Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes

A chemokine receptor, CXCR4, and its endogenous ligand, stromal cell-derived factor-1 (SDF-1), have been recognized to be involved in the metastasis of several types of cancers. T140 analogs are peptidic CXCR4 antagonists composed of 14 amino acid residues that were previously developed as anti-HIV agents having inhibitory activity against HIV-entry through its co-receptor, CXCR4. Herein, we report that these compounds effectively inhibited SDF-1-induced migration of human breast cancer cells (MDA-MB-231), human leukemia T cells (Sup-T1) and human umbilical vein endothelial cells at concentrations of 10–100 nM in vitro. Furthermore, slow release administration by subcutaneous injection using an Alzet osmotic pump of a potent and bio-stable T140 analog, 4F-benzoyl-TN14003, gave a partial, but statistically significant (P≤0.05 (t-test)) reduction in pulmonary metastasis of MDA-MB-231 in SCID mice, even though no attempt was made to inhibit other important targets such as CCR7. These results suggest that T140 analogs have potential use for cancer therapy, and that small molecular CXCR4 antagonists could potentially replace neutralizing antibodies as anti-metastatic agents for breast cancer.     

Normobaric hyperoxic stress in budgerigars: non-enzymic antioxidants

The effects of oxygen exposure on pulmonary and blood non-enzymic antioxidant concentrations was evaluated in budgerigars (Melopsittacus undulatus). Budgerigars were exposed to acute (3 h), repeated acute (3 exposures each of 3 h) or chronic (72 h) normobaric hyperoxic environments and the pulmonary and plasma concentrations of selected non-enzymic antioxidants, namely glutathione, uric acid, alpha- and gamma-tocopherol and carotenoids were assayed. With increasing duration of oxygen exposure, the ratio of oxidised to reduced glutathione was significantly increased, while the concentrations of uric acid, alpha- and gamma-tocopherol and carotenoids were significantly reduced, especially following chronic oxygen exposure. Following acute and repeated acute exposure, alteration in glutathione concentrations and reduction in alpha-tocopherol concentrations indicated oxygen stress. Following chronic exposure, depletion of non-enzymic antioxidants indicated exhaustion of these protective mechanisms and progression from oxygen stress to oxygen toxicity.     

过氧亚硝基阴离子介导内毒素致肺血管损伤及胆囊收缩素的保护作用

本文探讨过氧亚硝基阴离子（ONOO^-）在内毒素致肺血管损伤中的介导作用和八肽胆囊收缩素（CCK）的保护作用及其机制。结果发现,内毒素主要成分脂多糖（LPS）可诱导大鼠肺组织生成ONOO^-1,ONOO^-能导致肺微血管壁通透性明显增加和肺脏严重病理变化;ONOO^-可引起离体肺动脉反应性异常改变,LPS也可产生类似变化;ONOO^-有较弱的舒血管作用并受到内皮细胞的抑制性调节;LPS诱导培养的牛肺动脉内皮细胞（BPAEC）产生增多的ONOO^-参与介导内皮细胞本身的损伤;CCK能拮抗LPS对BPAEC的损伤效应,此作用由CCK受体介导,并与抑制ONOO^-生成有关。结果提示,清除ONOO^-或减少ONOO^-生成可为防治内毒素引起的急性肺损伤等病理过程提供新对策;CCK是一种有应用前景的细胞保护因子。     

Differential secretion of cytokines and adhesion molecules by HUVEC stimulated with low concentrations of bleomycin

Bleomycin (BLM) is known to induce lung inflammation and subsequent fibrosis. Endothelial cells have been reported to play an important role, producing cytokines and adhesion molecules during the inflammatory process in pulmonary fibrosis. To examine the effects of BLM on endothelial cells, we investigated the expression profiles of various cytokines and adhesion molecules produced by endothelial cells stimulated with BLM. Increased expressions of interleukin-8 and monocyte chemoattractant protein-1 measured as protein as well as mRNA by human umbilical vein endothelial cells (HUVECs) were detected after exposure to BLM. Similarly, increased expressions of E-selectin and intercellular adhesion molecule-3 were detected both at the protein and mRNA levels. Under these conditions, a small but significant decrease of [3H]thymidine uptake was detected. These findings indicate that HUVEC were stimulated to secrete cytokines and express adhesion molecules in the presence of low concentrations of BLM which have a mildly inhibitory effect on cellular proliferation.     

