| 1. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 2. |
- Andersson, Bodil, et al.
(författare)
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Surgical stress response after colorectal resection.
- 2013
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Ingår i: International Surgery. - 0020-8868. ; 98:4, s. 292-299
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Tidskriftsartikel (refereegranskat)abstract
- Abstract The human body's response to surgery is correlated with the extent of tissue damage. The aim of the present study was to, over time, map out parameters concerning inflammation, metabolism, nutrition, breathing function, muscle strength, and well-being in elective colorectal surgery. Eighteen patients were prospectively included: colon resection (n = 9) and rectum resection/amputation (n = 9). Postoperative interleukin 10 (IL-10) rose more in the rectum surgery group on day 0 (P = 0.007) and day 3 (P = 0.025). Furthermore, significant differences between groups were detected regarding albumin, prealbumin, and total iron-binding capacity (TIBC). For albumin and TIBC, this difference was seen even on day 7. C-reactive protein, IL-6, IL-8, glucose, cortisol, insulin, pain, fatigue, nausea, grip strength, and forced expiratory volume in 1 second did not show any differences. No correlation was revealed between measured parameters and postoperative complications. Postoperative levels of IL-10, albumin, prealbumin, and TIBC may be used as determinants of surgical stress after colorectal surgery.
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| 3. |
- Romanelli, F, et al.
(författare)
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Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 4. |
- Alenmyr, Lisa, et al.
(författare)
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Effect of Mucosal TRPV1 Inhibition in Allergic Rhinitis.
- 2012
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 110, s. 264-268
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Tidskriftsartikel (refereegranskat)abstract
- Transient receptor potential vanilloid-1 (TRPV1) has been implicated as a mediator of itch in allergic rhinitis. To address this possibility, we synthesized a TRPV1 blocker (SB-705498) for nasal administration in patients with seasonal allergic rhinitis. The pharmacological activity of SB-705498 was confirmed on human TRPV1-expressing HEK293 cells, using fluorometric calcium imaging, and in patients with allergic rhinitis subjected to nasal capsaicin challenges. The effect of SB-705498 was studied in patients with seasonal allergic rhinitis subjected to daily allergen challenges for seven days, using a double-blind, placebo-controlled, randomized and cross-over design. SB-705498 was delivered by nasal lavage 10 min. before each allergen challenge. Primary end-point was total nasal symptom score on days 5 to 7. Nasal peak inspiratory flow and eosinophil cationic protein content in nasal lavages were also monitored. Daily topical applications of SB-705498 at a concentration that inhibited capsaicin-induced nasal symptoms had no effect on total symptom score, nasal peak inspiratory flow and eosinophil cationic protein levels in allergen-challenged patients with seasonal allergic rhinitis. The individual symptom nasal itch or sneezes was also not affected. These findings may indicate that TRPV1 is not a key mediator of the symptoms in allergic rhinitis. However, additional studies, using drug formulations with a prolonged duration of action, should be conducted before TRPV1 is ruled out as a drug target in allergic rhinitis.
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| 5. |
- Andersson, Jessica, et al.
(författare)
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Quality of Demand-Driven Documentation
- 2014
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Ingår i: Proceedings of the 37th Information Systems Research Seminar in Scandinavia. - 9788773498767
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Konferensbidrag (refereegranskat)abstract
- In this case study we investigate how demand-driven documentation can be used in open source projects. The study relied on questions and answers (demand-driven documenta- tion) posted on Stack Overflow and studied two open source projects, Apache POI and Firefox for Android, in depth. We found that the demand driven documentation provided by the respec- tive community is in general of good quality and contributed within an acceptable amount of time. We conclude that demand driven documentation can be suitable as a primary information source if other resources accompany it. However, the suitability is closely related to the size and activity of the project’s community.
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| 6. |
- Andersson, Morgan, 1965
(författare)
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Användning och användbarhet i särskilda boendeformer för äldre. Aspekter på användning och användbarhet i boendemiljöer för äldre inom den kommunala äldreomsorgen i Göteborg.
