] [Thesis]. University of Vienna; 2010. [cited 2021 Jan 20].
Available from: http://othes.univie.ac.at/10319/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Priester E. Penetration of Hydroxypyridinones through the Blood-Brain Barrier based on a cell monolayer system. [Thesis]. University of Vienna; 2010. Available from: http://othes.univie.ac.at/10319/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
26.
Qanash, Husam.
Eltrombopag Improves Erythroid Differentiation in a Human iPSC Model of Diamond Blackfan Anemia.
Degree: 2020, The Catholic University of America
URL: http://hdl.handle.net/1961/cuislandora:214689
► Diamond Blackfan Anemia (DBA) is a congenital bone marrow (BM) failure syndrome characterized by defective erythropoiesis. In most patients, heterozygous mutations have been identified in…
(more)
▼ Diamond Blackfan Anemia (DBA) is a congenital bone marrow (BM) failure syndrome characterized by defective erythropoiesis. In most patients, heterozygous mutations have been identified in genes encoding ribosomal proteins (RP). The resulting RP haploinsufficiency delays globin translation in erythroid cells, whereas synthesis of heme, the iron-containing component of hemoglobin, proceeds normally. As a result, free heme is in excess of globin in these cells and induces proerythroblast cell death, and erythroid differentiation halts at an earlier progenitor stage. In this study, we investigated whether eltrombopag (Epag), an FDA-approved mimetic of thrombopoietin (TPO), could rescue erythropoiesis in DBA. We hypothesized that Epag might slow down heme synthesis by limiting iron availability due to its intracellular iron chelating properties, leading to increased proerythroblast survival and maturation. To test this possibility, we established an iPSC model of DBA by reprogramming mononuclear cells (MNCs) from a patient with inactivating mutations in RPS19. We also generated a control isogenic iPSC line by CRISPR/Cas9-mediated correction of RPS19 point mutations in the established DBA iPSC line. Both DBA and isogenic corrected iPSCs were subjected to hematopoietic differentiation for 21 days. Isogenic iPSCs efficiently gave rise to erythroid cells at various stages of maturation. In contrast, the majority of erythroid cells detected after differentiation of DBA iPSCs were blocked at early erythroid progenitor stages. Furthermore, in colony forming unit (CFU) assays, DBA iPSCs generated myeloid colonies comparable to isogenic iPSCs, but erythroid colonies were undetectable, consistent with DBA progenitor’s inability to differentiate. In support of our hypothesis, DBA iPSCs differentiated in the presence of Epag improved late erythroid maturation, as indicated by reduced percentages of early progenitors and a concomitant increase in more mature erythroblastic populations. To confirm that Epag-mediated iron restriction was the primary molecular mechanism underlying the improved erythroid maturation observed in DBA iPSC lines, we subjected DBA iPSCs to hematopoietic differentiation for 21 days in the presence or absence of either intracellular deferasirox (DFX) or extracellular deferoxamine (DFO) iron chelators. We observed a partial rescue of erythropoiesis in DFX-treated DBA cells comparable to Epag, but not in DFO-treated cells. Overall, our observations indicate that directed differentiation of DBA iPSCs recapitulates early erythroid maturation defects, and erythropoiesis can be rescued in part by addition of Epag or DFX during culture. These results suggest that Epag or DFX may improve red blood cell production in patients with DBA.
Medicine
Immunology
Pathology
Diamond blackfan anemia, Eltrombopag and iron chelators, Hematology and regenerative medicine, Heme and globin synthesis, Induced pluripotent stem cells (iPSCs), Inherited bone marrow failure
Biology
Degree Awarded: Ph.D. Biology. The…
Advisors/Committee Members: The Catholic University of America (Degree granting institution), Larochelle, Dr. Andre (Thesis advisor), Choy, Dr. John (Thesis advisor), Tuma, Dr. Pamela (Committee member), Chung, Dr. Byung Min (Committee member), Agazio, Dr. Janice (Committee member), Wilson, Dr. Otto (Committee member).
