铅对海马LTP的影响

综述了铅对海马“长时程增强”（ＬＴＰ）的影响,海马是学习记忆的关键部位,海马ＬＴＰ是记忆形成的基础。慢性铅暴露可使海马ＬＴＰ的幅度降低甚至抑制其诱导,铅可通过干扰海马ＬＴＰ过程,导致儿童的学习,记忆功能及心理行为异常,这可能是铅神经毒性机制之一。     

单唾液酸神经节苷脂GM1对大鼠海马CA1区LTP的作用

本工作在大鼠海马脑片上观察了不同剂量的GM1对CA1区长时程增强(LTP)的作用,并探讨了钙离子和NMDA受体在其中的可能作用。结果表明,GM1能增大强直刺激诱导的LTP,其剂量-效应曲线呈双向性变化,剂量为50mg/1时增大作用最强。在低钙条件下,经含GM1的人工脑脊液孵育的脑片上能诱导出与正常钙条件下相接近的LTP。在高钙条件下,GM1对LTP的增大作用相对较弱。结果还表明,在NMDA受体被阻断时,GM1的作用也就消失。本文还对GM1的作用机制进行了讨论。     

铅对海马齿状回L—LTP和双脉冲反应的影响

应用在位电生理技术研究了发育过程中的铅暴露对成年大白鼠海马齿状回超长时程增强（Ｌ－ＬＴＰ）和双脉冲反应（ＰＰＦ）的影响。结果表明，铅使海马神经元ＥＰＳＰ和ＰＳ诱导的Ｌ－ＬＴＰ幅度降低，维持时间缩短，提示铅可能对形成长期记忆中起关键作用的新蛋白合成过程造成损伤。铅使双脉冲易化幅度降低，易化时间宽度变窄，提示铅主要使突触后ＮＭＤＡ受体造成损伤。     

铅对大鼠海马谷氨酸递质体外摄取和释放的影响

为了探讨铅损害学习记忆功能的神经生物学机制，用海马突触小体和脑片分别观察了铅在体外对谷氨酸递质摄取和释放的影响。结果显示，3．1－50.0μmol／L铅使海马突触小体3H-DL-谷氨酸摄取量增加70．4％－193．2％，使脑片无钙状态下的自发性释放量增加23．2％－66．2％，并均有剂量-效应关系。但是在含钙介质中，当铅染毒剂量从1．0μmol/L增加为50．0μmol/L时，3H－DL-谷氨酸的自发性释放量减少22．6％－55．3％。而高钾去极化释放量增加89．3％－332．1％，而且也均存在剂量-效应关系。提示铅不仅能促进谷氨酸递质的灭活，而且还干扰它的释放过程。这可能会影响该递质的突触传递过程及其兴奋性作用，使LTP现象减弱或不能产生。     

钠通道阻滞剂作用机制的闸门相关受体假说及模型

本文提出了钠通道阻滞剂作用机制的新假说——闸门相关受体假说,并建立了相应的数学模型,用此模型模拟分析了利多卡因(Lidocaine Lid)、蝙蝠葛碱(dauricine,Dau)阻滞心肌钠通道的作用。模型预测结果不仅与文献报道的实验结果一致,而且还提供了解释这些药物阻滞钠通道作用机制的新资料。研究表明,闸门相关受体假说能较好地阐明心肌钠通道阻滞剂的作用机制。     

两种含锌化合物对慢性染铅大鼠海马NADPH-d阳性神经元影响的比较

为探讨硫酸锌(ZnSO4)和牛磺酸锌(TZC)拮抗铅对学习记忆的损害的不同，采用NADPH-黄递酶(NADPH-d)组化，观察了饮用含0.2g／L醋酸铅(PbAc)饮水和含不同剂量(5．0，15．0g／kg)ZnSO4、(5．9、17．7g／kg)TZC饲料喂养的大鼠海马一氧化氮合酶(NOS)活性的变化。结果表明，各补锌组均不同程度地缓解铅致NOS活力减低，铅 低TZC组、铅 高ZnSO4组和铅 低ZnSO4组大鼠海马神经元的NOS活性明显高于染铅组，其中铅 低TZC组的保护作用最显著，而铅 高TZC组的NOS活性明显低于对照组，而接近染铅组水平。结论是锌对抗铅的毒性作用与锌的化学结合形式、锌的剂量密切相关。     

单晶Pb纳米线及纳米粒子的溶液法制备

采用溶液法制备了较高长径比(～100)的铅的均匀纳米线及纳米粒子,并对产物进行了XRD,SEM和TEM表征.探讨了反应温度、反应物浓度及还原剂种类对产物成相及形貌的影响,初步讨论了铅钠米线的形成机制.     

单晶Pb纳米线及纳米粒子的溶液法制备

采用溶液法制备了较高长径比(～100)的铅的均匀纳米线及纳米粒子,并对产物进行了XRD,SEM和TEM表征.探讨了反应温度、反应物浓度及还原剂种类对产物成相及形貌的影响,初步讨论了铅钠米线的形成机制.     

低剂量铅对大鼠脑组织一氧化氮合酶表达及活性的影响

为探讨低水平铅损伤记忆功能的作用机理，采用ＮＡＤＰＨ－黄递酶组织化学方法和＾３Ｈ－瓜氨酸生成生物检测技术，观察了新生大鼠在４００ｍｇ／Ｌ醋酸铅染毒４０天后对脑组织内一氧化氮合酶表达及活性的影响。结果显示大脑皮质一氧化氮合酶阳性神经元数量明显减少（Ｐ〈０．０５），在海马区脑组织内一氧化氮合酶活性降低５４．４％。结论：低水平铅暴露后可抑制大鼠脑组织内一氧化氮合酶的表达及活性。     

铅对人体内分泌系统的影响

体内铅负荷增高可对某些激素 ,如甲状腺激素和肾上腺皮质激素的产生及其代谢产生影响。崔金山测定了沈阳某蓄电池厂铅作业工人的血中游离三碘甲状腺原氨酸 (FT3)、游离四碘甲状腺原氨酸(FT4 )、促甲状腺素 (TSH)及尿铅、尿δ ALA水平 ,发现铅吸收组和铅中毒组工人血中FT3和FT4 含量明显低于对照组和铅接触组 (P <0 0 1 ) ,铅中毒组工人血中TSH含量显著升高。铅作业工人的这些指标均与尿铅及尿δ ALA水平呈显著相关关系 (P <0 0 1 )。铅致甲状腺功能下降的机制可能是铅损伤了甲状腺腺泡 ,使其分泌功能受损 ,也可能是铅抑制了摄碘…     

Mie lidar observations of lower tropospheric aerosols and clouds

Mie lidar system is developed at Laser Science and Technology Centre, Delhi (28.38°N, 77.12°E) by using minimal number of commercially available off-the-shelf components. Neodymium Yttrium Aluminum Garnet (Nd:YAG) laser operating at 1064nm with variable pulse energies between 25 and 400 mJ with 10 Hz repetition rate and 7ns pulse duration is used as a transmitter and off-axis CASSEGRAIN telescope with 100mm diameter as a receiver. Silicon avalanche photodiode (Si-APD) module with built-in preamplifier and front-end optics is used as detector. This system has been developed for the studies of lower tropospheric aerosols and clouds. Some experiments have been conducted using this set up and preliminary results are discussed. The characteristics of backscattered signals for various transmitter pulse energies are also studied. Atmospheric aerosol extinction coefficient values are calculated using Klett lidar inversion algorithm. The extinction coefficient, in general, falls with range in the lower troposphere and the values lie typically in the range 7.5×10(-5) m(-1) to 1.12×10(-4) m(-1) in the absence of any cloud whereas this value shoots maximum up to 1.267×10(-3) m(-1) (peak extinction) in the presence of clouds.     

