| 1. |
- Abrahamsson, Camilla, et al.
(författare)
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Aerosolized particulate matter from fragmentation of carbon nanotube-enhanced concrete
- 2023
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Ingår i: Abstracts from the 2022 Airmon-10 conference and the 2023 Inhaled Particles and NanOEH conference. - 2398-7316 .- 2398-7308. ; 67:Supplement_1, s. i94-i95
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Konferensbidrag (refereegranskat)abstract
- Construction and demolition workers are exposed to high levels of particulate matter (PM) from building materials throughout their working life. Although nano-enabled building materials (NEBMs) may improve the performance and functionality of buildings, concerns are being raised regarding health risks from occupational exposure to PM from NEBMs. In this work, an experimental set-up for integrated resuspension and characterization of PM from NEBMs was developed and tested using three types of concrete (low density, normal, high strength), each enhanced with Carbon Nanotubes (CNTs) at different concentrations (0, low, high). The performance of portable devices used in occupational exposure assessments (DustTrak and NanoTracer) was compared with stationary instruments and gravimetric filter techniques. 40-70% of the mass and 90-98% of the number of particles were within the respirable fraction, with primary modes at 150 nm and 2-3 µm. Addition of CNTs significantly decreased mean particle number concentrations (PNCs) across the entire characterized size range (7 nm - 20 µm) for low density concrete, whereas the opposite was the case for normal strength and high strength concrete. It was hypothesised that the concrete matrix primarily governs the PM formation, which is in turn modulated by CNT-matrix interactions either suppressing or supporting fragmentation during crushing. SEM imaging could display partially submerged CNTs protruding from concrete fragments. Fundamental interactions at the interface of the nanomaterial and the surrounding matrix needs to be investigated to determine how the PM generated from NEBMs differ from their non-nano counterparts and how to prevent future exposure during demolition.
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| 2. |
- Abrahamsson, Camilla, et al.
(författare)
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Characterization of airborne dust emissions from three types of crushed multi-walled carbon nanotube-enhanced concretes
- 2024
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Ingår i: NanoImpact. - : Elsevier B.V.. - 2452-0748. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Dispersing Multi-Walled Carbon Nanotubes (MWCNTs) into concrete at low (<1 wt% in cement) concentrations may improve concrete performance and properties and provide enhanced functionalities. When MWCNT-enhanced concrete is fragmented during remodelling or demolition, the stiff, fibrous and carcinogenic MWCNTs will, however, also be part of the respirable particulate matter released in the process. Consequently, systematic aerosolizing of crushed MWCNT-enhanced concretes in a controlled environment and measuring the properties of this aerosol can give valuable insights into the characteristics of the emissions such as concentrations, size range and morphology. These properties impact to which extent the emissions can be inhaled as well as where they are expected to deposit in the lung, which is critical to assess whether these materials might constitute a future health risk for construction and demolition workers. In this work, the impact from MWCNTs on aerosol characteristics was assessed for samples of three concrete types with various amounts of MWCNT, using a novel methodology based on the continuous drop method. MWCNT-enhanced concretes were crushed, aerosolized and the emitted particles were characterized with online and offline techniques. For light-weight porous concrete, the addition of MWCNT significantly reduced the respirable mass fraction (RESP) and particle number concentrations (PNC) across all size ranges (7 nm – 20 μm), indicating that MWCNTs dampened the fragmentation process by possibly reinforcing the microstructure of brittle concrete. For normal concrete, the opposite could be seen, where MWCNTs resulted in drastic increases in RESP and PNC, suggesting that the MWCNTs may be acting as defects in the concrete matrix, thus enhancing the fragmentation process. For the high strength concrete, the fragmentation decreased at the lowest MWCNT concentration, but increased again for the highest MWCNT concentration. All tested concrete types emitted <100 nm particles, regardless of CNT content. SEM imaging displayed CNTs protruding from concrete fragments, but no free fibres were detected.
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| 3. |
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| 4. |
- Al-Rekabi, Zeinab, et al.
(författare)
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Uncovering the cytotoxic effects of air pollution with multi-modal imaging of in vitro respiratory models
- 2023
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Ingår i: Royal Society Open Science. - : Royal Society Publishing. - 2054-5703. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Annually, an estimated seven million deaths are linked to exposure to airborne pollutants. Despite extensive epidemiological evidence supporting clear associations between poor air quality and a range of short- and long-term health effects, there are considerable gaps in our understanding of the specific mechanisms by which pollutant exposure induces adverse biological responses at the cellular and tissue levels. The development of more complex, predictive, in vitro respiratory models, including two- and three-dimensional cell cultures, spheroids, organoids and tissue cultures, along with more realistic aerosol exposure systems, offers new opportunities to investigate the cytotoxic effects of airborne particulates under controlled laboratory conditions. Parallel advances in high-resolution microscopy have resulted in a range of in vitro imaging tools capable of visualizing and analysing biological systems across unprecedented scales of length, time and complexity. This article considers state-of-the-art in vitro respiratory models and aerosol exposure systems and how they can be interrogated using high-resolution microscopy techniques to investigate cell-pollutant interactions, from the uptake and trafficking of particles to structural and functional modification of subcellular organelles and cells. These data can provide a mechanistic basis from which to advance our understanding of the health effects of airborne particulate pollution and develop improved mitigation measures.
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| 5. |
- Ali, Neserin, et al.
(författare)
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Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
- 2016
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Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 10:2, s. 226-234
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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.
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| 6. |
- Ali, Neserin, et al.
(författare)
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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
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Ingår i: Clinical Proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 15:1
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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.
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| 7. |
- Berggren-Nylund, Rebecca, et al.
