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- Hedmer, Maria, et al.
(författare)
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148. Carbon Nanotubes
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)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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- Kåredal, Monica, et al.
(författare)
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Time-Dependent Proteomic iTRAQ Analysis of Nasal Lavage of Hairdressers Challenged by Persulfate.
- 2010
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; okt, s. 5620-5628
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Tidskriftsartikel (refereegranskat)abstract
- Hairdressers are frequently exposed to bleaching powder containing persulfates, a group of compounds that may induce hypersensitivity in the airways. The mechanism causing this reaction is not clear. The aim of this study was to identify changes in the nasal lavage fluid proteome after challenge with potassium persulfate in hairdressers with bleaching powder-associated rhinitis. Furthermore, we aimed to compare their response to that of hairdressers without nasal symptoms, and atopic subjects with pollen-associated nasal symptoms. To study the pathogenesis of persulfate-associated rhinitis, the response in protein expression from the upper airway was assessed by time-dependent proteomic expression analysis of nasal lavage fluids. Samples were prepared by pooling nasal lavage fluids from the groups at different time points after challenge. Samples were depleted of high-abundant proteins, labeled with iTRAQ and analyzed by online 2D-nanoLC-MS/MS. Differences in the protein pattern between the three groups were observed. Most proteins with differentially expressed levels were involved in pathways of lipid transportation and antimicrobial activities. The major finding was increased abundance of apolipoprotein A-1, 20 min postchallenge, detected solely in the group of symptomatic hairdressers. Our results suggest there may be differences between the mechanisms responsible for the rhinitis in the symptomatic and atopic group.
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- Matute Wilander, Anna, et al.
(författare)
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Inflammatory biomarkers in serum in subjects with and without work related neck/shoulder complaints
- 2014
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although it has recently been recognised that inflammation is important in the development of work-related musculoskeletal disorders (MSDs), the exact pathophysiological pathways are unknown. Methods: We investigated serum concentrations of inflammatory cytokines in 35 female supermarket cashiers with repetitive work tasks and work related neck/shoulder complaints, compared with those from 25 women without MSDs (6 supermarket cashiers and 19 middle-school teachers or faculty staff). None of the subjects were pregnant or lactating, and showed no signs of rheumatoid arthritis, systemic lupus erythematosus, cancer, diabetes, coronary artery disease or inadequately controlled hypertension. Serum levels of IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12, MCP-1, MIP-1 alpha, MIP-1 beta, TNF-alpha, GM-CSF, CTGF and CRP were analysed. Results: The women with pain related to MSD had higher serum concentrations of MIP-1 beta (median, 25th-75th percentile: 90.0 pg/mL, 62.5-110 vs. 73.1 pg/mL, 54.6-88.3; p = 0.018), IL-12 (0.26 pg/mL, 0.26-0.26 vs. 0.26 pg/mL, 0.26-0.26; p = 0.047) and CRP (0.5 mg/L, 0.5-1.6 vs. 0.5 mg/L, 0.5-0.5; p = 0.003), than control subjects. Levels of MIP-1 alpha, MIP-1 beta and CRP were correlated with the reported intensity of neck/shoulder pain (r = 0.29, p = 0.03 for MIP-1 alpha; r = 0.29, p = 0.02 for MIP-1 beta and r = 0.43, p = 0.001 for CRP). No statistically significant differences in serum levels were found for the remaining cytokines. Conclusions: Otherwise healthy females with ongoing work-related neck/shoulder pain showed higher serum concentrations of MIP-1 beta, IL-12 and CRP than controls, and the levels of MIP-1 alpha, MIP-1 beta and CRP were correlated to pain intensity. These results support previous findings that inflammatory processes play a part in work related MSDs.
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- Mörtstedt, Harriet, et al.
(författare)
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Screening Method Using Selected Reaction Monitoring for Targeted Proteomics Studies of Nasal Lavage Fluid.
- 2012
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907.
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Tidskriftsartikel (refereegranskat)abstract
- Proteomic-based studies of nasal lavage fluid (NLF) may identify molecular pathways associated with disease pathology and new biomarker candidates of upper airway diseases. However, most studies have used rather tedious untargeted MS techniques. Selected reaction monitoring (SRM) is a sensitive and specific technique that can be used with high throughput. In this study, we developed a semiquantitative SRM-based method targeting 244 NLF proteins. The protein set was identified through a literature study in combination with untargeted LC-MS/MS analyses of trypsin-digested NLF samples. The SRM assays were designed using MS/MS data either downloaded from a proteomic data repository or experimentally obtained. Each protein is represented by one to five peptides, resulting in 708 SRM assays. Three to four transitions per assay were used to ensure analyte specificity. The majority (69%) of the assays showed good within-day precision (coefficient of variation ≤20%). The accuracy of the method was evaluated by analyzing four samples prepared with varying amounts of four proteins. Peptide and protein ratios were in good agreement with expected ratios. In conclusion, a high throughput screening method for relative quantification of 244 NLF proteins was developed. The method should be of general use in any proteomic study of the upper airways.
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- Mörtstedt, Harriet, et al.
(författare)
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Strategy for identification and detection of multiple oxidative modifications within proteins applied on persulfate-oxidized hemoglobin and human serum albumin.
- 2011
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 1097-0231 .- 0951-4198. ; 25:2, s. 327-340
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress has been suggested as an underlying mechanism of many human diseases. However, definitive evidence for this association has not been presented due to different shortcomings of the methods used to measure biomarkers of oxidative stress. Persulfates are oxidizing agents known to elicit hypersensitive reactions from the airways and skin. Despite a frequent use of persulfates at many work places, no biomarkers for persulfate exposure are available. The aim of this study was to develop a strategy for the identification and detection of multiple oxidative modifications within proteins. This strategy was applied on persulfate-oxidized proteins to identify oxidized peptides suitable for further investigation as biomarkers of persulfate exposure or oxidative stress. A strategy for the identification and the relative quantification of multiple oxidative modifications within proteins was developed. The usage of two software packages facilitated the search for modified peptides to a great extent. Oxidized peptides were relatively quantified using liquid chromatography/tandem mass spectrometry in selected reaction monitoring mode. The result showed that persulfates oxidize tryptophans and methionines resulting in mass shifts of 16 and/or 32 Da. Also, oxidized albumin peptides in nasal lavage fluid samples from subjects challenged with persulfate were detected. The oxidation degree before and after challenge remained constant for peptides containing methionine sulfoxide. For peptides containing oxidized tryptophan the oxidation degree increased after exposure. Some of these oxidized peptides may be suitable as biomarkers; however, further evaluation is required.
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