| 1. |
- Posner, Stefan, et al.
(författare)
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Per- and polyfluorinated substances in the Nordic Countries : Use, occurence and toxicology
- 2013
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This Tema Nord report presents a study based on open information and custom market research to review the most common perfluorinated substances (PFC) with less focus on PFOS and PFOA.The study includes three major parts: 1) Identification of relevant per-and polyfluorinated substances and their use in various industrial sectors in the Nordic market by interviews with major players and database information. 2) Emissions to and occurence in the Nordic environment of the substances described in 1). 3) A summary of knowledge of the toxic effects on humans and the environment of substances prioritized in 2). There is a lack of physical chemical data, analystical reference substances, human and environmental occurrence and toxicology data, as well as market information regarding PFCs other than PFOA and PFOS and the current legislation cannot enforce disclosure of specific PFC substance information.
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| 2. |
- Serafini, Mauro, et al.
(författare)
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Dietary total antioxidant capacity and gastric cancer risk in the European prospective investigation into cancer and nutrition study
- 2012
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:4, s. 544-554
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Tidskriftsartikel (refereegranskat)abstract
- A high intake of dietary antioxidant compounds has been hypothesized to be an appropriate strategy to reduce gastric cancer (GC) development. We investigated the effect of dietary total antioxidant capacity (TAC) in relation to GC in the European Prospective Investigation into Cancer (EPIC) study including 23 centers in 10 European countries. A total of 521,457 subjects (153,447 men) aged mostly 3570 years old, were recruited largely between 1992 and 1998. Ferric reducing antioxidant potential (FRAP) and total radical-trapping antioxidant parameter (TRAP), measuring reducing and chain-breaking antioxidant capacity were used to measure dietary TAC from plant foods. Dietary antioxidant intake is associated with a reduction in the risk of GC for both FRAP (adjusted HR 0.66; 95%CI (0.460.95) and TRAP (adjusted HR 0.61; 95%CI (0.430.87) (highest vs. lowest quintile). The association was observed for both cardia and noncardia cancers. A clear effect was observed in smokers with a significant reduction in GC risk for the fifth quintile of intake for both assays (highest vs. lowest quintile: adjusted HR 0.41; 95%CI (0.220.76) p for trend <0.001 for FRAP; adjusted HR 0.52; 95%CI (0.280.97) p for trend <0.001 for TRAP) but not in nonsmokers. In former smokers, the association with FRAP intake was statistically significant (highest vs. lowest quintile: adjusted HR 0.4; 95%CI (0.210.75) p < 0.05); no association was observed for TRAP. Dietary antioxidant capacity intake from different sources of plant foods is associated with a reduction in the risk of GC.
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| 3. |
- Böiers, Charlotta, et al.
(författare)
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Expression and role of FLT3 in regulation of the earliest stage of normal granulocyte-monocyte progenitor development.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; May 4, s. 5061-5068
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient in FLT3 signalling have reductions in early multipotent and lymphoid progenitors, whereas no evident myeloid phenotype has been reported. However, activating mutations of Flt3 are among the most common genetic events in acute myeloid leukemia and mice harbouring internal tandem duplications within Flt3 (Flt3-ITD) develop myeloproliferative disease, with characteristic expansion of granulocyte-monocyte (GM) progenitors, possibly compatible with FLT3-ITD promoting a myeloid fate of multipotent progenitors. Alternatively, FLT3 might be expressed at the earliest stages of GM development. Herein, we investigated the expression, function and role of FLT3 in recently identified early GM progenitors. Flt3-cre fate mapping established that most progenitors and mature progeny of the GM lineage are derived from Flt3 expressing progenitors. A higher expression of FLT3 was found in preGMP compared to GMP, and preGMPs were more responsive to stimulation with FLT3 ligand (FL). Whereas preGMPs and GMPs were reduced in Fl(-/-) mice, megakaryocyte-erythroid progenitors were unaffected and lacked FLT3 expression. Notably, mice deficient in both Thrombopoietin (THPO) and FL, had a more pronounced GM progenitor phenotype than Thpo(-/-) mice, establishing a role of FL in THPO-dependent and independent regulation of GM progenitors, of likely significance for myeloid malignancies with Flt3-ITD mutations.