Microstructure and dynamic surface properties of surfactant protein SP-B/dipalmitoylphosphatidylcholine interfacial films spread from lipid-protein bilayers

 Suspensions of dipalmitoylphosphatidylcholine (DPPC) bilayers containing 5, 10 or 20% (w/w) surfactant protein SP-B have been reconstituted and spread at air-liquid interfaces. Compression isotherms of DPPC/SP-B monolayers spread from these preparations were qualitatively comparable to the isotherms of the corresponding DPPC/SP-B monolayers spread from solvents. SP-B was squeezed-out at higher pressures from vesicle-spread films than from solvent-spread monolayers. SP-B caused a marked decrease on the rate of relaxation of DPPC collapse phases to equilibrium pressures in all the lipid/protein films assayed. This stabilizing effect was higher in vesicle-spread than in solvent-spread monolayers. Inclusion in the films of traces of the fluorescent probe NBD-PC (1 mol%) and use of a fluorescent derivative of SP-B labeled with a rhodamine derivative, Texas Red, allowed for direct observation of protein and lipid domains at the interface by epifluorescence microscopy. Upon compression, SP-B altered the packing of phospholipids in the bilayer-spread films, observed as a SP-B-induced reduction of the area of liquid-condensed domains, in a way similar to its effect in solvent-spread monolayers. SP-B was not associated with condensed regions of the films. Fluorescence images from vesicle-spread films showed discrete fluorescent aggregates that could be consistent with the existence of lipid-protein vesicles in close association with the monolayer. Both the retention of SP-B at higher surface pressures and the greater stability of collapse phases of DPPC/SP-B films prepared by spreading from liposomes in comparison to those spread from solvents can be interpreted as a consequence of formation of complex bilayer-monolayer interacting systems. Received: 1 December 1999 / Revised version: 2 March 2000 / Accepted: 2 March 2000     

Cytotoxicity-Associated Effects of Reactive Oxygen Species on Endothelin-1 Secretion by Pulmonary Endothelial Cells

In this study bovine pulmonary artery endothelial cells (BPAEC) were used as a model system to investigate the effects of the hypoxanthine–xanthine oxidase (HXXO) oxygen radical donor system on ET-1 secretion into pulmonary vasculature. Incubation of BPAEC with HXXO for 4 h caused a significant reduction in ET-1 secretion, which was significantly offset by allopurinol or catalase, but not by Cu/Zn superoxide dismutase (SOD). ET-1 secretion was also reduced by H₂O₂, and this effect was again significantly offset by catalase. XO alone also reduced ET-1 secretion, but to a significantly lesser degree than did HXXO, and this effect was not offset by allopurinol, catalase, or SOD. None of the oxidant treatments were associated with a loss of immunoreactive ET-1 from endothelial cell medium containing synthetic peptide. The HXXO- and H₂O₂-mediated reductions in ET-1 secretion were accompanied by evidence of reduced cell viability. This loss of viability was absent when cells were treated with HXXO + catalase, allopurinol, or mercaptopropionyl glycine, but not when SOD was present. We conclude that under conditions of oxidative stress, the pulmonary vascular endothelium responds by secreting less ET-1. This may be relevant to its vasodilator functions in the pulmonary vasculature, which would therefore be compromised when the endothelium is exposed to oxidant stress.     