(författare)
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Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders
- 2023
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 14, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Chronic lung disorders involve pathological alterations in the lung tissue with hypoxia as a consequence. Hypoxia may influence the release of inflammatory mediators and growth factors including vascular endothelial growth factor (VEGF) and prostaglandin (PG)E 2. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis. Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O 2) or normoxia (21% O 2) during 24 h, with or without transforming growth factor (TGF)-β1. mRNA expression of genes and proteins related to disease pathology were analysed with qPCR, ELISA or immunocytochemistry. Alterations in cell viability and metabolic activity were determined. Results: In BEAS-2B and hAELVi, hypoxia significantly dowregulated genes related to fibrosis, mitochondrial stress, oxidative stress, apoptosis and inflammation whereas VEGF receptor 2 increased. Hypoxia increased the expression of Tenascin-C, whereas both hypoxia and TGF-β1 stimuli increased the release of VEGF, IL-6, IL-8 and MCP-1 in BEAS-2B. In hAELVi, hypoxia reduced the release of fibroblast growth factor, epidermal growth factor, PGE 2, IL-6 and IL-8, whereas TGF-β1 stimulus significantly increased the release of PGE 2 and IL-6. TGF-β1 stimulated BEAS-2B cells showed a decreased release of VEGF-A and IL-8, while TGF-β1 stimulated hAELVi cells showed a decreased release of PGE 2 and IL-8 during hypoxia compared to normoxia. Metabolic activity was significantly increased by hypoxia in both epithelial cell types. Discussion: In conclusion, our data indicate that bronchial and alveolar epithelial cells respond differently to hypoxia and profibrotic stimuli. The bronchial epithelium appears more responsive to changes in oxygen levels and remodelling processes compared to the alveoli, suggesting that hypoxia may be a driver of pathogenesis in chronic lung disorders.
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| 8. |
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| 9. |
- Dierschke, Katrin, et al.
(författare)
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Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates
- 2017
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 90:5, s. 451-463
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Tidskriftsartikel (refereegranskat)abstract
- 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. 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. 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. 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).
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| 10. |
- Franzén, Sara, et al.
(författare)
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Compositional tuning of gas-phase synthesized Pd–Cu nanoparticles
- 2023
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Ingår i: Nanoscale Advances. - 2516-0230. ; 5:22, s. 6069-6077
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Tidskriftsartikel (refereegranskat)abstract
- Bimetallic nanoparticles have gained significant attention in catalysis as potential alternatives to expensive catalysts based on noble metals. In this study, we investigate the compositional tuning of Pd–Cu bimetallic nanoparticles using a physical synthesis method called spark ablation. By utilizing pure and alloyed electrodes in different configurations, we demonstrate the ability to tailor the chemical composition of nanoparticles within the range of approximately 80 : 20 at% to 40 : 60 at% (Pd : Cu), measured using X-ray fluorescence (XRF) and transmission electron microscopy energy dispersive X-ray spectroscopy (TEM-EDXS). Time-resolved XRF measurements revealed a shift in composition throughout the ablation process, potentially influenced by material transfer between electrodes. Powder X-ray diffraction confirmed the predominantly fcc phase of the nanoparticles while high-resolution TEM and scanning TEM-EDXS confirmed the mixing of Pd and Cu within individual nanoparticles. X-ray photoelectron and absorption spectroscopy were used to analyze the outermost atomic layers of the nanoparticles, which is highly important for catalytic applications. Such comprehensive analyses offer insights into the formation and structure of bimetallic nanoparticles and pave the way for the development of efficient and affordable catalysts for various applications.
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| 11. |
- Gren, Louise, et al.
(författare)
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Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles
- 2022
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Ingår i: Particle and Fibre Toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system ('HVOPM+NOx' PM1: 93 mu g-m(-3), EC: 54 mu g-m(-3), NO: 3.4 ppm, -NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter ('HVONOx' PM1: similar to 1 mu g-m(-3), NO: 2.0 ppm, -NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, -NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study. Results: The average total respiratory tract deposition of PM1 during -HVO(PM+ NO)x was 27 mu g-h(-1). The estimated deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the -HVOPM+ NOx exhaust. Compared to FA, exposure to -HVOPM+ NOx and -HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, p < 0.03). Especially, exposure to -HVOPM+ NOx showed 40-50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the -HVONOx exposures (- 18.1, 95% CI: - 27.3 to - 8.8 L-min(-1), p < 0.001), and for the -HVOPM+ NOx (- 7.4 (- 15.6 to 0.8) L -min(-1), p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique). Conclusion: Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- 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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| 16. |
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| 17. |
- Janhäll, Sara, 1965-, et al.
(författare)
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Release of carbon nanotubes during combustion of polymer nanocomposites in a pilot-scale facility for waste incineration
- 2021
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Ingår i: NanoImpact. - : Elsevier BV. - 2452-0748. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Nanocomposites, formed by incorporating nanoparticles into a matrix of standard materials, are increasing on the market. Little focus has been directed towards safe disposal and recycling of these new materials even though the disposal has been identified as a phase of the products' life cycle with a high risk of uncontrolled emissions of nanomaterials. In this study, we investigate if the carbon nanotubes (CNTs), when used as a filler in two types of polymers, are fully destructed in a pilot-scale combustion unit designed to mimic the combustion under waste incineration. The two polymer nanocomposites studied, polycarbonate (PC) with CNT and high-density polyethylene (HDPE) with CNT, were incinerated at two temperatures where the lower temperature just about fulfilled the European waste incineration directive while the upper was chosen to be on the safe side of fulfilling the directive. Particles in the flue gas were sampled and analysed with online and offline instrumentation along with samples of the bottom ash. CNTs could be identified in the flue gas in all experiments, although present to a greater extent when the CNTs were introduced in PC as compared to in HDPE. In the case of using PC as polymer matrix, CNTs were identified in 3–10% of the analysed SEM images while for HDPE in only ~0.5% of the images. In the case of PC, the presence of CNTs decreased with increasing bed temperature (from 10% to 3% of the images). The CNTs identified were always in bundles, often coated with remnants of the polymer, forming particles of ~1–4 μm in diameter. No CNTs were identified in the bottom ash, likely explained by the difference in time when the bottom ash and fly ash are exposed to high temperatures (~hours compared to seconds) in the pilot facility. The results suggest that the residence time of the fly ash in the combustion zone is not long enough to allow full oxidation of the CNTs. Thus, the current regulation on waste incineration (requiring a residence time of the flue gas >850 °C during at least 2 s) may not be enough to obtain complete destruction of CNTs in polymer composites. Since several types of CNTs are known to be toxic, we stress the need for further investigation of the fate and toxicity of CNTs in waste treatment processes.