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Assisted living facilities for elderly represents the major costs within the budget for eldercare for municipalities in Sweden. As the municipalities are responsible for public eldercare, which consumes a fifth of the total municipal budget, the consequence of the demographic development within the coming decades will imply major challenges for this sector. It also stresses the importance of creating adequate living conditions for the growing number of frail, elderly people. Political measures are underway and involve new housing concepts for senior citizens and changed conditions for assisted living.This PhD-project is ongoing 2009-2013 and is jointly financed by the City of Gothenburg and Chalmers University of Technology. The City has a great interest in research about assisted living facilities, being responsible for the construction and maintenance, as well as the daily use represented by the eldercare providers. It is therefore crucial to understand the prerequisites for usability in existing facilities, in order to create new and adequate environments. The project is expected to contribute to building programming, eldercare facilities planning and property management in the eldercare sector. This thesis is based upon an observation study in five assisted living facilities in Gothenburg. The results provide partial answers to the question: "How are the environments used and how is the usability affected by the physical environment and by the users’ activities?" The results highlight a number of discrepancies between the actual use and the intended use of the environments and their various functions. It also highlights a number of conflicts in use between different users or groups of users, along with differing purposes for the use of the premises.The thesis points to the complex relationship between use and activity and emphasizes the need for adequate planning concerning eldercare facilities. Particular attention must to be given to the relationship between facilities, staff and elderly and their use of the facilities. From a practical point of view the study shows how changes in use over time can have a negative effect on the daily activities. To develop an understanding of processes evolving in daily use of assisted living facilities, further studies needs to include the users' attitudes in order to better understand the context for activities in the facilities.
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| 7. |
- Andersson, Morgan, 1965, et al.
(författare)
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ASSISTED LIVING FACILITIES FOR THE OLD – ASPECTS OF USE AND USABILITY
- 2010
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Ingår i: HaCIRIC 2010, Edinburgh Scotland, PhD Workshop: Better healthcare through better infrastructure. 22 September 2010. Conference proceedings. ; , s. 29-36
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Konferensbidrag (refereegranskat)abstract
- A growing number of old citizens and fewer working to support them is a reality in Sweden. More knowledge about assisted living facilities is crucial in creating appropriate care environments for the oldest. The study is part of a PhD project that explores use and usability in assisted living facilities for the old in Gothenburg, Sweden. This paper reports upon the observation study conducted November 2009-February 2010 in five facilities in Gothenburg, along with the other methods used in the PhD project. The aim of this study is to observe the daily use and thereby identify factors in the physical environment, affecting usability. Some preliminary findings are accounted for. Semi-structured interviews and a questionnaire survey are scheduled for 2011-2012. The city of Gothenburg and Chalmers finance the project and are the primary users of the results.
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| 8. |
- Andersson, Morgan, 1965
(författare)
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Assisted Living: Long-term housing solution or short-term care at the end of life?
- 2014
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Ingår i: 22nd Nordic Congress of Gerontology, Gothenburg, 25-28 May 2014.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This research project displays the objectives for AL – residence and care – from the architectural discipline. These dichotomous objectives bring about conflicts in the use of the physical environments. It is suggested that the long-term perspective of residence and home is in conflict with the short-term care perspective. Assisted Living (AL) in Sweden displays great similarities with AL in other countries, although eldercare may be differently organized. The similarities entail a physical structure with subdivision in residential groups of apartments with shared common spaces for communal activities. They also entail an organizational structure with common activities, medical care and front-line staff (FLS) available around the clock. Residents in Swedish AL facilities are increasingly old and more multi-diseased, mainly due to increased efforts in home-based care and services. In order to meet with the changing user requirements the typology of AL has to be discussed both in a national and international context.The research is based on empirical material from observations, interviews and questionnaires in Swedish eldercare and relates to the ongoing discussion on special housing for older people in Sweden and other countries. The results suggest that efforts to create a long-term home-like residential environment are discernible on several levels: in legislation and guidelines, in the organizations and in the local routines. In contrast to these efforts, short-term care aspects tend to dominate as more AL residents become in need of end-of-life (EOL) care. This entails changing user requirements with increased focus on medical measures and more use of supportive technology. Swedish legislation equals AL and ordinary housing, with the exception that AL contains common spaces in addition to the individual apartments. The typological discussion contains issues concerning physical structure; size, number of residents, the design of common spaces and differences between specialized units or groups for people with dementia (SDUs) and ordinary AL.
