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- Alijagic, Andi, 1992-, et al.
(författare)
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Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
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Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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| 2. |
- Andersson Lundell, Anna-Carin, 1976, et al.
(författare)
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Cat allergen induces proinflammatory responses by human monocyte-derived macrophages but not by dendritic cells
- 2005
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Ingår i: Allergy. ; 60:9, s. 1184-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The upper airway mucosa of healthy humans contains a dense network of cells with dendritic morphology of which the majority express a macrophage-like phenotype (CD14+CD64+CD68+), whereas the smaller population are immature dendritic cells (DC; CD11c+CD14-). Our aim was to study the proinflammatory response of human monocytes and in vitro-generated macrophages and DC after contact with cat allergens. METHODS: Monocyte-derived DC and monocyte-derived macrophages were exposed to cat allergen extract or Escherichia coli. Purified monocytes were stimulated with allergen extracts from cat or house dust mite (HDM) or the major allergenic protein Fel d 1 and induction of proinflammatory cytokines by monocytes was analyzed before and after blocking CD14. RESULTS: We show that cat allergen extract induced tumor necrosis factor (TNF) and interleukin (IL)-6 production by CD14-positive macrophages but not by CD14-negative DC. Moreover, monocytes produced significantly higher levels of TNF in response to cat allergens than in response to HDM allergens. We observed no differences in levels of TNF and IL-6 from either macrophages or monocytes after exposure to cat allergen when comparing healthy and cat-allergic individuals. Finally, the proinflammatory cytokine production from monocytes in response to cat allergen extract but not to HDM allergen was significantly reduced by blocking CD14. CONCLUSION: These results indicate that closely related innate immune cells from the myeloid lineage respond differentially to cat allergen extract and that the pattern-recognition receptor CD14 might be one of the mediators involved in the inflammatory responses to inhalant allergens.
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| 4. |
- Beazer, Jack D., et al.
(författare)
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High-density lipoproteins vascular protective functions in metabolic and cardiovascular disease - could extracellular vesicles be at play?
- 2020
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Ingår i: Clinical Science. - : Portland Press on behalf of the Medical Research Society and the Biochemical Society. - 0143-5221 .- 1470-8736. ; 134:22, s. 2977-2986
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Forskningsöversikt (refereegranskat)abstract
- High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health - including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases - both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDLs vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.
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| 5. |
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| 6. |
- Helmfrid, Ingela, 1964-
(författare)
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Exposure and body burden of environmental pollution and risk of cancer in a historically contaminated areas
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There are many villages where environmental contamination is substantial due to historical industrial activities. According to the European Environment Agency, there are about 2.5 million potentially contaminated sites in the European member states. In Sweden, there are about 80 000 more or less contaminated areas. About 1000 of them are classified into the highest risk category, Hazard Class 1, and should be remediated. Population exposure due to these industrially contaminated sites may contribute to adverse health effects and is a global environmental problem.The general aim of this thesis was to evaluate the occurrence of cancer in populations residing in contaminated areas in relation to indirect exposure via the long-term consumption of locally produced food, taking into account residential, occupational and lifestyle factors. Associations between reported local food consumption frequencies, biomarker concentrations and environmental and lifestyle factors were explored. The Swedish national cancer registers and questionnaire information was used to identify cancer risk groups in the study population. The questionnaire was evaluated regarding how well it reflected measured levels of biomarkers in human biological samples, and how the consumption of local food from contaminated areas contributed to the total body burden of contaminants.Despite historically high environmental levels of contaminants in the soil and sediments, current contaminant exposure in the studied population living in the contaminated areas was similar to or only moderately higher than that of the general population.No significant associations with increased cancer risk were detected in the highest tertile of metals concentrations in blood or PAH in urine.Reported long-term high consumption of certain local foods was associated with higher cadmium (vegetarian food) and lead (fish, meat) concentrations in blood and urine. Long-term high consumption of non-local food from places outside the study areas was not associated with increased concentrations of metals compared with consumers of local food. It was concluded that the questionnaire information on consumption of locally produced food describes differences in food consumption in the study population reasonably well.An increased risk of cancer was associated with smoking, family history of cancer and obesity. Residing in a contaminated area during the first five years of life was associated with an increased risk of cancer, which may indicate exposure to contaminants in early life. Also, long-term high consumption of particular local foods (fish, chicken, lamb, game meat) was associated with an increased risk of various forms of cancer, while reported high consumption of these foods from non-local sources was not associated with increased risk of cancer. The associations between habitual consumption of local food and different types of cancer may reflect a higher exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than previously. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.In conclusion, the questionnaire that was developed for the present thesis can identify risk groups within populations and can be used as a tool in a health-risk assessment.