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| 18. |
- Jeppsson, Marina, et al.
(författare)
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Identification of Covalent Binding Sites of Phthalic Anhydride in Human Hemoglobin.
- 2008
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; Oct 3, s. 2156-2163
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Tidskriftsartikel (refereegranskat)abstract
- Phthalic anhydride (PA) is a reactive low molecular weight compound used in the chemical industry. The exposure of PA may lead to work-related airway diseases such as rhinitis, chronic bronchitis, and asthma. The exposure gives rise to an increase in hapten-specific IgG antibodies in workers but with a low presence of specific IgE antibodies. In this study, the binding of PA to human hemoglobin (Hb) in vitro was investigated. Trypsin and Pronase E digestion, LC, LC/MS/MS, GC/MS analysis, and nanoelectrospray hybrid quadrupole time-of-flight MS were used to identify the adducted amino acids of the synthesized PA-Hb conjugates. In the conjugate with the molar ratio 1:0.1, a total of six adducted amino acids were identified. N-Terminal valine was found adducted in both the alpha- and the beta-chains as well as a total of four lysines, Val 1, Lys 16, and Lys 61 on the alpha-chain and Val 1, Lys 66, and Lys 144 on the beta-chain. Two types of lysine adducts were found, a phthalamide and a phthalimide. It was also found that PA differs in its binding site as compared to hexahydrophthalic anhydride. The result of this study suggests several interesting applications of biological monitoring.
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| 19. |
- Jeppsson, Marina, et al.
(författare)
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Methylhexahydrophthalic anhydride adducted albumin tryptic peptides in nasal lavage fluid.
- 2009
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Ingår i: Inhalation Toxicology. - : Informa UK Limited. - 0895-8378 .- 1091-7691. ; 21:12, s. 1013-1020
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Tidskriftsartikel (refereegranskat)abstract
- Methylhexahydrophthalic anhydride (MHHPA) is a reactive, low molecular weight chemical used in products such as plastics, paints, and electronic components. Exposure to MHHPA may lead to work-related airway diseases such as rhinitis, conjunctivitis, and asthma. Twelve subjects employed at a plant manufacturing electrical capacitors using MHHPA were included in this study. Nasal lavages were collected from subjects before work Monday morning and after work Tuesday afternoon. The levels of MHHPA adducted to serum albumin were analyzed with a straightforward work-up method. The samples were trypsinated before being analyzed with a liquid chromatography-triple quadrupole mass spectrometer. The mass spectrometer was run using selected reaction monitoring for six adducted peptides. Also, some biomarkers of effect (albumin, total protein, eosinophil cationic protein, and tryptase) were analyzed in nasal lavages. Furthermore, the metabolite MHHP acid in urine after work on Tuesday was analyzed by gas chromatography-mass spectrometry. Symptoms from the airways and the eyes and sensitization were registered. The main result of this study is that protein adducts can be analyzed in vivo after low occupational exposures to MHHPA. The results also show a correlation between adducted peptides and albumin in nasal lavage. Furthermore, there may be a difference in the potential to induce hyperresponsiveness between adducts bound to different amino acids.
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| 20. |
- Johannesson, Gunvor, et al.
(författare)
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Evaluation of an immunoaffinity extraction column for enrichment of adducts between human serum albumin and hexahydrophthalic anhydride in plasma.
- 2008
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Ingår i: Biomedical Chromatography. - : Wiley. - 0269-3879 .- 1099-0801. ; 22:3, s. 327-332
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Tidskriftsartikel (refereegranskat)abstract
- An immunoaffinity extraction (IAE) column was prepared for extraction of adducts between human serum albumin (HSA) and hexahydrophthalic anhydride (HHPA). HHPA is a strong sensitizer inducing immunoglobulin E antibodies in vivo. Polyclonal antibodies from a rabbit immunized with keyhole limpet hemocyananin-HHPA conjugate were purified using a Protein A Sepharose gel. To obtain antibodies with optimal affinity towards HHPA-protein adducts, HHPA-specific antibodies were selected using an N-hydroxysuccinimide-Sepharose column coupled with albumin-HHPA conjugate. Antibodies eluted from this column at pH 2.2 were selected to prepare the IAE column. The column was evaluated using 2 mL plasma spiked with HSA-HHPA conjugate. The column was eluted with glycine buffer at pH 2.0. The conjugates in the eluate were hydrolyzed to the corresponding HHP acid and quantified by mass spectrometry. The average recovery of HHPA adducts in 11 experiments was 68% with a coefficient of variation (CV) of 7%. The column's capacity to bind protein-HHPA adducts was found to be linear in the range of 0.15-1.2 nmol conjugate. The evaluation showed that the IAE column had adequate affinity towards the HHPA adducts and that the adducts could be extracted with good recovery and precision from a large volume of plasma.
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| 21. |
- Jönsson, Linnéa, et al.
