| 1. |
- Klarström-Engström, Kristin, 1986-, et al.
(författare)
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Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation
- 2014
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 9:4, s. 041003-
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Tidskriftsartikel (refereegranskat)abstract
- Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam(3)CSK(4) (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and Fc gamma RII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam(3)CSK(4) and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam(3)CSK(4)- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam(3)CSK(4) activated platelets utilize the same pathway as Fc gamma RII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam(3)CSK(4). These results clarify the importance of TLR2/1 and Fc gamma RII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- Andersson, Viktor, et al.
(författare)
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Preparation of amyloidlike fibrils containing magnetic iron oxide nanoparticles: Effect of protein aggregation on proton relaxivity
- 2012
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 419:4, s. 682-686
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Tidskriftsartikel (refereegranskat)abstract
- A method to prepare amyloid-like fibrils functionalized with magnetic nanoparticles has been developed. The amyloid-like fibrils are prepared in a two step procedure, where insulin and magnetic nanoparticles are mixed simply by grinding in the solid state, resulting in a water soluble hybrid material. When the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid material self assembles to form amyloid-like fibrils incorporating the magnetic nanoparticles. This results in magnetically labeled amyloid-like fibrils which has been characterized by Transmission Electron Microscopy (TEM) and electron tomography. The influence of the aggregation process on proton relaxivity is investigated. The prepared materials have potential uses in a range of bio-imaging applications.
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| 5. |
- Bengtsson, Kenneth, et al.
(författare)
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Så kan Sverige bli ledande nation i resurseffektivitet
- 2016
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Ingår i: Dagens Nyheter. - 1101-2447. ; :2016-04-30
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ny rapport. Det svenska näringslivet kan bli mer hållbart, resurssmart och därmed internationellt konkurrenskraftigt. Men för det behövs en tydlig politisk avsiktsförklaring och riktlinjer. Vi har listat sex områden där policyutveckling brådskar, skriver företrädare för näringsliv, forskning och myndigheter i en gemensam uppmaning.
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| 6. |
- Bengtsson, Torbjörn, et al.
(författare)
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The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation
- 2008
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Ingår i: Journal of Internal Medicine. - : Institutionen för medicin och hälsa. - 0954-6820 .- 1365-2796. ; 263:5, s. 558-571
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims to investigate the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system by using a proteomic approach and analyze the effects of P. gingivalis-modifed LDL on cell proliferation.Methods: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analyzing reactive oxygen species (ROS) production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analyzing the formation of protein carbonyls. The effects of P. gingivalis-modifed LDL on fibroblast proliferation were studied using the MTS-assay.Results: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS-production, indicating platelet and leukocyte activation. LDL prepared from the bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. P. gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.Conclusions: The ability of P. gingivalis to change the protein expression and the proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.
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| 7. |
- Bergström, Göran, 1964, et al.
(författare)
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Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
- 2023
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
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| 8. |
- Bäfver, Linda, et al.
(författare)
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Slambränsleblandningar : Förbränning och fosforutvinning
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- For sustainable phosphorus recycling, the phosphorus in sewage sludge needs to be recovered, as it is a major phosphorus-source. However, all sludge is not suitable for direct recycling on agricultural land, e.g. when the content of heavy metals is too high. To achieve an increased recycling of phosphorus from sewage sludge there is a need of research and development of alternative methods to return the phosphorus from sewage sludge to agricultural land.The aim of the project is to show that sewage sludge can be co-combusted with demolition wood in existing boilers, and that the ash can be processed for extraction of phosphorus, together with valuable by-products from the process. Further effects of the project will be the development of new knowledge about combustion with a high sludge to demolition wood ratio in a grate boiler (up to 45 % sludge with respect to wet mixture), which has not been studied in full-scale combustion earlier. The project's goal is to demonstrate mixing and combustion of fuel mixtures of sludge and demolition wood, and subsequent extraction of phosphorus from ash. The target groups for this work are energy companies, suppliers of grate boilers, municipalities, wastewater treatment plants and authorities.The project involves the mixing of sewage sludge and demolition wood, combustion-tests of the fuel mixtures and laboratory experiments on bottom ash and fly ash for phosphorus extraction using EasyMining Sweden's method for phosphorus extraction from ash. Extensive analyses have been carried out on fuel, bottom ash and fly ash, as well as thermodynamic equilibrium calculations on the formed compounds containing phosphorus.The experience of preparing sludge fuel mixtures shows that the mixtures should be prepared in the near future to when they are to be combusted, to avoid a composting process in the fuel. The project shows that it is possible to combust sludge fuel mixtures with an admixture of up to 45 % sludge relative wet fuel, in an existing grate boiler during one day. However, to combust sludge fuel mixtures over a longer period of time and at a higher load, modifications of the de-ashing system and the flue gas cleaning system are needed. The results indicate a reduced tendency of slagging on the fuel bed at the combustion of sludge mixtures. The analyses of the fly ash showed a trend towards less corrosive ash at combustion of sludge mixtures. The phosphorus content in the ash in this work was 3-4 %. For process economics and from the phosphorus extraction point, as high phosphorus content as possible in the ash is preferable. Higher phosphorus content can be accomplished by mixing sludge with a fuel with lower ash content than demolition wood, co-combustion with a fuel with higher phosphorus content than demolition wood, or by increasing the percentage of sewage sludge in the fuel mixture. Still, a higher proportion of sludge in the mixture would require a higher dry matter content of the sludge in order to get proper combustion conditions. It is primarily bottom ash that is suitable for phosphorus extraction using Easy Mining Sweden's method. If fly ash are to be used for phosphorus extraction, an optimization of the dissolution conditions is required, which was not included in this project. In this project, phosphorus is extracted as ammonium phosphate. The purity of ammonium phosphate is very high, which means that unwanted substances and heavy metals in sewage sludge will not be returned to contaminate fields.
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| 9. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 10. |
- Hagstrom, Emil, et al.
(författare)
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IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
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