槲皮素抑制血小板活化因子受体结合作用的研究

目的 :观察槲皮素对氚标记的血小板活化因子与血小板膜上受体结合的影响 ,试图证明该药为一新型血小板激活因子 (PAF)受体拮抗剂。方法 :以放射配基结合试验观察 [3H]PAF与兔血小板受体特异性结合的作用 ;以分光光度法测定PAF诱发血小板黏附的强度。结果 :槲皮素可浓度依赖地抑制2 5 ,5 0 ,10 0nmol·L- 1 [3H]PAF与兔血小板受体的特异性结合 ;该药可明显抑制PAF诱发的血小板黏附 ,具明显的量效关系 ,其IC50 为 39 8μmol·L- 1 。结论 :槲皮素具抗PAF作用 ,为一新的PAF受体拮抗剂。     

Integrin and extracellular matrix interactions regulate engraftment of transplanted hepatocytes in the rat liver

BACKGROUND & AIMS: Recognition and circumvention of the hepatic endothelial barrier is critical in the engraftment of transplanted cells. We examined whether interactions between integrin and extracellular matrix component receptors could be manipulated for improving transplanted cell engraftment and liver repopulation. METHODS: Fischer 344 rat hepatocytes were transplanted into syngeneic dipeptidyl peptidase IV-deficient rats. Coating of cells or of liver sinusoids with natural collagen, natural laminin, or an engineered fibronectin-like polymer was studied with analysis of cell engraftment and liver repopulation using histologic and molecular assays. Focal adhesion complexes were identified by vinculin immunostaining. The role of integrin receptors in cell engraftment was analyzed with RGD peptide inhibition assays. RESULTS: Coating of cells with extracellular matrix components before transplantation did not enhance cell engraftment. In contrast, intraportal infusion of collagen or fibronectin-like polymer in recipients prior to cell transplantation increased cell engraftment. Adherence of transplanted cells to the hepatic endothelium resulted in rapid activation of vinculin-containing focal adhesion complexes. Superior cell engraftment in animals treated with fibronectin-like polymer was RGD sensitive, verifying the integrin-dependent nature of this process. Moreover, studies in the retrorsine-partial hepatectomy rat model showed that intraportal infusion of the fibronectin-like polymer before cell transplantation significantly accelerated liver repopulation. CONCLUSIONS: Integrin-extracellular matrix component interactions can be manipulated for enhancing cell engraftment in the liver. Such mechanisms will be relevant for engraftment of other cell types and for strategies concerning liver-directed cell therapy.     

Mediator-Directed Therapy in Pancreatitis and Trauma

Both acute pancreatitis and severe trauma induce a systemic sterile inflammatory process which leads to a high incidence of remote organ dysfunction and death. Several attributes of these two entities make them ideal for evaluation of the effects of mediator-directed therapy. The rationale and evidence for mediator-directed therapy in pancreatitis and trauma are reviewed. In pancreatitis, organ dysfunction and death are best prevented using strategies designed to limit the inflammatory response, particularly IL-1a and IL-10. By contrast, the sequelae of a post-traumatic systemic inflammatory response are best mitigated using strategies designed to limit neutrophil adhesion.     

辛伐他汀对老年急性冠状动脉综合征患者hsC和sICAM-1及预后的影响

目的:研究辛伐他汀对急性冠状动脉综合征(ACS)患者外周血清可溶性细胞间黏附分子-1(sICAM-1)、超敏C反应蛋白(hsC)和心血管事件预后的影响。方法:将73例经冠状动脉造影证实的ACS患者随机分为对照组35例和治疗组38例。对照组给予控制血压、降糖、抗凝、抗血小板及改善心肌供血等治疗,调脂药物采用血脂康治疗,治疗组在此基础上加用辛伐他汀20 mg。治疗前及治疗3周后,分别测定血总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、sICAM-1及hsC,观察2组患者出院后6个月内因不稳定型心绞痛再住院、急性心肌梗死、血运重建及死亡等MACE事件发生情况。结果:辛伐他汀治疗组TC、LDL-C、hsC、sICAM-1水平降低(P<0.05);6个月内的不良心脏事件(MACE)显著减少。结论:辛伐他汀可显著减少老年ACS患者MACE的发生率,降低血hsC、sICAM-1水平,改善预后。     

