ATP敏感性钾通道P266T突变对离子通道特性的影响

目的： 通过通道蛋白特定位点(P266T)突变,观察对ATP敏感性钾通道电生理特性的影响。 方法: 将Kir6.2及其突变子P266T的cDNA导入人胚肾细胞，表达ATP敏感性钾通道，用膜片钳方法研究K_ATP电生理特性。 结果: K_ATP(P266T)开放能力是野生型的2倍; K_ATP(P266T)密度仅是野生型20%; K_ATP(P266T)对ATP敏感性降低;对pH敏感性增高。 结论: K_ATP特定位点(P266T)突变可改变K_ATP电生理特性。     

Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter,randomized, double-blind,double-dummy,active-controlled,non-inferiority trial

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.

一氧化氮供体对缺血再灌注肾脏ICAM-1表达的影响

目的 观察缺血再灌注后加用NO供体对肾脏ICAM-1表达及白细胞浸润的影响。方法 分别采用ICAM-1和整合素β2多克隆抗体，免疫组化方法观察加有NO供体后大鼠肾脏缺血再灌注24hICAM-1表达的变化及肾功能改变。结果 缺血再灌注24h大鼠肾脏ICAM-1及β2阳性细胞表达显著增强，以外髓直小血管，皮质肾小管外毛细血管较为明显，再灌注同时灌注NO供体SIN-1可显著抑制缺血再灌注后ICAM-1的表达增强，减少局部炎细胞浸润，改善肾功能，结论 NO供体可减少肾组织ICAM-1的表达及炎细胞浸润，发挥对急性缺血性肾衰的治疗作用。     

Social isolation stress augments angiogenesis induced by colon 26-L5 carcinoma cells in mice

We have previously shown that tumor necrosis factor-α (TNF-α), which is an important angiogenesis-related factor, was over-secreted in male BALB/c mice under social isolation stress as compared with the control, and closely associated with a remarkable elevation of tumor invasion and metastasis of colon 26-L5 carcinoma cells. In the present study, we explored the effect of isolation stress on the angiogenesis caused by colon 26-L5 carcinoma cells in vivo and in vitro. Social isolation lead to the enhancement of tumor growth after intrahepatic implantation with a fragment of colon 26-L5 tumor. Angiogenic response (number of vessels oriented towards tumor mass) and tumor growth (size) were significantly increased in the socially isolated mouse relative to that in the group-housed mice. Furthermore, higher protein level of hepatic TNF-α was found in the stressed mice than that in the control. Expression of mRNA for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were also elevated in the tumor regions and liver tissues of the stressed mice in comparison with that in group-housed mice. On the other hand, hepatic sinusoidal endothelial (HSE) cells treated with TNF-α exhibited a marked promotion of the migration, invasion, expression of mRNA for matrix metalloproteinase (MMP)-9, and tube-like formation, but no cytotoxicity against the cells in vitro. The above data suggest that the social isolation stress augmented the tumor-induced angiogenesis probably by up-regulating the angiogenesis-related factors, including TNF-α, VEGF and HGF, and consequently mediating the functions of endothelial cells such as migration, invasion, and tube-like formation.     

Differential involvement of mu(1)-opioid receptors in endomorphin- and beta-endorphin-induced G-protein activation in the mouse pons/medulla

Several genetic mouse models of differential sensitivity to opioids have been used to investigate the mechanisms underlying individual variation in responses to opioids. The CXBK mice are inbred recombinant mice which have a lower level of mu(1)-opioid receptors than their parental strain. Endomorphin-1 and endomorphin-2 are endogenous opioid peptides that are highly selective for mu-opioid receptors, while beta-endorphin, which is also an endogenous opioid peptide, is non-selective for mu-, delta- and putative epsilon-opioid receptors. The present study was designed to investigate the effects of these endogenous opioid peptides on G-protein activation by monitoring guanosine-5'-o-(3-[35S]thio)triphosphate binding to pons/medulla membranes of CXBK mice and their parental strain C57BL/6 ByJ mice. Endomorphin-1 (0.1-10 microM), endomorphin-2 (0.1-10 microM) and beta-endorphin (0.1-10 microM) increased guanosine-5'-o-(3-[35S]thio)triphosphate binding to the pons/medulla membranes from C57BL/6 ByJ and CXBK mice in a concentration-dependent manner. However, the increases of guanosine-5'-o-(3-[35S]thio)triphosphate binding induced by either endomorphin-1 or endomorphin-2 in CXBK mice were significantly much lower than those in C57BL/6ByJ mice. However, no significant difference was found in the increases of the guanosine-5'-o-(3-[35S]thio)triphosphate binding induced by beta-endorphin in C57BL/6 ByJ and CXBK mice. Moreover, whereas the increase of guanosine-5'-o-(3-[35S]thio)triphosphate binding induced by 10 microM endomorphin-1 or endomorphin-2 were almost completely blocked by a mu-opioid receptor antagonist beta-funaltrexamine (10 microM) in both strains, the increase of guanosine-5'-o-(3-[35S]thio)triphosphate binding induced by 10 microM beta-endorphin was attenuated to approximately 70% of stimulation by co-incubation with 10 microM beta-funaltrexamine in both strains. The residual stimulation of [35S]guanosine-5'-o-(3-thio)triphosphate binding by 10 microM beta-endorphin in the presence of 10 microM beta-funaltrexamine was further attenuated by the addition of putative epsilon-opioid receptor partial agonist beta-endorphin (1-27) (1 microM) in both strains. Like the endomorphins, the synthetic mu-opioid receptor agonist [D-Ala(2),N-MePhe(4), Gly-ol(5)]enkephalin at 10 microM showed lower increases of guanosine-5'-o-(3-[35S]thio)triphosphate binding in CXBK mice than those in C57BL/6ByJ mice. However, there was no strain difference in the stimulation of guanosine-5'-o-(3-[35S]thio)triphosphate binding induced by 10 microM of the selective delta(1)-opioid receptor agonist [D-Pen(2,5)]enkephalin, delta(2)-opioid receptor agonist [D-Ala(2)]deltorphin II or kappa-opioid receptor agonist U50,488H. The results indicate that the G-protein activation by endomorphin-1 and endomorphin-2 in the mouse pons/medulla is mediated by both mu(1)- and mu(2)-opioid receptors. Moreover, beta-endorphin-induced G-protein activation in the mouse pons/medulla is, in part, mediated by mu(2)- and putative epsilon-, but not by mu(1)-opioid receptors.     

