| 1. |
- Bergquist, Maria, et al.
(författare)
-
Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma
- 2014
-
Ingår i: BMC Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 14, s. 110-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL). Methods: BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex T assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts. Results: Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex T analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation. Conclusion: Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes.
|
|
| 2. |
- Gustafsson, Åsa, et al.
(författare)
-
Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles
- 2014
-
Ingår i: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 326, s. 74-85
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This study examines the immunological responses in rats following inhalation to titanium dioxide nanoparticles (TiO2 NPs), in naïve rats and in rats with induced allergic airway disease. The responses of two different inbred rat strains were compared: the Dark Aguoti (DA), susceptible to chronic inflammatory disorders, and the Brown Norwegian (BN), susceptible to atopic allergic inflammation. Naïve rats were exposed to an aerosol of TiO2 NPs once daily for 10 days. Another subset of rats was sensitized to the allergen ovalbumin (OVA) in order to induce airway inflammation. These sensitized rats were exposed to TiO2 NPs before and during the allergen challenge. Naïve rats exposed to TiO2 NPs developed an increase of neutrophils and lymphocytes in both rat strains. Airway hyperreactivity and production of inflammatory mediators typical of a T helper 1 type immune response were significantly increased, only in DA rats. Sensitization of the rats induced a prominent OVA-specific-IgE and IgG response in the BN rat while DA rats only showed an increased IgG response. Sensitized rats of both strains developed airway eosinophilia following allergen challenge, which declined upon exposure to TiO2 NPs. The level of neutrophils and lymphocytes increased upon exposure to TiO2 NPs in the airways of DA rats but remained unchanged in the airways of BN rats. In conclusion, the responses to TiO2 NPs were strain-dependent, indicating that genetics play a role in both immune and airway reactivity. DA rats were found to be higher responder compared to BN rats, both when it comes to responses in naïve and sensitized rats. The impact of genetically determined factors influencing the inflammatory reactions pinpoints the complexity of assessing health risks associated with nanoparticle exposures.
|
|
| 3. |
- Jonasson, Sofia, 1980-, et al.
(författare)
-
Concomitant administration of nitric oxide and glucocorticoids improves protection against bronchoconstriction in a murine model of asthma
- 2010
-
Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 109:2, s. 521-531
-
Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids (GC) remain the first choice of treatment in asthma, but GC therapy is not always effective and is associated with side effects. In a porcine study in our laboratory, simultaneous administration of GC and nitric oxide (NO) attenuated the endotoxin-induced inflammatory response and made GC treatment more effective than inhaled NO or steroids alone. In the present study, we aimed to further investigate the interactions between NO and GC treatment in two murine models of asthma. Inflammation was induced by endotoxin, ovalbumin, or a combination of both. With an animal ventilator and a forced oscillation method (FlexiVent), lung mechanics and airway reactivity to methacholine in response to various treatments were assessed. We also describe histology and glucocorticoid receptor (GR) protein expression in response to inhaled NO treatment [40 ppm NO gas or NO donors sodium nitroprusside (SNP) or diethylamine NONOate (DEA/NO)]. SNP and GC provided protection against bronchoconstriction to a similar degree in the model of severe asthma. When GC-treated mice were given SNP, maximum airway reactivity was further reduced. Similar effects were seen after DEA/NO delivery to GC-treated animals. Using 1-H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), a soluble guanylate cyclase inhibitor, we found this effect of NO donors to be mediated through a cGMP-independent mechanism. In the severe model, prolonged NO treatment restored or even increased the nuclear levels of GR. In conclusion, in our murine model of severe asthma GC treatment provided protection to only a limited degree against bronchoconstriction, while concomitant treatment with a NO donor was markedly more potent than the use of either NO or GC alone.
|
|
| 4. |
|
|
| 5. |
- Jonasson, Sofia, et al.
