| 1. |
- Abat, E., et al.
(author)
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Study of the response of the ATLAS central calorimeter to pions of energies from 3 to 9 GeV
- 2009
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002 .- 1872-9576. ; 607:2, s. 372-386
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Journal article (peer-reviewed)abstract
- A fully instrumented slice of the ATLAS central detector was exposed to test beams from the SPS (Super Proton Synchrotron) at CERN in 2004. in this paper, the response of the central calorimeters to pions with energies in the range between 3 and 9 GeV is presented. The linearity and the resolution of the combined calorimetry (electromagnetic and hadronic calorimeters) was measured and compared to the prediction of a detector simulation program using the toolkit Geant 4. (C) 2009 Elsevier B.V. All rights reserved.
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| 2. |
- Hjortswang, Henrik, et al.
(author)
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Infliximab in clinical routine : Experience with Crohn's disease and biomarkers of inflammation over 5 years
- 2009
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In: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 21:10, s. 1168-1176
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Journal article (peer-reviewed)abstract
- Introduction: Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. Aim: To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). Methods: During 1999–2008, CD patients were monitored for disease activity by Harvey–Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. Results: A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey–Bradshaw index decreased with infusions during the first year of treatment (P<0.0001), whereas hemoglobin (P<0.01) and albumin (P<0.001) increased, C-reactive protein (P<0.01) decreased, platelets (P<0.001) increased, and leukocytes (P<0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P<0.0001), and nitrite (P<0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Conclusion: Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.
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| 3. |
- Jansson, Emmelie A, et al.
(author)
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Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate
- 2007
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 42:4, s. 510-518
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Journal article (peer-reviewed)abstract
- Nitrate is abundant in our diet with particularly high levels in many vegetables. Ingested nitrate is concentrated in saliva and reduced to nitrite by bacteria in the oral cavity. We recently reported that application of nitrite-containing saliva to the gastric mucosa increases superficial blood flow and mucus generation via acid-catalyzed formation of bioactive nitrogen oxides including nitric oxide. Here we studied if dietary supplementation with nitrate would protect against gastric damage caused by a nonsteroidal anti-inflammatory drug. Rats received sodium nitrate in the drinking water for 1 week in daily doses of 0.1 or 1 mmol kg− 1. Control rats received 1 mmol kg− 1 sodium chloride. Diclofenac (30 mg kg− 1) was then given orally and the animals were examined 4 h later. In separate experiments we studied the effects of dietary nitrate on intragastric NO levels and mucus formation. Luminal levels of NO gas were greatly increased in nitrate-fed animals. The thickness of the mucus layer increased after nitrate supplementation and gene expression of MUC6 was upregulated in the gastric mucosa. Nitrate pretreatment dose dependently and potently reduced diclofenac-induced gastric lesions. Inflammatory activity was reduced in the rats receiving nitrate as indicated by lower mucosal myeloperoxidase activity and expression of inducible NO synthase. We conclude that dietary nitrate protects against diclofenac-induced gastric ulcers likely via enhanced nitrite-dependent intragastric NO formation and concomitant stimulation of mucus formation. Future studies will reveal if a diet rich in nitrate can offer an additional nutritional approach to preventing and treating peptic ulcer disease.
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| 4. |
- Jansson, Emmelie Å, et al.
(author)
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A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis
- 2008
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In: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 4:7, s. 411-417
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Journal article (peer-reviewed)abstract
- Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here we report on nitrate reductase activity in rodent and human tissues that results in formation of nitrite and nitric oxide (NO) and is attenuated by the xanthine oxidoreductase inhibitor allopurinol. Nitrate administration to normoxic rats resulted in elevated levels of circulating nitrite that were again attenuated by allopurinol. Similar effects of nitrate were seen in endothelial NO synthase-deficient and germ-free mice, thereby excluding vascular NO synthase activation and bacteria as the source of nitrite. Nitrate pretreatment attenuated the increase in systemic blood pressure caused by NO synthase inhibition and enhanced blood flow during post-ischemic reperfusion. Our findings suggest a role for mammalian nitrate reduction in regulation of nitrite and NO homeostasis.
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| 5. |
- Jensen, Lasse Dahl, et al.
