| 11. |
- Bølling, Anette Kocbach, et al.
(author)
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Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines.
- 2012
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In: Particle and fibre toxicology. - : Springer Science and Business Media LLC. - 1743-8977. ; 9:1
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Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Exposure to particulate matter (PM) has been linked to several adverse cardiopulmonary effects, probably via biological mechanisms involving inflammation. The pro-inflammatory potential of PM depends on the particles' physical and chemical characteristics, which again depend on the emitting source. Wood combustion is a major source of ambient air pollution in northern countries during the winter season. The overall aim of this study was therefore to investigate the cellular responses to wood smoke particles (WSPs) collected from different phases of the combustion cycle, and from combustion at different temperatures. RESULTS: WSPs from different phases of the combustion cycle induced very similar effects on pro-inflammatory mediator release, cytotoxicity and cell number, whereas WSPs from medium-temperature combustion were more cytotoxic than WSPs from high-temperature incomplete combustion. Furthermore, comparisons of effects induced by native WSPs with the corresponding organic extracts and washed particles revealed that the organic fraction was the most important determinant for the WSP-induced effects. However, the responses induced by the organic fraction could generally not be linked to the content of the measured polycyclic aromatic hydrocarbons (PAHs), suggesting that also other organic compounds were involved. CONCLUSION: The toxicity of WSPs seems to a large extent to be determined by stove type and combustion conditions, rather than the phase of the combustion cycle. Notably, this toxicity seems to strongly depend on the organic fraction, and it is probably associated with organic components other than the commonly measured unsubstituted PAHs.
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| 12. |
- Callaghan, Terry, et al.
(author)
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Multi-Decadal Changes in Tundra Environments and Ecosystems : Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF)
- 2011
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In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:6, s. 705-716
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Journal article (peer-reviewed)abstract
- Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
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| 13. |
- Friberg, Lena E, et al.
(author)
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Scaling the time-course of myelosuppression from rats to patients with a semi-physiological model
- 2010
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In: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 28:6, s. 744-753
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Journal article (peer-reviewed)abstract
- AIM: To investigate the potential of a model for chemotherapy-induced myelosuppression to predict the full time-course of myelosuppression in patients based on rat data. METHODS: White blood cell counts were determined in rats after administration of 5-fluorouracil, epirubicin, cyclophosphamide, docetaxel, paclitaxel or etoposide. Pharmacokinetic models were used to predict the concentration-time profile in each rat. A semi-physiological model of myelosuppression was applied to the rat data. The drug-related parameter Slope was allowed to differ between drugs. The analysis was performed in NONMEM VI. Time-courses of myelosuppression in patients were predicted for each drug based on patient pharmacokinetic models, typical system-related parameters previously determined in patients and the rat Slope estimates in the present study. RESULTS: The semi-physiological model of myelosuppression fit the rat data well and the estimated maturation time in rats (53 h) was approximately half of the previous estimate in patients. The relative difference in Slope estimates for rats and patients based on total drug concentrations ranged between 28% to 8-fold for the six drugs. The differences reduced to 8-37% for all drugs when correcting the rat Slope estimates for species difference in protein binding and in CFU-GM assay sensitivity. CONCLUSIONS: This method for interspecies scaling was successful in predicting the time-course of myelosuppression in patients based on rat data. Predictions improved when species differences in protein binding and CFU-GM assay sensitivity were accounted for. The approach appears promising for predicting myelosuppression in patients early in development.
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| 14. |
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| 15. |
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| 16. |
- Hansson, Emma K., et al.
(author)
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Limited inter-occasion variability in relation to inter-individual variability in chemotherapy-induced myelosuppression
- 2010
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 65:5, s. 839-848
-
Journal article (peer-reviewed)abstract
- Purpose: A previously developed semi-physiological model of chemotherapy-induced myelosuppression has shown consistent system-related parameter and inter-individual variability (IIV) estimates across drugs. A requirement for dose individualization to be useful is relatively low variability between treatment courses (IOV) in relation to IIV. The objective of this study was to evaluate and compare magnitudes of IOV and IIV in myelosuppression model parameters across six different anti-cancer drug treatments.Methods: Neutrophil counts from several treatment courses following therapy with docetaxel, paclitaxel, epirubicin-docetaxel, 5-fluorouracil-epirubicin-cyclophosphamide, topotecan and etoposide were included in the analysis. The myelosuppression model was fitted to the data using NONMEM VI. IOV in the model parameters baseline neutrophil counts (ANC0), mean transit time through the non-mitotic maturation chain (MTT) and the parameter describing the concentration-effect relationship (Slope) were evaluated for statistical significance (P < 0.001).Results: IOV in MTT was significant for all the investigated datasets, except for topotecan, and was of similar magnitude (8-16 CV %). IOV in Slope was significant for docetaxel, topotecan and etoposide (19-39 CV %). For all six investigated datasets the IOV in myelosuppression parameters was lower than the IIV. There was no indication of systematic shifts in the system- or drug sensitivity-related parameters over time across data sets.Conclusion: This study indicates that the semi-physiological model of chemotherapy-induced myelosuppression has potential to be used for prediction of the time-course of myelosuppression in future courses and is thereby a valuable step towards individually tailored anticancer drug therapy.