Subjects/Keywords: Diamond blackfan anemia; Eltrombopag and iron chelators; Hematology and regenerative medicine; Heme and globin synthesis; Induced pluripotent stem cells (iPSCs); Inherited bone marrow failure
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Qanash, H. (2020). Eltrombopag Improves Erythroid Differentiation in a Human iPSC Model of Diamond Blackfan Anemia. (Thesis). The Catholic University of America. Retrieved from http://hdl.handle.net/1961/cuislandora:214689
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Qanash, Husam. “Eltrombopag Improves Erythroid Differentiation in a Human iPSC Model of Diamond Blackfan Anemia.” 2020. Thesis, The Catholic University of America. Accessed January 20, 2021.
http://hdl.handle.net/1961/cuislandora:214689.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Qanash, Husam. “Eltrombopag Improves Erythroid Differentiation in a Human iPSC Model of Diamond Blackfan Anemia.” 2020. Web. 20 Jan 2021.
Vancouver:
Qanash H. Eltrombopag Improves Erythroid Differentiation in a Human iPSC Model of Diamond Blackfan Anemia. [Internet] [Thesis]. The Catholic University of America; 2020. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1961/cuislandora:214689.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Qanash H. Eltrombopag Improves Erythroid Differentiation in a Human iPSC Model of Diamond Blackfan Anemia. [Thesis]. The Catholic University of America; 2020. Available from: http://hdl.handle.net/1961/cuislandora:214689
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
27.
Sáez Avaria, Claudio.
Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus.
Degree: PhD, 2014, University of Plymouth
URL: http://hdl.handle.net/10026.1/3008
► Brown algae have been the focus of metal ecotoxicology research for over 60 years, mainly because of their high metal accumulation capacity and reputed resistance.…
(more)
▼ Brown algae have been the focus of metal ecotoxicology research for over 60 years, mainly because of their high metal accumulation capacity and reputed resistance. Now that Ectocarpus siliculosus has been positioned as a model for the study of brown algae, and that the genome has been recently sequenced and annotated, new lines of research have been made possible on these ecologically and economically important organisms, including the field of ecotoxicology. Several strains of E. siliculosus have been collected and isolated from locations around the world, thus providing the opportunity to study inter-population differences in their responses to environmental stress. This investigation can be split into three main sections. In the first part Cu exposure experiments were carried out under laboratory conditions using three strains of E. siliculosus: Es524 from a Cu polluted location in Chile, REP10-11 from a metal polluted (including Cu) location in England and LIA4A from a pristine site in Scotland. Strains were exposed for 10 d to concentrations ranging between 0 and 2.4 μM Cu. We measured different parameters: relative growth rates; metal accumulation (extracellular and intracellular); phytochelatins and the expression of related enzymes; oxidative stress responses as manifested in lipid peroxidation and levels of H2O2, and levels of pigments; levels of antioxidants glutathione and ascorbate (in reduced and oxidised forms), and phenolic compounds; and the activity of the antioxidant enzymes superoxide dismutase, catalase, and ascorbate peroxidise. Strain Es524 was the most efficient in counteracting the effects of Cu stress as manifested by a combination of Cu exclusion production of metal chelators, upregulation of oxidative enzymes, and strong antioxidant metabolism. REP10-11 also showed effective Cu defences, especially related to glutathione-ascorbate interactions. LIA4A was the least tolerant strain, with metabolic defences significantly less effective against Cu exposure. In part two a novel transplantation experiment was developed to compare responses in the field with those obtained in the laboratory. The study was carried out at a metal polluted and a low-impacted site in central Chile using strain Es524 (as in the laboratory experiments) and Es147, isolated from a low metal-polluted site in Chile. From the biomass, we conducted similar measurements of Reactive Oxygen Metabolism (ROM) as for the laboratory experiments described in the first part. In agreement with the laboratory experiments, strain Es524 displayed a higher resistance to metal stress. Because they behaved similarly between strains, the best suggested biomarker candidates for future assessments are metal accumulation, glutathione and ascorbate in reduced and oxidised forms, phenolic compounds, and the activity of superoxide dismutase. The method is simple, widely applicable in temperate environments, cost-effective, and provides a reliable representation of metal bioavailability in the environment. In the final part of the study a novel…
Subjects/Keywords: 579.8; metal; algae; reactive oxygen; chelators; gene expression; biomonitoring; biomarkers
…Phenolics are
metal chelators and reducing agents, properties attributable to the electron donor… …chelators in brown algae
Phenolic compounds also represent an effective metal detoxification… …chelators are metal-binding
polypeptides (Cobbett and Goldsbrough, 2002). These proteins…
Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sáez Avaria, C. (2014). Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus. (Doctoral Dissertation). University of Plymouth. Retrieved from http://hdl.handle.net/10026.1/3008
Chicago Manual of Style (16th Edition):
Sáez Avaria, Claudio. “Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus.” 2014. Doctoral Dissertation, University of Plymouth. Accessed January 20, 2021.