成年烟雾病患者血清血管细胞黏附分子1、基质金属蛋白酶9、转化生长因子β、血管内皮生长因子水平变化及其临床意义研究

背景目前,烟雾病(MMD)的病因及发病机制尚不完全明确,此类患者通常在发生脑血管事件后才被确诊,因此探讨MMD的预测因子及评估其严重程度的指标具有重要的临床意义。目的探讨成年MMD患者血清血管细胞黏附分子1(VCAM-1)、基质金属蛋白酶9(MMP-9)、转化生长因子β(TGF-β)、血管内皮生长因子(VEGF)水平及其临床意义。方法选取2016年3月-2019年1月四川大学华西广安医院收治的成年MMD患者114例作为病例组,其中缺血型68例,出血型46例;另选取同期在本院门诊健康体检中心体检健康者30例作为对照组。比较对照组受试者体检当日与病例组患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平,比较出血型与缺血型患者入院第1、7、14天血清VCAM-1、MMP-9、TGF-β、VEGF水平,并比较不同Suzuki分级成年MMD患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平;成年MMD患者入院第1天血清VCAM-1、MMP-9水平与血清TGF-β、VEGF水平的相关性分析采用Pearson相关分析。结果病例组患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平高于对照组(体检当日)(P<0.05)。时间与方法在血清VCAM-1、MMP-9水平上不存在交互作用(P>0.05),在血清TGF-β、VEGF水平上存在交互作用(P<0.05);时间在血清VCAM-1、MMP-9、TGF-β、VEGF水平上主效应显著(P<0.05);方法在血清VCAM-1、MMP-9水平上主效应不显著(P>0.05),在血清TGF-β、VEGF水平上主效应显著(P<0.05);出血型患者入院第1、7、14天血清TGF-β、VEGF水平高于缺血型患者(P<0.05)。Suzuki分级3级缺血型患者血清入院第1天MMP-9、VEGF水平高于Suzuki分级2级患者,Suzuki分级3级出血型患者入院第1天血清VEGF水平高于Suzuki分级2级患者(P<0.05);Suzuki分级4级缺血型、出血型患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平分别高于Suzuki分级2、3级缺血型、出血型患者(P<0.05);Suzuki分级5、6级缺血型、出血型患者入院第1天血清VCAM-1、MMP-9、TGF-β、VEGF水平分别高于Suzuki分级2、3、4级缺血型、出血型患者(P<0.05);Suzuki分级6级缺血型、出血型患者入院第1天血清VEGF水平分别高于Suzuki分级5级缺血型、出血型患者(P<0.05)。Pearson相关分析结果显示,缺血型、出血型MMD患者入院第1天血清VCAM-1、MMP-9水平分别与血清TGF-β、VEGF水平呈正相关(P<0.05)。结论缺血型和出血型成年MMD患者血清VCAM-1、MMP-9、TGF-β、VEGF水平均异常升高,且均与患者病情严重程度相关;血清VCAM-1、MMP-9水平分别与缺血型、出血型MMD患者血清TGF-β、VEGF水平呈正相关,VCAM-1、MMP-9可能参与了成年MMD患者颅内出血过程。     

Nicotine and sympathetic neurotransmission

Summary Nicotine increases heart rate, myocardial contractility, and blood pressure. These nicotine-induced cardiovascular effects are mainly due to stimulation of sympathetic neurotransmission, as nicotine stimulates catecholamine release by an activation of nicotinic acetylcholine receptors localized on peripheral postganglionic sympathetic nerve endings and the adrenal medulla. The nicotinic acetylcholine receptor is a ligand-gated cation channel with a pentameric structure and a central pore with a cation gate, which is essential for ion selectivity and permeability. Binding of nicotine to its extracellular binding site leads to a conformational change of the central pore, which results in the influx of sodium and calcium ions. The resulting depolarization of the sympathetic nerve ending stimulates calcium influx through voltage-dependent N-type calcium channels, which triggers the nicotine-evoked exocytotic catecholamine release. In the isolated perfused guinea-pig heart, cardiac energy depletion sensitizes cardiac sympathetic nerves to the norepinephrine-releasing effect of nicotine, as indicated by a leftward shift of the concentration-response curve, a potentiation of maximum transmitter release, and a delay of the tachyphylaxis of nicotine-evoked catecholamine release. This sensitization was also shown to occur in the human heart under in vitro conditions. Through the intracardiac release of norepinephrine, nicotine induces a beta-adrenoceptormediated increase in heart rate and contractility, and an alpha-adrenoceptor-mediated increase in coronary vasomotor tone. The resulting simultaneous increase in oxygen demand and coronary resistance has a detrimental effect on the oxygen balance of the heart, especially in patients with coronary artery disease. Sensitization of the ischemic heart to the norepinephrine-releasing effect of nicotine may be a trigger for acute cardiovascular events in humans, such as acute myocardial infarction and/or life-threatening ventricular tachyarrhythmias.     

靶向表达的逆转录病毒载体LN.ALBTRS.TK的构建

目的构建出在肝细胞中具靶向表达潜能的逆转录TK基因载体。方法用p2335A-1中的一段2.0kb的人白蛋白组织特异性转录调节序列(ALBTRS)取代pSTK中的SV40启动子,所构建的载体命名为LN.ALBTRS.TK。结果载体LN.ALBTRS.TK的结构中,含有ALBTRS启动子,具有在表达白蛋白的肝细胞中特异表达的潜能,载体经酶切鉴定表明结构符合要求。结论成功地构建出具靶向表达潜能的逆转录载体LN.ALBTRS.TK。     

18F‐Fluorodeoxyglucose (FDG)‐PET features of focal nodular hyperplasia (FNH) of the liver

Abstract: Aim: The aim of this paper is to describe the imaging pattern of focal nodular hyperplasia (FNH) by ¹⁸F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET). Methods: Eight consecutive asymptomatic patients with histologic proof of FNH underwent 18F‐FDG PET imaging. The lesions were found incidentally. The 18F‐FDG PET imaging was performed with a dedicated PET tomograph after intravenous injection of 300–370 MBq 18F‐FDG. The 18F‐FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (n=2) and colorectal carcinoma (n=6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm±2.37) and from 1.5 to 6 cm (mean 3.28±1.52), respectively. Results: While in malignant liver lesions the accumulation of 18F‐FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F‐FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12±0.38), whereas all liver metastases showed an increased SUV ranging between 6.20 and 16.00 (mean 10.07±3.79). The SUV corrected for LMB (SUV_LBM) was similar to the SUV and ranged between 0.9 and 2.2 (mean 1.81±0.41) for FNH and between 5.9 and 16.3 (mean 9.15±4.03), respectively. Conclusion: In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F‐FDG‐PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic.