| 1. |
- Klarström-Engström, Kristin, 1986-, et al.
(författare)
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Toll like receptor 2/1 mediated platelet adhesion and activation on bacterial mimetic surfaces is dependent on src/Syk-signaling and purinergic receptor P2X1 and P2Y12 activation
- 2014
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 9:4, s. 041003-
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Tidskriftsartikel (refereegranskat)abstract
- Platelets are considered to have important functions in inflammatory processes as key players in innate immunity. Toll like receptors (TLRs), expressed on platelets, recognize pathogen associated molecular patterns and trigger immune responses. Pathogens are able to adhere to human tissues and form biofilms which cause a continuous activation of the immune system. The authors aimed to investigate how immobilized Pam(3)CSK(4) (a synthetic TLR2/1 agonist) and IgG, respectively, resembling a bacterial focus, affects adhesion and activation of platelets including release of two cytokines, regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage migration inhibitory factor (MIF). The authors also aim to clarify the signaling downstream of TLR2/1 and Fc gamma RII (IgG receptor) and the role of adenine nucleotides in this process. Biolayers of Pam(3)CSK(4) and IgG, respectively, were confirmed by null-ellipsometry and contact angle measurements. Platelets were preincubated with signaling inhibitors for scr and Syk and antagonists for P2X1 or P2Y1 [adenosine triphosphate (ATP), adenosine diphosphate (ADP) receptors] prior to addition to the surfaces. The authors show that platelets adhere and spread on both Pam(3)CSK(4)- and IgG-coated surfaces and that this process is antagonized by scr and Syc inhibitors as well as P2X1 and P2Y antagonists. This suggests that Pam(3)CSK(4) activated platelets utilize the same pathway as Fc gamma RII. Moreover, the authors show that ATP-ligation of P2X1 is of importance for further platelet activation after TLR2/1-activation, and that P2Y12 is the prominent ADP-receptor involved in adhesion and spreading. RANTES and MIF were secreted over time from platelets adhering to the coated surfaces, but no MIF was released upon stimulation with soluble Pam(3)CSK(4). These results clarify the importance of TLR2/1 and Fc gamma RII in platelet adhesion and activation, and strengthen the role of platelets as an active player in sensing bacterial infections.
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| 2. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 3. |
- Abrikossova, Natalia, et al.
(författare)
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Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes
- 2012
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Ingår i: Nanotechnology. - Bristol, United Kingdom : IOP Publishing Ltd.. - 0957-4484 .- 1361-6528. ; 23:27
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.
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| 4. |
- Ahrén, Maria, et al.
(författare)
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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
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Tidskriftsartikel (refereegranskat)abstract
- Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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| 5. |
- Bengtsson, Anna, et al.
(författare)
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Outdoor Environments at Three Nursing Homes: Semantic Environmental Descriptions
- 2015
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Ingår i: Journal of Housing for the Elderly. - : Informa UK Limited. - 0276-3893 .- 1540-353X. ; 29, s. 53-76
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Tidskriftsartikel (refereegranskat)abstract
- Research suggests that the outdoor environment is an important source of variety and change as well as health and well-being for nursing home residents. However, not every outdoor environment has the potential to be a positive resource in the life of older persons at nursing homes, and in this respect we need to study the particular design and content of the outdoor environment. The semantic environmental description (SMB) is a quantitatively based standardized tool intended to systematically describe an environment through assessments of 8 dimensions, namely: pleasantness, complexity, unity, enclosedness, potency, social status, affection, and originality. In this study the SMB was used to compare the outdoor environment of an imagined ideal nursing home and the outdoor environments of 3 existing nursing homes. Furthermore, assessments of an imagined ideal nursing home by pensioners and by nursing home staff were compared. The environment that was the closest to the ideal environment according to the assessments was a park-like environment that was larger and had more variation in vegetation than the other environments. The article concludes by discussing the SMB dimensions in relation to important environmental qualities in nursing home gardens.
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| 6. |
- Bengtsson, Caroline, et al.