http://hdl.handle.net/10026.1/3008.
MLA Handbook (7th Edition):
Sáez Avaria, Claudio. “Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus.” 2014. Web. 20 Jan 2021.
Vancouver:
Sáez Avaria C. Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus. [Internet] [Doctoral dissertation]. University of Plymouth; 2014. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10026.1/3008.
Council of Science Editors:
Sáez Avaria C. Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus. [Doctoral Dissertation]. University of Plymouth; 2014. Available from: http://hdl.handle.net/10026.1/3008

Duke University
28.
Dickens, Marina Grace.
Masked Metal Chelators of Variable Denticity to Prevent Oxidative Stress
.
Degree: 2010, Duke University
URL: http://hdl.handle.net/10161/3056
► Cellular damage due to oxidative stress is implicated in a wide variety of conditions including degenerative diseases like Alzheimer's and Parkinson's Diseases. One source…
(more)
▼ Cellular damage due to oxidative stress is implicated in a wide variety of conditions including degenerative diseases like Alzheimer's and Parkinson's Diseases. One source of oxidative stress is the interaction of redox-active metals such as copper and iron with hydrogen peroxide to produce hydroxyl radicals. Preventing metal-induced oxidative stress by metal chelation is one potential approach to treat some of these diseases, but there remain significant challenges in designing
chelators that target damaging metals while not disturbing healthy metal ion distribution. To overcome this challenge, prochelators that are responsive to conditions of oxidative stress have been introduced. By designing ligands that only bind metal ions in the presence of oxidants, damaging metals can be bound and removed while not perturbing the metals necessary for cell function. Masking the phenol of a chelator with a boronic ester creates a prochelator that has little to no affinity for metal ions until exposure to H
2O
2 converts the prochelator to the chelator, which is then available to bind metal ions. Described here is the development of boronate-based prochelators that react with H
2O
2 to produce chelating agents of variable denticity, ranging from 2 to 6. Quinoline boronic acid pinanediol ester, or QBP, is a new bidentate prochelator introduced here that reacts with H
2O
2 with a rate of 0.22 M
-1s
-1 to produce 8-hydroxyquinoline, a known metal-binding agent. Results in Chapter 2 show that QBP can be activated in vitro under conditions that mimic early Alzheimer's Disease pathology where copper, amyloid beta peptide, and ascorbic acid exacerbate formation of reactive oxygen species. QBP does not bind metal ions, nor does it disaggregate metal-promoted amyloid beta peptide aggregates. However, the released 8-hydroxyquinoline sequesters copper from amyloid beta and both diminishes further formation of reactive oxygen species and inhibits further aggregation of amyloid-beta. The syntheses and crystal structures of hexadentate prochelators are described in Chapter 3, along with their rates of oxidation in response to hydrogen peroxide exposure and their ability to protect against hydroxyl radicals formed in vitro by iron (or copper), ascorbic acid, and hydrogen peroxide. The hexadentate
chelators are based on a tripodal architecture in which three phenol moieties are linked via nitrogens on three alkyl arms to a central nitrogen to provide an N
3O
3 donor set for metal complexation. Of three prochelator/chelator pairs prepared, the pair (trenBsalam/trensalam) with amine linkages was deemed most suitable for potential biological studies. The prochelator trenBsalam oxidizes at a rate of 0.72 M
-1s
-1 to produce the chelator trensalam in the presence of hydrogen peroxide. The transition metal coordination chemistry and metal ion affinities of trensalam were further studied in…
Advisors/Committee Members: Franz, Katherine J (advisor).