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| 7. |
- Helmfrid, Ingela, 1964-, et al.
(författare)
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Exposure of metals and PAH through local foods and risk of cancer in a historically contaminated glassworks area
- 2019
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 131, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProduction of crystal glass and colored art glassware have been going on in the south-eastern part of Sweden since the 1700s, at over 100 glassworks and smaller glass blowing facilities, resulting in environmental contamination with mainly arsenic (As), cadmium (Cd), lead (Pb) and polycyclic hydrocarbons (PAH). High levels of metals have been found in soil, and moderately elevated levels in vegetables, mushrooms and berries collected around the glassworks sites compared with reference areas. Food in general, is the major exposure source to metals, such as Cd and Pb, and PAHs. Exposure to these toxic metals and PAH has been associated with a variety of adverse health effects in humans including cancer.ObjectiveThe aim of the present study was to evaluate the occurrence of cancer in a cohort from the contaminated glasswork area in relation to long-term dietary intake of locally produced foods, while taking into account residential, occupational and life styles factors.MethodsThe study population was extracted from a population cohort of 34,266 individuals who, at some time between the years 1979–2004, lived within a 2 km radius of a glassworks or glass landfill. Register information on cancer incidence and questionnaire information on consumption of local foods (reflecting 30 years general eating habits), life-time residence in the area, life style factors and occupational exposure was collected. Furthermore, blood (n = 660) and urine (n = 400) samples were collected in a subsample of the population to explore associations between local food consumption frequencies, biomarker concentrations in blood (Cd, Pb, As) and urine (PAH metabolite 1-OHPy) as well as environmental and lifestyle factors. The concurrent exposure to persistent organic pollutants (POPs) from food was also considered. A case-control study was performed for evaluation of associations between intakes of local food and risk of cancer.ResultsDespite high environmental levels of Cd, Pb and As at glasswork sites and landfills, current metal exposure in the population living in the surrounding areas was similar or only moderately higher in our study population compared to the general population. Reported high consumption of certain local foods was associated with higher Cd and Pb, but not As, concentrations in blood, and 1-OHPy in urine. An increased risk of cancer was associated with smoking, family history of cancer, obesity, and residence in glasswork area before age 5 years. Also, a long-term high consumption of local foods (reflecting 30 years general eating habits), i.e. fish and meat (game, chicken, lamb), was associated with increased risk of various cancer forms.ConclusionsThe associations between consumption of local food and different types of cancer may reflect a higher contaminant exposure in the past, and thus, if consumption of local food contributes to the risk of acquiring cancer, that contribution is probably lower today than before. Furthermore, it cannot be ruled out that other contaminants in the food contribute to the increased cancer risks observed.
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| 9. |
- Karlsson, Helen, 1961-, et al.
(författare)
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Lipids and Lipoproteins in Atherosclerosis / Special issue
- 2011
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Ingår i: Journal of Lipids. - : Hindawi Publishing Corporation. - 2090-3030 .- 2090-3049.
