Volatile general anaesthetics activate a novel neuronal K+ current

Although it is still controversial whether the primary target sites underlying general anaesthesia are proteins or lipids, it is generally thought that the ultimate targets are ion channels in nerve membranes. One approach to finding these targets is to study the effects of general anaesthetics on identified neurons, where differential effects on neuronal activity can be pursued to the molecular level. Here we report that amongst a group of apparently identical molluscan neurons having endogenous firing activity, a single cell displays an unusual sensitivity to volatile agents (which, at surgical levels, completely inhibit its activity). We further show that this sensitivity is due to a novel anaesthetic-activated K+ current, which is found in the sensitive cell but not in the surrounding insensitive cells. This K+ conductance is not appreciably voltage-gated and persists for as long as the anaesthetic is present. The response to anaesthetics is completely reversible and saturates at low anaesthetic partial pressures: the half-maximal response for halothane occurs at 0.0063 atm, close to its minimum alveolar concentration (0.0075 atm) in man.     

Interaction of anaesthetics with electrical synapses

Studies of the interaction of anaesthetics with various preparations, from whole animals to organic solvents, have been continuing since Overton and Meyer found a correlation between anaesthetic potency and solubility in olive oil. Although the physiological basis of anaesthesia is far from clear, one popular hypothesis is that anaesthetics act primarily by interfering with the normal functioning of chemical synapses. This hypothesis is supported by experiments showing that these synapses are more sensitive to both local and general anaesthetics than are axons. The effects of anaesthetics on electrical synapses (gap-junctions or nexus) have not previously been studied. These ubiquitous structures, presumably responsible for cell-to-cell communication, are found in most vertebrate and invertebrate tissues. We report here the effects of several anaesthetics on electronic coupling between nerve cells, and show that electrical synapses are less sensitive to most anaesthetics than are chemical synapses and axonal membranes.     

Do general anaesthetics act by competitive binding to specific receptors?

Most proteins are insensitive to the presence of anaesthetics at concentrations which induce general anaesthesia, while some are inhibited by certain agents but not others. Here we show that, over a 100,000-fold range of potencies, the activity of a pure soluble protein (firefly luciferase) can be inhibited by 50% at anaesthetic concentrations which are essentially identical to those which anaesthetize animals. This identity holds for inhalational agents (such as halothane, methoxyflurane and chloroform), aliphatic and aromatic alcohols, ketones, ethers and alkanes. This finding is all the more striking in view of the fact that the inhibition is shown to be competitive in nature, with anaesthetic molecules competing with substrate (luciferin) molecules for binding to the protein. We show that the anaesthetic-binding site can accommodate only one large, but more than one small, anaesthetic molecule. The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.     

Tropospheric lifetimes of halogenated anaesthetics

Concern has been expressed over the use of the halogenated anaesthetics halothane (CF3CClBrH), enflurane (CF2HOCF2CFClH) and isoflurane (CF2HOCHClCF3) because of their potential for stratospheric ozone destruction. Halogenated species also contribute to global warming. The significance of the anaesthetics in stratospheric ozone loss or in 'greenhouse' heating depends on their atmospheric lifetimes. Because reaction with hydroxyl (OH) radicals is likely to be the main homogeneous sink for these species in the troposphere, we have measured absolute rates of reaction with OH. Comparison with a one-dimensional model indicates that the lifetimes of halothane, enflurane and isoflurane with respect to this reaction are 2, 6 and 5 years, respectively. Thus the small production of the anaesthetics is not offset by anomalously long atmospheric lifetimes to give a large atmospheric burden of the compounds. The anaesthetics will contribute at most a fraction of approximately 5 x 10(-4) to the total atmospheric content of chlorine-containing species.     

Mapping of general anaesthetic target sites provides a molecular basis for cutoff effects

A longstanding and unresolved problem in general anaesthesia is the so-called 'cutoff' effect; as one ascends a homologous series of anaesthetic agents, the potencies progressively increase with anaesthetic size but then, rather suddenly, anaesthetic potency disappears. Curiously, this cutoff in potency occurs at very different points in different series. Various explanations have been offered, usually based on the notion that lipid bilayers are the primary target sites in general anaesthesia. However, accumulating evidence now suggests that proteins are the primary sites of action. Here we demonstrate cutoff effects for the anaesthetic inhibition of a soluble protein (firefly luciferase) which mirror those found for general anaesthesia, and we describe how the molecular architecture of the binding site accounts for the different cutoffs in the different homologous series. We show that this behaviour is a natural consequence of anaesthetics binding to an amphiphilic protein pocket of circumscribed dimensions. When general anaesthetic target sites in animals and the luciferase protein are mapped out using the fine details of the potency data, remarkable similarities are revealed. Our results thus suggest that the target sites in general anaesthesia are amphiphilic pockets on proteins.     

