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1.
  • Schulte-Oehlmann, U, et al. (author)
  • COMPRENDO: Focus and approach.
  • 2006
  • In: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 114:Supplement 1, s. 98-100
  • Journal article (peer-reviewed)abstract
    • Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that "the dose makes the poison" may not always be the case because some EDCs do not induce the classical dose-response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters--Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates) .
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  • Attoff, Kristina, et al. (author)
  • Acrylamide affects proliferation and differentiation of the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y
  • 2016
  • In: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 35, s. 100-111
  • Journal article (peer-reviewed)abstract
    • Acrylamide is a well-known neurotoxic compound and people get exposed to the compound by food consumption and environmental pollutants. Since acrylamide crosses the placenta barrier, the fetus is also being exposed resulting in a risk for developmental neurotoxicity. In this study, the neural progenitor cell line C17.2 and the neuroblastoma cell line SH-SY5Y were used to study proliferation and differentiation as alerting indicators for developmental neurotoxicity. For both cell lines, acrylamide reduced the number of viable cells by reducing proliferation and inducing cell death in undifferentiated cells. Acrylamide concentrations starting at 10 fM attenuated the differentiation process in SH-SY5Y cells by sustaining cell proliferation and neurite outgrowth was reduced at concentrations from 10 pM. Acrylamide significantly reduced the number of neurons starting at 1 mu M and altered the ratio between the different phenotypes in differentiating C17.2 cell cultures. Ten micromolar of acrylamide also reduced the expression of the neuronal and astrocyte biomarkers. Although the neurotoxic concentrations in the femtomolar range seem to be specific for the SH-SY5Y cell line, the fact that micromolar concentrations of acrylamide seem to attenuate the differentiation process in both cell lines raises the interest to further investigations on the possible developmental neurotoxicity of acrylamide.
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  • Ekdahl, A. W., et al. (författare)
  • Frailty and comprehensive geriatric assessment organized as CGA-ward or CGA-consult for older adult patients in the acute care setting : a systematic review and meta-analysis
  • 2015
  • Ingår i: European Geriatric Medicine. - : Elsevier. - 1878-7649 .- 1878-7657. ; 6:6, s. 523-540
  • Forskningsöversikt (refereegranskat)abstract
    • Background: With worldwide population aging, increasing numbers of people need hospital care. Evidence suggests comprehensive geriatric assessment (CGA) is superior to usual care.Objective: To summarize the evidence for the effects of CGA in frail and moderately frail patients compared with usual care in acute care settings.Data sources: CINAHL, PsycInfo, Cochrane Library, EMBASE, and PubMed were searched in October 2011, January 2013, and February 2015.Study eligibility: Randomized controlled trials.Participants: Older adults aged ≥ 65 years who were admitted to hospital with a complex condition, divided into frail and moderately frail groups.Intervention: CGA.Control: Usual care.Outcomes: Change in housing, personal activities of daily living (PADL), instrumental activities of daily living (IADL), readmission, cognitive function, depression, quality-of-life care-giver burden, and mortality.Study appraisal and synthesis: The grading of recommendations assessment development and evaluation (GRADE) system to assess the quality of evidence and PRISMA-guidelines for meta-analyses and reviews. Continuous data were presented as standardized mean differences and dichotomous data were presented as risk differences.Results: Twenty-nine articles based on 17 unique studies (6005 patients in total). CGA was categorized as CGA-ward or CGA-consult. In the frail group, CGA-ward was superior to usual care for change in housing, PADL, and depression. CGA-consult was superior to usual care for PADL and IADL in the moderately frail group.Conclusion: There was a stronger effect for frail older adults and CGA-ward compared with usual care. This highlights the importance of detecting frailty. However, the degree of evidence was limited.