乙醇对人绒毛孕酮分泌的影响

本工作利用灌流技术观察了四种不同浓度的乙醇(0.5％、1％、2.5％、5％)对妊娠早期人工流产新鲜胎盘绒毛分泌孕酮的影响。结果表明,乙醇具有促进孕酮分泌的作用,并存在剂量依赖的关系。提示乙醇可能破坏胎盘激素内分泌的平衡,从而影响胎儿的正常生长与发育。     

动物痛行为学检测方法的研究进展

疼痛研究的最终目的是寻找有效镇痛手段。目前临床治疗方法不能充分控制顽固性疼痛,主要归结于疼痛的机制仍不十分清楚,对实验室动物痛行为学进行研究有助于揭示疼痛的相关机制。经典刺激诱发痛行为学检测,如vonFrey痛阈实验、甩尾实验、热板实验哈格里夫斯实验等,已用于大鼠和小鼠动物研究多年,且在检测镇痛效果方面存在一定的缺陷和不足,急需新的可靠的行为学检测助力痛觉机制研究和镇痛策略研发。本文对动物痛行为学检测的最新研究进展进行综述,重点介绍了8种检测方法:鬼脸量表、自主行为、转轮跑步行为、挖洞行为、筑巢行为、家庭笼监控、步态分析以及条件性位置偏爱/厌恶。每种检测方法均给出其优缺点,以帮助研究者选择最合适的行为学检测方法。     

Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan

This article describes the pathological studies of fatal severe acute respiratory syndrome (SARS) in a 73-year-old man during an outbreak of SARS in Taiwan, 2003. Eight days before onset of symptoms, he visited a municipal hospital that was later identified as the epicenter of a large outbreak of SARS. On admission to National Taiwan University Hospital in Taipei, the patient experienced chest tightness, progressive dyspnea, and low-grade fever. His condition rapidly deteriorated with increasing respiratory difficulty, and he died 7 days after admission. The most prominent histopathologic finding was diffuse alveolar damage of the lung. Immunohistochemical and in situ hybridization assays demonstrated evidence of SARS-associated coronavirus (SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and in alveolar macrophages in the lung. Electron microscopic examination also revealed coronavirus particles in the pneumocytes, and their identity was confirmed as SARS-CoV by immunogold labeling electron microscopy. This report is the first to describe the cellular localization of SARS-CoV in human lung tissue by using a combination of immunohistochemistry, double-stain immunohistochemistry, in situ hybridization, electron microscopy, and immunogold labeling electron microscopy. These techniques represent valuable laboratory diagnostic modalities and provide insights into the pathogenesis of this emerging infection.     

Factors affecting the outcome of distal realignment for patellofemoral disorders of the knee

This study correlated the risk factors with the clinical outcome of distal realignment for patellofemoral disorders in 48 patients with 53 knees with 25 to 96 months follow-up. The indications for surgery included pain and disability due to patellofemoral disorders with failure of at least 6 months of conservative treatments. The evaluations included pain scores, Lysholm functional scores and radiographs of the knee. The overall results were satisfactory in 47 knees (88.7%) and unsatisfactory in six knees (11.3%). There was no correlation of the clinical results with age, sex, body weight and body height, preoperative pain scores and Lysholm scores. However, the clinical outcome correlated with the severity of articular damage and the correction of patellar malalignment. Error in patient selection and inadequate surgical technique were attributable to poor outcomes.     

Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of expression and correlation with clinical outcome

Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and Epstein-Barr virus infection has been reported to be a cause of this disease. Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF-1), exhibited high expression in organs in which breast cancer metastases are often found. The metastatic pattern of NPC is quite similar to that of malignant breast tumors. In this study, we investigated the expression of CXCR4 in nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different staining patterns, which included localization in the nucleus, membrane, cytoplasm or a combination of them. The staining intensity was also variable among samples. The metastatic rates in patients with high compared to low or absent expression was 38.6% versus 19.8%, respectively (P = 0.004). High expression of CXCR4 was associated with poor overall survival (OS = 67.05% versus 82.08%, P = 0.0225). These results suggest that CXCR4 may be involved in the progression of NPC and that a high level of CXCR4 expression could be used as a prognostic factor.