Determination of thermal degradation of vulcanized rubbers using diffracted SH ultrasonic waves

Thermal degradation of NBR and CR heated in air was determined by analysis of diffracted SH ultrasonic waves. Thermal degradation was evaluated by examining wave pattern characteristics of SH waves passing through the surface depth between transmitter and receiver. Thermal crosslinking of main chains in thermally degraded NBR and CR, accompanied by lowering of mechanical properties, can evaluate by decrease of launched time and appearance of 0.9 MHz side peak of the power spectrum. The thermal degradation also causes phase delay at high frequencies, showing regression of viscoelasticity associated with formation of dangling ends. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 497–503, 1999     

Photodynamic effect of hypericin and a water-soluble derivative on isolated crayfish neuron and surrounding glial cells

Hypericin (Hyp) has been proposed as a fluorochrome for fluorescence diagnostics and as a photosensitizer for photodynamic therapy of cancer. However, its insolubility in water is a serious drawback. A novel water-soluble hypericin derivative (Hyp-S) has been constructed, using polyvinylpyrrolidone as a carrier. We used the crayfish stretch receptor, consisting of receptor neuron and satellite glial cells, for comparison of the photodynamic effects of Hyp and Hyp-S. Hyp-S was more toxic in the dark than Hyp and inactivated the neurons at concentrations exceeding 4 microM while Hyp was toxic to the neurons only at the concentrations larger than 20 microM. Electrophysiological investigations revealed polyphasic neuron responses to photosensitization with Hyp as well as with Hyp-S (1 microM concentration, 30 min incubation; irradiation with filtered light from a lamp with an emission maximum near 600 nm and an intensity of 0.2 W/cm2). In the concentration range 1-4 microM Hyp-S was more phototoxic than Hyp. Fluorescence microscopy showed that both sensitizers were predominately localized in the glial envelope surrounding the neuron. A minor fraction of hypericin was found in the neuron perinuclear area rich in cytoplasm organelles. This suggests the potential application of Hyp and Hyp-S for visualization and selective photodynamic treatment of malignant gliomas.     

Simultaneous detection of vesicular content and exocytotic release with two electrodes in and at a single cell

We developed a technique employing two electrodes to simultaneously and dynamically monitor vesicular neurotransmitter storage and vesicular transmitter release in and at the same cell. To do this, two electrochemical techniques, single-cell amperometry (SCA) and intracellular vesicle impact electrochemical cytometry (IVIEC), were applied using two nanotip electrodes. With one electrode being placed on top of a cell measuring exocytotic release and the other electrode being inserted into the cytoplasm measuring vesicular transmitter storage, upon chemical stimulation, exocytosis is triggered and the amount of release and storage can be quantified simultaneously and compared. By using this technique, we made direct comparison between exocytotic release and vesicular storage, and investigated the dynamic changes of vesicular transmitter content before, during, and after chemical stimulation of PC12 cells, a neuroendocrine cell line. While confirming that exocytosis is partial, we suggest that chemical stimulation either induces a replenishment of the releasable pool with a subpool of vesicles having higher amount of transmitter storage, or triggers the vesicles within the same subpool to load more transiently at approximately 10–20 s. Thus, a time scale for vesicle reloading is determined. The effect of l-3,4-dihydroxyphenylalanine (l-DOPA), the precursor to dopamine, on the dynamic alteration of vesicular storage upon chemical stimulation for exocytosis was also studied. We found that l-DOPA incubation reduces the observed changes of vesicular storage in regular PC12 cells, which might be due to an increased capacity of vesicular transmitter loading caused by l-DOPA. Our data provide another mechanism for plasticity after stimulation via quantitative and dynamic changes in the exocytotic machinery.

Simultaneous measurements of IVIEC and SCA by two nanotip electrodes allows direct and dynamic comparison between vesicular transmitter content and vesicular transmitter release to shed light on stimulation-induced plasticity.     

Combined Amperometry and Electrochemical Cytometry Reveal Differential Effects of Cocaine and Methylphenidate on Exocytosis and the Fraction of Chemical Release

Amperometry with nanotip electrodes has been applied to show cocaine and methylphenidate not only trigger declines in vesicle content and exocytotic catecholamine release in a model cell line but also differentially change the fraction of transmitter released from each individual vesicle. In addition, cocaine accelerates exocytotic release dynamics while they remain unchanged after methylphenidate treatment. The parameters from pre‐spike feet for the two drugs are also in opposition, suggesting this aspect of release is affected differentially. As cocaine and methylphenidate are psychostimulants with similar pharmacologic action but have opposite effects on cognition, these results might provide a missing link between the regulation of exocytosis and vesicles and the effect of this regulation on cognition, learning, and memory. A speculative chemical mechanism of the effect of these drugs on vesicle content and exocytosis is presented.     

