Amphiphysin IIm is required for survival of Chlamydia pneumoniae in macrophages

Macrophages play a critical role in both innate and acquired immunity because of their unique ability to internalize, kill, and degrade bacterial pathogens through the process of phagocytosis. The adaptor protein, amphiphysin IIm, participates in phagocytosis and is transiently associated with early phagosomes. Certain pathogens, including Chlamydia pneumoniae, have evolved mechanisms to subvert macrophage phagosome maturation and, thus, are able to survive within these cells. We report here that, although amphiphysin IIm is usually only transiently associated with the phagosome, it is indefinitely retained on vacuoles containing C. pneumoniae. Under these wild-type conditions, C. pneumoniae do not elicit significant nitric oxide (NO) production and are not killed. Abrogation of amphiphysin IIm function results in C. pneumoniae-induced NO production and in the sterilization of the vacuole. The data suggest that C. pneumoniae retains amphiphysin IIm on the vacuole to survive within the macrophage.     

糖耐量低减患者的血管内皮生长因子及血清C反应蛋白水平分析

目的探讨糖耐量低减患者血管内皮生长因子、血清C反应蛋白水平的变化。方法口服75g葡萄糖耐量试验筛查出糖耐量低减患者61例和糖耐量正常的体检健康者30例，测定两组人群血清内皮生长因子、血清C反应蛋白水平。结果糖耐量低减组血管内皮生长因子、血清C反应蛋白水平均高于糖耐量正常组（P〈0．01）。结论在糖耐量低减阶段，患者血管内皮生长因子、血清C反应蛋白已开始升高，提示糖耐量低减人群具备了发生血管并发症的危险。     

Contrast agent comparison for three‐dimensional micro‐CT angiography: A cadaveric study

Barium sulfate and lead oxide contrast media are frequently used for cadaver‐based angiography studies. These contrast media have not previously been compared to determine which is optimal for the visualisation and measurement of blood vessels. In this study, the lower limb vessels of 16 embalmed Wistar rats, and four sets of cannulae of known diameter, were injected with one of three different contrast agents (barium sulfate and resin, barium sulfate and gelatin, and lead oxide combined with milk powder). All were then scanned using micro‐computed tomography (CT) angiography and 3‐D reconstructions generated. The number of branching generations of the rat lower limb vessels were counted and compared between the contrast agents using ANOVA. The diameter of the contrast‐filled cannulae, were measured and used to calculate the accuracy of the measurements by comparing the bias and variance of the estimates. Intra‐ and inter‐observer reliability were calculated using intra‐class correlation coefficients. There was no significant difference (mean difference [MD] 0.05; MD 95% confidence interval [CI] ‐0.83 to 0.93) between the number of branching generations for barium sulfate‐resin and lead oxide‐milk powder. Barium sulfate‐resin demonstrated less bias and less variance of the estimates (MD 0.03; standard deviation [SD] 1.96 mm) compared to lead oxide‐milk powder (MD 0.11; SD 1.96 mm) for measurements of contrast‐filled cannulae scanned at high resolution. Barium sulfate‐resin proved to be more accurate than lead oxide‐milk powder for high resolution micro‐CT scans and is preferred due to its non‐toxicity. This technique could be applied to any embalmed specimen model. Copyright © 2016 John Wiley & Sons, Ltd.     

丹参对兔急性胰腺炎早期中性粒细胞与内皮细胞黏附抑制作用的实验研究

目的：探讨中性粒细胞(PMN)与内皮细胞(EC)黏附在急性胰腺炎(AP)早期发病中的机制及丹参对AP的治疗作用。方法：采用兔AP模型，24只日本大耳兔随机分为生理盐水组和丹参治疗组。分别于术前、术后即刻及2、4、8、12、16和24h取血分离获得PMN，与体外培养的兔血管EC作用，测定PMN—EC黏附率及PMN表面黏附分子CD11a／CD18和CD11b／CDl8值。结果：术后即刻两组黏附分子CD11a／CD18、CD11b／CD18及PMN—EC黏附率均升高，生理盐水组术后4h达到高峰；丹参治疗组术后2、4、8、12、16和24h的CD11a／CD18、CD11b／CD18显著低于生理盐水组。结论：丹参能降低黏附分子CD11a／CD18、CD11b／CD18表达，抑制PMN—EC黏附，改善微循环及减轻PMN—EC黏附所致的组织损伤，有助于AP的早期治疗。     

Reduction of postchallenge hyperglycaemia prevents acute endothelial dysfunction in subjects with impaired glucose tolerance

OBJECTIVES: To investigate whether selective reduction of postchallenge hyperglycaemia influences acute endothelial dysfunction, a very early manifestation of vascular disease, in patients with impaired glucose tolerance. METHODS: In a randomized, double-blind, placebo-controlled, cross-over study the acute effect of 200-mg acarbose was investigated in 28 subjects with diagnosed impaired glucose tolerance. Flow-mediated dilation (FMD) of the brachial artery was determined as a measure of endothelial function before and 2 and 3 h after ingestion of 100-g saccharose. Asymmetrical dimethylarginine (ADMA) was measured by high-performance liquid chromatography. RESULTS: A negative correlation was observed between the changes of glucose and FMD (r = 0.416, P = 0.0018) 2 h after ingestion of saccharose. At 3 h, neither blood glucose nor FMD were different from baseline. Changes of both blood glucose (P = 0.0007) and FMD (P = 0.046) were significantly lower after administration of acarbose. Subgroup analysis revealed that the effect of acarbose was restricted to those subjects with an increase of blood glucose above the median increase of glycaemia. No changes of plasma ADMA were observed. CONCLUSIONS: Our data clearly demonstrate that the postchallenge alteration of vascular function in patients with impaired glucose tolerance is caused by the acute elevation of glycaemia but not mediated by ADMA.     

