氟比洛芬酯复合小剂量芬太尼对腹腔镜胆囊切除术患者镇痛效果及凝血功能的影响

目的:探讨氟比洛芬酯复合小剂量芬太尼在腹腔镜胆囊切除术后静脉自控镇痛中的应用及对患者凝血功能的影响。方法:选择2015年11月~2016年11月于我院行腹腔镜胆囊切除术的患者102例,随机分为对照组和研究组,每组51例。对照组患者术后采用小剂量芬太尼静脉自控镇痛,研究组患者术后采用氟比洛芬酯复合小剂量芬太尼静脉自控镇痛。观察并比较两组患者手术前后血清纤维蛋白原(Fg),活化部分凝血酶原时间(APTT),凝血酶原时间(PT),血小板计数(PLT),P物质,5-烃色胺(5-HT),白细胞介素-6、8(IL-6、IL-8)水平以及术后并发症的发生情况。结果:术前,比较两组Fg、APTT、PT、PLT、P物质、5-HT、IL-6、IL-8无差异(P0.05);术后,两组Fg、APTT、PT、PLT、P物质、5-HT、IL-6、IL-8均较术前上升,研究组低于对照组,差异均有统计学意义(P0.05)。研究组术后并发症率低于对照组(P0.05)。结论:氟比洛芬酯复合小剂量芬太尼能够提高腹腔镜胆囊切除术患者静脉自控镇痛的效果,改善凝血功能,降低炎症因子水平。     

Generation of an ABCG2 transgenic line - A tool to study ABCG2 expression in mice

The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells in many organs and in stem cells of solid tumors. These cells are isolated based on the side population (SP) phenotype, a Hoechst 3342 dye efflux property believed to be conferred by ABCG2. Because of the limitations of this approach we generated transgenic mice that express Nuclear GFP (GFPn) coupled to the Puromycin-resistance gene, under the control of ABCG2 promoter/enhancer sequences. We show that ABCG2 is expressed in neural progenitors of the developing forebrain and spinal cord and in embryonic and adult endothelial cells of the brain. Using the neurosphere assay, we isolated tripotent ABCG2-expressing neural stem cells from embryonic mouse brain. This transgenic line is a powerful tool for studying the expression of ABCG2 in many tissues and for performing functional studies in different experimental settings.     

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

A markedly reduced blood flow, an elevation of hematocrit and an increased aggregability of erythrocytes [red blood cells (RBCs)] are risk factors for venous thrombus formation (intravascular blood coagulation). However, these risk factors alone seem to be insufficient to stimulate the coagulation cascade in the absence of a primary triggering mechanism. In this paper, our rheological and biochemical studies on blood coagulation, especially focusing on procoagulant activity of RBCs, are summarized. It is shown that the intrinsic coagulation pathway is triggered by the activation of factor IX (F-IX) by RBCs. The F-IX-activating enzyme in normal human erythrocyte (RBC) membranes was purified, identified and characterized. The activation of F-IX by RBCs was enhanced by a decrease in flow shear rate and an elevation in hematocrit. The procoagulant ability of RBCs and coagulation of blood obtained from individuals with a relatively high level of hypercoagulability were enhanced compared with those for normals. The studies demonstrated a new triggering mechanism for coagulation or thrombus formation that may occur under stagnant flow conditions.     

How to evaluate the risk-benefit ratio of the low-dose hormone replacement therapy?

Since the results of the women health initiative study showing an overall negative risk-benefit ratio with 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate, the use of the lowest effective dose of steroids in hormone replacement therapy (HRT) is recommended.

A low-dose regimen appears to induce less side effects such as breast tenderness or leg pain than do higher dose preparations.

The decrease in hot flashes with low-dose estrogens, range 60–70%, is less than the 80–90% reduction with standard dosing. But this mean that 60–70% of menopausal women do not need higher doses.

The same applies to bone preservation which is dose dependent: the number of non-respondant women will be higher than with standard doses. However, randomized double-blind, placebo controls trials have defined positive effects on bone of low doses of HRT with adequate calcium and Vitamin D in elderly women. The use of bone densitometry and of biochemical markers of bone turnover is mandatory in women using low or ultra-low-dose preparations.

In spite of the lack of trials conducted with low-dose HRT, this treatment seems to be safer:

• the plasma levels of estradiol are lower; as far as breast cancer risk is concerned, the decrease of this subrogate marker is considered as favourable;

• the increase in breast density is less pronounced;

• the nurses's health study found a dose relationship for stroke, with no increase in risk with low-dose of estrogens;

• the effects on subrogate markers of cardiovascular risk seem to be more favourable.

Beside the low-dose HRT, one must consider some other facts:

• the “critical window” theory: it is biologically plausible that HRT, if started early after the menopause can slow the progression of coronary atherosclerosis;

• the way of administration of HRT: some observational studies have shown no increase in the risk of venous thromboembolism risk among women treated with transdermal estrogens;

• the progestogen used: a French cohort study recently performed found no increase in breast cancer risk with the use of micronized progesterone meanwhile the increase in risk observed with other progestogens was similar to the findings of the WHI study.

In the future, it is conceivable that more comprehensive pharmacogenomic studies will lead to effective algorithms for individualizing the right dose of steroids to be used in HRT.     

Toxoplasma gondii: myenteric neurons of intraperitoneally inoculated rats show quantitative and morphometric alterations

Several studies have demonstrated that the myenteric plexus experiences quantitative and morphometric changes in rats inoculated orally with Toxoplasma gondii. This paper aims to verify if these alterations are also seen when the same animals are inoculated intraperitoneally with the parasite. In order to do that, six Wistar rats (Rattus norvegicus) 60 days of age were infected intraperitoneally with 10⁶ tachyzoites of a genotype I T. gondii strain (BTU IV). After 60 days, the animals were anaesthetised and underwent laparotomy. All organs from the small and large intestines were removed, measured, dissected and underwent whole-mount Giemsa technique to stain the neurons in the myenteric plexus. A quantitative and morphometric analysis of these cells was made, and it showed that the parasite causes the death of myenteric neurons in the jejunum and morphometric alterations in these cells throughout the intestine. However, the cellular response of myenteric neurons to T. gondii is heterogeneous compared the different organs from the gut.     

