Non-invasive assessment of cardiovascular autonomic activity induced by brief exposure to 50% nitrous oxide in children

Background. The use of the equimolecular mixture of oxygen andnitrous oxide is widely recommended for relief of pain in childrenundergoing minor procedures. Although the benefits and adverseeffects of the clinical use of nitrous oxide seem well known,its effects on the autonomic nervous system have never beenstudied in children. The aim of this study was to evaluate changesin autonomic cardiovascular activity induced by brief exposureto 50% nitrous oxide in children. This study was based on non-invasivecontinuous recordings of RR-interval and non-invasive arterialpressure. Vascular and cardiac sympathetic activity and cardiacparasympathetic activity were investigated using spectral analysisof systolic arterial pressure variability (SAPV) and RR-intervalvariability (RRIV). In addition, the sensitivity of the spontaneousbaroreflex (SBR) was assessed using the sequences and the cross-spectralanalysis methods. Methods. Sixteen non-pre-medicated pre-pubertal children undergoingmiddle-ear surgery, were studied. Data analysis was performedat three points: baseline, when the end-tidal concentrationof nitrous oxide was stabilized at 50%, and after withdrawingnitrous oxide. Low (0.04–0.14 Hz) and high frequency (0.2–0.6Hz) components of the spectral power of RRIV and SAPV, and SBRsensitivity were calculated using these 2-min data epochs. Results. Our results show that brief exposure to 50% nitrousoxide in children results in: (1) absence of effect on meanAP and SAPV; (2) attenuation of the low frequency componentof heart rate variability with a shift of the sympathetic–parasympatheticcardiac balance toward a parasympathetic predominance; and (3)absence of alteration of spontaneous baroreflex sensibility. Conclusions. Unlike the results demonstrated in adults, ourfindings show very few cardiovascular effects of nitrous oxidein children. Furthermore, whereas in adults nitrous oxide isassociated with an excitatory cardiovascular profile, in childrenthis agent seems to be associated with a depressant cardiovascularprofile. The rapid return to baseline after discontinuationof administration and the absence of baroreflex changes arepositive attributes for the use of nitrous oxide in children. Br J Anaesth 2002; 88: 637–43     

腔内血栓降低大鼠腹主动脉瘤壁残余应力对瘤壁保护作用的评价

目的：用测量张开角的方法研究大鼠单纯腹主动脉瘤（AAA）和腔内血栓AAA模型的应力分布，对比两种模型瘤壁的顺就生，评估腔内血栓对瘤壁的保护作用。方法：用猪弹力蛋白酶灌注Wistar大鼠腹主动脉建立梭形肾下AAA模型，相似的方法并机械破坏内腹建立腔内血栓AAA模型，测量并对比单纯AAA和腔内血栓AAA动脉环的蠕变速度，残余应力，对比两组AAA同一瘤体不同部位的残余应力，动脉环内径和瘤壁厚度。结果：单纯AAA模型建立的成功率90%，腔内血栓AAA模型建立的成功率为60%，单纯AAA动脉环蠕变速度较腔内血栓AAA慢，单纯AAA入口和出口的残余应力值最大，内径和瘤壁厚度最小；腔内血栓AAA的残余应力分布规律相似，但总体残余应力较低。结论：残余应力量化反映AAA瘤壁的顺应性，腔内血栓AAA较单纯AAA的顺应性大；单纯AAA和腔内血栓AAA入口和出口附近应力最大，腔内血栓通过降低血管的残余应力对AAA起保护作用。     

Modulation of vascular smooth muscle cell alignment by cyclic strain is dependent on reactive oxygen species and P38 mitogen-activated protein kinase

PURPOSE: The aim of this study was to investigate the molecular targets of reactive oxygen species (ROS) and to determine whether cyclic strain induces smooth muscle cell (SMC) alignment via the ROS system. We assessed stretch-induced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activation and the redox sensitivity of cyclic strain-stimulated activation of the mitogen-activated protein kinase (MAPK) family. METHODS: SMCs were seeded on flexible collagen I-coated plates and exposed to cyclic strain. NAD(P)H oxidase activation was measured with lucigenin-enhanced chemiluminescent detection of superoxide. Activation of MAPK was detected by determining phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), c-jun N-terminal kinase (JNK1/2), and p38 MAPK with immunoblotting. In other experiments, SMCs were exposed to diphenylene iodonium (DPI), an NAD(P)H inhibitor, 30 minutes before stretch. MAPK activation and cell orientation were then assessed. RESULTS: Cyclic strain elicits a rapid increase in intracellular NADH/NADPH oxidase in SMCs. There was also a rapid and robust phosphorylation of ERK1/2, JNK1/2, and p38 MAPK. Cyclic strain-induced intracellular NAD(P)H generation was almost completely blocked with DPI. DPI also inhibited the strain-induced phosphorylation of ERK1/2, JNK1/2, and p38 MAPK. Both the p38 MAPK specific inhibitor, SB 202190, and DPI blocked cyclic strain-induced cell alignment, but PD98059, an ERK1/2-specific inhibitor, and SP600125, an anthrazolone inhibitor of JNK, did not. CONCLUSION: Our results provide evidence that p38 MAPK is a critical component of the oxidant stress ROS-sensitive signaling pathway and plays a crucial role in vascular alignment induced by cyclic stain.     

Hyperconnectivity of local neocortical microcircuitry induced by prenatal exposure to valproic acid

Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render cortical modules more sensitive to stimulation and once activated, more autonomous, isolated, and more difficult to command. This could underlie some of the core symptoms observed in humans prenatally exposed to valproic acid.     

Ultramicroscopic structures of the leptomeninx of mice with communicating hydrocephalus induced by human recombinant transforming growth factor-beta 1

An experimental model of communicating hydrocephalus was developed based on intrathecal injection of human recombinant transforming growth factor-beta 1 (hrTGF-beta 1) in the mouse. To clarify the mechanism of this hydrocephalus model, the ultrastructure of the leptomeninx in the process of ventricular dilation was examined in C57/BL6 mice injected intrathecally with 60 ng of hrTGF-beta 1. The leptomeninx was examined at various periods after injection by light and electron microscopy. Immunostaining for fibroblasts and macrophages was also performed. Leptomeninx within a week after injection showed that the thin cytoplasmic processes of leptomeningeal cells formed a laminated structure with a meshwork, which was almost the same as the controls. In the second week, many cells with a round nucleus appeared in the leptomeninx. Immunohistochemically, these cells were positive for anti-fibroblast antibody and negative for anti-Mac-1 and anti-macrophage BM-8 antibodies. Three weeks later, the laminated structure was disrupted and abundant deposition of collagen fibers was found in the inter-cellular space of the leptomeninx. Such inter-meningeal fibrosis would disturb cerebrospinal fluid flow in the mouse leptomeninx and cause slowly progressive ventricular dilation.     

美白化妆品导致的汞中毒相关性肾损害一例

膜性肾病和微小病变肾病(MCD)是汞中毒相关性肾损害的主要病理类型,但MCD伴IgA沉积并不常见。本文报道了1例使用美白化妆品导致的以肾病综合征为主要临床表现,病理诊断为MCD伴IgA沉积的汞中毒相关性肾损害,并阐述了其病因、临床表现、治疗及预后。     

Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan

PURPOSE: We examined the effects of atrasentan (endothelin-A receptor antagonist) on bone deposition and resorption markers and on bone scan index. MATERIALS AND METHODS: This double-blind, randomized, placebo controlled clinical trial of hormone refractory prostate cancer patients was done at 74 medical centers in the United States and Europe. A total of 288 asymptomatic patients with hormone refractory prostate adenocarcinoma and evidence of metastatic disease were randomized to 1 of 3 treatment groups, namely 2.5 mg. atrasentan, 10 mg. atrasentan or placebo administered orally daily until disease progression. The main outcomes measures were changes in bone deposition markers (total alkaline phosphatase and bone alkaline phosphatase) and bone resorption (N-telopeptides, C-telopeptides and deoxypyridinoline), and in the bone scan index. RESULTS: At baseline markers of bone deposition and resorption were elevated 1.4 to 2.7-fold above respective upper limits of normal. Subjects receiving placebo experienced a 58% elevation in mean total alkaline phosphatase and a 99% elevation in mean bone alkaline phosphatase (p < 0.001), whereas subjects receiving 10 mg. atrasentan maintained stable mean total alkaline phosphatase and bone alkaline phosphatase values compared with baseline. N-telopeptides, C-telopeptides and deoxypyridinoline elevation from baseline were consistently less in patients receiving 10 mg. atrasentan compared with placebo. Similar trends were observed in subjects who received 2.5 mg. atrasentan. Changes in clinical bone scan studies paralleled bone marker changes. CONCLUSIONS: Atrasentan suppressed markers of biochemical and clinical prostate cancer progression in bone and demonstrates clinical activity for hormone refractory prostate cancer.     

纤维蛋白凝胶立体培养诱导血管样结构的形成

目的探讨微血管内皮细胞(MVEC)在体外培养中形成血管样结构的细胞外基质条件，为体外组织工程血管化提供实验基础。方法在纤维蛋白原浓度为2g／L的纤维蛋白凝胶中加入不同浓度的血管内皮细胞生长因子165(VEGF165)，进行MVEC的立体培养，观察有无血管样结构形成。结果在VEGF165为10μg／L组和20μg／L组中，MVEC在立体培养中形成血管样结构。VEGF165为20μg／L组比VEGF165为10μg／L组形成血管样结构的时间更早、结构更长。VEGF165为5μg／L组和对照组均无血管样结构形成，但可见细胞团聚。结论VEGF165浓度为20μg/L或10μg／L时，MVEC在纤维蛋白凝胶立体培养中可形成血管样结构。VEGF165诱导形成血管样结构的长度与剂量有依赖关系。     

Olmesartan inhibits the expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α and improves vascular remodeling after vascular injury in mouse

Vscularinjuryinducesmigrationofsmoothmusclecells (SMCs)fromthemediatotheintimaandsubsequent proliferationofSMCswithintheintima .Thesevascularresponsesareproposedtobecriticalprocessesofneointimalformationandinducenarrowingofthevascularlumenandarteriosclerosis .1,3Manystudieshavedemonstratedthatangiotensinconvertingenzyme(ACE)inhibitors4 ,5inhibitneointimalformationintheinjuredmodelofsmallanimal,whereasotheragentsthathaveblood pressuredeclinedfailtopreventit.4 Ininjuredarteries,theexpression…     

高迁移率族蛋白1在内毒素性急性肺损伤大鼠肺血管重构中的作用

目的 评价高迁移率族蛋白1 (HMGB1)在内毒素性急性肺损伤大鼠肺血管重构中的作用.方法 健康清洁级雄性Wistar大鼠30只,体重220 ～ 250 g,采用随机数字表法,将大鼠随机分为3组(n=10)∶对照组(C组)、内毒素性急性肺损伤模型组(M组)和HMGB1抗体组(H组).C组尾静脉输注生理盐水5 ml/1.5 h;M组输注生理盐水3 ml/1.0h,再输注LPS 2 ml(1 mg/kg)/0.5 h;H组于注射LPS后12、24和36 h时尾静脉注射HMGB1抗体2 mg/kg.于注射LPS后72 h时处死取肺,光镜下观察肺组织病理学结果,采用图像分析软件测量并计算肺小动脉中膜/血管面积百分比,免疫组化法检测肺血管增殖细胞核抗原(PCNA)表达,Western bolt法检测HMGB1表达.结果 与C组比较,M组和H组肺小动脉中膜/血管面积百分比、PCNA和HMGB1表达水平升高(P＜0.05),肺组织急性炎症细胞增多,血管壁明显增厚;与M组比较,H组肺小动脉中膜/血管面积百分比、PCNA和HMGB1表达水平降低(P＜0.05),肺组织急性炎症和血管壁增厚明显减轻.结论 HMGB1可能是诱发内毒素性急性肺损伤大鼠肺血管重构的重要因素.     