(författare)
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The effect of electrode composition on bimetallic AgAu nanoparticles produced by spark ablation
- 2024
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Ingår i: Journal of Aerosol Science. - 0021-8502. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- A flexible way to generate bimetallic nanoparticles with high control of their composition is to use spark ablation of alloyed electrodes. It has been generally accepted and stated that particles produced using spark ablation of alloyed electrodes obtain the same chemical composition as the electrodes. However, we identify a lack of studies fully supporting the connection between electrode and particle composition, presented in a small literature survey. The aim of the study is, hence, to explore the validity of the statement by analysing the relation between alloyed electrodes and their resulting particle composition using three sets of AgAu electrodes containing Au and 25, 50, and 75 atomic % Ag, respectively. The resulting composition is thoroughly investigated using both single particle (scanning- and transmission electron microscopy) and ensemble particle techniques (inductive coupled plasma-mass spectroscopy, x-ray photoelectron spectroscopy, x-ray fluorescence, and optical measurements of surface plasmon resonance. We also investigate how sample size (e.g., the number of particles analysed) affects the reliability of the resulting sample mean. For single-particle measurements of a sample with a compositional standard deviation of a few atomic percentage points, a sample size of 20 particles is a good benchmark for obtaining reliable results of the sample mean. Furthermore, this article aims to challenge the practice in which the composition of nanoparticles is measured, presented, and interpreted, to improve and facilitate future research related to this topic. From the results of this study, it could be concluded that for the investigated Ag–Au material system, the particles obtained a composition very similar to the alloyed AgAu electrodes.
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| 22. |
- Kåredal, Monica, et al.
(författare)
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A quantitative LC-MS method to determine surface contamination of antineoplastic drugs by wipe sampling
- 2022
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Ingår i: Journal of Occupational and Environmental Hygiene. - : Informa UK Limited. - 1545-9624 .- 1545-9632. ; 19:1, s. 50-66
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Tidskriftsartikel (refereegranskat)abstract
- The main objective was to develop a wipe sampling test to measure surface contamination of the most frequently used antineoplastic drugs (ADs) in Swedish healthcare and, furthermore, to develop an analysis method sensitive enough to assess low levels of contamination. Two wipe sampling tests with separate sample processing methods assessing (i) cyclophosphamide (CP), ifosfamide (IF), 5-fluorouracil (5-FU), etoposide (ETO), gemcitabine (GEM) and cytarabine (CYT) (Wipe Test 1); and (ii) GEM, CYT and methotrexate (MTX) (Wipe Test 2), respectively, were developed by optimization of absorption and extraction efficiencies using different wipe tissue materials, tissue wetting solution, and extraction solvents. A fast liquid chromatography tandem mass spectrometry method was developed for simultaneous detection of the studied ADs. The limit of quantification for the method was between 0.04 to 2.4 ng/wipe sample (0.10 to 6.1 pg/cm2 for an area of 400 cm2) and at 50 ng/sample the within-day precision was between 1.3 and 15%, and the accuracy between 102 and 127%. Wipe Test 1 was applied in an assessment of cleaning efficiency of five different cleaning solutions (formic acid, water, sodium hydroxide, ethanol, and sodium dodecyl sulfate (SDS) for removal of ADs from surfaces made of stainless steel or plastic. For CP, IF, 5-FU, GEM, and CYT 92% of the AD were removed regardless of surface and cleaning solution. In conclusion, a user-friendly assessment method to measure low levels of seven ADs in the work environment was developed and validated. Assessment of the decontamination efficiency of cleaning solutions concerning removal of ADs from stainless steel showed that efficiencies differed depending on the AD with water being the least effective cleaning agent. The results suggests that a combination of different cleaning agents including detergent and a solution with an organic component would be optimal to efficiently remove the measured ADs from surfaces in the workplace.
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| 23. |
- Kåredal, Monica, et al.
(författare)
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Comparative Time-Dependent Analysis of Potential Inflammation Biomarkers in Lymphoma-Bearing SJL Mice.
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:5, s. 1735-1744
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Tidskriftsartikel (refereegranskat)abstract
- SJL mice colonized with RcsX lymphoma cells undergo a rapid inflammatory response associated with biological and physiological effects including increased nitric oxide production and mutations in spleen DNA. By 2 weeks postcolonization, these changes were accompanied by both up- and down-regulation of a number of plasma proteins. In the experiments reported here, plasma from individual SJL mice was analyzed at several time-points over the 2-week period to determine if there were sets of proteins whose expression varied in concert and thus might serve as early biomarkers for inflammation-related disorders. Samples were collected just prior to injection of the RcsX cells and then after 4, 8, and 12 days. Albumin and immunoglobulins were depleted, and the samples were resolved by 1D gel electrophoresis. The gels were cut into 20 slices, and the proteins were digested in-gel with trypsin. The digests were treated with iTRAQ reagents and then analyzed using LC/MS/MS. The resulting data were processed with two software packages, that is, ProQuant and Spectrum Mill, and then subjected to K-means cluster analysis (K = 4). The four clusters revealed a set of highly up-regulated proteins, a set of progressively up-regulated proteins, a set with no major changes, and a set that declined. The first cluster included haptoglobin and serum amyloid A; the second included groups with several functions including protease inhibition, cell motility, and transport. The iTRAQ results for a selection of the up-regulated proteins, including haptoglobin, hemopexin, serum amyloid P component, and ceruloplasmin, were confirmed with Western blots. Prominent down-regulated proteins included esterase-1, paraoxonase, and alpha-2-macroglobulin. Approximately 50% of the up-regulated proteins are canonical acute phase proteins, while the remainder are regulated by the Nrf2 transcription factor. Keywords: inflammation center dot SJL mouse center dot lymphoma center dot iTRAQ center dot tumor progression center dot biomarker center dot cluster analysis center dot acute phase proteins
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| 24. |
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| 25. |
- Kåredal, Monica, et al.
