| 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. |
- 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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| 7. |
- 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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| 8. |
- Midtvedt, Daniel, 1988, et al.
(author)
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Direct measurement of nitric oxide (NO) in the gastrointestinal tract of cod (Gadus morhua)
- 2009
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In: Microbial Ecology in Health and Disease. - : Informa UK Limited. - 0891-060X .- 1651-2235. ; 21:3-4, s. 175-177
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Journal article (peer-reviewed)abstract
- Objective: In mammals, the biological messenger nitric oxide (NO) is generated throughout the gastrointestinal (GI) tract from the reduction of dietary nitrate and nitrite. The aim of the present study was to investigate the amount of GI NO in Atlantic cod (Gadus morhua) in relation to intake of food. Methods: A total of 28 cod were divided into 3 groups, fed at different times before the experiment (1 week, 1 day, and 3 h, respectively). Results: In the stomach, the measured NO concentrations were consistently higher in the group fed 3 h before the measurement, implying that the NO3-NO2-NO pathway is present in the stomach of cod. We also measured the NO concentration in the large intestine. Again, the values were higher in cod fed 3 h before the experiment. Conclusion: We conclude that NO is formed in the GI tract of cod, likely via the reduction of dietary nitrate and nitrite. The physiological importance of this NO production remains to be determined.
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| 9. |
- Petersson, Joel, et al.
(author)
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Dietary nitrate increases gastric mucosal blood flow and mucosal defense
- 2007
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In: American Journal of Physiology - Gastrointestinal and Liver Physiology. - : American Physiological Society. - 0193-1857 .- 1522-1547. ; 292:3, s. G718-G724
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Journal article (peer-reviewed)abstract
- Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to bioactive nitrogen oxides, including nitric oxide (NO). In this study, we investigated the gastroprotective role of nitrate intake and of luminally applied nitrite against provocation with diclofenac and taurocholate. Mucosal permeability (51Cr-EDTA clearance) and gastric mucosal blood flow (laser-Doppler flowmetry) were measured in anesthetized rats, either pretreated with nitrate in the drinking water or given acidified nitrite luminally. Diclofenac was given intravenously and taurocholate luminally to challenge the gastric mucosa. Luminal NO content and nitrite content in the gastric mucus were determined by chemiluminescence. The effect of luminal administration of acidified nitrite on the mucosal blood flow was also investigated in endothelial nitric oxide synthase-deficient mice. Rats pretreated with nitrate or given nitrite luminally had higher gastric mucosal blood flow than controls. Permeability increased more during the provocation in the controls than in the nitrate- and nitrite-treated animals. Dietary nitrate increased luminal NO levels 50 times compared with controls. Nitrate intake also resulted in nitrite accumulation in the loosely adherent mucous layer; after removal of this mucous layer, blood flow was reduced. Nitrite administrated luminally in endothelial nitric oxide synthase-deficient mice increased mucosal blood flow. We conclude that dietary nitrate and direct luminal application of acidified nitrite decrease diclofenac- and taurocholate-induced mucosal damage. The gastroprotective effect likely involves a higher mucosal blood flow caused by nonenzymatic NO production. These data suggest an important physiological role of nitrate in the diet.
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| 10. |
- Petersson, Joel, et al.
(author)
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Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash
- 2009
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In: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 46:8, s. 1068-1075
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Journal article (peer-reviewed)abstract
- Recently, it has been suggested that the supposedly inert nitrite anion is reduced in vivo to form bioactive nitric oxide with physiological and therapeutic implications in the gastrointestinal and cardiovascular systems. Intake of nitrate-rich food such as vegetables results in increased levels of circulating nitrite in a process suggested to involve nitrate-reducing bacteria in the oral cavity. Here we investigated the importance of the oral microflora and dietary nitrate in regulation of gastric mucosal defense and blood pressure. Rats were treated twice daily with a commercial antiseptic mouthwash while they were given nitrate-supplemented drinking water. The mouthwash greatly reduced the number of nitrate-reducing oral bacteria and as a consequence, nitrate-induced increases in gastric NO and circulating nitrite levels were markedly reduced. With the mouthwash the observed nitrate-induced increase in gastric mucus thickness was attenuated and the gastroprotective effect against an ulcerogenic compound was lost. Furthermore, the decrease in systemic blood pressure seen during nitrate supplementation was now absent. These results suggest that oral symbiotic bacteria modulate gastrointestinal and cardiovascular function via bioactivation of salivary nitrate. Excessive use of antiseptic mouthwashes may attenuate the bioactivity of dietary nitrate.
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