(författare)
-
Inhalation exposure of nano-scaled titanium dioxide (TiO2) particles alters the inflammatory responses in asthmatic mice
- 2013
-
Ingår i: Inhalation Toxicology. - : Informa Healthcare. - 0895-8378 .- 1091-7691. ; 25:4, s. 179-191
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Titanium dioxide (TiO2) nanoparticles (NPs) are regarded as relatively non-toxic in concentrations occurring in occupational environments. Nevertheless, it is conceivable that adverse health effects may develop in sensitive populations such as individuals with respiratory diseases.Objective: We investigated whether single or repeated exposure to TiO2 could aggravate inflammatory responses in naive mice and mice with ovalbumin (OVA)-induced airway inflammation.Methods: Exposure to aerosolized TiO2 was performed during OVA sensitization, before, or during the OVA challenge period. The effects on respiratory physiology, inflammatory cells in bronchoalveolar lavage (BAL) and inflammatory mediators in BAL and serum were assessed 24 h after the last OVA challenge or TiO2 exposure.Results: A single exposure of TiO2 had a marked effect on responses in peripheral airways and increasing infiltration of neutrophils in airways of naive animals. Marked aggravation of airway responses was also observed in animals with allergic disease provided that the single dose TiO2 was given before allergen challenge. Repeated exposures to TiO2 during sensitization diminished the OVA-induced airway eosinophilia and airway hyperresponsiveness but concomitant exposure to TiO2 during the OVA challenge period resulted in neutrophilic airway inflammation and a decline in general health condition as indicated by the loss of body weight.Conclusion: We conclude that inhalation of TiO2 may aggravate respiratory diseases and that the adverse health effects are highly dependent on dose and timing of exposure. Our data imply that inhalation of NPs may increase the risk for individuals with allergic airway disease to develop symptoms of severe asthma.
|
|
| 6. |
- Utsi, Sofia, et al.
(författare)
-
Estimation of the risk for early thermal cracking for SCC containing fly ash
- 2012
-
Ingår i: Materials and Structures. - : Springer Science and Business Media LLC. - 1359-5997 .- 1871-6873. ; 45:1-2, s. 153-169
-
Tidskriftsartikel (refereegranskat)abstract
- Cracking of concrete must be avoided during the hardening phase in order to minimize the risk of durability problems in the future, such as corrosion of the reinforcement, water tightness and damages due to frost. Estimation of the risk of early age cracking requires knowledge of the combined effects from temperature development and mechanical behaviour during the hydration. In the present paper, the influence of fly ash on the young concrete behaviour has been investigated. The concrete is based on a Swedish cement aimed for civil engineering structures, and the fly ash is of class F. A comparison of crack risks between concrete containing fly ash in different amounts with concrete without fly ash is presented. Also a previously tested concrete containing limestone filler is considered. The fly ash was added to replace a part of the aggregate, which gives a higher heat evolution. However, a numerical stress analysis showed that the risk for early age through cracking for a typical civil engineering structure is significantly decreased in the mixes containing fly ash. The denotation typical civil engineering structure is used here for concrete structures such as tunnels, bridges, and ramps of common cross-section dimensions. In the case of fly ash added to concrete by a partial replacement of cement, the crack risk will probably be further decreased. For a self-balancing structure of young concrete there is no restraint from adjacent structures, and the temperature and moisture gradients within the young concrete cause self-stresses governed by equilibrium with zero external forces for any cut. The estimated risk for surface cracking on a self-balancing wall or slab was not improved by an addition of fly ash. It is probably an effect of the increased heat development, which most likely counteracts the positive effect of the increased early age creep for concrete containing fly ash. If the heat evolution decreases when cement is partly replaced with fly ash, the use of fly ash might reduce the risk of surface cracks.
|
|
| 7. |
- Utsi, Sofia, et al.
