Origin and course of the coronary arteries in normal mice and in iv/iv mice

This paper reports on the origin and distribution of the coronary arteries in normal mice and in mice of the iv/iv strain, which show situs inversus and heterotaxia. The coronary arteries were studied by direct observation of the aortic sinuses with the scanning electron microscope, and by examination of vascular corrosion casts. In the normal mouse, the left and right coronaries (LC, RC) arise from the respective Valsalva sinus and course along the ventricular borders to reach the heart apex. Along this course the coronary arteries give off small branches at perpendicular or acute angles to supply the ventricles. The ventricular septum is supplied by the septal artery, which arises as a main branch from the right coronary. Conus arteries arise from the main coronary trunks, from the septal artery and/or directly from the Valsalva sinus. The vascular casts demonstrate the presence of intercoronary anastomoses. The origin of the coronary arteries was found to be abnormal in 84% of the iv/iv mice. These anomalies included double origin, high take-off, slit-like openings and the presence of a single coronary orifice. These anomalies occurred singly or in any combination, and were independent of heart situs. The septal artery originated from RC in most cases of situs solitus but originated predominantly from LC in situs inversus hearts. Except for this anomalous origin no statistical correlation was found between the coronary anomalies and heart situs or a particular mode of heterotaxia. The coronary anomalies observed in the iv/iv mice are similar to those found in human hearts. Most coronary anomalies appear to be due to defective connections between the aortic root and the developing coronaries. iv/iv mice may therefore constitute a good model to study the development of similar anomalies in the human heart.     

黄芪甲苷对肾小管上皮细胞诱导单核细胞分化的影响

目的本研究通过体外细胞共培养,观察肾小管上皮细胞对单核细胞分化影响及中药组分黄芪甲苷对单核细胞分化的影响。方法体外建立单核细胞(U937)与人近端肾小管上皮细胞(human proximal tubular epithelial cell line,HK-2)共培养系统,实验分3组:对照组(U937细胞组),实验组(U937+HK-2细胞组),干预组(U937+HK-2细胞+黄芪甲苷组)。观察黄芪甲苷对HK-2细胞诱导U937细胞分化及其Toll样受体4(Toll-like receptors 4,TLR4)的表达以及黄芪甲苷对U937细胞TBK/IRF3信号通路的影响。应用Real-time PCR观察黄芪甲苷对HK-2细胞诱导的U937细胞分化影响,应用流式细胞仪及WR观察U937细胞表面Toll样受体4(Toll-like receptors4,TLR-4)的表达,应用Real-time PCR及WB观察黄芪甲苷对U937细胞TBK/IRF3信号通路的影响。结果黄芪甲苷通过抑制U937细胞TLR-4表达[对照组、实验组、干预组TLR-4表达分别为(27.32±1.34)、(34.67±1.23)、(30.12±1.67)]抑制TBK/IRF3信号通路[对照组、实验组、干预组TBK分别为(0.60±0.05)、(1.10±0.12)、(0.80±0.21),对照组、实验组、干预组IRF3分别为(0.92±0.08)、(1.35±0.23)、(1.10±0.27)],从而抑制U937细胞iNOs mRNA表达[对照组、实验组、干预组iNOs mRNA表达分别为(0.80±0.15)、(1.18±0.23)、(1.00土0.11)],上调Arg-1 mRNA表达[对照组、实验组、干预组Arg-1 mRNA表达分别为(1.10±0.23)、(0.56±0.24)、(0.78±0.23)],从而抑制U937细胞发生M1型转化。结论黄芪甲苷可能通过抑制U937细胞TLR-4表达减弱TBK/IRF3信号通路,从而抑制U937发生M1型转化,进一步抑制炎症因子产生,阻断肾脏纤维化。     

IL-13 attenuates early local CXCL2-dependent neutrophil recruitment for Candida albicans clearance during a severe murine systemic infection

To investigate the role of IL-13 during a severe systemic Candida albicans infection, BALB/c control and IL-13^?/? mice were examined for colony forming units (CFU) in the kidneys and survival days after intravenous infection. Proinflammatory mediators and cell recruitment into the tissue were measured by quantitative real-time PCR, a multiple ELISA system, and morphological cell differentiation. The IL-13^-/- group exhibited a lower CFU number in the kidneys at 4 days and survived longer than the control mice, which was accompanied by significantly higher expression of C-X-C motif ligand 2 (CXCL2), IFN-γ, and polymorphonuclear neutrophils (PMNs) in the infected kidneys. By contrast, the expression of transforming growth factor β (TGF-β) and IL-17?A on day 10 were significantly higher in the control mice than in the IL-13^-/- group. When using an intratracheal infection model, the IL-13^-/- group recruited a greater number of PMNs in 6?h, with rapidly increased CXCL2 in the alveolar space. In vitro testing with cultured bone-marrow-derived cells demonstrated rapid CXCL2 mRNA upregulation at 3?h after contact with C. albicans, which decreased with recombinant IL-13 pretreatment, whereas rIL-13 retained TGF-β upregulation. In a murine model of Candida systemic infection, preexistent IL-13 limits both the rapid CXCL2 elevation and PMN aggregation in the target organ to suppress inflammatory mediators, which also attenuates local pathogen clearance within four days.     

The kidneys play an important role in the clearance of rFVIIa in rats

Introduction

Previous distribution and histological studies have indicated that the kidneys and renal proximal tubular cells play a role in clearance of rFVIIa. However, the relative importance of the kidneys in clearance of rFVIIa has not previously been addressed. The objective of the present study was to evaluate the importance of the kidneys in the clearance process of rFVIIa after iv administration to rats using a nephrectomy model.

Materials and Methods

A nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance and several physiological parameters were monitored to ensure viability and robustness of the model. The model was then used for pharmacokinetic evaluation of renal clearance of rFVIIa. The pharmacokinetic parameters for rFVIIa were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats.

Results

Nephrectomized animals showed stable rectal temperature, SpO₂ and pulse and as expected, clearance of inulin was essentially abolished compared to control animals (p < 0.001). For rFVIIa, nephrectomy resulted in a clearance and terminal half-life of 34 mL/h/kg and 2.8 h compared to 68 mL/h/kg and1.9 h in rats exposed to sham surgery (p < 0.0001 for both parameters).

Conclusion

The present data show that about 50% of the total clearance of rFVIIa from circulation in rats under isoflurane anaesthesia is due to renal clearance.     

Morphology,Kinetics and Secretory Activity of Antibody-forming Cells

Specific antibody-forming cells from spleen, bone marrow and popliteal lymph nodes were studied in mice after subcutaneous priming and intravenous boosting with horseradish peroxidase (HRP).Functional antibody-secreting capacity of these cells was correlated with their morphology at the cell population level. For this purpose, cells synthesizing anti-HRP antibody from the same cell suspensions were studied simultaneously by light and electron microscopy and by a plaque assay. It appeared that the population of cells responsible for antibody synthesis as well as antibody secretion was morphologically heterogeneous: besides plasma cells, considerable numbers of antibody-forming lymphocytes, antibody-forming plasmablasts and antibody-forming immature plasma cells were observed. Immature plasma cells constituted the majority of antibody-forming as well as antibody-secreting cells. Among the immature plasma cells in the popliteal lymph nodes proliferation occurred.Evidence is presented that the light-microscopically identified mature plasma cell is not the main antibody-forming cell. It does not show 3H-Thymidine incorporation and should be considered as a non-dividing end-cell.     

Should noncurative resection of the primary tumour be performed in patients with stage iv colorectal cancer? A systematic review and meta-analysis

Purpose

Surgical resection of the primary tumour in patients with advanced colorectal cancer (crc) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (qol).

Methods

Reports in the central, medline, and embase databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle–Ottawa Scale. Data were collected and synthesized per protocol.

