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- García, Maria C, et al.
(author)
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Mature-onset obesity in interleukin-1 receptor I knockout mice.
- 2006
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:5, s. 1205-13
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Journal article (peer-reviewed)abstract
- Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(-/-) mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.
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- Ahrén, Maria, 1979-
(author)
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Metal Oxide Nanoparticles for Contrast Enhancement in Magnetic Resonance Imaging : Synthesis, Functionalization and Characterization
- 2013
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Doctoral thesis (other academic/artistic)abstract
- This thesis work focuses on the design and production of nanoparticle based contrast agents for signal enhancement in magnetic resonance imaging (MRI). Three different synthesis routes are explored, primarily to produce crystalline gadolinium oxide (Gd2O3) nanoparticles, and surface modification is done to obtain stable, dispersible, biocompatible probes inducing high proton relaxivities.In Paper I and II we utilized the polyol synthesis method and nanoparticle purification was performed with dialysis. Active surface functionalization was achieved by an innermost layer of 3-mercaptopropyl trimetoxy silanes (MPTS) and an outer layer of bifunctional PEG. Surface capping was shown to greatly affect the water proton relaxation to a degree which is strongly dependent on the purification time. PEGylation also induced stabilizing effects and the ability to provide the nanoparticles with luminescent properties was proven by linking the fluorescent dye Rhodamine to the bifunctional PEG.In Paper III the magnetic behavior of yttrium (Y) alloyed Gd2O3 nanoparticles was investigated as a function of Y concentration. This was done by performing magnetic measurements and by studying the signal line width in electron paramagnetic resonance spectroscopy for Gd2O3, Y2O3 and a series of (GdxY1-x)2O3 samples produced using the combustion synthesis. The results verified that the signal line width is dependent on the percent of yttrium dilution. This is considered as an indication of that yttrium dilution changes the electron spin relaxation time in Gd2O3.Paper IV and V present a novel precipitation synthesis method for Gd2O3 nanoparticles. Acetate molecular groups were found to coordinate the nanoparticle surface increasing the water dispersability. The Gd2O3 nanoparticles induce a twice as high relaxivity per gadolinium atom, as compared to the commercially available contrast agent Magnevist. Incorporation of luminescent europium (Eu3+) ions into the Gd2O3 nanoparticles in combination with surface modification with a fluorescent branched carboxyl terminated TEG, produced dual probes with tunable luminescence, maintained relaxivity and thus a bright contrast in MRI.In Paper VI, a new approach to accomplish a dual probe was investigated. Luminescent ZnO nanoparticles decorated with Gd ions bound in an organic matrix were evaluated for MR signal enhancement and ability to function as fluorescent probes. Interestingly, these nanoprobes did show an enhanced capability to both strengthen the MR signal and increase the fluorescent quantum yield, as compared to the pure oxides.In Paper VII we investigate sub 5 nm crystalline manganese based nanoparticles produced by the precipitation synthesis used for Gd2O3 nanoparticles. Manganese oxide was chosen as another candidate for MRI contrast enhancement as it is expected to have a straight forward surface coupling chemistry. Characterization of the crystal structure and chemical composition indicated nanoparticles with a MnO core and presence of manganese species of higher valences at the nanoparticle surface. The MnO nanomaterial showed a superparamagnetic behavior and less capability to increase the MR signal as compared to Gd2O3.Characterization of the nanoparticle crystal structure and size is, throughout the work, performed by means of transmission electron microscopy, X-ray diffraction and dynamic light scattering. The chemical composition is studied with X-ray photoelectron spectroscopy, infrared spectroscopy and near edge X-ray absorption fine structure spectroscopy and the fluorescence characteristics are evaluated with fluorescence spectroscopy. In addition, theoretical models and calculated IR spectroscopy and near edge X-ray absorption fine structure spectroscopy data have been used for evaluation of experimental results.To conclude, the aim of this work is the design, production and characterization of ultrasmall rare earth based nanoparticles for signal enhancement in biomedical imaging. Surface modification clearly increases the colloidal stability and biocompatibility of the nanoparticles. Compared to the agents in clinical use today, these nanoprobes have a higher capability to enhance the MR-signal, and they will in the near future be equipped with tags for specific targeting.
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