(författare)
-
Influence of different amount of fly ash for early age concrete containing Swedish cement : Part II: Calculation of form stripping times and the risk for early freezing for different amounts of fly ash
- 2010
-
Ingår i: Nordic Concrete Research. - 0800-6377. ; :41, s. 93-108
-
Tidskriftsartikel (refereegranskat)abstract
- A recently presented numerical tendency model has been applied on an assumed civil engineering structure. With the model parameters for heat and strength development calculations in early age period can be calculated. This paper shows the possibility to evaluate e.g. form removal times and estimations of need for protection against early freezing for concrete mixes containing fly ash in different amounts, with different water-to-cement ratios and at different outer conditions. The tendency model has shown to be a useful tool for production planning for concrete containing fly ash. According to the performed calculations, any replacement of cement with fly ash will significantly influence the young concrete properties. The effect on delayed strength growth increases with the increased amount of fly ash and will also increase for lower temperatures. In addition, the effect from fly ash increases at higher water-to-cement ratios
|
|
| 8. |
|
|
| 9. |
- Wallén, Sofia, et al.
(författare)
-
Poliomyelitis Patients In South India – A Study Measuring Quality Of Life
- 2013
-
Konferensbidrag (refereegranskat)abstract
- Introduction The aim of this study was to examine and compare quality of life scores for three different groups with different living situations, all with a history of poliomyelitis and explore factors affecting their scores in four different quality of life domains in India.Method 91 participants with poliomyelitis from three different settings were included in the study. The groups were recruited from city, rural area and urban slum. The WHOQOL-Bref questionnaire was used to measure quality of life in four domains; physical health, psychological health, social relationships and environment.Results Significant difference (p<0,05) were found between the groups in three of the domains. In the physical health and the social relationship domain the group from the city scored significantly higher than the group from the urban slum. In the environmental domain the group from the city and the group from the rural areas scored significantly higher than the group from the urban slum. No significant difference was found in the psychological health domain between any of the three groups.Discussion When treating disabled persons, it is important to not only provide a person with an orthotic device, rehabilitation and inclusion in society is also very important to work with to increase a person’s quality of life.Conclusion It was found that the possibility to maintain the orthopedic devices and the opportunity earn an income influenced the quality of life scores positively. The living environment and rehabilitations services did not influence the scores in the psychological health domain.The study was conducted in collaboration between Mobility India and School of health science, Jönköping University, Sweden.
|
|
| 10. |
- Wigenstam, Elisabeth, et al.
(författare)
-
Corticosteroid treatment inhibits airway hyperresponsiveness and lung injury in a murine model of chemical-induced airway inflammation
- 2012
-
Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 301:1-3, s. 66-71
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Exposure to toxic alkylating mustard agents causes both acute and long-term effects to the lungs as indicated by increased number of inflammatory cells in airways, lung edema and lung tissue fibrosis. We have previously demonstrated that treatment with the corticosteroid dexamethasone 1 h after lung exposure to the nitrogen mustard analog melphalan protects mice from acute and sub-acute inflammatory responses, as well as from lung tissue fibrosis. Objective: In order to address the importance of early anti-inflammatory treatment, we investigated the therapeutic effect of dexamethasone administered 1, 2 or 6 h following exposure to melphalan. Methods: C57BL/6 mice were exposed to melphalan and treated with dexamethasone 1,2 or 6 h after exposure. Twenty hours or 14 days post exposure mice were subjected to analysis of respiratory mechanics where the effects of incremental doses of methacholine on central and peripheral lung components were measured. We also determined the amount of inflammatory cells in the bronchoalveolar lavage fluid and measured the amount of collagen content in the lungs. Results: Melphalan exposure increased airway hyperresponsiveness in both central and peripheral airways and induced an airway inflammation dominated by infiltration of macrophages and neutrophils. Dexamethasone given 1 h after exposure to melphalan provided better protection against airway inflammation than administration 2 or 6 h after exposure. Collagen deposition 14 days after exposure was decreased due to dexamethasone treatment. Conclusion: Early treatment with dexamethasone is important in order to reduce the airway hyperresponsiveness and inflammation caused by toxic alkylating mustards such as melphalan. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
|
|