Sigmoid colon perforation induced by the vascular type of Ehlers-Danlos syndrome: report of a case

The vascular type of Ehlers-Danlos syndrome (vEDS) is a rare inherited disease of the connective tissues, and is caused by abnormal type III collagen resulting from heterogeneous mutations of the type III collagen COL3A1 gene. We herein report the case of a vEDS patient who developed a sigmoid colon perforation and was given a definitive diagnosis by a genetic and biomolecular assay. The patient demonstrated clinical manifestations caused by tissue weakness such as frequent pneumothorax events and a detached retina. During the operation, we noticed easy bruising and thin skin with visible veins on the patient's abdominal wall. Finally, a diagnosis was confirmed by the reduction of type III collagen synthesis and by the identification of a mutation in the gene for type III collagen. We conclude that it is difficult to diagnose a vEDS patient without clinical experiences and specialized genetic methods. Furthermore, all organs must be treated gently during therapy, because the tissues of vEDS patients are extremely fragile.     

The effects of nicotine on vascular smooth muscle cell chemotaxis induced by thrombospondin-1 and fibronectin

Background

Vascular smooth muscle cell (VSMC) migration is an important process in many vascular disorders. Nicotine, thrombospondin-1 (TSP-1) and fibronectin (Fn) separately induce VSMC migration. The hypothesis of this study was that nicotine treatment of vascular cells would augment TSP-1-induced and Fn-induced VSMC migration.

Methods

VSMCs or endothelial cells (ECs) were treated with serum-free medium or nicotine. Migration of VSMCs was assessed using a modified Boyden chemotaxis chamber to serum-free medium, TSP-1, Fn, EC basal medium, and conditioned EC medium or nicotine-treated conditioned EC medium alone or with supplemented TSP-1 or Fn.

Results

Nicotine treatment increased VSMC chemotaxis to serum-free medium, but TSP-1 or Fn had no further effect on chemotaxis. Conditioned EC and nicotine-treated conditioned EC enhanced VSMC chemotaxis, which was further augmented by Fn supplementation.

Conclusions

Nicotine-stimulated EC derived factors induce VSMC migration, which is augmented by the addition of Fn.     

细胞因子诱导的杀伤细胞对胆囊癌细胞株GBC-SD杀伤活性的影响

目的 研究脐血单个核细胞体外多向诱导分化为LAK,CD3AK,CIK细胞及体外对胆囊癌细胞株GBC-SD杀瘤活性的变化. 方法 采用IL-2刺激诱生LAK细胞;用CD3单抗和IL-2刺激诱生扩增CD3AK细胞;加入IFN-γ,24 h后加入IL-1,CD3单抗,IL-2刺激诱生CIK细胞,观察它们的扩增情况,并分析其相互关系;取培养的CIK细胞用流式细胞仪分析表型;用MTT法以胆囊癌细胞株GBC-SD为靶细胞,分组测定LAK,CD3AK,CIK细胞的杀伤活性. 结果 CD3AK和CIK细胞的扩增能力远大于LAK细胞(P<0.05).CIK细胞和CD3AK相比,在前期无明显差异,至第20天左右时CIK细胞的扩增倍数显著高于CD3AK(P<0.05).流式细胞仪分析结果显示CIK细胞培养后,其主要效应细胞CD3+ CD56+细胞较培养前显著增加(P<0.05),CD8+细胞也较培养前显著增加(P<0.05).CD3AK和CIK细胞对胆囊癌细胞株GBC-SD的杀伤活性均显著高于LAK细胞(P<0.05),而CIK细胞杀伤活性又强于CD3AK细胞(P<0.05). 结论 CIK细胞具有更高的扩增能力和更强的杀伤活性,是肿瘤过继免疫治疗中更为有效的杀伤效应细胞.