(författare)
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Determination of hexahydrophthalic anhydride adducts to human serum albumin
- 2003
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Ingår i: Biomarkers. - : Informa UK Limited. - 1366-5804 .- 1354-750X. ; 8:5, s. 343-359
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Tidskriftsartikel (refereegranskat)abstract
- Hexahydrophthalic anhydride (HHPA) is a highly sensitizing industrial chemical that is known to covalently bind to endogenous proteins. The aim of this study was to determine the binding sites of HHPA to human serum albumin (HSA). Conjugates between HSA and HHPA, at two different molar ratios, were synthesized under physiological conditions. The conjugates were digested with trypsin and Pronase E to obtain specific peptides and amino acids, which were separated by liquid chromatography (LC). Fractions containing modified peptides were detected through quantification of hydrolysable HHPA using LC coupled to a triple quadrupole mass spectrometer with electrospray ionization. Modified residues in albumin were identified by sequence analyses using nanoelectrospray quadrupole time-of-flight mass spectrometry. A total of 36 HHPA adducts were found in the HSA - HHPA conjugate with 10 times molar excess of added HHPA. In the conjugate with a molar ratio of 1: 0.1 of added HHPA, seven HHPA adducts were found bound to Lys(137) (domain IB), Lys(190), Lys(199) and Lys(212) (domain IIA), Lys(351) (domain IIB), and Lys(432) and Lys(436) (domain IIIA). Moreover, several of these adducted albumin peptides were detected in nasal lavage fluid from one volunteer exposed to HHPA. The binding sites of HHPA to HSA have been determined, thus identifying potential allergenic chemical structures. This knowledge generates the possibility of developing methods for the biological monitoring of HHPA exposure by analysing tryptic peptides including these binding sites.
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| 26. |
- Kåredal, Monica, et al.
(författare)
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Mass spectrometric characterization of human hemoglobin adducts formed in vitro by hexahydrophthalic anhydride.
- 2002
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 1520-5010 .- 0893-228X. ; 15:4, s. 562-569
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Tidskriftsartikel (refereegranskat)abstract
- Primary structural information of anhydride binding to endogenous proteins is of interest in order to determine the mechanism causing the type-I allergy seen in many anhydride-exposed workers. In addition, studies on specific protein adducts may generate new methods for biological monitoring. In this study, the binding of hexahydrophthalic anhydride (HHPA) to human hemoglobin (Hb) in vitro was investigated. The in vitro synthesized conjugates were analyzed using a hybrid quadrupole-time-of-flight mass spectrometer (Q-TOF) with electrospray ionization (ESI) to determine the number of HHPA adducts per Hb molecule. Structural information on the locations of the adducts was obtained through nanospray Q-TOF, liquid chromatography-ESI mass spectrometric analysis, and gas chromatography/mass spectrometric analysis of Pronase E and tryptic digests. Up to six adducts were found on the alpha-chain and five on the beta-chain. The HHPA-adducts were localized to the N-terminal valine of the alpha- and beta-chains of Hb and to lysine residues at positions 7, 11, 16, and 40 of the alpha-chain and 8, 17, 59, 66, and 144 of the beta-chain. These results will constitute a basis for studies on structure-activity relationships as well as for development of methods for biological monitoring of acid anhydrides.
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| 27. |
- Kåredal, Monica, et al.
(författare)
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Mass spectrometric monitoring of in vitro formed ad ducts between hexahydrophthalic anhydride (HHPA) and cysteine and lysine
- 2002
-
Ingår i: Proceedings 50th ASMS Conference on Mass Spectrmetry and Allied Topics. ; , s. 325-326
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Konferensbidrag (refereegranskat)abstract
- The in vitro formed adducts between hexahydrophthalic anhydride (HHPA) and cysteine and lysine were monitored by mass spectrometry. Freshly synthesized N-acetyl-S-hexahydrophthaloyl-L-cysteine was dissolved in dry acetonitrile and added to a solution of N-acetyl-L-lysine in 0.1 M sodium phosphate buffer (pH 7.4) an incubated at 37°C. The reactions were monitored by LC/MS on a triple quadrupole mass spectrometer with electrospray ionization coupled to a HPLC system from Perkin Elmer. The results show that there was a rapid rearrangement of HHPA from most of the cysteines to the lysines, and that HHPA-adducts of cysteine will be transferred to lysine when encountered.
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| 28. |
- Kåredal, Monica, et al.
(författare)
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Pilot study : External surface contamination of gemcitabine and 5-fluorouracil on drug packaging
- 2024
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Ingår i: Journal of oncology pharmacy practice. - : SAGE Publications. - 1078-1552 .- 1477-092X.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Antineoplastic drugs (ADs) are commonly used pharmaceuticals for anticancer treatments. It has previously been shown that the external surface of drug vials frequently is contaminated with ADs. More than a decade ago methods to prevent occupational exposure were introduced by using plastic coverage of the glass vials or packing vials in a secondary plastic container. The aim of the pilot study was to determine contamination levels of ADs on different parts of AD packaging of two different commercially available drug vials on the Swedish market and to investigate the occurrence of cross contamination of ADs. Methods: Packagings of gemcitabine (GEM) and 5-fluorouracil (5-FU) were tested by wipe sampling. Five ADs; GEM, 5-FU, cyclophosphamide (CP), ifosfamide and etoposide were quantified using liquid chromatography mass spectrometry. Results: AD contaminations were detected in 69% and 60% of the GEM and 5-FU packaging samples. Highest levels, up to approximately 5 µg/sample, were observed on the glass vials. The protective shrink-wrap of 5-FU vials and the plastic container of GEM were contaminated with low levels of 5-FU and GEM, respectively, and furthermore the 5-FU vials with shrink-wrap were cross-contaminated with GEM. Cross-contamination of CP and GEM was detected on 5-FU vials with plastic shrink-wrap removed. Conclusions: External contamination of ADs are still present at primary drug packagings on the Swedish market. Protection of AD vials by plastic shrink-wrap or a secondary plastic container does not remove the external contamination levels completely. The presence of cross contamination of ADs on drug packagings was also observed.