急性高浓度PM2.5暴露对小鼠认知能力的影响

流行病学证据表明,老年人长期接触PM2.5可能导致记忆障碍.为了探究短期、严重雾霾天气对人们健康的影响,以C57BL/6J小鼠为研究对象,用不同浓度的PM2.5(0、193、1 930、19 300 μg·kg－1·day－1),通过鼻腔滴注的实验,染毒1 w,探究急性高浓度PM2.5污染所造成的神经毒性.首先通过Morris水迷宫实验对小鼠认知能力进行检测,暴露结束后对小鼠脑组织进行组织病理学检测(H&E)、氧化应激水平测定(ROS、MDA、SOD).实验结果表明,急性高浓度PM2.5暴露虽然不影响小鼠大脑的生长发育,但会导致小鼠认知能力下降,高剂量19 300 μg·kg－1·day－1PM2.5染毒组小鼠与空白对照组小鼠5 d逃避潜伏期的平均值有显著性差异(为P＜0.05);小鼠脑组织海马区出现病理学损伤;小鼠脑组织中的ROS水平、MDA含量上升,SOD活性下降.实验揭示了急性高浓度PM2.5暴露对小鼠脑组织能造成氧化损伤,破坏海马神经中枢细胞结构,影响小鼠的学习记忆能力.     

间苯三酚对碱性条件下铜体系化学振荡反应的影响

通过研究间苯三酚对Cu(Ⅱ)-H2O2-NaSCN振荡体系(简称铜体系)的影响,并考察间苯三酚浓度在1.268×10-3~1.296×10-4mol·L-1范围内,间苯三酚的浓度与振荡反应周期的改变值△T之间的相关关系,从而可初步解释间苯三酚对铜体系振荡反应影响的机理,为其分析测试奠定了基础.     

DNA与CdS-COOH-EcoRI复合物相互作用的研究

采用荧光光谱、原子力显微镜、琼脂糖凝胶电泳等技术探究CdS-COOH-EcoRI复合物与DNA的相互作用.研究发现,小粒径的CdS-COOH-EcoRI复合物与DNA除了有特异性结合,还发生非特异性结合.DNA相对浓度比较大以及恒温孵育时间较短时,以特异性结合为主;而随着DNA相对浓度的减小以及恒温孵育时间的延长,会伴有非特异性结合.Ca2+存在时,可以通过延长孵育时间“激活”酶切反应,使得DNA被剪切.因此可以通过改变DNA相对浓度和孵育时间来调控EcoRI对DNA的剪切.     

Block of acetylcholine-activated ion channels by an uncharged local anaesthetic

It is now thought that amine local anaesthetic compounds (procaine, lignocaine and related molecules) depress electrical activity in nerve and muscle cells by binding to sites within ion channels and blocking current flow. Such mechanisms have been proposed to account for the effects of these local anaesthetics on both the voltage-dependent sodium current and the postsynaptic actylcholine (ACh)-activated ionic current. Recently, strong evidence for block of ion channels by cationic drug molecules has been obtained by recording current from single ACh-activated channels in the presence of permanently charged quaternary derivatives of lignocaine. Most amine local anaesthetic compounds are, however, weak bases, present in both charged and uncharged forms at physiological pH, and some question remains as to whether a charged group is essential for blockade of ion channels. To resolve this question, we studied the action of the uncharged local anaesthetic benzocaine (ethyl-4-aminobenzoate) on postsynaptic ACh-activated endplate current and extrajunctional single channel current of frog muscle. We report here evidence that strongly suggests that benzocaine blocks ACh-activated ion channels.     

Analysis with NMR localized spectroscopy of rat brainin vivo andex vivo

The volume-selected MRS of rat brain was performed on a 200 MHz broad horizontal-bore nuclear magnetic resonance imaging spectromete;. The localized proton spectroscopy of rat brain was acquired using the double spin-echo pulse sequence (PRESS) to select the position and size of the volume. Water signal was suppressed by CHESS sequence which was composed of chemical shift selective rf pulses and dephasing gradients. The parameterTE was taken as 40 ms and 135 ms in the experiment. The localized MRS of the rat brain with the status of live and death was obtained in variousTE values. Results showed that volume-selected proton MRS of the rat brainin vivo with longerTE consisted mainly of signals produced by N-acetylaspartate (NAA), creatine (Cre), choline (Cho) and the lactate spectral peak occurred in the MRS of the rat brainex vivo. On the other hand, the MRS of the rat brain with shorterTE contained glutamine/glutamate and lipid signals besides those signals mentioned previously. Although the information abstracted from the MRS of the rat brain with shorterTE may be more than that with longerTE, the spectral resolution of the MRS with shorterTE was slightly worse. In addition, it might indicate that the absolute concentration of NAA was decreased in dead rat brain because the SNR of NAA peak in the MRSex vivo got lower.     