去自主神经效应对环肺静脉消融房颤疗效的影响

目的：探讨去自主神经效应对环肺静脉消融(CPVA)治疗心房颤动(房颤)的远期成功率的影响。方法：选择104 例药物治疗无 效的、有临床症状的阵发性房颤患者作为研究对象,所有患者均接受CPVA 术。分别于术前、术后进行动态心电图检查,术后每3 个月复查一次动态心电。随访房颤消融成功率(术后3个月无房颤被定义为无复发);并记录动态心电心率变异性(HRV)以反映自 主神经功能。结果：本组研究共104 例患者完成了CPVA术,平均手术次数为(1.35术次数为。变次,成功率为77.9%,共随访(24.27 次数为。变异性个月。根据术后是否发生房颤,将患者分为成功组(81例)和复发组(23 例),所有患者CPVA术后的时域和频域各项 参数均显著降低(P<0.01),两组术后心率变异性(HRV) 各项参数均较术前明显降低,成功组患者的SNDD、SDANN、rMSSD、 PNN50、HF、TF、LF、VLF 较对照组患者呈现不同程度的降低。结论：CPVA术可使心房出现去自主神经效应,进而增加去神经化 效应,有利于提高其治疗房颤的远期成功率。     

低氧诱导因子抑制因子在低氧性肺动脉高压中的作用

目的:研究低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)形成过程中低氧诱导因子抑制因子(factor inhibiting hypoxia-inducible factor-1,FIH)在肺小动脉的表达变化及在HPH发病中的可能作用。方法:将36名患者分为慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)并肺动脉高压组(pulmonary hypertension,PH)组(PH组)、COPD非PH组(COPD组)、对照组,收集肺组织,观察其肺血管重塑指标,原位杂交法与免疫组织化学法检测肺小动脉壁FIH m RNA和蛋白的表达水平。结果:COPD组患者肺小动脉出现血管重塑,PH组患者肺小动脉重塑更明显(P0.05)。FIH m RNA在各组患者肺小动脉壁的表达无明显差异(P0.05);FIH蛋白在对照组患者肺小动脉壁高表达,COPD组表达降低,PH组表达进一步减少(P0.05)。直线相关分析表明,FIH蛋白与FIH m RNA无相关(P0.05);FIH蛋白与肺小动脉重塑指标、肺动脉收缩压均呈负相关(P0.01)。结论:慢性肺泡性低氧下调患者肺小动脉壁FIH表达,进而参与患者HPH发病。     

颅内动脉瘤开颅术后患者肺部感染的危险因素分析

目的:探讨颅内动脉瘤开颅术后发生肺部感染的危险因素。方法:回顾性分析在我院接受开颅手术治疗的211例颅内动脉瘤患者的性别、年龄、吸烟史、糖尿病史、高血压病史、Hunt-Hess分级、动脉瘤部位、动脉瘤直径、手术时机及术后肺部感染的情况,对可能导致肺感染的因素行X2检验及Logistic回归分析。结果:单因素分析显示影响颅内动脉瘤患者术后肺感染的因素主要包括年龄、吸烟、糖尿病、Hunt-Hess分级(P0.05)。多因素Logistic回归分析结果显示影响颅内动脉瘤患者开颅术后发生肺部感染的因素为吸烟和Hunt-Hess分级。结论:吸烟、高Hunt-Hess分级是影响颅内动脉瘤开颅术后发生肺部感染的独立危险因素。     

双水平气道正压通气治疗重叠综合征合并呼吸衰竭患者的临床疗效

目的：探讨鼻面罩双水平正压通气（BIPAP）治疗重叠综合征合并呼吸衰竭患者的临床疗效及对血气指标和肺功能的影响。 方法：选取2011 年10 月到2014 年6 月期间我院收治的重叠综合征合并呼吸衰竭患者46 例,将其随机分为观察组（23 例）和对 照组（23 例）,在常规抗感染、支气管扩张剂、激素、纠正酸碱失衡、呼吸兴奋剂、针对原发病等治疗基础上,对照组给予持续气道正 压通气(CPAP),观察组给予BIPAP 通气治疗,对比治疗后两组患者的临床疗效,比较两组治疗前后24h 动脉血气、肺功能以及多 导睡眠监测(PSG)结果。结果：治疗后,观察组患者的总有效率为87.0%（20/23）,显著高于对照组的73.9%(17/23),差异有统计学意 义（P<0.05）;两组患者的24 h动脉血气、肺功能和PSG 结果均显著优于治疗前,且观察组优于对照组,差异具有统计学意义（P<0. 05）。结论：BIPAP治疗重叠综合征合并呼吸衰竭临床疗效显著,可以改善患者的血气指标及肺功能,有效降低气管插管率,值得 在临床推广应用。