(author)
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Nitric oxide permits hypoxia-induced lymphatic perfusion by controlling arterial-lymphatic conduits in zebrafish and glass catfish
- 2009
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:43, s. 18408-18413
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Journal article (peer-reviewed)abstract
- The blood and lymphatic vasculatures are structurally and functionally coupled in controlling tissue perfusion, extracellular interstitial fluids, and immune surveillance. Little is known, however, about the molecular mechanisms that underlie the regulation of bloodlymphatic vessel connections and lymphatic perfusion. Here we show in the adult zebrafish and glass catfish (Kryptopterus bicirrhis) that blood-lymphatic conduits directly connect arterial vessels to the lymphatic system. Under hypoxic conditions, arterial-lymphatic conduits (ALCs) became highly dilated and linearized by NO-induced vascular relaxation, which led to blood perfusion into the lymphatic system. NO blockage almost completely abrogated hypoxia-induced ALC relaxation and lymphatic perfusion. These findings uncover mechanisms underlying hypoxia-induced oxygen compensation by perfusion of existing lymphatics in fish. Our results might also imply that the hypoxia-induced NO pathway contributes to development of progression of pathologies, including promotion of lymphatic metastasis by modulating arterial-lymphatic conduits, in the mammalian system.
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| 6. |
- Larsen, Filip, et al.
(author)
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Effects of dietary nitrate on blood pressure in healthy volunteers
- 2006
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 28:355(26), s. 2792-3
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Journal article (peer-reviewed)abstract
- To the Editor: Nitric oxide, generated by nitric oxide synthase, is a key regulator of vascular integrity. This system is dysfunctional in many cardiovascular disorders, including hypertension. A fundamentally different pathway for the generation of nitric oxide was recently described in which the anions nitrate (NO3 ) and nitrite (NO2 ) are converted into nitric oxide and other bioactive nitrogen oxides.1-3 Nitrate is abundant in our diet, and particularly high levels are found in many vegetables.3 We examined the effect of 3-day dietary supplementation with either sodium nitrate (at a dose of 0.1 mmol per kilogram of body weight per day) or placebo (sodium chloride, at a dose of 0.1 mmol per kilogram per day) on blood pressure in 17 physically active, healthy volunteers, none of whom smoked (15 men and 2 women; mean age, 24 years). The study had a randomized, double-blind, crossover design with two different treatment periods during which the subjects received either nitrate or placebo; the treatment periods were separated by a washout period of at least 10 days. The compounds were dissolved in water and could not be distinguished by taste or appearance. During the two treatment periods, the subjects were instructed to avoid all foods with a moderate or high nitrate content.3 Systolic blood pressure Effects of 3-Day Dietary Supplementation with Inorganic Nitrate or Placebo on Systolic (Panel A) and Diastolic (Panel B) Blood Pressure in 17 Healthy Volunteers.) and pulse rate did not change significantly after nitrate supplementation, as compared with placebo supplementation. However, the diastolic blood pressure was on average 3.7 mm Hg lower after nitrate supplementation than after placebo supplementation (P<0.02) (Figure 1B), and the mean arterial pressure was 3.2 mm Hg lower (P<0.03). Plasma nitrate levels were higher after nitrate ingestion than after placebo ingestion (mean [±SD], 178±51 and 26±11 μM, respectively; P<0.001), as were plasma nitrite levels (219±105 and 138±38 nM, respectively; P<0.01). The daily nitrate dose used in the study corresponds to the amount normally found in 150 to 250 g of a nitrate-rich vegetable such as spinach, beetroot, or lettuce. It is clear from earlier studies, such as the Dietary Approaches to Stop Hypertension (DASH) trial, that a diet rich in fruits and vegetables can reduce blood pressure,4,5 but attempts to modify single nutrients have been inconsistent. Therefore, it has been argued that the effect of any individual nutrient is too small to detect in trials. In our study, reduced blood pressure was associated with nitrate supplementation alone; this effect was evident in young normotensive subjects. In fact, it was similar to that seen in the healthy control group in the DASH study.4 The exact mechanism behind the blood-pressure–lowering effect of nitrate needs to be clarified in future studies. We conclude that short-term dietary supplementation with inorganic nitrate reduces diastolic blood pressure in healthy young volunteers.
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| 7. |
- Larsson Callerfelt, Anna-Karin, et al.
(author)
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Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction.