公园绿地及周边环境PM2.5浓度特征及影响因素

【目的】评价城市公园对降低大气PM_2.5质量浓度的作用,同时探讨环境因素对PM_2.5质量浓度的影响。【方法】以北京市北小河公园为研究对象,通过PM_2.5质量浓度监测仪测定公园绿地内、公园附近建筑室内及公园道路旁(开敞空间)的PM_2.5质量浓度,对公园及其附近建筑室内与道路旁PM_2.5浓度做差异对比分析,同时监测温湿度、风速及气压、车流量,以分析环境因素对PM_2.5质量浓度的影响。【结果】①公园及其附近建筑室内与道路旁PM_2.5浓度日变化趋势基本一致,呈现双峰单谷型,即早晚高、白天低。②无污染或轻度污染时,公园绿地PM_2.5质量浓度均低于道路旁及附近建筑室内,PM_2.5质量浓度分别降低了5.7%和6.9%,说明公园绿地对PM_2.5有一定的滞留作用; 中度污染天气条件下,公园内PM_2.5浓度同样低于道路旁与建筑室内,降幅分别为3.6%和7.3%,公园绿地对PM_2.5仍有一定的滞留作用; 重度污染质量条件下,公园内PM_2.5质量浓度略低于道路旁,降幅仅为0.3%,而比建筑室内升高了5.5%。③公园绿地PM_2.5质量浓度与温度、风速呈负相关关系,与相对湿度、气压呈正相关关系; 道路旁PM_2.5质量浓度与车流量呈正相关。【结论】在中度污染及以下环境空气质量条件下,公园绿地对PM_2.5有一定的滞留作用,说明公园绿地对PM_2.5滞留作用的发挥受一定的环境空气质量条件的制约。     

Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential.

Extrinsic optical probes have become important tools for monitoring membrane potential, with probes now available for many tissue or cell suspension systems. In each case that has been studied in detail, it seems that the mechanism involves a shift in the equilibrium population of the probe from one chemical environment to another in response to the transmembrane potential; the environments perturb the probe's spectrum differently. As this indirect mechanism involves a redistribution of dye between chemical environments that are likely to vary if a given probe is transferred from one membrane to another, a potential probe that is effective and calibrated for all membrane systems has not been realised. We present here evidence for a direct response of a probe chromophore to the electric field across membrane systems. The results suggest it might be possible to develop a universal set of membrane probes.     

对苯二酚对Cu(Ⅱ)-H_2O_2-NaSCN振荡反应的影响

对苯二酚在碱性条件下对Cu催化H2O2和NaSCN的化学振荡反应(以下简称铜体系)的干扰,考察了在2.24×10-6-5.45×10-5mol·L-1和2.24×10-6-2.87×10-5mol·L-1范围内,对苯二酚的浓度与振荡反应的周期的改变△T1、△T2之间的关系 结合铜体系振荡反应的机理,提出了对苯二酚干扰振荡反应的机理,为其应用奠定基础     

Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function.     

典型行业废水生物毒性与污染物浓度关系

通过对辽宁省4种典型行业的工业废水理化与生物毒性指标的监测和评价,结果表明造纸和金属冶金行业废水的COD和SS污染物浓度超标严重,化学工业行业废水主要是COD浓度超标.造纸、石油焦化、金属冶金行业废水发光菌相对抑光率的毒性级别较高,多数处于中毒-剧毒之间,化学工业各生物毒性级别在低毒-中毒范围内.造纸行业废水的COD浓度和SS浓度与各生物毒性指标间的相关性极显著.石油焦化、化学工业行业废水中挥发酚浓度与各生物毒性指标间具有较好的相关性,金属冶金行业废水中COD浓度与生物毒性指标具有较好的相关性.     

宜昌市城区PM_(2.5)污染形成灰霾天气的规律研究

2012年选取与气象站点相邻的一个环境空气质量测点对PM2.5进行了研究性监测,测点距地面23m,全年PM2.5质量浓度在19~284μg/m3之间,年均质量浓度为89μg/m3,月均质量浓度最高的为1月.系统分析全年PM2.5监测质量浓度与相邻气象测点灰霾、能见度观测数据之间的关系,得到以下结论:宜昌市城区PM2.5污染质量浓度与灰霾观测值相关性不强,但与能见度的观测值显著相关;全年能见度降低受PM2.5污染的影响具有季节性,2、5~6三个月与7~9三个月及4、10~11三个月,这3组月份内的PM2.5与能见度之间的回归曲线基本一致,全年中3月份影响最大,而1月份最小,主要与气温、风速、降雨因素有关.     