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| 29. |
- Kåredal, Monica
(författare)
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Protein adducts of hexahydrophthalic anhydride- chemical structures and biomarkers
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic acid anhydrides (OAAs) are low molecular weight chemicals used in the industry for manufacturing of plastics such as epoxy resins. Exposure to these chemicals may lead to symptoms from the eyes and the respiratory tract in form of conjunctivitis, rhinitis and asthma. In many workers production of specific IgE antibodies are induced suggesting that a type-1 allergy mediated mechanism is involved. The OAAs act as haptens and the binding to endogenous proteins is probably an important part of the pathophysiological mechanism. The aim of this thesis was to identify potentially allergenic chemical structures using hexahydrophthalic anhydride (HHPA), a highly sensitising OAA, as a model substance. The aim was also to develop a new method for biological monitoring of HHPA. The binding of HHPA to several nucleophilic amino acids and a model peptide was initially studied. Stable adducts to lysine and the N-terminal amino group were found. Unstable adducts to cysteine, histidine, tyrosine and tryptophan were also identified. The cysteine adduct could be transferred to lysine residues. Studies of potential allergenic structures were performed on hapten-protein conjugates between HHPA and hemoglobin (Hb) and human serum albumin (HSA), respectively, synthesised in vitro. Enzyme digestions of the conjugates were performed and the binding sites of HHPA were identified through analysis of the peptides using liquid chromatography coupled to tandem mass spectrometry. HHPA adducts were found with several lysine residues and the N-terminal amino group both in Hb and HSA. Further studies must be performed to determine the allergenic potential of these identified adducts. Based on the identifications of the binding sites of HHPA to HSA a method was developed to measure HHPA-adducted tryptic peptides of HSA in nasal lavage samples. The nasal lavages were obtained from five volunteers exposed to HHPA at different air concentrations of HHPA. The major binding sites of HHPA found in the in vitro studies were detected in the in vivo samples as well. The levels of these adducted peptides were highly correlated with the air levels of HHPA on an individual basis but there were large inter-individual differences. Thus, it should be investigated whether these peptides may be used as biomarkers of effective dose, which then would better reflect the risk than more traditional biomarkers.
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| 30. |
- 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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| 31. |
- Leeman, Mats, et al.
(författare)
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Development and validation of a quantitative wipe sampling method to determine platinum contamination from antineoplastic drugs on surfaces in workplaces at Swedish hospitals
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Ingår i: Journal of oncology pharmacy practice. - 1078-1552.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Antineoplastic drugs (ADs) are frequently used pharmaceuticals in the healthcare, and healthcare workers can be occupationally exposed to ADs. Monitoring of surface contamination is a common way to assess occupational exposure to ADs. The objective was to develop and validate a sensitive and quantitative monitoring method to determine surface contaminations of Pt as a marker for Pt-containing ADs. The surface contaminations of Pt-containing ADs were monitored at four Swedish hospital workplaces.METHODS: An analytical method was developed based on inductively coupled plasma mass spectrometry. The wipe sampling procedure was validated regarding different surface materials. The stability of collected wipe samples was investigated. Workplace surfaces were monitored by wipe sampling to determine contaminations of Pt-containing ADs.RESULTS: A wipe sampling and analytical method with a limit of detection of 0.1 pg Pt/cm 2 was developed. Pt was detected in 67% of the wipe samples collected from four workplaces, and the concentrations ranged from <0.10 to 21100 pg/cm 2. In 4% of samples, the detected surface contaminations of Pt in three hospital wards were above proposed hygienic guidance value (HGV) of Pt. In the hospital pharmacy, 9% of the detected surface contaminations of Pt were above lowest proposed HGV. CONCLUSIONS: A user-friendly, specific, and sensitive method for determination of surface contaminations of Pt from ADs in work environments was developed and validated. A large variation of contaminations was observed between detected surface contaminations of Pt in samples collected in wards, and it likely reflects differences in amounts handled and work practices between the wards.
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| 32. |
- Li, Huiqi, et al.
(författare)
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A Cross-Sectional Study of the Cardiovascular Effects of Welding Fumes.
- 2015
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Occupational exposure to particulate air pollution has been associated with an increased risk of cardiovascular disease. However, the risk to welders working today remains unclear. We aimed to elucidate the cardiovascular effects of exposure to welding fumes. METHODS: In a cross-sectional study, structured interviews and biological sampling were conducted for 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal breathing zone sampling of respirable dust was performed. Blood pressure (BP) and endothelial function (using peripheral arterial tonometry) were measured. Plasma and serum samples were collected from peripheral blood for measurement of C-reactive protein, low-density lipoprotein, homocysteine, serum amyloid A, and cytokines. RESULTS: Welders were exposed to 10-fold higher levels of particles than controls. Welders had significantly higher BP compared to controls, an average of 5 mm Hg higher systolic and diastolic BP (P≤0.001). IL-8 was 3.4 ng/L higher in welders (P=0.010). Years working as a welder were significantly associated with increased BP (β=0.35, 95%CI 0.13 - 0.58, P=0.0024 for systolic BP; β=0.32, 95%CI 0.16 - 0.48, P<0.001 for diastolic BP, adjusted for BMI) but exposure to respirable dust was not associated with BP. No clear associations occurred between welding and endothelial function, or other effect markers. CONCLUSIONS: A modest increase in BP was found among welders compared to controls suggesting that low-to-moderate exposure to welding fumes remains a risk factor for cardiovascular disease.
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| 33. |
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| 34. |
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| 35. |
- Lovén, Karin, et al.
