| 1. |
- Abrikossova, Natalia, et al.
(författare)
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Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes
- 2012
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Ingår i: Nanotechnology. - Bristol, United Kingdom : IOP Publishing Ltd.. - 0957-4484 .- 1361-6528. ; 23:27
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.
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| 2. |
- Ahrén, Maria, et al.
(författare)
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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
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Tidskriftsartikel (refereegranskat)abstract
- Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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| 3. |
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| 4. |
- Alverson, George, et al.
(författare)
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Experimental Search for W / Z Pairs and Higgs Bosons at Very High-Energy Hadron Hadron Colliders
- 1986
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Ingår i: Physics of the Superconducting Supercollider: Proceedings, 1986 Summer Study. ; C860623
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We study, from an experimental point of view, the main ways to detect standard high mass Higgs bosons (from 300 Gev up to about 1 TeV) when they decay into W- and Z- pairs at the SSC. We also consider the corresponding W- and Z”-pair continuum which may itself provide interesting physics, and we pay some attention to the case of an intermediate mass charged Higgs decaying into rvr, (met =300 GeV). We first explain why and how high energy pp colliders may search for Higgs’ and we compare their possible performances to those of the e+e- and ep colliders at all possible m-s scale (from few tens of GeV’s up to 1 TeV). We then estimate the rates of the signals and the main backgrounds. Wede5ne the main characteristics of these events as reproduced by M.C. generators (especially implemented with these processes) and simulated through an idealiied In fine-grained calorimeter. A trigger strategy for W- and Z-pairs is derived from this study.
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| 5. |
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| 6. |
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| 7. |
- Asplund Persson, Anna, 1966-, et al.
(författare)
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Cross-talk between adenosine and the oxatriazole derivative GEA 3175 in platelets
- 2005
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 517:3, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- We examined the interplay between adenosine and the nitric oxide (NO)-containing oxatriazole derivative GEA 3175 in human platelets. The importance of cyclic guanosine 3′5′-monophosphate (cGMP)-inhibited phosphodiesterases (PDEs) was elucidated by treating the platelets with adenosine combined with either GEA 3175 or the PDE3-inhibitor milrinone. The drug combinations provoked similar cyclic adenosine 3′5′-monophosphate (cAMP) responses. On the contrary, cGMP levels were increased only in GEA 3175-treated platelets. Both drug combinations reduced P-selectin exposure, platelet adhesion and fibrinogen-binding. However, adenosine together with GEA 3175 was more effective in inhibiting platelet aggregation and ATP release. Thrombin-induced rises in cytosolic Ca2+ were suppressed by the two drug combinations. Adenosine administered with GEA 3175 was, however, more effective in reducing Ca2+ influx.In conclusion, the interaction between adenosine and GEA 3175 involves cGMP-mediated inhibition of PDE3. The results also imply that inhibition of Ca2+ influx represent another cGMP-specific mechanism that enhances the effect of adenosine.
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| 8. |
- Bengtsson, Anders A., et al.
(författare)
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Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
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| 9. |
- Bengtsson, Bengt Olle, et al.
(författare)
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Recombination promotes canalization against deleterious mutations in sexual haploid organisms
- 2018
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Konferensbidrag (refereegranskat)abstract
- Deleterious mutations are an unavoidable part of life. In sufficiently large populations, all such mutations are removed by natural selection, though always with a concomitant loss of population fitness equal to the mutation rate. A natural question to ask is then: What happens if at another locus a rare allele appears (selectively neutral in itself) that decreases, but does not abolish, the negative phenotypic effect of mutations at the first locus ? or, in other words, makes the organism more canalized against the mutational damage? In the long run this new allele will not affect the mean fitness of the population, since the mutation load will always equal the mutation rate, but will this modifying allele be favoured in some indirect way? The answer is yes, but it is interesting to note how recombination affects this process: With less linkage between the two loci, the easier it becomes for the modifying allele to spread. Thus, recombination promotes mutational canalization in sexual haploids, in a manner that is impossible in asexual haploids. This result is easy to derive but has been surprisingly overlooked, probably because the underlying question was originally discussed in diploids and then phrased in terms of "the evolution of dominance". The secondary selective forces involved are, however, easier to grasp in haploid organisms, where the process instead becomes a question of the "evolution of canalization". That the outlined secondary selective force may be of evolutionary importance is shown by studying a modifying allele that acts on the trait-output of many loci. The force of secondary selection favouring canalization does then depend on the sum of all the mutation rates involved, which gives the process a chance to become evolutionarily effective.
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| 10. |
- Bengtsson, Hans-Uno, et al.
(författare)
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PYTHIA: THE LUND MONTE CARLO FOR HADRONIC PROCESSES
- 1986
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Ingår i: Physics of the Superconducting Supercollider: Proceedings, 1986 Summer Study, June 23 - July 11, 1986, Snowmass, Colorado. ; C860623, s. 311-311
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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