996 resultados para 2,2 `-methylenedi-8-quinolinol dihydrochloride dihydrate


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3B carbon dust, H and HH carbon pencils, and 9H graphite pencil on video paper; Dr. Norman W. Thompson, University of Michigan Department of Surgery

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Thesis (doctoral)--Friedrich-Wilhelms-Universitat zu Berlin.

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Statins possess anti-inflammatory effects that may contribute to their ability to slow atherogenesis, whereas nitric oxide (NO) also influences inflammatory cell adhesion. This study aimed to determine whether a novel NO-donating pravastatin derivative, NCX 6550 [(1S-[1∝(ßS*,dS*),2∝,6a∝,8ß-(R*),8a∝]]-1,2,6,7,8,8a-hexahydro-ß,δ,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-heptanoic acid 4-(nitrooxy)butyl ester)], has greater anti-inflammatory properties compared with pravastatin in normal and atherosclerotic apolipoprotein E receptor knockout (ApoE-/-) mice. C57BL/6 and ApoE-/- mice were administered pravastatin (40 mg/kg), NCX 6550 (48.5 mg/kg), or vehicle orally for 5 days. Ex vivo studies assessed splenocyte adhesion to arterial segments and splenocyte reactive oxygen species (ROS) generation. NCX 6550 significantly reduced splenocyte adhesion to artery segments in both C57BL/6 (8.8 ± 1.9% versus 16.6 ± 6.7% adhesion; P < 0.05) and ApoE-/- mice (9.3 ± 2.9% versus 23.4 ± 4.6% adhesion; P < 0.05) concomitant with an inhibition of endothelial intercellular adhesion molecule-1 expression. NCX 6550 also significantly reduced phorbol 12-myristate 13-acetate-induced ROS production that was enhanced in isolated ApoE-/- splenocytes. Conversely, pravastatin had no significant effects on adhesion in normal or ApoE-/- mice but reduced the enhanced ROS production from ApoE-/- splenocytes. In separate groups of ApoE-/- mice, NCX 6550 significantly enhanced endothelium-dependent relaxation to carbachol in aortic segments precon-tracted with phenylephrine (-logEC50, 6.37 ± 0.37) compared with both vehicle-treated (-logEC50, 5.81 ± 0.15; P < 0.001) and pravastatin-treated (-logEC50, 5.57 ± 0.45; P < 0.05) mice. NCX 6550 also significantly reduced plasma monocyte chemoattractant protein-1 levels (648.8 pg/ml) compared with both vehicle (1191.1 pg/ml; P < 0.001) and pravastatin (847 ± 71.0 pg/ml; P < 0.05) treatment. These data show that NCX 6550 exerts superior anti-inflammatory actions compared with pravastatin, possibly through NO-related mechanisms.

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Understanding the response of the Antarctic ice sheets during the rapid climatic change that accompanied the last deglaciation has implications for establishing the susceptibility of these regions to future 21st Century warming. A unique diatom d18O record derived from a high-resolution deglacial seasonally laminated core section off the west Antarctic Peninsula (WAP) is presented here. By extracting and analysing single species samples from individual laminae, season-specific isotope records were separately generated to show changes in glacial discharge to the coastal margin during spring and summer months. As well as documenting significant intra-annual seasonal variability during the deglaciation, with increased discharge occurring in summer relative to spring, further intra-seasonal variations are apparent between individual taxa linked to the environment that individual diatom species live in. Whilst deglacial d18O are typically lower than those for the Holocene, indicating glacial discharge to the core site peaked at this time, inter-annual and inter-seasonal alternations in excess of 3 per mil suggest significant variability in the magnitude of these inputs. These deglacial variations in glacial discharge are considerably greater than those seen in the modern day water column and would have altered both the supply of oceanic warmth to the WAP as well as regional marine/atmospheric interactions. In constraining changes in glacial discharge over the last deglaciation, the records provide a future framework for investigating links between annually resolved records of glacial dynamics and ocean/climate variability along the WAP.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)