不同足球水平女大学生反应抑制能力的差异及其脑结构基础

采用磁共振成像技术,结合Stop-Signal任务范式测评不同足球训练水平女大学生反应抑制能力的差异并探究其脑结构基础．34名被试按照足球训练水平分为对照组（CG）、业余组(AG)和专业组(PG),采用Stop-Signal任务评估反应抑制能力;基于体素形态学对T1结构像进行组间差异分析,并进行FDR校正;采用相关分析探究反应抑制能力和差异脑区之间的关系．结果表明:1）与CG相比,PG和AG的反应时分别缩短48和44 ms（P<0.05）;PG、AG较CG的停止信号反应时分别减少116和96 ms（P<0.05）,PG较AG停止信号反应时显著减少10 ms（P<0.05）;PG(57%)抑制正确率显著高于CG(55%)（P<0.05）．2）与CG相比,PG右侧小脑Crus1、丘脑、中央前后回及小脑蚓部Ⅷ,左侧小脑Crus1、苍白球、丘脑,灰质体积显著增大（P<0.05, FDR）;PG较AG右侧梭状回、中央前回、左侧扣带中回灰质体积显著增大（P<0.001）;AG较CG在双侧苍白球灰质体积显著增大（P<0.001）．3）小脑蚓部Ⅷ灰质密度和反应时存在显著负相关（P<0.05, r= ?0.12）;停止信号反应时与右侧丘脑(P<0.05, r= ?0.41)、左侧苍白球(P<0.01, r= ?0.49)呈显著负相关;抑制正确率与右侧梭状回(P<0.05, r=0.46)、左侧苍白球（P<0.01, r=0.47）呈显著正相关．长期足球训练显著提高女大学生反应抑制能力,且反应抑制能力与小脑蚓部Ⅷ、左侧苍白球、右侧丘脑、右侧梭状回灰质密度显著相关．推测长期足球训练通过诱导基底神经节、小脑灰质体积的变化来调节反应抑制能力的提升．因为本文采用了横断面研究,不能得出反应抑制和足球训练之间的直接因果关系,但在一定程度上表明二者之间存在显著相关关系．因此,后续还需要更多纵向对照研究,进一步确定因果关系．      

无机陶瓷膜分离沙枣多糖的研究

以沙枣多糖的回收率、浓缩效率、膜污染率和膜通量为指标,优化了无机陶瓷膜分离沙枣多糖的工艺参数及膜的清洗方案。在操作压力0.1 MPa,温度30℃,料液比1∶60的条件下分离沙枣多糖提取液,多糖的回收率、浓缩效率、膜污染率和膜通量分别为98.6%、28.4 L//m2·h、11.6%和46 8L//m2·h;采用不同化学清洗方法对陶瓷膜清洗效果进行分析,结果表明用0.5%的HNO3清洗效果最好,可使膜通量的恢复率达到92%。该研究表明利用陶瓷膜分离沙枣多糖是可行的,并且为膜分离多糖的研究提供一定的技术依据。     

石家庄市冬春季环境空气中挥发性有机物的污染特征

为了深入探究石家庄市冬春季环境空气中挥发性有机物的污染特征,采用EPA TO-15方法定性定量分析了石家庄市冬春季环境空气中62种挥发性有机物的污染特征,对比了环境空气中VOCs浓度的季度、月度变化情况,以及VOCs与PM2.5浓度之间的相关性,分析了环境空气中主要VOCs组分的来源。结果表明:在石家庄市冬春季环境空气中定量检测到其中的40种VOCs,主要有丙酮、苯、四氯化碳、二氯甲烷、甲苯、乙酸乙酯等;未定量的组分中,检测出了较高的乙酸丁酯、丁烷、乙醇等。在雾霾天气,PM2.5浓度和环境空气中VOCs浓度具有较好的正相关性。     

聚四氟乙烯微孔膜表面亲水改性研究

用化学法对PTFE微孔膜表面进行亲水改性,利用红外光谱（ATR—FTIR）和扫描电镜（SEM）观察了改性膜表面形态和微观结构的变化,FTIR图表明膜的表面产生了极性基团,SEM图显示膜的孔径和孔隙率发生了变化。研究了钠萘处理液浓度与膜改性效果的关系,结果表明：随着钠萘处理液浓度的提高,膜表面接触角减小,亲水性增强。钠萘处理液浓度以0．6mol／L为最佳。