Subjects/Keywords: Chemistry, Inorganic;
Chemistry, Organic;
Chemistry, General;
Alzheimer's Disease;
Chelators;
Metals;
Oxidative Stress
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dickens, M. G. (2010). Masked Metal Chelators of Variable Denticity to Prevent Oxidative Stress
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/3056
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dickens, Marina Grace. “Masked Metal Chelators of Variable Denticity to Prevent Oxidative Stress
.” 2010. Thesis, Duke University. Accessed January 20, 2021.
http://hdl.handle.net/10161/3056.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dickens, Marina Grace. “Masked Metal Chelators of Variable Denticity to Prevent Oxidative Stress
.” 2010. Web. 20 Jan 2021.
Vancouver:
Dickens MG. Masked Metal Chelators of Variable Denticity to Prevent Oxidative Stress
. [Internet] [Thesis]. Duke University; 2010. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10161/3056.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dickens MG. Masked Metal Chelators of Variable Denticity to Prevent Oxidative Stress
. [Thesis]. Duke University; 2010. Available from: http://hdl.handle.net/10161/3056
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ohio University
29.
Ketterman, Joshua K.
Is Zinc a New Class of Neurotransmitter? A Presynaptic
Model.
Degree: MS, Biological Sciences (Arts and Sciences), 2006, Ohio University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1156349584
► Using the zinc specific intracellular indicator Zinpyr-1, we describe a new technique for observing the presynaptic uptake and release of zinc in the MF→CA3…
(more)
▼ Using the zinc specific intracellular
indicator Zinpyr-1, we describe a new technique for observing the
presynaptic uptake and release of zinc in the MF→CA3 circuit of the
mammalian hippocampus. Our model is sensitive to the addition of
exogenous Zn
2+ and responds to
K
+ depolarization, providing evidence for
the synaptic release and reuptake of vesicular
Zn
2+. We also examine the sensitivity of our
technique to vesicular Zn
2+ depletion by
metal
chelators. Finally, the model we describe presents new and
novel evidence for the translocation of synaptically released zinc
to the postsynaptic cell bodies. Our results provide compelling
supporting evidence for Zn
2+ as a substance
that undergoes release as a neurotransmitter and should be of
interest to researchers investigating the physiological role of
Zn
2+ in such models as LTP and ischemia.
Finally, the data we provide support the hypothesis that
Zn
2+ is a representative of a new class of
neurotransmitters made up of divalent metal cations, functionally
unique in their ability to translocate across the synaptic cleft
and into the postsynaptic cell body to affect cellular signaling
pathways.
Advisors/Committee Members: Li, Yang (Advisor).
Subjects/Keywords: Biology, Neuroscience; zn; zinc; fluorescence; presynaptic; model; neurotransmitter; release; chelator; chelators; caedta; tpen
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ketterman, J. K. (2006). Is Zinc a New Class of Neurotransmitter? A Presynaptic
Model. (Masters Thesis). Ohio University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1156349584
Chicago Manual of Style (16th Edition):
Ketterman, Joshua K. “Is Zinc a New Class of Neurotransmitter? A Presynaptic
Model.” 2006. Masters Thesis, Ohio University. Accessed January 20, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1156349584.
MLA Handbook (7th Edition):
Ketterman, Joshua K. “Is Zinc a New Class of Neurotransmitter? A Presynaptic
Model.” 2006. Web. 20 Jan 2021.
Vancouver:
Ketterman JK. Is Zinc a New Class of Neurotransmitter? A Presynaptic
Model. [Internet] [Masters thesis]. Ohio University; 2006. [cited 2021 Jan 20].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1156349584.
Council of Science Editors:
Ketterman JK. Is Zinc a New Class of Neurotransmitter? A Presynaptic
Model. [Masters Thesis]. Ohio University; 2006. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1156349584

Universiteit Utrecht
30.
Kartikasari, Apriliana E. R.
Iron modulates phagocyte-endothelial cell interactions: Implications for atherosclerosis.