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  • Fredlund, J O, et al. (författare)
  • Ornithine decarboxylase and S-adenosylmethionine decarboxylase expression during the cell cycle of Chinese hamster ovary cells
  • 1995
  • Ingår i: Experimental Cell Research. - : Elsevier BV. - 1090-2422 .- 0014-4827. ; 216:1, s. 86-92
  • Tidskriftsartikel (refereegranskat)abstract
    • Cells in mitosis were harvested from exponentially growing Chinese hamster ovary cells by the mitotic detachment technique. Immediately after harvesting, the mitotic cells were seeded in tissue culture flasks and incubated at 37 degrees C in a CO2 incubator. Care was taken not to perturb the progression of cells through the cell cycle. At every hour after seeding for 14 h, cells were collected for analysis of cell cycle distribution, cellular polyamine content, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities, and relative mRNA contents. The progression through the cell cycle was monitored by DNA flow cytometry. The putrescine, spermidine, and spermine levels were approximately doubled during the cell cycle: putrescine mainly during late S and G2, spermidine continuously during the entire cell cycle, and spermine mainly during G1 and S. The ODC activity was low in seeded mitotic cells and the enzyme was activated in late G1 and reached a plateau in S phase. A second burst in activity was observed during late S phase and maximal ODC activity was found at the S/G2 transition. The relative ODC mRNA level approximately doubled during the cell cycle and the increase in the relative level mainly took part during mid and late S phase. AdoMetDC activity increased in late G1 and a first maximum was observed during the G1/S transition. A second burst in activity was found in mid S phase. Maximal AdoMetDC activity was found in G2. The relative AdoMetDC mRNA approximately doubled during the cell cycle and the increase in the relative level mainly took place during late G1 and early S phase. Our results indicate that polyamine synthesis was regulated at transcriptional and translational/post-translational levels during the cell cycle of Chinese hamster ovary cells.
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  • Freiburghaus, Catja, et al. (författare)
  • Identification of ubiquitin in bovine milk and its growth inhibitory effects on human cancer cell lines.
  • 2010
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 93:8, s. 3442-3452
  • Tidskriftsartikel (refereegranskat)abstract
    • Bovine milk is associated with improved health and reduced risk of several diseases, among them cancer. Milk is a complex mixture of known and unknown components. The components and the mechanisms that contribute to the cancer-preventive effects are largely unknown. We set out to find new peptides in milk and identified ubiquitin (Ub) using matrix-assisted laser desorption ionization-time of flight mass spectrometry and Western blot. Using quantitative Western blot, we estimated the Ub concentration to be about 0.003 micromol/L in milk. We then decided to investigate the effect of treating human colon cancer CaCo-2 cells with Ub, using higher concentrations than in milk. CaCo-2 cells treated with 0.02 to 2.0 micromol/L Ub showed significantly decreased proliferation compared with untreated control cells. A higher growth inhibitory effect than in CaCo-2 cells was found in the neuroblastoma cell line SH-SY5Y treated with 0.02 to 0.2 micromol/L Ub. A bromodeoxyuridine DNA flow cytometric method was used to study cell cycle kinetics in Ub-treated CaCo-2 cells. The data point toward a prolongation of the G(1) phase. The levels of several cell cycle regulatory proteins were affected. Our data point to Ub possibly being one of the components in milk reducing the risk of cancer.
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  • Janicke, Birgit, et al. (författare)
  • Differential Effects of Ferulic Acid and p-Coumaric Acid on S Phase Distribution and Length of S Phase in the Human Colonic Cell Line Caco-2
  • 2005
  • Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 53:17, s. 6658-6665
  • Tidskriftsartikel (refereegranskat)abstract
    • Ferulic acid (FA) and para-coumaric acid (p-CA) may mediate the protective effects of whole-grain cereals against colon cancer. Therefore, the effects of FA and p-CA on the metabolic activity, proliferation, cell cycle phase distribution, and kinetics of the colonic endothelial tumor cell line Caco-2 was studied. Both compounds at 1500 M decreased the number of cells to 43-75% of control after 2-3 days of treatment. Cell cycle phase distribution and cell cycle kinetics were determined by flow cytometric analysis after bromodeoxyuridine labeling. Each compound at 1500 M decreased the proportion of cells in the G1 phase and increased the proportion of cells in the S and G2 phases. Treatment with 1500 M FA significantly increased the length of the S phase, while p-CA did not. It was concluded that FA and p-CA inhibited cell proliferation by presumably affecting different cell cycle phases, and this warrants further investigations because this inhibition may be one explanation for the diet-related protection against cancer.
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  • Olsson, Marie, et al. (författare)
  • Effects of extracts of apple peel from organically and integrated production cultivated apples and ursolic acid on cancer cell proliferation
  • 2014
  • Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. - 9789462610286 ; 1040, s. 227-230
  • Konferensbidrag (refereegranskat)abstract
    • The effects of extract of apple peel, 'Aroma', organically cultivated or cultivated according to integrated production, on cell proliferation in vitro of colon cancer HT29 cells and breast cancer MCF-7 cells, were investigated. Different sequences of solvents were used, and the inhibiting effect on cancer cell proliferation of the different extracts was investigated. The solvents used were ethanol, methanol, DMSO and hexane in different sequences. The extracts decreased the proliferation of both HT29 and MCF-7 cells, the effect was different for the different extracts, and ethanol showed the highest inhibition effect. The inhibiting effect of the extracts also varied between both apple production methods, and extracts from peels of organically produced apples showed in some cases higher inhibition effects, while sometimes no differences were found. In addition, as ursolic acid, a component of apple peel, has been proposed to inhibit cancer cell proliferation, the inhibiting effect of pure ursolic acid on cancer cell proliferation was compared with the effect of the apple peel solvent fraction with the highest ursolic acid concentration. The inhibiting effect was higher in the apple fraction extract than in pure ursolic acid. Further, a range of different apple cultivars, integrated production and organically cultivated, were analysed by HPLC for their content of ursolic acid to investigate possible differences in concentrations.
