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| 2. |
- Brannan, J D, et al.
(författare)
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Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing
- 2006
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 27:5, s. 944-50
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Tidskriftsartikel (refereegranskat)abstract
- Mannitol inhalation increases urinary excretion of 9alpha,11beta-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that beta2-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release. Fourteen asthmatic subjects inhaled mannitol (mean dose 252+/-213 mg) in order to induce a fall in forced expiratory volume in one second (FEV1) of > or = 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 microg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9alpha,11beta-prostaglandin F2 and leukotriene E4. The maximum fall in FEV1 of 32+/-10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9alpha,11beta-prostaglandin F2 concentration from 61 to 92 ng.mmol creatinine(-1), but no significant increase in 9alpha,11beta-prostaglandin F2 concentration in the presence of either formoterol (69 versus 67 ng.mmol creatinine(-1)) or SCG (66 versus 60 ng.mmol creatinine(-1)). The increase in urinary leukotriene E4 following placebo (from 19 to 31 ng.mmol creatinine(-1)) was unaffected by the drugs. These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D2 release.
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| 3. |
- Chew, D M, et al.
(författare)
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The tectonothermal evolution and provenance of the Tyrone Central Inlier, Ireland: Grampian imbrication of an outboard Laurentian microcontinent?
- 2008
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Ingår i: Journal of the Geological Society. - : Geological Society of London. - 2041-479X .- 0016-7649. ; 165:3, s. 675-685
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Tidskriftsartikel (refereegranskat)abstract
- The Tyrone Central Inlier is a metamorphic terrane of uncertain affinity situated outboard of the main Dalradian outcrop (south of the Fair Head-Clew Bay Line) and could represent sub-arc basement to part of the enigmatic Midland Valley Terrane. Using a combination of isotopic, structural and petrographic evidence, the tectonothermal evolution of the Tyrone Central Inlier was investigated. Sillimanite-bearing 14 metamorphic assemblages (c. 670 degrees C, 6.8 kbar) and leucosomes in paragneisses are cut by granite pegmatites, which post-date two deformation fabrics. The leucosomes yield a weighted average Pb-207/Ph-206 zircon age of 467 +/- 12 Ma whereas the main fabric yields a Ar-40-Ar-39 biotite cooling age of 468 +/- 1.4 Ma. The pegmatites yield 457 +/- 7 Ma and 458 +/- 7 Ma Rb-Sr muscovite-feldspar ages and Ar-40-Ar-39 step-heating plateaux of 466 +/- 1 Ma and 468 +/- 1 Ma, respectively. The metasedimentary rocks yield Palaeoproterozoic Sm-Nd model ages and laser ablation inductively coupled plasma mass spectrometry detrital zircon U-Pb analyses from a psammitic gneiss yield age populations at 1.05-1.2, 1.5, 1.8, 2.7 and 3.1 Ga. Combined, these data permit correlation of the Tyrone Central Inlier with either the Argyll or the Southern Highland Group of the Dalradian Supergroup. The inlier was thus part of Laurentia onto which the Tyrone ophiolite was obducted.
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| 5. |
- Connor, K. M., et al.
(författare)
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Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
- 2007
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Ingår i: Nat Med. - 1078-8956.
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Tidskriftsartikel (refereegranskat)abstract
- Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.
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| 6. |
- Elwood, Chelsea N., et al.
(författare)
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Triclosan Inhibits Uropathogenic Escherichia coli-Stimulated Tumor Necrosis Factor-α Secretion in T24 Bladder Cells in Vitro
- 2007
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Ingår i: Journal of endourology. - New York : Mary Ann Liebert. - 0892-7790 .- 1557-900X. ; 21:10, s. 1217-1222
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Triclosan is an antimicrobial agent commonly used in consumer and medical products that inhibits bacterial fatty acid synthesis. In addition to its bactericidal effects, sublethal concentrations of triclosan reduce local inflammation, inhibit the growth of bacterial uropathogens, induce membrane stress, and inhibit P-fimbrial expression in uropathogenic Escherichia coli (UPEC). We tested whether sublethal concentrations of triclosan could reduce the adherence of UPEC to bladder and kidney cells and reduce the amount of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) produced by these cells during bacterial challenge in vitro. MATERIALS AND METHODS: Assays of bacterial growth, adhesion, and intracellularization were performed using UPEC GR12 incubated for 4 hours on monolayers of human T24 bladder cells or A498 kidney cells with various sublethal concentrations of triclosan. The expression profile of TNF-alpha from bladder cells was evaluated using ELISA. RESULTS: No significant decreases were observed in the adherence or invasion percentages of UPEC GR12 with either cell line when treated with sublethal amounts of triclosan. However, treatment with triclosan 0.5 microg/mL led to a significant decrease in the total number of UPEC GR12 recovered from T24 monolayers (P < 0.05). Importantly, a reduction in the expression of TNF-alpha by T24 cells was shown when UPEC GR12 was treated with triclosan (P < 0.05). CONCLUSIONS: Sublethal concentrations of triclosan did not inhibit the adhesion or intracellularization of UPEC into kidney or bladder cell lines but did significantly reduce the amount of TNF-alpha secreted by bladder cells. Therefore, the use of triclosan on ureteral stents may prove clinically beneficial, not only by inhibiting bacterial survival and growth within the urinary tract, but by reducing local inflammation as well.