Degree: 2006, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/8129
► Atherosclerotic heart disease has claimed the lives of millions of people each year in the Western world, and rapidly increases in prevalence in many other…
(more)
▼ Atherosclerotic heart disease has claimed the lives of millions of people each year in the Western world, and rapidly increases in prevalence in many other places. The disease results from cholesterolemia, coupled with a chronic inflammatory condition of the vascular wall that lead to vessel occlusion and various clinical manifestations.In 1981, Sullivan suggested possible benefits of iron depletion against coronary artery disease, from the observations where men and menopausal women were more prone to develop this disease. Following Sullivan’s proposal, basic and clinical data have begun to provide explanations for a link between iron and atherosclerosis (Chapter 1). This thesis has aimed to investigate the role of iron in the inflammatory events crucial in atherogenesis, especially in the course of phagocyte-endothelial cell interactions.In vitro studies described in this thesis reveals an immunomodulatory function of iron in inflammation. Chapter 2 and Chapter 3 show that NTBI promotes accumulation of intracellular labile iron and production of oxygen-derived free radicals, leading to cell activation. Activation of endothelial cells is a well-characterized phenotype that leads to endothelial dysfunction in vivo, which not only will initiate the development of atherosclerosis, but also plays a role at a critical late step of thrombosis, promoting vessel occlusion and acute cardiovascular events. In combination with chronic infections iron enhances infection-induced endothelial activation (Chapter 4), implying that in the presence of other stressors, iron may contribute significantly in aggravating atherogenesis. In addition, in Chapter 6, the drawbacks of EDTA chelation therapy particularly in inducing endothelial activation are described. The use of this alternative therapy for atherosclerosis therefore needs to be critically reconsidered, especially in regards to its effectiveness and safety. Furthermore, iron also promotes monocyte (Chapter 2 and Chapter 5) and neutrophil (Chapter 7) activation. An increased number of phagocyte infiltrates may thus complicate the progression of atherosclerotic vascular diseases. The infiltration of monocytes also play a role in neuroinflammation, stimulating the development of neurodegenerative diseases. Finally, Chapter 8 demonstrates the involvement of iron in enhancing the rate and the production of oxidised LDL cholesterol, especially through interactions with phagocyte-derived oxygen metabolites. Based on the findings in this thesis, iron depletion and iron chelation could be beneficial for such unfavourable conditions generated by iron. The identified modifying role of iron in inflammation described in this study (Chapter 9) offers an additional strategy for prevention and therapy of inflammatory diseases, like atherosclerotic vascular diseases and neurodegenerative diseases.
Subjects/Keywords: Geneeskunde; cardiovascular disease; neurodegenerative diseases; phagocyte; vascular endothelium; atherosclerosis; iron; infection; inflamation; iron chelators; cholesterol
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kartikasari, A. E. R. (2006). Iron modulates phagocyte-endothelial cell interactions: Implications for atherosclerosis. (Doctoral Dissertation). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/8129
Chicago Manual of Style (16th Edition):
Kartikasari, Apriliana E R. “Iron modulates phagocyte-endothelial cell interactions: Implications for atherosclerosis.” 2006. Doctoral Dissertation, Universiteit Utrecht. Accessed January 20, 2021.
http://dspace.library.uu.nl:8080/handle/1874/8129.
MLA Handbook (7th Edition):
Kartikasari, Apriliana E R. “Iron modulates phagocyte-endothelial cell interactions: Implications for atherosclerosis.” 2006. Web. 20 Jan 2021.
Vancouver:
Kartikasari AER. Iron modulates phagocyte-endothelial cell interactions: Implications for atherosclerosis. [Internet] [Doctoral dissertation]. Universiteit Utrecht; 2006. [cited 2021 Jan 20].
Available from: http://dspace.library.uu.nl:8080/handle/1874/8129.
Council of Science Editors:
Kartikasari AER. Iron modulates phagocyte-endothelial cell interactions: Implications for atherosclerosis. [Doctoral Dissertation]. Universiteit Utrecht; 2006. Available from: http://dspace.library.uu.nl:8080/handle/1874/8129
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