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  • Plate, G., et al. (författare)
  • Thrombolysis for acute lower limb ischaemia - a prospective, randomised, multicentre study comparing two strategies
  • 2006
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 31, s. 651-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To test if initial high-dose, pulse-spray thrombolysis improves the early and late outcome of lower limb ischaemia as compared with low-dose infusion alone. Design Prospective randomised multicentre study. Material and methods Patients with acute and sub-acute (<30 days) lower limb ischaemia were randomised following angiography. Group 1 (n=58) received pulse-spray infusion of recombinant plasminogen activator (rt-PA, 15 mg/h) for 2 h followed by low-dose infusion if needed. Group 2 (n=63) were only treated with low-dose infusion (0.5 mg/h) of rt-PA for 48 h. Underlying lesions were corrected if required. Results The study was stopped prematurely. Complications were equally frequent in both groups. More than 75% lysis was accomplished in 78 versus 67% of the patients (p=0.21). Primary endpoints (re-occlusion, incomplete lysis, life-threatening complication, amputation, or death) were reached in 24 versus 32% of the patients (p=0.35). Neither vascular patency nor clinical parameters differed during the first year, but re-interventions tended to be more frequent (p=0.040 at 1 month; p=0.090 at 1 year) and of a greater magnitude (p=0.028) in group 2. Conclusions There was no obvious advantage with initial high-dose thrombolysis, which may be a type-2 error. A reduction of major re-interventions was recorded. Objectives To test if initial high-dose, pulse-spray thrombolysis improves the early and late outcome of lower limb ischaemia as compared with low-dose infusion alone. Design Prospective randomised multicentre study. Material and methods Patients with acute and sub-acute (<30 days) lower limb ischaemia were randomised following angiography. Group 1 (n=58) received pulse-spray infusion of recombinant plasminogen activator (rt-PA, 15 mg/h) for 2 h followed by low-dose infusion if needed. Group 2 (n=63) were only treated with low-dose infusion (0.5 mg/h) of rt-PA for 48 h. Underlying lesions were corrected if required. Results The study was stopped prematurely. Complications were equally frequent in both groups. More than 75% lysis was accomplished in 78 versus 67% of the patients (p=0.21). Primary endpoints (re-occlusion, incomplete lysis, life-threatening complication, amputation, or death) were reached in 24 versus 32% of the patients (p=0.35). Neither vascular patency nor clinical parameters differed during the first year, but re-interventions tended to be more frequent (p=0.040 at 1 month; p=0.090 at 1 year) and of a greater magnitude (p=0.028) in group 2. Conclusions There was no obvious advantage with initial high-dose thrombolysis, which may be a type-2 error. A reduction of major re-interventions was recorded.
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  • Plate, G., et al. (författare)
  • When is Thrombolysis for Acute Lower Limb Ischemia Worthwhile?
  • 2009
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 37:2, s. 206-212
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To find variables associated with outcome following thrombolytic treatment for acute lower limb ischemia. Design: Re-analysis of a prospective multicentre study. Material and methods: One hundred and twenty-one patients with acute lower limb ischemia previously included in a randomised study comparing high- with low-dose thrombolysis were re-analysed ignoring the mode of lytic treatment. All possibly predictive variables were subjected to multivariate analyses to find associations with outcome. Results: Previous successful thrombolysis, ankle-brachial index over 0.33, absence of motor dysfunction, presence of cardiac arrhythmia, and lysis of a vascular graft were all associated with successful thrombolysis (p = 0.003). Previous thrombolysis, age less than 70 years, and ankle-brachial index over 0.33 were all perfect predictors of absence of life-threatening complications or death. Successful lysis, age < 70, and lysis of a native artery as opposed to a vascular graft were all associated with clinical success (preserved patency, limb, and life) after one year (p = 0.002). Conclusions: Previous thrombolysis, age under 70 years, and non-severe ischemia predict successful thrombolysis free from severe complications. Successful thrombolysis is strongly predictive of amputation-free survival with vascular patency for at least one year. Occluded grafts could often be reopened, but long-term outcome is better after thrombolysis of native arteries. (C) 2008 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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