(författare)
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Chronic rhinosinusitis impairs sleep quality : results of the GA(2)LEN study
- 2017
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 40:1
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVES: To analyse the prevalence of sleep problems in subjects with CRS and to determine whether the disease severity of CRS affects sleep quality.METHODS: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria. The disease severity of CRS was defined by the number of reported CRS symptoms. Sleep quality was assessed using the Basic Nordic Sleep Questionnaire.RESULTS: Of the 26 647 subjects, 2249 (8.4%) had CRS. Reported sleep problems were 50-90% more common among subjects with CRS compared with those without or the total population. The prevalence of reported sleep problems increased in conjunction with the severity of CRS. After adjusting for gender, BMI, age, tobacco use, asthma, somatic diseases, physical activity level and educational level, participants with four symptoms of CRS (compared with subjects without CRS symptoms) displayed a higher risk of snoring (adj. OR (95% CI): 3.13 (2.22-4.41)), difficulties inducing sleep (3.98 (2.94-5.40)), difficulties maintaining sleep (3.44 (2.55-4.64)), early morning awakening (4.71 (3.47-6.38)) and excessive daytime sleepiness (4.56 (3.36-6.18)). The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems.CONCLUSIONS: Sleep problems are highly prevalent among subjects with CRS. The disease severity of CRS negatively affects sleep quality.
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| 7. |
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| 8. |
- Bengtsson, Caroline, et al.
(författare)
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Impact of nasal obstruction on sleep quality : a community-based study of women
- 2015
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Ingår i: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 272:1, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to analyse the impact of self-reported nasal obstruction on sleep quality in women. A community-based sample of 400 women underwent a full night of polysomnography. Airway diseases, allergies and sleep-related symptoms were assessed by questionnaires. Women with subjective nasal obstruction were subdivided into three groups: persistent nasal obstruction (PNO, n = 46), hay fever (n = 88) and nasal obstruction at night (NON, n = 30). Sleep problems and related daytime symptoms were most prevalent among women with NON. After adjusting for age, BMI, smoking and asthma, NON was an independent predictor of 'Difficulties inducing sleep due to nasal obstruction' [adjusted odds ratio (95 % CI): 89.5 (27.0-296.7)], 'Snoring' [4.2 (1.7-10.2)], 'Sweating at night' [2.6 (1.1-6.1)], 'Difficulties maintaining sleep' [2.7 (1.2-6.2)], and 'Waking up hastily gasping for breath' [32.2 (8.7-119.1)]. 'Dry mouth on awakening' [7.7 (3.2-18.4)], 'Waking up unrefreshed' [2.7 (1.2-6.0)], 'Excessive daytime sleepiness' [2.6 (1.1-6.0)], and 'Daytime nasal obstruction' [12.2 (4.8-31.2)] were also associated with NON. Persistent nasal obstruction and hay fever were both associated with some reported sleep problems due to an overlap with NON. When women with NON were excluded, only 'Daytime nasal obstruction' was still significantly associated with PNO, while hay fever was associated with 'Daytime nasal obstruction' and 'Waking up hastily gasping for breath'. There were no significant differences in objectively measured sleep variables between any of the three subgroups and the study cohort. Self-reported nasal obstruction at night in women has a significant effect on several subjective day- and nighttime symptoms, but it does not appear to affect objectively measured sleep quality.
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| 9. |
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| 10. |
- Bengtsson, Caroline, et al.
(författare)
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Incident chronic rhinosinusitis is associated with impaired sleep quality: Results of the RhiNE study
- 2019
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Ingår i: Journal of Clinical Sleep Medicine. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:6, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Study Objectives: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the nasal cavity and paranasal sinuses. Associations between CRS and poor sleep quality have been reported. This 10-year follow-up study investigates possible associations between incident CRS and sleep quality. Methods: A questionnaire was sent to 16,500 individuals in Sweden, Norway, Denmark, Iceland and Estonia in 2000. It included questions on airway diseases, age, sex, body mass index, smoking habits, comorbidities, education and sleep quality. In 2010, a second questionnaire was sent to the same individuals, with a response rate of 53%. A subgroup of 5,145 individuals without nasal symptoms in 2000 was studied. Multiple logistic regression was performed to examine associations between CRS (defined according to the European position paper on rhinosinusitis and nasal polyps epidemiological criteria) at follow-up and sleep quality, with adjustment for potential confounders. Individuals with the respective sleep problem at baseline were excluded. Results: Over 10 years, 141 (2.7%) of the individuals without nasal symptoms in 2000 had developed CRS. CRS was associated with difficulties inducing sleep (adjusted odds ratio 2.81 [95% CI 1.67–4.70]), difficulties maintaining sleep (2.07 [1.35–3.18]), early morning awakening (3.03 [1.91–4.81]), insomnia (2.21 [1.46–3.35]), excessive daytime sleepiness (2.85 [1.79–4.55]), and snoring (3.31 [2.07–5.31]). Three insomnia symptoms at baseline increased the risk of CRS at follow-up by 5.00 (1.93–12.99). Conclusions: Incident CRS is associated with impaired sleep quality and excessive daytime sleepiness. Insomnia symptoms may be a risk factor for the development of CRS. © 2019 American Academy of Sleep Medicine. All rights reserved.
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