Results

From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10–30.7 months) in the resection group and 11.4 months (range: 3–22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (ci): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% ci: 0% to 9.7%) and 25.9% (95%ci: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% ci: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 ci: 15.4% to 39.9%). No study provided qol data.

Conclusions

Although this review supports primary tumour resection in advanced crc, the results have significant biases. Randomized trials are warranted to confirm the findings.     

Therapy of MS

The era of disease-modifying drugs (DMDs) in multiple sclerosis (MS) treatment began in the 1990s, first with interferon-β (IFNβ), and the number of agents has increased steadily since then. Currently, there are six different parenteral formulations approved for MS treatment and many other oral and parenteral ones are in different stages of investigation or awaiting approval by federal agencies.     

葡萄糖对下丘脑腹内侧核损伤性肥胖大鼠脂质代谢的影响

大鼠下丘脑腹内侧核损伤性肥胖模型(ventromedial hypothalamus-lesioned obesity,VMH)是常用的肥胖模型 ,表现有肥胖、食欲亢进、高胰岛素血症、高甘油三酯血症 [1～ 3] 。血浆甘油三酯是形成肥胖的物质基础 ,它在脂蛋白脂酶的作用下 ,分解为游离脂肪酸和甘油 ,前者进入脂肪细胞重新酯化为甘油三酯而贮存[4 ] 。以往的研究已经证实VMH肥胖大鼠肝脏合成甘油三酯增加 [2 ] 。在 VMH肥胖的形成过程中 ,葡萄糖对甘油三酯的代谢有什么影响还不清楚 ,为此 ,利用静脉葡萄糖耐量实验探讨了葡萄糖对甘油三酯代谢的影响。1　材　料　与　方　法1 …     

哌拉西林钠舒巴坦钠持续静滴治疗重症肺炎的疗效观察

目的探讨哌拉西林钠舒巴坦钠持续静滴治疗重症肺炎的临床疗效和安全性。方法选取2012年6月—2014年2月内蒙古林业总医院收治的重症肺炎90例,随机分为治疗组（46例）和对照组（44例）。治疗组患者首先给予注射用哌拉西林钠舒巴坦钠5.0 g溶入到200 m L生理盐水中,1 h内静滴完,然后将注射用哌拉西林钠舒巴坦钠5.0 g溶入至20 m L生理盐水中,将微量泵泵入速度调整为2 m L/h持续泵入,2次/d。对照组静脉滴注注射用哌拉西林钠舒巴坦钠5.0 g溶入至200m L生理盐水中,1 h静滴完,每8小时一次。两组均持续治疗3 d以上。比较两组的临床疗效,同时比较两组咳嗽消失时间、啰音消失时间、体温恢复正常时间、白细胞恢复正常时间。结果治疗后,治疗组和对照组的总有效率分别为80.44%、59.09%,两组总有效率比较差异有统计学意义（P〈0.05）。治疗组咳嗽消失时间、啰音消失时间、体温恢复正常时间、白细胞恢复正常时间均显著短于对照组,两组比较差异有统计学意义（P〈0.05）。结论哌拉西林钠舒巴坦钠持续静滴对重症肺炎有较好的临床疗效,可缩短各观察指标的时间,值得临床推广应用。     

老年人术后持续静脉泵入吗啡止痛的应用研究

目前临床上老年人术后止痛常规使用肌肉注射杜冷丁，但不良反应较重，本文采用微量输液泵持续静脉泵入吗啡止痛，两者进行比较。将６０例老年术后病人随机分为２组进行研究，Ⅰ组用微量泵持续静脉泵入吗啡止痛；Ⅱ组采用肌肉注射杜冷丁止痛。观察２４小时内病人的止痛效果及用药后的不良反应。２组在止痛效果上无明显差异，但Ⅰ组不良反应明显少于Ⅱ组，有明显差异（Ｐ＜０．０５）。本组结果显示：老年人术后止痛采用微量输液泵持续静脉泵入吗啡较肌肉注射杜冷丁更安全、可靠、持续有效。