Secreted and intracellular phospholipases A2 inhibition by 1-decyl 2-octyl-glycerophosphocholine in rat peritoneal macrophages

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.     

Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation

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.     

间充质干细胞的来源

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。     

Stress test and aortic stenosis

In patients with severe asymptomatic aortic stenosis (AS), the decision to operate is difficult. In effect, the operative mortality is not negligible (about 5% in subjects age over 75 years) while spontaneous mortality from sudden death is low (about 0.4% per year). The aim of the stress test is to detect patients who are falsely asymptomatic (due to subconscious self limitation of daily physical activity) for whom aortic valvular replacement should be proposed because of the risk of sudden death. On the other hand, if the stress test is negative (normal blood pressure elevation on effort, the absence of either any symptoms, ST segment depression of more than 2 mm, or severe ventricular rhythm disorders linked to effort), surgical intervention could (and probably should) be postponed. This article presents the studies which have allowed integration of the stress test as an aid to the decision of when to operate in patients with asymptomatic severe AS with good left ventricular function into the European and North American recommendations.     

Abdominal drainage after liver resection for hepatocellular carcinoma in cirrhotic patients: a randomized controlled study

BACKGROUND/AIMS: The use of drainage after liver resection remains controversial. Data of the usefulness of drains in cirrhotic patients undergoing surgical resection are scarce. The objective of our study is to assess the usefulness of intra-abdominal drainage after liver resection for hepatocellular carcinoma in cirrhotic patients. METHODOLOGY: We performed a randomized controlled trial to assess the benefits of abdominal drainage after resection of hepatocellular carcinoma in cirrhotic patients. The main end point was to compare postoperative complications and hospital stay in both groups. RESULTS: Abdominal drainage decreased ascites leakage and significantly reduced hospital stay in comparison to the non-drainage group. In addition, local complications were less frequent in the drainage group. Postoperative ascites leakage significantly complicated patients with clinically relevant portal hypertension. CONCLUSIONS: Intra-abdominal closed drainage is advisable in cirrhotic patients undergoing liver resection for hepatocellular carcinoma, mainly if presenting preoperative portal hypertension.