Implementation of radiotelemetry in a lab-in-a-pill format

A miniaturised lab-in-a-pill device has been produced incorporating a temperature and pH sensor with wireless communication using the 433.92 MHz ISM band. The device has been designed in order to enable real time in situ measurements in the gastrointestinal (GI) tract, and accordingly, issues concerning the resolution and accuracy of the data, and the lifetime of the device have been considered. The sensors, which will measure two key parameters reflecting the physiological environment in the GI (as indicators for disease) were both controlled by an application specific integrated circuit (ASIC). The data were sampled at 10-bit resolution prior to communication off chip as a single interleaved data stream. This incorporated a power saving serial bitstream data compression algorithm that was found to extend the service lifetime of the pill by 70%. An integrated on-off keying (OOK) radio transmitter was used to send the signal to a local receiver (base station), prior to acquisition on a computer. A permanent magnet was also incorporated in the device to enable non-visual tracking of the system. We report on the implementation of this device, together with an initial study sampling from within the porcine GI tract, showing that measurements from the lab-on-a-pill, in situ, was within 90% of literature values.     

Effects of L-glutamine, glutaminase and glutamine synthetase on CAP threshold of cochlear nerve of guinea pig.

Negative direct current (-DC 300 microA) stimulation was applied to the round window of the guinea pig cochlea to exhaust the pre-synaptic intracellular reserves of the transmitter in hair cells, and then the scala tympani was perfused respectively with L-glutamine, glutamine synthetase and glutaminase. Experimental results showed that the negative DC electrical stimulation applied to the round window elevated the CAP threshold of the cochlear nerve in the basal turn of the cochlea, which recovered over a period of approximately 17-39 min. The perfusion of L-glutamine apparently elevated the CAP threshold. The recovery of the CAP threshold following electrical stimulation, however, was accelerated by the perfusion of 10 mmol/L L-glutamine. The time for recovery only took about 5-6 min. The perfusion of enzyme glutamine synthetase elevated the CAP threshold by 50 dB, while glutaminase had little effect. These results suggest that the effect of L-glutamine on the CAP threshold in the cochlea of the guinea pig appears to be that of a potent depolarizing agent which accelerates the recovery of the CAP threshold during the depletion of the transmitter, and L-glutamine may be the candidate for the afferent excitatory transmitter.     

Receiver gain function: the actual NMR receiver gain

The observed NMR signal size depends on the receiver gain parameter. We propose a receiver gain function to characterize how much the raw FID is amplified by the receiver as a function of the receiver gain setting. Although the receiver is linear for a fixed gain setting, the actual gain of the receiver may differ from what the gain setting suggests. Nevertheless, for a given receiver, we demonstrate that the receiver gain function can be calibrated. Such a calibration enables accurate comparison of separately acquired NMR signals in quantitative analysis, which frequently requires different receiver gain settings to avoid receiver saturation or achieve optimum sensitivity. The application of receiver gain function, along with the definition of receiving efficiency, allows easy concentration determination by a single internal or external concentration reference. Copyright © 2010 John Wiley & Sons, Ltd.     

Recording from an Identified Neuron Efficiently Reveals Hazard for Brain Function in Risk Assessment

Modern societies use a continuously growing number of chemicals. Because these are released into the environment and are taken up by humans, rigorous (but practicable) risk assessment must precede the approval of new substances for commerce. A number of tests is applicable, but it has been very difficult to efficiently assay the effect of chemicals on communication and information processing in vivo in the adult vertebrate brain. Here, we suggest a straightforward way to rapidly and accurately detect effects of chemical exposure on action potential generation, synaptic transmission, central information processing, and even processing in sensory systems in vivo by recording from a single neuron. The approach is possible in an identified neuron in the hindbrain of fish that integrates various sources of information and whose properties are ideal for rapid analysis of the various effects chemicals can have on the nervous system. The analysis uses fish but, as we discuss here, key neuronal functions are conserved and differences can only be due to differences in metabolism or passage into the brain, factors that can easily be determined. Speed and efficiency of the method, therefore, make it suitable to provide information in risk assessment, as we illustrate here with the effects of bisphenols on adult brain function.