Vascular mechanisms involved in angiotensin II-induced venoconstriction in hypertensive rats

To investigate the venoconstrictor effect of angiotensin II (Ang II) in spontaneously hypertensive rats (SHR), we used preparations of mesenteric venular beds and the circular muscle of the portal veins. Vessels were tested with Ang II in the presence or absence of losartan, PD 123319, HOE 140, L-NAME, indomethacin, or celecoxib. In the mesenteric venular bed of SHR, the effect of Ang II (0.1 nmol) was nearly abolished by losartan and enhanced by HOE 140, indomethacin, and celecoxib, while PD123319 and L-NAME had no effect. In portal vein preparations, cumulative-concentration response curves (CCRC) to Ang II (0.1–100 nmol/L) exhibited a lower maximal response (E_max) in SHR compared to Wistar rats. AT₁ receptor expression was similar in the two strains, while AT₂ receptor levels were lower in SHR portal veins when compared to Wistar. In SHR portal veins, losartan shifted the CCRC to Ang II to the right, while indomethacin and HOE 140 increased the E_max to Ang II. PD 123319, celecoxib, and L-NAME had no effect. Taken together, our results suggest that Ang II-induced venoconstriction in SHR is mediated by activation of AT₁ receptors and this effect may be counterbalanced by kinin B₂ receptor and COX metabolites. Furthermore, our data indicate that there are different cellular and molecular mechanisms involved in the regulation of venous tonus of normotensive and hypertensive rats. These differences probably reflect distinct factors that influence arterial and venous bed in hypertension.     

24S-hydroxycholesterol induces cholesterol release from choroid plexus epithelial cells in an apical- and apoE isoform-dependent manner concomitantly with the induction of ABCA1 and ABCG1 expression

The release of cholesterol from choroid plexus epithelial cells (CPE) plays an important role in cholesterol homeostasis in the CSF. The purpose of this study was to clarify the molecules involved in cholesterol release in CPE and the regulation mechanisms of the cholesterol release by the liver X receptor (LXR) using a conditionally immortalized CPE line (TR-CSFB3). The mRNA expression of LXRalpha, LXRbeta and their target genes, ATP-binding cassette transporter (ABC)A1, ABCG1, ABCG4 and ABCG5, were detected in rat choroid plexus. ABCA1 and ABCG1 protein were detected in the plasma membrane of TR-CSFB3 cells. Following treatment with 24S-hydroxycholesterol, an endogenous LXR ligand, the expression of ABCA1 and ABCG1 were induced in TR-CSFB3 cells. Moreover, apolipoprotein (apo)AI- and high-density lipoprotein (HDL)-mediated cholesterol release to the apical side of TR-CSFB3 cells was facilitated by this treatment, whereas that to the basal side was not affected. Following 24S-hydroxycholesterol treatment, apoE3-dependent cholesterol release from TR-CSFB3 cells was enhanced more than the apoE4-dependent release. These results suggest that LXR activation facilitates cholesterol release into the CSF from CPE through the functional induction of ABCA1 and ABCG1. The difference between apoE3 and apoE4 suggests that the cholesterol release from CPE is related to the development of neurodegenerative diseases.     

静脉留置部位导管相关菌血症的病原学研究

目的调查静脉留置导管相关性血流感染病原学特点。方法回顾性调查杭州医学院附属第一医院2003年1月至2005年9月静脉留置治疗患者感染的发生情况,并对其病原菌及耐药特点进行分析。结果165例患者共送检留置导管标本184份,140份标本检有病原菌,检出率为76.1%(140/184)。在165例患者中有150例进行了血液培养,发生血流感染的有103例,感染率为68.7%(103/150)。从140份静脉留置导管标本中共分离出171株病原菌,主要为表皮葡萄球菌、金黄色葡萄球菌、铜绿假单胞菌、大肠埃希菌等。有44例患者静脉留置导管和血液培养出同一种病原菌,主要为表皮葡萄球菌。导管留置后到第一次血液培养出现阳性的时间大约为4~8d。同时从静脉留置导管和血液分离的21株表皮葡萄球菌全部对呋喃妥因和万古霉素敏感,除对利福平的耐药率较低外,对其它抗生素的耐药率都超过50%。结论静脉留置导管较易引起血流感染,引起血流感染病原菌主要以表皮葡萄菌为主,且耐药性严重。     

基于人类信号网络和表达谱数据研究静脉血栓复发机制

目的:静脉血栓是一种高复发风险和高致死率的疾病,其形成和复发的分子机制尚不明确。基于人类信号网络和基因表达谱数据可针对静脉血栓经华法令抗凝治疗后的复发机制进行研究。方法:结合表达谱数据和人类信号网络,设计差异模块筛选策略,通过功能分析、差异表达分析和已知血栓相关基因及药物靶基因的互作关联研究,获得与静脉血栓复发相关的显著差异模块。结果:最终获得8个与静脉血栓复发密切相关的显著差异模块,评估了华法令治疗静脉血栓的效能,提出了联合用药的3种可能途径。结论:应用本文提出的整合筛选策略,能识别与静脉血栓复发相关的模块,探究静脉血栓复发的分子机制和评估华法令的治疗效能。还提供了潜在的联合用药途径,这对治愈血栓、防治血栓复发及复发机制的研究具有重要意义。