Differences in inflammatory pain in nNOS-, iNOS- and eNOS-deficient mice.

To assess the relative importance of the isoforms of nitric oxide synthase (NOS) in inflammatory pain, we directly compared pain behaviour and paw thickness after intraplantar injection of complete Freund's adjuvant (CFA) in wild-type (WT) mice and in mice lacking either inducible (iNOS), endothelial (eNOS) or neuronal NOS (nNOS). In mice deficient for nNOS, thermal hyperalgesia was reduced by approximately 50% compared to wild type mice at 4 and 8h after CFA injection, and mechanical hypersensitivity was absent. The only change in pain behaviour in iNOS and eNOS deficient mice compared to WT mice was a more rapid recovery from thermal hyperalgesia. A compensatory up-regulation of nNOS in dorsal root ganglia (DRG) and spinal cords of iNOS and eNOS knockout mice was excluded using RT-PCR. However, an increase of iNOS gene expression was found in spinal cords of eNOS and nNOS deficient mice. To study the downstream effects of nNOS deficiency on DRG neurones, we assessed their immunoreactivity for calcitonin gene-related peptide (CGRP) and cytokines. We found a significant reduction in the CFA induced increase in CGRP immunoreactive neurones as well as in CGRP gene expression in nNOS deficient mice, whereas the percentage of cells immunopositive for tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was unchanged. These results support the proposed role of nNOS in sensitization of DRG neurones, and might indicate that CGRP is involved in this process.     

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n=5), an 84% Hx group (n=5) and an 84% Hx+PSS group (n=5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immuno-histochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.     

Two faces of high-molecular-weight kininogen (HK) in angiogenesis: bradykinin turns it on and cleaved HK (HKa) turns it off.

High-molecular-weight kininogen (HK) is a plasma protein that possesses multiple physiological functions. Originally identified as a precursor of bradykinin, a bioactive peptide that regulates many cardiovascular processes, it is now recognized that HK plays important roles in fibrinolysis, thrombosis, and inflammation. HK binds to endothelial cells where it can be cleaved by plasma kallikrein to release bradykinin (BK). The remaining portion of the molecule, cleaved HK, is designated cleaved high-molecular-weight kininogen or HKa. While BK has been intensively studied, the physiological implication of the generation of HKa is not clear. Recent studies have revealed that HKa inhibits angiogenesis while BK promotes angiogenesis. These findings represent novel functions of the kallikrein-kinin system that have not yet been fully appreciated. In this review, we will briefly discuss the recent progress in the studies of the molecular mechanisms that mediate the antiangiogenic effect of HKa and the proangiogenic activity of BK.     

血管内皮生长因子及其受体在门静脉高压性胃病中的表达及其意义

目的 探讨血管内皮生长因子（VEGF）及其受体FLT-1、FLK-1mRNA在门静脉高压性胃病（PHG）中的作用。方法 采用逆转录聚合酶链反应（RT-PER）对44例肝硬化门静脉高压症患者PHG动态变化过程中病变部位的VEGF、FLT-1及FLK-1mRNA的表达进行检测。结果 轻度胃病组VEGF、FLT-1、FLK-1mRNA的表达量分别为（2．28±0．33）、（0．59±0．17）和（0.56±0．14），与无胃病组及正常对照组比较差异均有显著性（均P〈0．01）；重度胃病组VEGF、FLT-1、FLK-1mRNA分别为（3．48±1．02）、（0．68±0．20）和（0.71±0．18），与轻度胃病组、无胃病组及正常对照组比较差异均有显著性（均P〈0．01）。结论 VEGF及其受体FLT-1、FLK-1过度表达是胃病胃黏膜损害的重要因素之一。     

米非司酮抑制葡萄胎血管内皮生长因子与微血管密度生成及其对临床预后的影响

目的通过研究米非司酮治疗葡萄胎前后血管内皮生长因子(VEGF)及微血管密度(MVD)的改变,探讨米非司酮对滋养细胞肿瘤组织微血管生成的影响,寻求妊娠滋养细胞肿瘤治疗新途径。方法应用免疫组织化学方法染色检测32例葡萄胎组织的VEGF表达及MVD的改变;以正常早孕人工流产胚胎组织30例作为对照组。选取葡萄胎组织VEGF阳性表达病例11例,给予米非司酮治疗,1周后再次清宫,取组织重复染色,观察VEGF染色及MVD情况,分析米非司酮治疗对葡萄胎组织VEGF及MVD的影响。结果葡萄胎组织VEGF表达阳性率为34.4%,高于正常早孕人工流产胚胎组织的6.7%,VEGF阳性表达区多位于滋养细胞增生区或向正常组织浸润的边缘。米非司酮治疗前、后MVD值分别为43.03±10.11和21.32±8.03,差异有统计学意义(P<0.05)。全部治疗病例随访13～37个月,无一例进展成侵蚀性葡萄胎。结论葡萄胎组织VEGF高表达可能与肿瘤性滋养细胞的浸润性有关,米非司酮对葡萄胎组织新生血管形成具有抑制作用,对预后未见不良影响。