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排序方式: 共有487条查询结果,搜索用时 78 毫秒
91.
Andrew M. Haidle Kaleen K. Childers Anna A. Zabierek Jason D. Katz James P. Jewell Yongquan Hou Michael D. Altman Alexander Szewczak Dapeng Chen Andreas Harsch Mansuo Hayashi Lee Warren Michael Hutton Hugh Nuthall Matt G. Stanton Ian W. Davies Ben Munoz Alan Northrup 《Bioorganic & medicinal chemistry letters》2017,27(1):109-113
Attempts to optimize pharmacokinetic properties in a promising series of pyrrolopyrimidinone MARK inhibitors for the treatment of Alzheimer’s disease are described. A focus on physical properties and ligand efficiency while prosecuting this series afforded key tool compounds that revealed a large discrepancy in the rat in vitro–in vivo DMPK (Drug Metabolism/Pharmacokinetics) correlation. These differences prompted an in vivo rat disposition study employing a radiolabeled representative of the series, and the results from this experiment justified the termination of any further optimization efforts. 相似文献
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BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB), the anti-inflammatory effects of individual statins, within the context of various treatment regimes, need further examination. The present study evaluates the anti-inflammatory effectiveness of the short-term, preoperative and intensive postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing CPB were enrolled in a randomized, prospective clinical study. One group (n = 21), received pravastatin, the other (n = 22) did not. Patients in the pravastatin group received one dose of 40 mg per day for nine days, starting 48 hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6) levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values, for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus 251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/- 56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p < 0.001). C-reactive protein (CRP) decreased significantly on the seventh postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1 and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels. Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB. 相似文献
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Matthias Grenié Pierre Denelle Caroline M. Tucker François Munoz Cyrille Violle 《Diversity & distributions》2017,23(12):1365-1371
Emphasis has been put in recent ecological research on investigating phylogenetic, functional and taxonomic facets of biological diversity. While a flourishing number of indices have been proposed for assessing functional diversity, surprisingly few options are available to characterize functional rarity. Functional rarity can play a key role in community and ecosystem dynamics. We introduce here the funrar R package to quantify functional rarity based on species trait differences and species frequencies at local and regional scales. Because of the increasing availability of big datasets in macroecology and biogeography, we optimized funrar to work with large datasets of thousands of species and sites. We illustrate the use of the package to investigate the functional rarity of North and Central American mammals. 相似文献
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Fernandez-Rodriguez A Munoz M Fernandez A Pena RN Tomas A Noguera JL Ovilo C Fernandez AI 《Biology of reproduction》2011,84(2):299-307
Previous results from a genome scan in an F(2) Iberian × Meishan pig intercross showed several chromosome regions associated with litter size traits in this species. In order to identify candidate genes underlying these quantitative trait loci (QTL), we performed an ovary gene expression analysis during the sow's pregnancy. F(2) sows were ranked by their estimated breeding values for prolificacy: six sows with the highest estimated breeding value (EBV) (i.e., high prolificacy) and six sows with the lowest EBV (low prolificacy) were selected. Samples were hybridized using an Affymetrix GeneChip porcine genome array. Statistical analysis with a mixed model approach identified 221 differentially expressed probes, representing 189 genes. These genes were functionally annotated in order to identify genetic pathways overrepresented in this list. Among the functional groups most represented was, in first position, immune system response activation against external stimulus. The second group consisted of integrated genes that regulate maternal homeostasis by complement and coagulation cascades. A third group was involved in lipid and fatty acid enzymes of metabolic processes, which participate in the steroidogenesis pathway. In order to identify powerful candidate genes for prolificacy, the second approach of this study was to merge microarray data with the QTL positional information affecting litter size, previously detected in the same experimental cross. As a result, we have identified 27 differentially expressed genes colocalizing with QTL for litter size traits, which fulfill the biological, positional, and functional criteria. 相似文献
100.
Sopjani M Alesutan I Dërmaku-Sopjani M Gu S Zelenak C Munoz C Velic A Föller M Rosenblatt KP Kuro-o M Lang F 《FEBS letters》2011,585(12):1759-1764
Klotho-hypomorphic (Klotho(hm)) mice suffer from renal salt wasting and hypovolemia despite hyperaldosteronism. The present study explored the effect of Klotho on renal Na(+)/K(+) ATPase activity. According to immunohistochemistry and confocal microscopy Na(+)/K(+) ATPase protein abundance in isolated collecting ducts was lower in Klotho(hm) mice than in their wild type littermates (Klotho(+/+)). Analysis with dual electrode voltage clamp recording showed that expression of Klotho in Xenopus oocytes increased the Na(+)/K(+) ATPase pump current. Treatment of Xenopus oocytes with Klotho protein similarly increased the pump current. In conclusion, Klotho increases the membrane abundance and activity of the Na(+)/K(+) ATPase. Decreased Na(+)/K(+) ATPase activity could thus contribute to the volume-depletion of klotho(hm) mice. 相似文献