(författare)
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Effects of cleaning spray use on eyes, airways, and ergonomic load
- 2023
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCleaning workers are exposed to chemicals and high physical workload, commonly resulting in airway problems and pain. In this study the response in the upper airways and the physical workload following airborne and ergonomic exposure of cleaning spray was investigated.MethodsA survey was answered by professional cleaning workers to investigate their use of cleaning sprays and the perceived effects on eyes, airways and musculoskeletal pain. A human chamber exposure study was then conducted with 11 professional cleaning workers and 8 non-professional cleaning workers to investigate the airborne exposure, acute effects on eyes and airways, and physical load during cleaning with sprays, foam application and microfiber cloths premoistened with water. All cleaning products used were bleach, chlorine, and ammonia free. The medical assessment included eye and airway parameters, inflammatory markers in blood and nasal lavage, as well as technical recordings of the physical workload.ResultsA high frequency of spray use (77%) was found among the 225 professional cleaning workers that answered the survey. Based on the survey, there was an eight times higher risk (p < 0.001) of self-experienced symptoms (including symptoms in the nose, eyes and throat, coughing or difficulty breathing) when they used sprays compared to when they cleaned with other methods. During the chamber study, when switching from spray to foam, the airborne particle and volatile organic compound (VOC) concentrations showed a decrease by 7 and 2.5 times, respectively. For the whole group, the peak nasal inspiratory flow decreased (-10.9 L/min, p = 0.01) during spray use compared to using only water-premoistened microfiber cloths. These effects were lower during foam use (-4.7 L/min, p = 0.19). The technical recordings showed a high physical workload regardless of cleaning with spray or with water.ConclusionSwitching from a spraying to a foaming nozzle decreases the exposure of both airborne particles and VOCs, and thereby reduces eye and airway effects, and does not increase the ergonomic load. If the use of cleaning products tested in this study, i.e. bleach, chlorine, and ammonia free, cannot be avoided, foam application is preferable to spray application to improve the occupational environment.
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| 36. |
- Lovén, Karin, et al.
(författare)
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Size-resolved characterization of particles >10 nm emitted to air during metal recycling
- 2023
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Ingår i: Environment International. - : Elsevier Ltd. - 0160-4120 .- 1873-6750. ; 174
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the strive towards a circular economy, metal waste recycling is a growing industry. During the recycling process, particulate matter containing toxic and allergenic metals will be emitted to the air causing unintentional exposure to humans and environment. Objective: In this study detailed characterization of particle emissions and workplace exposures were performed, covering the full size range from 10 nm to 10 µm, during recycling of three different material flows: Waste of electrical and electronic equipment (WEEE), metal scrap, and cables. Methods: Both direct-reading instruments (minute resolution), and time-integrated filter measurements for gravimetric and chemical analysis were used. Additionally, optical sensors were applied and evaluated for long-term online monitoring of air quality in industrial settings. Results: The highest concentrations, in all particle sizes, and with respect both to particle mass and number, were measured in the WEEE flow, followed by the metal scrap flow. The number fraction of nanoparticles was high for all material flows (0.66–0.86). The most abundant metals were Fe, Al, Zn, Pb and Cu. Other elements of toxicological interest were Mn, Ba and Co. Significance: The large fraction of nanoparticles, and the fact that their chemical composition deviate from that of the coarse particles, raises questions that needs to be further addressed including toxicological implications, both for humans and for the environment. © 2023 The Authors
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| 37. |
- Lovén, Karin, et al.
(författare)
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Toxicological effects of zinc oxide nanoparticle exposure : an in vitro comparison between dry aerosol air-liquid interface and submerged exposure systems
- 2021
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Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:4, s. 494-510
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Tidskriftsartikel (refereegranskat)abstract
- Engineered nanomaterials (ENMs) are increasingly produced and used today, but health risks due to their occupational airborne exposure are incompletely understood. Traditionally, nanoparticle (NP) toxicity is tested by introducing NPs to cells through suspension in the growth media, but this does not mimic respiratory exposures. Different methods to introduce aerosolized NPs to cells cultured at the air-liquid-interface (ALI) have been developed, but require specialized equipment and are associated with higher cost and time. Therefore, it is important to determine whether aerosolized setups induce different cellular responses to NPs than traditional ones, which could provide new insights into toxicological responses of NP exposure. This study evaluates the response of human alveolar epithelial cells (A549) to zinc oxide (ZnO) NPs after dry aerosol exposure in the Nano Aerosol Chamber for In Vitro Toxicity (NACIVT) system as compared to conventional, suspension-based exposure: cells at ALI or submerged. Similar to other studies using nebulization of ZnO NPs, we found that dry aerosol exposure of ZnO NPs via the NACIVT system induced different cellular responses as compared to conventional methods. ZnO NPs delivered at 1.0 µg/cm2 in the NACIVT system, mimicking occupational exposure, induced significant increases in metabolic activity and release of the cytokines IL-8 and MCP-1, but no differences were observed using traditional exposures. While factors associated with the method of exposure, such as differing NP aggregation, may contribute toward the different cellular responses observed, our results further encourage the use of more physiologically realistic exposure systems for evaluating airborne ENM toxicity. © 2021 The Author(s).
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| 38. |
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| 39. |
- Löfdahl, Anna, et al.
(författare)
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Silver nanoparticles alter cell viability ex vivo and in vitro and induce proinflammatory effects in human lung fibroblasts
- 2020
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Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PCLS) and in vitro in human lung fibroblasts (HFL-1), and immunomodulatory responses in fibroblasts. PCLS and HFL-1 were exposed to AgNPs with different sizes, 10 nm and 75 nm, at concentrations 2 µg/mL and 10 µg/mL. Changes in synthesis of ECM proteins, growth factors and cytokines were analyzed in HFL-1. Ag10 and Ag75 affected cell viability, with significantly reduced metabolic activities at 10 µg/mL in both PCLS and HFL-1 after 48 h. AgNPs significantly increased procollagen I synthesis and release of IL-8, prostaglandin E2, RANTES and eotaxin, whereas reduced IL-6 release was observed in HFL-1 after 72 h. Our data indicate toxic effects of AgNP exposure on cell viability ex vivo and in vitro with altered procollagen and proinflammatory cytokine secretion in fibroblasts over time. Hence, careful characterizations of AgNPs are of importance, and future studies should include timepoints beyond 24 h.
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| 40. |
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| 41. |
- 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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| 42. |
- 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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| 43. |
- 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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| 44. |
- Mörtstedt, Harriet, et al.