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| 9. |
- Andersson, Morgan, 1965, et al.
(författare)
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Att skapa hemkänsla på särskilt boende
- 2014
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Ingår i: Vårdmiljöns betydelse. - 9789144078113 ; , s. 123-144
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Vårdmiljöforskning genomgår en expansiv utveckling och är i fokus inom vård och arkitektur. Denna bok gör något så ovanligt som att omfatta bägge perspektiven i beaktandet av såväl de fysiska som psykosociala aspekterna av vårdmiljön. Den röda tråden genom boken är att se vårdmiljön som en central del i vårdandet och behandlingen, oavsett om det handlar om intensivvårdens högteknologiska miljöer, den psykiatriska slutenvården eller skapandet av hemkänsla inom äldrevårdens särskilda boenden.
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| 10. |
- Andersson, Morgan, et al.
(författare)
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Barrier-enforcing measures as treatment principle in allergic rhinitis: a systematic review
- 2014
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 30:6, s. 1131-1137
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Forskningsöversikt (refereegranskat)abstract
- Background and objectives Barrier-enforcing measures have been suggested as treatment options for allergic rhinitis. This review identifies and describes the literature on the subject. Methods Relevant publications were searched for in the PubMed database (search entries: 'allergic rhinitis' and 'treatment'). The evaluation comprised condition (seasonal or perennial allergic rhinitis), type of intervention, duration of treatment, study design, peer review status or not, number of test subjects, type of allergen exposure, and outcome in terms of effects or not on nasal symptoms of allergic rhinitis. Results Fifteen studies were either identified in the PubMed database search or from the reference lists of identified publications. Seven were placebo-controlled, randomized, and peer-reviewed, and symptom-reducing effects were reported by all of these reports. Limitations of this review reflect that the remainder of the studies had inferior designs, particularly lack of placebo control. Conclusions Barrier-enforcing measures as achieved by nasal administrations of cellulose powder and microemulsions, respectively, have symptom-reducing effects in allergic rhinitis.
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| 11. |
- Andersson, Morgan, 1965
(författare)
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Common spaces in assisted living for older persons. Aspects of usability from the residential and workplace perspectives.
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is about space. It assumes that space forms a necessary part of the structure of existence. The architectural space becomes an existential space in the encounter with the user. Common unit spaces in assisted living (AL) for older persons are the principal venue for social interaction and have no parallel in ordinary housing. The usability of these spaces is discussed here from the residential and workplace perspectives. These perspectives are explored in relation to the concept of AL and involve residents, staff and other stakeholders in buildings in use. Special housing for older people is currently in focus worldwide due to demographic develop-ments, entailing an increasing proportion of older people. Residents in AL are increasingly old and multi-diseased, which changes the conditions for residential care in its present form.Four methods were used, involving 14 AL facilities (ALFs) in Sweden: observations, group interviews, individual interviews and self-completion questionnaires. An explorative strategy was adopted, combining qualitative and quantitative methods to enhance the validity of the results. The results were analysed using statistical analyses, Qualitative Content Analysis (QCA) and triangulation.The results show functional demarcations between apartments, dining rooms, sitting rooms and kitchens in a private-public continu¬um, with varying adherence to the respective residential and workplace perspectives. It also shows that these perspectives entail diverging objectives for use of the common spaces. The dining rooms were utilized most by the residents, but the kitchens were not used at all. The daily activities promote a focus on collective aspects above individual needs. The increasing use of assistive technology causes space shortages and suggests a mismatch between the actual users and the users conceptualised at the planning stage, which entails a focus on care aspects at the expense of the residential perspective. It shows that the common spaces are not perceived as a part of the home environment; rather an addition. The dementia and somatic units presented diverging objectives for use, but the physical environ-ments did not differ significantly. The functions of the common spaces were perceived differently among users, planners and architects. This suggests that these spaces have ambiguous meanings in a social context and may lead to ineffective use of the spaces. Along with a complicated body of regulations, this calls for a redefinition of AL. Design strategies are suggested that are more up-to-date with the users’ needs in relation to the usability of the common spaces. The residential and workplace perspectives have to be considered concomitantly when planning ALFs, otherwise inherent conflicts will become manifest as a result of the physical design, which affects usability.
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| 12. |
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| 13. |
- Andersson, Morgan, et al.
(författare)
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Effects of a topical microemulsion in house dust mite allergic rhinitis.
- 2011
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 108:2, s. 146-148
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Tidskriftsartikel (refereegranskat)abstract
- We have previously demonstrated that a topical microemulsion can attenuate symptoms and signs of seasonal allergic rhinitis. This likely reflects that the microemulsion interferes with the interaction between the allergen and the mucosa. Whether or not the finding translates to conditions caused by other inhaled agents such as house dust mite allergen is unknown. Patients with perennial allergic rhinitis caused by house dust mite were subjected to topical microemulsion treatment in a randomized, double-blinded and crossover design with isotonic saline as control. Morning symptoms were monitored, change from baseline was assessed and the treatments were compared. On the first days of the isotonic saline and microemulsion runs, before any treatment was given, total nasal symptoms were scored to 2.8 and 3.1 (range 0-9), respectively. Nasal symptoms were reduced by intervention with the microemulsion: the change from baseline was consistent for the microemulsion and the difference between the microemulsion and isotonic saline reached statistical significance in favour of the former. We conclude that intervention with a microemulsion may reduce symptoms of house dust mite allergic rhinitis at natural allergen exposure. Our findings suggest the possibility that topical microemulsions can be a useful option to reduce nasal mucosal exposure to allergen in perennial allergic rhinitis..
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| 14. |
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| 15. |
- Andersson, Morgan, 1965, et al.
(författare)
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Exploring the Function and Use of Common Spaces in Assisted Living for Older Persons
- 2014
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Ingår i: HERD. - : SAGE Publications. - 2167-5112 .- 1937-5867. ; 7:3, s. 98-119
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This exploratory study examines the function and use of common spaces in assisted living facilities (ALFs) from the residential and workplace perspectives.BACKGROUND: The impact of the physical environment on human activities in healthcare settings has been emphasized in many studies. Few studies, however, have explored the daily use of common spaces and theimpact on the usability of ALFs.METHODS: Four explorative methods–observation, group interviews, individual interviews, and questionnaires—were used to investigate 14 ALFs in Sweden. The study involves residents, staff, relatives, architects, and people responsible for planning and construction of eldercare.This research strategy combines quantitative and qualitative methods to enhance the validity of the results. Method triangulation and data triangulationwere used and the data were analyzed using Qualitative Content Analysis (QCA).RESULTS: The results show that residents and staff have different objectives for use and these differences affect usability, although explicit conflicts are rare. The residents, staff, and other stakeholders have differentviews about the demarcation of home and workplace and the role of common spaces as venues for social interaction.CONCLUSIONS: Both the residential and the workplace perspective must be considered when planning assisted living facilities. Otherwise, inherent conflicts between these perspectives will manifest as a result of thephysical design. Common spaces have diverse functions that are reflected in their spatial organization. Therefore, ALFs should be designed so the intended function of a specific space is apparent to all users.
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| 16. |
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| 17. |
- Andersson, Morgan, 1965, et al.
(författare)
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New Swedish forensic psychiatric facilities: visions and outcomes.
- 2013
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Ingår i: Facilities. - : Emerald. - 0263-2772 .- 1758-7131. ; 31:1/2, s. 24-38
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – The purpose of this paper is to map significant features of the physical design of nine recently planned facilities for forensic psychiatric care in Sweden. The present paper is focused on differences in the physical design, static security adaptations, visions and goals for the projects, economy and steering processes. Design/methodology/approach – In June 2008, records concerning major forensic psychiatric construction projects, planned or carried out between 1970 and 2008, were requested from all 21 regions in Sweden. The documents were collected, organized, critically examined, and analyzed in their contexts. Extensive data have also been retrieved from the internet. Findings – In spite of the common national legislation governing forensic psychiatric care, the projects show great diversity in the physical design and, after 2006, increasing emphasis on static security. The collected material indicates different visions and goals and little coordination between them. It also suggests that the decisions rarely have been preceded by scientific studies or, as it appears, systematic needs assessments. There were also considerable variations in the interpretation of the legislation stipulating public access to official documentation and the time-frame allowed for such requests. Research limitations/implications – Limitations of the project especially relate to the incompleteness of the documents received. Originality/value – This mainly descriptive paper provides an overview of contemporary Swedish forensic psychiatric construction projects, planned for or realized after 2000. This paper points out structural and physical differences between these projects. The systematised documents are made available for research purposes within different disciplines.
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| 18. |
- Andersson, Morgan, 1965, et al.
(författare)
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Participant Observation Study of Use and Usability on five Assisted Living Facilities for the Old in Gothenburg Sweden
- 2010
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Ingår i: ENHR 2010, 4-7 July, ISTANBUL, 22nd International Housing Research Conference. WS-15: HOUSING AND LIVING CONDITIONS OF AGEING POPULATIONS. Conference proceedings. ; , s. 1-14
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Konferensbidrag (refereegranskat)abstract
- This participant observation study was conducted November 2009-February 2010 in 14 units in five assistantliving facilities for the old in Gothenburg, Sweden. The aim is to study the daily use and aspects of use, related tothe design of the physical environments. Areas of interest, based upon these aspects and related to usability, arepresented and discussed in this paper. The study is the first part of a case study, within a PhD-project, comprisingparticipant observations and qualitative interviews. More knowledge about assisted living facilities is asked forboth by the eldercare providers and by the construction clients in order to enable appropriate care environmentsfor the oldest. This knowledge is now produced in the architecture academies. The City of Gothenburg andChalmers jointly finance the project and are the primary users of the project results. This paper presents anddiscusses some preliminary findings and gives a short description of methods and the research field.
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| 19. |
- Andersson, Morgan, 1965
(författare)
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The relativity of common room usability in assisted living
- 2014
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Ingår i: Proceedings of the RGS-IBG Annual International Conference 2014. London 26-29 August. Session title: The geographies of architecture, knowledge and care..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Usability is created in negotiation between environment and users, or between human and non-human actors. In contrast to this relational approach, architecture practices focus on normative aspects of the built environment from artistic and technological perspectives. The usability of care environments, here in assisted living, is related to a necessary architectural generality of institutional contexts, which counteracts personalization. Common rooms in assisted living are designed for shared social activities, in which ambiguous meanings emerge to the users and position the rooms in an unclear location in a private-public continuum. The usability of these rooms is generated both by the users’ disparate understanding of the spaces in a social context and the evasiveness of a private-public dichotomy. Normative aspects of the design processes are discernible, in contrast to relational aspects of usability, which are the result of user-artefact interaction over time.
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| 20. |
- Andersson, Morgan, 1965, et al.
(författare)
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Use and Usability of Assisted Living Facilities for the Elderly. An observation study in Gothenburg Sweden.
- 2011
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Ingår i: Journal of Housing for the Elderly. - : Informa UK Limited. - 0276-3893 .- 1540-353X. ; 25:4, s. 380-400
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Tidskriftsartikel (refereegranskat)abstract
- To meet the demographic development, measures were initiated by the Swedish government entailing changed conditions for municipal eldercare, such as assisted living. Participant observation is used to study the daily use of common spaces in 14 assisted living units in Gothenburg. The results show examples where the currentuse diverges from the intended use and suggest diverging objectives and conflicts of use. The observations indicate that the degree of usability is determined by the physical environment itself in some cases, by the users and by changes in use in other cases, and by a combination of both in some cases.
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| 21. |
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| 22. |
- Brandelius, Angelica, et al.
(författare)
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dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.