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| 7. |
- Kirkland, C. L., et al.
(författare)
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The Finnmarkian Orogeny revisited: An isotopic investigation in eastern Finnmark, Arctic Norway
- 2008
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Ingår i: Tectonophysics. - : Elsevier BV. - 0040-1951. ; 460:1-4, s. 158-177
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Forskningsöversikt (refereegranskat)abstract
- The Scandinavian Caleclonides have been viewed as resulting from either a single Silurian (i.e. Scandian) event or from polycyclic orogenies involving several collisions on the margin of Baltica. Early studies of the Kalak Nappe Complex (KNC) in Finnmark, Arctic Norway, led to the hypothesis of an Early Cambrian-Early Ordovician (520-480 Ma) Finnmarkian Crogeny, though the nature of this tectonic event remains enigmatic. In this contribution we have employed in situ UV laser ablation Ar-Ar dating of fine-grained phyllite and schist from the eastern Caledonides of Arctic Norway to investigate the presence of pre-Scandian tectonometamorphic events. U-Th-Pb detrital zircon and whole rock Sm-Nd analyses have been used to test the regional stratigraphic correlations of these metasedimentary rocks. These results indicate that the Berlevag Formation within the Tanafjord Nappe, previously assumed to be part of the KNC, was deposited after 1872 Ma and prior to a low temperature hydrothermal event at 555 +/- 15 Ma. It has a likely provenance on the Baltica continent, lacks any Grenville-Sveconorwegian detrital zircons, and thus cannot be part of the KNC which contains abundant detritus in this age range. Instead the Berlevag Formation is interpreted as part of the Laksefjord Nappe Complex, which structurally underlies the KNC. Laser-ablation argon-argon dating also shows that late Caledonian (i.e. Scandian) tectonometamorphism affected both the KNC and its immediate footwall at c. 425 +/- 15 Ma. This is corroborated by a step-heating argon-argon muscovite age of 424 +/- 3 Ma which is interpreted as dating cooling. However, within two samples from the KNC, an earlier (Middle-Late Cambrian) metamorphic event is also recorded. A biotite-grade schist yielded an Ar-Ar inverse isochron age of 506 +/- 17 Ma from whole rock surfaces, in which the mineral domains are too fine-grained to date individually. An early generation of muscovite from a coarser-grained amphibolite-facies sample yielded an inverse isochron of 498 +/- 13 Ma. Both isochron ages have atmospheric argon intercept values. Previous studies have documented similar Cambrian ages in the Caledonian nappes below the KNC. These results suggest correlative tectonometamorphic events in the eastern KNC and its footwall at c. 500 Ma. This Cambrian event may reflect the arrival of the Kalak Nappe Complex as a previously constructed exotic mobile belt onto the margin of Baltica. Combined with recent studies from the western Kalak Nappe Complex, the results do not support the traditional constraint on the Finnmarkian Orogeny sensu stricto. However they vindicate classic tectonic models involving a Cambrian accretion event. (c) 2008 Elsevier B.V. All rights reserved.
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| 8. |
- Meade, F. C., et al.
(författare)
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Magma Ascent along a Major Terrane Boundary: Crustal Contamination and Magma Mixing at the Drumadoon Intrusive Complex, Isle of Arran, Scotland
- 2009
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Ingår i: Journal of Petrology. - : Oxford University Press (OUP). - 0022-3530 .- 1460-2415. ; 50:12, s. 2345-2374
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Tidskriftsartikel (refereegranskat)abstract
- The composite intrusions of Drumadoon and An Cumhann crop out on the SE coast of the Isle of Arran, Scotland and form part of the larger British and Irish Palaeogene Igneous Province, a subset of the North Atlantic Igneous Province. The intrusions (shallow-level dykes and sills) comprise a central quartz-feldspar-phyric rhyolite flanked by xenocryst-bearing basaltic andesite, with an intermediate zone of dark quartz-feldspar-phyric dacite. New geochemical data provide information on the evolution of the component magmas and their relationships with each other, as well as their interaction with the crust through which they travelled. During shallow-crustal emplacement, the end-member magmas mixed. Isotopic evidence shows that both magmas were contaminated by the crust prior to mixing; the basaltic andesite magma preserves some evidence of contamination within the lower crust, whereas the rhyolite mainly records upper-crustal contamination. The Highland Boundary Fault divides Arran into two distinct terranes, the Neoproterozoic to Early Palaeozoic Grampian Terrane to the north and the Palaeozoic Midland Valley Terrane to the south. The Drumadoon Complex lies within the Midland Valley Terrane but its isotopic signatures indicate almost exclusive involvement of Grampian Terrane crust. Therefore, although the magmas originated at depth on the northern side of the Highland Boundary Fault, they have crossed this boundary during their evolution, probably just prior to emplacement.
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| 9. |
- Perez-Martinez, Pablo, et al.
(författare)
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Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states
- 2009
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89:1, s. 391-399
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C -> T, APOA5 -1131T -> C, and APOA5 56C -> G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies in US whites (n = `1061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). Results: Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend < 0.001). Conclusions: SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment. Am J Clin Nutr 2009;89:391-9. Clin Nutr 2009; 89: 391-9.
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