(författare)
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Targeted Proteomic Analyses of Nasal Lavage Fluid in Persulfate-Challenged Hairdressers with Bleaching Powder-Associated Rhinitis
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:2, s. 860-873
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Tidskriftsartikel (refereegranskat)abstract
- Hairdressers have an increased risk for developing airway symptoms, for example, asthma and rhinitis. Persulfates, which are oxidizing agents in bleaching powder, are considered important causal agents for these symptoms. However, the underlying mechanisms are unclear. The aim was therefore to measure proteomic changes in nasal lavage fluid from persulfate-challenged subjects to identify proteins potentially involved in the pathogenesis of bleaching powder-associated rhinitis or candidate effect biomarkers for persulfate. Also, oxidized peptides were measured to evaluate their usefulness as biomarkers for persulfate exposure or effect, for example, oxidative stress. Samples from hairdressers with and without bleaching powder-associated rhinitis were analyzed with liquid chromatography tandem mass spectrometry using selected reaction monitoring to target 246 proteins and five oxidized peptides. Pathway analysis was applied to obtain a functional overview of the proteins. Several proteins involved in biologically meaningful pathways, functions, or disorders, for example, inflammatory responses, oxidative stress, epithelium integrity, and dermatological disorders, changed after the persulfate challenge. A list with nine proteins that appeared to be affected by the persulfate challenge and should be followed up was defined. An albumin peptide containing oxidized tryptophan increased 2 h and 5 h after the challenge but not after 20 min, which indicates that such peptides may be useful as oxidative stress biomarkers.
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| 45. |
- Nielsen, Jörn, et al.
(författare)
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Dust-free bleaching powder may not prevent symptoms in hairdressers with bleaching-associated rhinitis
- 2016
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Ingår i: Journal of Occupational Health. - 1341-9145 .- 1348-9585. ; 58:5, s. 470-476
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hairdressers have an increased risk for airway symptoms especially when using hairbleaching powder containing persulfate. To minimize exposure, dust-free bleaching powder (DFP) has been made available. We studied the effects of regular powder (RP) or DFP on the airway symptoms of hairdressers with hair-bleaching associated rhinitis. Methods: Twelve hairdressers each performed three hair-bleachings on a wig in an exposure chamber. Half of the subjects used RP and half used DFP. Exposure to persulfate and ammonia was measured. Before and after each bleaching, the participants stated their degree of airway symptoms on a visual analogue scale. Nasal lavage and blood were sampled before exposure, after the last bleaching, and in the morning after exposure to measure inflammatory markers. Results: Exposure to persulfate was higher when using RP compared to DFP, 22 (11-55) vs. 12 (8- 13) μg/m3; median (min-max). Exposure to ammonia did not differ between the groups. Both groups reported an increase in asthma-like symptoms and this increase was significant. Neutrophils, lymphocytes, and monocytes increased after exposure in both groups; monocytes decreased the day after. In nasal lavage, IL-8 was increased the morning after for both types of powder, and the increase was significant in the total group. IL-6 increased immediately after exposure and the day after only in the group using RP. Conclusions: Although DFP powder emits lower levels of persulfate, effects are still elicited in symptomatic hairdressers.
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| 46. |
- Nilsson, Patrik, et al.
(författare)
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Characterization of Hairdresser Exposure to Airborne Particles during Hair Bleaching.
- 2016
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 1475-3162 .- 0003-4878. ; 60:1, s. 90-100
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory symptoms among hairdressers are often ascribed to the use of bleaching powders that contain persulfate salts. Such salts can act as allergens and airway irritants but the mechanisms behind the negative health effects are not fully known. In order to understand why some hairdressers experience respiratory symptoms during, and after, sessions of hair bleaching, it is of importance to characterize how exposure occurs. In this work we used time and particle size resolved instrumentation with the aim to measure the concentration of particles that hairdressers are exposed to during sessions of hair bleaching. We also used filter samples to collect particles for quantitative determination of persulfate (S2O8 (2-)) content and for analysis by light microscopy. Two different types of bleaching powders were used, one marked as dust-free and one without this marking (denoted regular). The time resolved instrumentation revealed that particles <10 µm were emitted, specifically when the regular powder was prepared and mixed with hydrogen peroxide. In contrast to other research our work also revealed that supercoarse particles (>10 µm) were emitted during application of the bleaching, when both the regular and the dust-free powders were used. The measured level of persulfate, sampled in the breathing zone of the hairdressers, was on average 26 µg m(-3) when the regular powder was used and 11 µg m(-3) when the dust-free powder was used. This indicates that use of dust-free powder does not eliminate exposure to persulfates, it only lowers the concentration. We show that the site of sampling, or position of the hairdresser with regards to the hair being bleached, is of high importance in the determination of persulfate levels and exposure. This work focuses on the physical and chemical characterization of the particles released to the air and the results are important for accurate exposure assessments. Accurate assessments may in turn lead to a better understanding of why some hairdressers experience respiratory symptoms from hair bleaching sessions.
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| 47. |
- Opstal-van Winden, Annemieke W. J., et al.
(författare)
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Searching for early breast cancer biomarkers by serum protein profiling of pre-diagnostic serum; a nested case-control study
- 2011
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort. Methods: In a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS). Results: Two SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3a(desArg)), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3a(desArg) and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer. Conclusions: We show that serum protein profiles are already altered up to three years before breast cancer detection.
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| 48. |
- Petersson Sjögren, Madeleine, et al.
(författare)
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Sensitive methods for assessment of lung health in welders and controls
- 2023
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Ingår i: Respiratory Medicine. - : W.B. Saunders Ltd. - 0954-6111 .- 1532-3064. ; 212
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Tidskriftsartikel (refereegranskat)abstract
- Background: Welders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. Methods: This study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). Results: According to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. Conclusions: This study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so. © 2023 The Authors
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