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is a focal disease of the arterial wall that leads to cardiovascular disease (CVD), the biggest cause of morbidity and mortality in Western societies. Atherosclerosis is a complex, chronic, progressive disease that affects large and medium-sized arteries. Atherosclerotic lesions are promoted by low-density lipoproteins and form from accumulation of fatty substances, cholesterol, cellular waste products, calcium, and fibrin in the inner lining of the arterial wall. Lipoproteins are complexes of amphipathic proteins with lipids at variable ratios, densities, and sizes. Their role is to transport water-insoluble lipids in the blood. Plasma lipoproteins have traditionally been grouped into five major classes, based on their buoyant density: chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). It is believed that atherogenic lipoproteins, such as LDL and lipoprotein remnants, that float in the VLDL IDL region, promote atherosclerosis, and antiatherogenic lipoproteins, such as HDL, protect from atherosclerosis. Despite many advances in cardiology, atherosclerosis remains an important medical problem suggesting that some steps in pathogenic mechanisms remain unclear.This special issue contains a series of reviews and original research articles that seek to provide insight into the role of lipids and lipoproteins in health and disease with emphasis given on their implication in atherosclerosis.
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| 10. |
- Karlsson, Helen, 1961-
(författare)
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Lipoproteomics : mapping of proteins in LDL and HDL
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- High-density lipoprotein (HDL) and (LDL)-density lipoprotein (LDL) are important lipoprotein fractions in human plasma. HDL is the most abundant lipoprotein particle and a negative risk factor of atherosclerosis while LDL is considered to possess atherogenic properties. The molecular mechanisms underlying the relationship between LDU/HDL and the development of atherosclerosis are not clear. Therefore, detailed information about the protein composition of LDU/HDL may contribute to reveal their role in atherogenesis and the mechanisms that lead to or protect from coronary disease in humans. Here, we sought to map the proteins in human LDL/HDL by a proteomic approach.LDL and HDL were isolated by two-step discontinuous density-gradient ultracentrifugation and the proteins were separated with two-dimensional gel electrophoresis and identified with peptide mass fingerprinting, using matrix assisted laser desorption/ionization-time of flight-mass spectrometry and with amino acid sequencing using electrospray ionization tandem mass spectrometry.In LDL these procedures identified apo B-100, apo C-II, apo C-I (three isoforms), apo E (four isoforms), apo A-I (three isoforms), apo A-IV, apo J and apo M (three isoforms not previously described). In addition, three proteins that have not previously been identified in LDL were found: serum amyloid A-IV (two isoforms). calgranulin A and lysozyme C. The identities of apo M, calgranulin A, and lysozyme C were confirmed by sequence information obtained after collision-induced dissociation fragmentation of pep tides characteristic for these proteins. Moreover, the presence of lysozyme C was further corroborated by demonstrating enriched hydrolytic activity in LDL against Micrococcus lysodeikticus.Identified proteins in HDL were: the dominating apo A-1 as seven isoforms, four of them with a modification pattern and one of them with retained propeptide, apo A-II, apo A-IV, apo C-I. apo C-II, apo C-III (two isoforms), apo E (five isoforms), apo J, the recently discovered apo M (two isoforms), serum amyloid A (two isoforms) and serum amyloid A-IV (six isoforms). Furthermore, alpha-1-antitrypsin was identified in HDL for the first time. Additionally, salivary alpha-amylase was identified as two isoforms in HDL2 , and apo L and aglycosylatcd apo A-II were identified in HDL3.These results indicate that both LDL and HDL contains a number of apolipoproteins, many of them occurs in different isoforms. The demonstration, for the first time, that LDL contains calgranulin A, lysozyme C and apo J raises the possibility that LDL proteins may play hitherto unknown role(s) in immune and inflammatory reactions of the arterial wall. Additionally, new patterns of glycosylated apo A-I and apo A-II and new proteins; alpha-1-antitrypsin and salivary alpha-amylase were detected in HDL. Further investigations about these proteins may give new insight into the functional role of LDL and HDL in coronary artery disease.
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