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| 17. |
- Hedberg, Maria E., et al.
(author)
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Prevotella jejuni sp. nov., isolated from the small intestine of a child with celiac disease.
- 2013
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In: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5034 .- 1466-5026. ; 63:11, s. 4218-4223
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Journal article (peer-reviewed)abstract
- Five obligately anaerobic, Gram-negative, saccharolytic and proteolytic, non-spore-forming bacilli (CD3:27, CD3:28T, CD3:33, CD3:32 and CD3:34) are described. All five strains were isolated from the small intestine of a female child with celiac disease. The cells of the five strains were observed to be short rods or coccoid cells with longer filamentous forms seen sporadically. The organisms produced acetic acid and succinic acid as major metabolic end products. Phylogenetic analysis, based on comparative 16S rRNA gene sequence analysis revealed close relationships between CD3:27, CD3:28T and CD3:33 on one hand, between CD3:32 and P. histicola CCUG 55407T and between CD3:34 and P. melaninogenica CCUG 4944BT on the other. The strains CD3:27, CD3:28T and CD3:33 were clearly different from any other species within the genus Prevotella and most closely related to but distinct from P. melaninogenica. Based on 16S rRNA gene, RNA polymerase β-subunit gene and 60-kDa chaperonin protein subunit gene sequencing, phenotypic, chemical and biochemical properties strains CD3:27, CD3:28T and CD3:33 have been determined to represent a novel species within the genus Prevotella, named Prevotella jejuni sp. nov. Strain CD3:28T (CCUG 60371T = DSM 26989T) is the type strain of the proposed new species. All five strains were able to form homologous aggregates, in which tube-like structures were connecting individual bacteria cells. The five strains were able to bind to human intestinal carcinoma cell lines at 37 °C.
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| 18. |
- Hellström, Karin, et al.
(author)
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Fall-related self-efficacy in instrumental activities of daily living is associated with falls in older community-living people
- 2013
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In: Physical & Occupational Therapy in Geriatrics. - : Informa UK Limited. - 0270-3181 .- 1541-3152. ; 31:2, s. 128-139
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Journal article (peer-reviewed)abstract
- Introduction: The aim of this study was to identify fall risk factors in community-living people 75 years or older. Methods: From a random selection of 525 older adults, a total of 378 (72%) individuals participated in the study. Mean age was 81.7 years (range 75-101 years). A study-specific questionnaire including self-reported fall history for the past 6 months, the Falls-Efficacy Scale (Swedish version: FES(S)) and EuroQol 5 Dimensions (EQ5D) was used. Logistic regression analysis was conducted to find risk factors for falls. Results: The strongest significant predictor of falls was scoring low on FES(S) in instrumental activities of daily living (IADL), with an odds ratio of 7.89 (95% confidence interval 2.93-21.25). One fifth had experienced one or more falls during the past 6 months. Both fall-related self-efficacy and health-related quality of life were significantly lower among fallers. Conclusion: Our results imply that identifying community-living older adults with an increased risk of falling should include a measure of fall-related self-efficacy in IADL.
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| 19. |
- Hunter, Amanda, et al.
(author)
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Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters
- 2014
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In: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 11
-
Journal article (peer-reviewed)abstract
- Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.
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| 20. |
- Högberg, Lotta, et al.
(author)
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Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine
- 2011
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In: ACTA PAEDIATRICA. - : Blackwell Publishing Ltd. - 0803-5253 .- 1651-2227. ; 100:7, s. 1023-1027
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Journal article (peer-reviewed)abstract
- Aim: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. Methods: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. Results: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p andlt; 0.001). Conclusion: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.
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