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Sökning: WFRF:(Kåredal Monica)

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  • Ali, Neserin, et al. (författare)
  • Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix
  • 2018
  • Ingår i: Clinical Proteomics. - Humana Press. - 1542-6416. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. Methods: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. Results: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Conclusion: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.
  • Ali, Neserin, et al. (författare)
  • Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
  • 2015
  • Ingår i: Nanotoxicology. - Informa Healthcare. - 1743-5404. ; 10:2, s. 226-234
  • Tidskriftsartikel (refereegranskat)abstract
    • Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
  • Dierschke, Katrin, et al. (författare)
  • Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates
  • 2017
  • Ingår i: International Archives of Occupational and Environmental Health. - Springer. - 1432-1246. ; 90:5, s. 451-463
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day.METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure.RESULTS: No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms.CONCLUSION: Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).
  • Hedmer, Maria, et al. (författare)
  • 148. Carbon Nanotubes
  • 2013
  • Rapport (övrigt vetenskapligt)abstract
    • Carbon nanotubes (CNTs) can be seen as graphene sheets rolled to form cylinders. CNTs may be categorised as single- (SWCNT) or multi-walled (MWCNT). Due to the small size, the number of particles as well as the surface area per mass unit is extremely high. CNTs are highly diverse, differing with respect to e.g., diameter, length, chiral angles, chemical functionalisation, purity, stiffness and bulk density. Today, CNTs are utilised primarily for the reinforcement of composite polymers, but there is considerable potential for other applications. The rapidly growing production and use of CNTs increases the risk for occupational exposure. Since CNTs in bulk form are of very low density and much dust is produced during their handling, exposure by inhalation appears to represent the greatest potential risk in the work place. However, most work place measurements involved sampling periods that are too short, varying sampling techniques and non-specific analytical methods. CNTs may be absorbed via inhalation and ingestion. Systemic uptake via the skin has not been demonstrated. Human toxicity data on CNTs are lacking and interpretation of animal studies is often problematic since the physical properties and chemical composition are diverse, impurities may be present and data are sometimes omitted. Because of the physical similarities between asbestos and CNTs, it can be suspected that the latter may also cause lung fibrosis, mesothelioma and lung cancer following inhalation. Intraperitoneal and intrascrotal administration of CNTs causes mesothelioma in animals, but no inhalation carcinogenicity studies have been conducted. Thus, it is too early conclude whether CNTs cause mesothelioma and lung cancer in humans. Both SWCNTs and MWCNTs cause inflammation and fibrosis in the lungs of relevant animal types and for MWCNTs these effects are also seen in the pleura. For instance, minimal histiocytosis and mild granulomatous inflammation in the lungs and lung-draining lymph nodes have been observed in rats exposed for 13 weeks to 0.1 mg/m3 MWCNTs (lowest observed adverse effect level, LOAEL), with more pronounced inflammation in both mice and rats at higher doses. Thus, inflammatory responses in the lungs may be considered as the critical effect. However, the LOAEL of CNTs should be interpreted cautiously, since their toxicity is likely to vary widely, depending on the structure and physicochemical properties, as well as the contribution from non-carbon components. It is also uncertain which dose metric (e.g., mass, number or surface area per air volume unit) is most appropriate. Some studies indicate that longer straight CNTs evoke more pronounced biological effects than shorter or tangled fibres.
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