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P Boucrot C Bobin-Dubigeon L Elkihel Y Letourneux M Jugé G Gandemer and JY Petit 《Fundamental & clinical pharmacology》1998,12(4):433-441
Summary— Compounds able to inhibit phospholipases A2 can be considered as potential anti-inflammatory drugs. In this respect, the inhibitory effect of the phospholipid analogue 1-decyl 2-octyl-rac-glycero-3-phosphocholine (decyloctyl-GPC) added to the culture medium of rat peritoneal macrophages stimulated with ionophore A23187 was determined, (a) The substrate of phospholipase A2 1-octadecanoyl 2-[14C]eicosatetraenoyl-sn-glycero-3-phosphocholine ([14C]20:4-GPC) was added to the culture medium. In macrophages + extracellular fluids, its hydrolysis at the 2-position, produced [14C]non-phosphorous lipids which reached 12% of the dose at 0.14 μM, 73% at 0.9 and > 90% at 1.6 μM; in experiments where macrophages and extracellular fluids were analyzed separately, decyloctyl-GPC initially added at 4 μM, significantly inhibited the release of [14C]fatty acids and the eicosanoid synthesis, demonstrating its ability to inhibit secreted and/or intracellular phospholipases A2. (b) Extracellular fluids were separated from the macrophages and incubated with [14C]20:4-GPC: 48% of the dose was hydrolyzed by extracellular fluid-associated secreted phospholipase A2 and decyloctyl-GPC at 3 μM, reduced this hydrolysis by 50%. (c) [3H]arachidonic acid ([3H]20:4) was added to the culture medium and was esterified in the macrophage membrane phospholipids. Activation of intracellular phospholipase A2 induced the release of [3H] fatty acids and eicosanoid synthesis. These releases were inhibited by 50% with decyloctyl-GPC added at 4 μM. (d) [3H]20:4 and [14C]20:4-GPC were added to the culture medium of the macrophages. [3H] and [14C] fatty acids and eicosanoids were released in macrophages or extracellular fluids. They were significantly reduced by the phospholipid analogue added at 4 μM. It is concluded that secreted and intracellular phospholipases A2 were both inhibited by decyloctyl-GPC which extensively reduced the 20:4 release from exogenous and membrane phospholipids and therefore eicosanoid synthesis. 相似文献
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W. JY J. J. JIMENEZ L. M. MAURO L. L. HORSTMAN P. CHENG E. R. AHN C. J. BIDOT Y. S. AHN 《Journal of thrombosis and haemostasis》2005,3(6):1301-1308
Endothelial microparticles (EMP) released from activated or apoptotic endothelial cells (EC) are emerging as useful markers for detection of EC dysfunction. Our recent observation that EMP carry von Willebrand factor (vWf) led us to investigate their interaction with platelets. EMP were incubated with normal washed platelets in the presence or absence of ristocetin, then platelet aggregates were measured by flow cytometry. In the absence of ristocetin, negligible EMP conjugated with platelets (< 5%) but in the presence of ristocetin (1 mg mL(-1)), EMP induced up to 95% of platelets to aggregate. EMP-platelet interaction was 80% blocked by anti-CD42b, or by 0.1 microm filtration to remove EMP. Platelet aggregates induced by normal plasma or high molecular weight vWf (Humate-P) dissociated 50% within 15-25 min following 1:20 dilution. In contrast, aggregates formed with EMP persisted two- to threefold longer with the same treatment, indicating greater stability. A similar degree of prolongation of dissociation was observed using plasma from thrombotic thrombocytopenic purpura (TTP) patients compared with normal plasma. Addition of EMP to plasma from severe von Willebrand disease restored his ristocetin-induced platelet aggregation. Multimer analysis of vWf on EMP showed unusually large vWf (ULvWf). In summary, EMP carries ULvWf multimers, promote platelet aggregates, and increase the stability of the aggregates thus formed. 相似文献
54.