- 2009
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In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 10:Jun 4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung. METHODS: The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA. RESULTS: Cumulatively increasing concentrations of OVA (1-10,000 ng/ml) induced concentration-dependent contractions of the GPLP that were reduced by NCX 2057 (100 microM, p < 0.001) and SNP (100 microM, p < 0.05). Antigen-induced eicosanoid release was decreased by NCX 2057 (100 microM, p < 0.001) but not by SNP (100 microM), whereas the release of histamine was reduced by SNP (100 microM, p < 0.001) but not by NCX 2057 (100 microM). In addition, NCX 2057 (0.1-100 microM), but not SNP (0.1-100 microM), relaxed leukotriene D4 (10 nM) precontracted GPLP (p < 0.01). The guanylyl cyclase inhibitor ODQ had no effect on the NCX 2057 mediated relaxation. SNP released significantly less nitrite than NCX 2057. CONCLUSION: Although both SNP and NCX 2057 reduced the release of pro-inflammatory mediators, their profiles were distinctly different. Furthermore, NCX 2057 also induced smooth muscle dilation in the GPLP. The findings point to specific anti-inflammatory effects of different NO donors in the peripheral lung tissue.
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| 8. |
- Lundberg, Jon O., et al.
(author)
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Nitrate and nitrite in biology, nutrition and therapeutics
- 2009
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In: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 5:12, s. 865-869
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Journal article (peer-reviewed)abstract
- Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.
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| 9. |
- Lundberg, Johanna, 1975-
(author)
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Social status : a state of mind?
- 2008
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Doctoral thesis (other academic/artistic)abstract
- This thesis is concerned with social stratification of psychosocial factors and social position measurement in population samples collected in mid-Sweden 2000-2006. Traditional resource-based measures of social position (occupation, education) and so far less explored prestige-based measures (subjective status, status incongruence) are tested with respect to their associations with psychosocial factors, emotions, and selfrated health. Three papers in this thesis are based on data from the Life Conditions, Stress, and Health (LSH) study, using a randomly selected population sample. Data for the fourth paper is a regional sample drawn from the health-related survey “Liv och Hälsa 2000”. Statistical methods range from correlation analysis to logistic regression and repeated measures analyses.Results from studies I and IV show that psychosocial factors are unequally distributed within the population in a linear manner, so that the lower the socioeconomic position (SEP), the more unfavourable levels. This is independent of whether we study this in a highly unequal setting such as Russia, or in a more egalitarian society such as Sweden. The stability of psychometric instruments over two years tend to be lower for all instruments among low SEP groups, and differ significantly for self-esteem and perceived control among groups with high and low education, and for cynicism among groups with high and low occupational status. Results from studies II and III point to the relevance of individuals’ own thoughts about themselves, and the potential impact on the self by normative judgements of social position in a certain hierarchical setting. In paper II, the prestige-based measure of subjective status was influenced by resource-based measures, such as self-rated economy and education, but also by life satisfaction and psychosocial factors. The importance of self-evaluation was especially obvious from the study on status incongruence (study III) where the traditionally protective effecs of a high education seem to disappear when combined with a lowstatus occupation. Shaming experiences may play an important role here for our understanding of self-perception.
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| 10. |
- Lundberg, Olle, et al.
(author)
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The role of welfare state principles and generosity in social policy programmes for public health : an international comparative study
- 2008
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 372:9650, s. 1633-1640
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Journal article (peer-reviewed)abstract
- Background Many important social determinants of health are also the focus for social policies. Welfare states contribute to the resources available for their citizens through cash transfer programmes and subsidised services. Although all rich nations have welfare programmes, there are clear cross-national differences with respect to their design and generosity These differences are evident in national variations in poverty rates, especially among children and elderly people. We investigated to what extent variations in family and pension policies are linked to infant mortality and old-age excess mortality. Methods Infant mortality rates and old-age excess mortality rates were analysed in relation to social policy characteristics and generosity. We did pooled cross-sectional time-series analyses of 18 OECD (Organisation for Economic Co-operation and Development) countries during the period 1970-2000 for family policies and 1950-2000 for pension policies. Findings Increased generosity in family policies that support dual-earner families is linked with lower infant mortality rates, whereas the generosity in family policies that support more traditional families with gainfully employed men and homemaking women is not. An increase by one percentage point in dual-earner support lowers infant mortality by 0.04 deaths per 1000 births. Generosity in basic security type of pensions is linked to lower old-age excess mortality, whereas the generosity of earnings-related income security pensions is not. An increase by one percentage point in basic security pensions is associated with a decrease in the old age excess mortality by 0.02 for men as well as for women. Interpretation The ways in which social policies are designed, as well as their generosity, are important for health because of the increase in resources that social policies entail. Hence, social policies are of major importance for how we can tackle the social determinants of health.
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