- 2011
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Ingår i: Pulmonary Pharmacology & Therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; 24, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Thymic Stromal Lymphopoietin (TSLP) is considered a hub cytokine that activates dendritic cells and T-cells producing asthma-like Th(2)-inflammation. Viral stimuli, a major cause of asthma exacerbations, have been shown to induce overexpression of TSLP in asthmatic epithelium. Capsazepine has multiple effects and is of interest because it relaxes human small airways. Here we have explored effects of capsazepine on viral surrogate (dsRNA)-induced TSLP and other cytokines (TNF-alpha, IL-8) in human bronchial epithelial cells (HBEC) from healthy and asthmatic donors. METHODS: HBEC obtained from healthy and asthmatic subjects were grown and stimulated with dsRNA. Cells pre-treated with capsazepine (3-30μM), dexamethasone (0.1-10μM) or an IkappaB-kinase inhibitor (PS1145, 30μM) were also exposed to dsRNA (10μg/ml). Cells and supernatants were harvested for analyses of gene expression (RT-qPCR) and protein production (ELISA,Western blot). RESULTS: dsRNA-induced TSLP, TNF-alpha, and IL-8 in asthmatic and non-asthmatic HBEC. Dexamethasone attenuated gene expression and protein release whereas capsazepine dose-dependently, and similar to a non-relaxant NFkB inhibitor (PS1145), completely inhibited dsRNA-induced TSLP and TNF-alpha in both healthy and asthmatic HBEC. Capsazepine reduced dsRNA-induced IL-8 and it prevented dsRNA-induced loss of the NF-κB repressor protein IkBα. CONCLUSION: Additional to its human small airway relaxant effects we now demonstrate that capsazepine has potent anti-inflammatory effects on viral stimulus-induced cytokines in HBEC from healthy as well as asthmatic donors. Based on these data we suggest that exploration of structure-activity amongst the multifaceted capsazepinoids is warranted in search for compounds of therapeutic value in viral-induced, steroid-resistant asthma.
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| 23. |
- Brandelius, Angelica, et al.
(författare)
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Selective inhibition by simvastatin of IRF3 phosphorylation and TSLP production in dsRNA-challenged bronchial epithelial cells from COPD donors.
- 2012
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188.
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Statin treatment may ameliorate viral infection-induced exacerbations of chronic obstructive pulmonary disease (COPD), which exhibit Th2-type bronchial inflammation. Thymic stromal lymphopoietin (TSLP), a hub cytokine switching on Th2-inflammation, is overproduced in viral and dsRNA-stimulated bronchial epithelial cells from COPD donors. Hence, TSLP may be causally involved in exacerbations. This study tests our hypothesis that simvastatin may inhibit dsRNA-induced TSLP. Experimental approach: Epithelial cells, obtained by bronchoscopy from COPD (n=7) and smoker control (n=8) donors, were grown and stimulated with viral infection and danger signal surrogate, dsRNA (10 µg·mL(-1) ). Cells were treated with simvastatin (0.2-5 µg·mL(-1) ), with or without mevalonate (13-26 µg·mL(-1) ), or dexamethasone (1 µg·mL(-1) ) prior to dsRNA. Cytokine expression and production, and transcription factor (IRF3 and NF-κB) activation were determined. Key results: dsRNA induced TSLP, TNFα, CXCL8, and IFNβ. TSLP was overproduced in dsRNA-exposed COPD cells compared to control. Simvastatin, concentration-dependently, but not dexamethasone, inhibited dsRNA-induced TSLP. Unexpectedly, simvastatin acted independent of mevalonate and did not affect dsRNA-induced NF-κB activation nor did it reduce production of TNFα and CXCL8. Instead, simvastatin inhibited dsRNA-induced IRF3 phosphorylation and generation of IFNβ. Conclusions and implications: Independent of mevalonate and NF-κB, previously acknowledged anti-inflammatory mechanisms of pleiotropic statins, simvastatin selectively inhibited dsRNA-induced IRF3 activation and production of TSLP and IFNβ in COPD epithelium. These data provide novel insight into epithelial generation of TSLP and suggest paths to be exploited in drug discovery aimed at inhibiting TSLP-induced pulmonary immunopathology.
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| 24. |
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| 25. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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