目的:间充质干细胞具有强大的增殖能力和多向分化潜能,文章对其主要的来源途径予以综述。资料来源:应用计算机检索Medline1991-01/2006-01期间的相关文章,检索词为“mesenchyma stem cells,origin,research progress”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1998-01/2006-10期间的相关文章,检索词为“间充质干细胞,来源,研究进展”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:①间充质干细胞的起源。②间充质干细胞研究进展、干细胞的分离及鉴定。排除标准:重复研究、个案报告或Meta分析类文章。资料提炼:共收集到96篇相关文献,40篇文献符合纳入标准,排除的56篇文献为内容陈旧或重复。符合纳入标准的40篇文献中,分别涉及骨髓、肌肉、脐血、胎盘、外周血、脂肪组织、血管及其他来源的间充质干细胞。资料综合:间充质干细胞是属于中胚层的一类多能干细胞,具有强大的增殖能力和多向分化潜能,动物模型试验和临床应用研究也取得了一定的效果。间充质干细胞来源广泛,易于获得,临床上为神经损伤及其他系统的损伤修复提供了更为广泛的途径。结论:间充质干细胞主要来源于骨髓、肌肉、脐血、外周血、胎盘等组织,具有广阔的应用前景。 相似文献
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56.
Oliver C. Singer MD Joachim Berkefeld MD Christian H. Nolte MD Georg Bohner MD Hans‐Peter Haring MD Johannes Trenkler MD Klaus Gröschel MD Wibke Müller‐Forell MD Kurt Niederkorn MD Hannes Deutschmann MD Tobias Neumann‐Haefelin MD Carina Hohmann PhD Matthias Bussmeyer Anastasios Mpotsaris MD Anett Stoll MD Albrecht Bormann MD Johannes Brenck MD Marc U. Schlamann MD Sebastian Jander MD Bernd Turowski MD Gabor C. Petzold MD Horst Urbach MD David S. Liebeskind MD for the ENDOSTROKE Study Group 《Annals of neurology》2015,77(3):415-424
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Effect of steroids on Acanthamoeba cysts and trophozoites. 总被引:6,自引:0,他引:6
K McClellan K Howard J Y Niederkorn H Alizadeh 《Investigative ophthalmology & visual science》2001,42(12):2885-2893
PURPOSE: Topical steroids are frequently used to control corneal inflammation and uveitis or is administered after surgery, to prevent corneal graft rejection. This study was undertaken to determine whether steroids could affect the pathogenicity of Acanthamoeba castellanii. METHODS: The effect of dexamethasone phosphate on excystment, proliferation, and encystment of trophozoites and cysts of A. castellanii was examined in vitro. Cytolysis capacity of steroid-treated Acanthamoeba was quantified by a spectrophotometric assay, and plasminogen activators were measured by a fibrinolysis assay. The influence of steroid treatment on corneal infection in a Chinese hamster model of Acanthamoeba keratitis was examined in vivo. RESULTS: Treatment of Acanthamoeba cysts with dexamethasone induced 4- to 10-fold increases in the number of trophozoites compared with untreated control cultures. Acceleration of trophozoite proliferation was observed when trophozoites were treated with dexamethasone. However, dexamethasone treatment did not affect encystment of Acanthamoeba trophozoites. Dexamethasone-treated trophozoites or cysts induced a significant cytopathic effect on corneal epithelial cells compared with untreated organisms. Supernatants collected from either dexamethasone-treated or untreated organisms failed to lyse corneal epithelial cells. Treatment of organisms with dexamethasone had no effect on production of plasminogen activators by Acanthamoeba trophozoites. Intramuscular injection of dexamethasone had a profound effect on the incidence, severity, and chronicity of keratitis. Keratitis in dexamethasone-treated hamsters was significantly more severe at all time points than in untreated animals (P < 0.05). CONCLUSIONS: These findings indicate that exposure of Acanthamoeba trophozoites and cysts to dexamethasone increases the pathogenicity of the organisms. The results emphasize the importance of maintaining adequate amebicidal therapy if a topical steroid is used in the management of Acanthamoeba keratitis. 相似文献
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Ohne Zusammenfassung 相似文献
60.
Steven JY Wang Claire Cornick Jacqueline O'Dowd Michael A Cawthorne Jonathan R S Arch 《Lipids in health and disease》2007,6(1):2