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| 4. |
- Böiers, Charlotta, et al.
(författare)
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Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells.
- 2013
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 13:5, s. 535-548
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Tidskriftsartikel (refereegranskat)abstract
- In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the embryonic lymphoid commitment process initiates earlier than previously appreciated, prior to emergence of definitive HSCs, through establishment of a previously unrecognized entirely immune-restricted and lymphoid-primed progenitor. Notably, this immune-restricted progenitor appears to first emerge in the yolk sac and contributes physiologically to the establishment of lymphoid and some myeloid components of the immune-system, establishing the lymphomyeloid lineage restriction process as an early and physiologically important lineage-commitment step in mammalian hematopoiesis.
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| 5. |
- Çevik Aras, Hülya, 1975, et al.
(författare)
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A non-peptide receptor inhibitor with selectivity for one of the neutrophil formyl peptide receptors, FPR 1.
- 2012
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Ingår i: Biochemical pharmacology. - : Elsevier BV. - 1873-2968 .- 0006-2952. ; 83:12, s. 1655-1662
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Tidskriftsartikel (refereegranskat)abstract
- The neutrophil formyl peptide receptors (FPR1 and FPR2) are members of the G-protein coupled receptor family. The signals generated by occupied FPRs are both pro-inflammatory and anti-inflammatory. Accordingly, these receptors have become a therapeutic target for the development of novel drugs that may be used to reduce injuries in inflammatory diseases including asthma, rheumatoid arthritis, Alzheimer's disease and cardiovascular diseases. To support the basis for a future pharmacological characterization, we have identified a small molecular non-peptide inhibitor with selectivity for FPR1. We used the FPR1 and FPR2 specific ligands fMLF and WKYMVM, respectively, and an earlier described ratio technique, to determine inhibitory activity combined with selectivity. We show that the compound 3,5-dichloro-N-(2-chloro-5-methyl-phenyl)-2-hydroxy-benzamide (BVT173187) fulfills the criteria for an FPR1 inhibitor selective for FPR1 over FPR2, and it inhibits the same functional repertoire in neutrophils as earlier described peptide antagonists. Accordingly, the new inhibitor reduced neutrophil activation with FPR1 agonists, leading to mobilization of adhesion molecules (CR3) and the generation of superoxide anion from the neutrophil NADPH-oxidase. The effects of a number of structural analogs were determined but these were either without activity or less active/specific than BVT173187. The potency of the new inhibitor for reduction of FPR1 activity was the same as that of the earlier described FPR1 antagonist cyclosporine H, but signaling through the C5aR and CXCR (recognizing IL8) was also affected by BVT173187.
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| 6. |
- Demmelmaier, Ingrid, et al.
(författare)
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Current and Maintained Health-Enhancing Physical Activity in Rheumatoid Arthritis : A Cross-Sectional Study
- 2013
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Ingår i: Arthritis Care and Research. - : Wiley. - 0893-7524 .- 1529-0123 .- 2151-464X .- 2151-4658. ; 65:7, s. 1166-1176
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe and identify the explanatory factors of variation in current and maintained health-enhancing physical activity (HEPA) in persons with rheumatoid arthritis (RA).METHODS: In this cross-sectional study, current HEPA was assessed with the International Physical Activity Questionnaire and maintained HEPA with the Exercise Stage Assessment Instrument, the latter explicitly focusing on both aerobic physical activity and muscle strength training. Sociodemographic, disease-related, and psychosocial data were retrieved from the Swedish Rheumatology Quality (SRQ) registers and a postal questionnaire. The explained variations in the respective HEPA behaviors were analyzed with logistic regression.RESULTS: In all, 3,152 (58.5%) of 5,391 persons identified as eligible from the SRQ registers responded to the questionnaire. Current HEPA was reported by 69%, and maintained HEPA by 11% of the respondents. The most salient and consistent factors explaining variation in both current and maintained HEPA were self-efficacy, social support, and outcome expectations related to physical activity.CONCLUSION: To our knowledge, this is the first study exploring maintained physical activity in a large well-defined sample of persons with RA. Our results indicate that a minority perform maintained HEPA, including both aerobic physical activity and muscle strength training, and that psychosocial factors are the most salient and consistent in the explanation of HEPA variation.
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| 7. |
- Deville, Walter, et al.
(författare)
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Health care for immigrants in Europe : Is there still consensus among country experts about principles of good practice? A Delphi study
- 2011
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 11, s. Art. no. 699-
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Tidskriftsartikel (refereegranskat)abstract
- Background: European Member States are facing a challenge to provide accessible and effective health care services for immigrants. It remains unclear how best to achieve this and what characterises good practice in increasingly multicultural societies across Europe. This study assessed the views and values of professionals working in different health care contexts and in different European countries as to what constitutes good practice in health care for immigrants. Methods: A total of 134 experts in 16 EU Member States participated in a three-round Delphi process. The experts represented four different fields: academia, Non-Governmental Organisations, policy-making and health care practice. For each country, the process aimed to produce a national consensus list of the most important factors characterising good practice in health care for migrants. Results: The scoring procedures resulted in 10 to 16 factors being identified as the most important for each participating country. All 186 factors were aggregated into 9 themes: (1) easy and equal access to health care, (2) empowerment of migrants, (3) culturally sensitive health care services, (4) quality of care, (5) patient/health care provider communication, (6) respect towards migrants, (7) networking in and outside health services, (8) targeted outreach activities, and (9) availability of data about specificities in migrant health care and prevention. Although local political debate, level of immigration and the nature of local health care systems influenced the selection and rating of factors within each country, there was a broad European consensus on most factors. Yet, discordance remained both within countries, e. g. on the need for prioritising cultural differences, and between countries, e. g. on the need for more consistent governance of health care services for immigrants. Conclusions: Experts across Europe asserted the right to culturally sensitive health care for all immigrants. There is a broad consensus among experts about the major principles of good practice that need to be implemented across Europe. However, there also is some disagreement both within and between countries on specific issues that require further research and debate.
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| 8. |
- Forsman, Huamei, et al.
(författare)
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Stable formyl peptide receptor agonists that activate the neutrophil NADPH-oxidase identified through screening of a compound library.
- 2011
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Ingår i: Biochemical pharmacology. - : Elsevier BV. - 1873-2968 .- 0006-2952. ; 81:3, s. 402-411
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Tidskriftsartikel (refereegranskat)abstract
- The neutrophil formyl peptide receptors (FPR1 and FPR2) are G-protein coupled receptors that can induce pro-inflammatory as well as anti-inflammatory activities when activated. Accordingly, these receptors may become therapeutic targets for the development of novel drugs to be used for reducing the inflammation induced injuries in asthma, rheumatoid arthritis, Alzheimer's disease, cardiovascular diseases and traumatic shock. We screened a library of more then 50K small compounds for an ability of the compounds to induce a transient rise in intracellular Ca(2+) in cells transfected to express FPR2 (earlier called FPRL1 or the lipoxin A(4) receptor). Ten agonist hits were selected for further analysis representing different chemical series and five new together with five earlier described molecules were further profiled. Compounds 1-10 gave rise to a calcium response in the FPR2 transfectants with EC(50) values ranging from 4×10(-9)M to 2×10(-7)M. All 10 compounds activated human neutrophils to release superoxide, and based on the potency of their activity, the three most potent activators of the neutrophil NADPH-oxidase were further characterized. These three agonists were largely resistant to inactivation by neutrophil produced reactive oxygen species and shown to trigger the same functional repertoire in neutrophils as earlier described peptide agonists. Accordingly they induced chemotaxis, granule mobilization and secretion of superoxide. Interestingly, the oxidase activity was largely inhibited by cyclosporine H, an FPR1 selective antagonist, but not by PBP10, an FPR2 selective inhibitor, suggesting that FPR1 is the preferred receptor in neutrophils for all three agonists.
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| 9. |
- Fredengren, Christina, et al.
(författare)
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I valet och kvalet : grundläggande frågor kring värdering och urval av kulturarv
- 2012
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Riksantikvarieämbetet kraftsamlar kring området värdering och urval. Det behövs mer kunskap om hur kulturarvens värden tas tillvara i arbetet för utvecklingen av ett hållbart samhälle med goda livsmiljöer. Den här boken lyfter angelägna frågor kring kulturarv och kulturarvsaktiviteters värden.
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| 10. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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