Monte Carlo simulation of vesicular release, spatiotemporal distribution of glutamate in synaptic cleft and generation of postsynaptic currents

 The release of vesicular glutamate, spatiotemporal changes in glutamate concentration in the synaptic cleft and the subsequent generation of fast excitatory postsynaptic currents at a hippocampal synapse were modeled using the Monte Carlo method. It is assumed that glutamate is released from a spherical vesicle through a cylindrical fusion pore into the synaptic cleft and that S-α-amino-3-hydroxy -5-methyl-4-isoxazolepropionic acid (AMPA) receptors are uniformly distributed postsynaptically. The time course of change in vesicular concentration can be described by a single exponential, but a slow tail is also observed though only following the release of most of the glutamate. The time constant of decay increases with vesicular size and a lower diffusion constant, and is independent of the initial concentration, becoming markedly shorter for wider fusion pores. The cleft concentration at the fusion pore mouth is not negligible compared to vesicular concentration, especially for wider fusion pores. Lateral equilibration of glutamate is rapid, and within ≈50 μs all AMPA receptors on average see the same concentration of glutamate. Nevertheless the single-channel current and the number of channels estimated from mean-variance plots are unreliable and different when estimated from rise- and decay-current segments. Greater saturation of AMPA receptor channels provides higher but not more accurate estimates. Two factors contribute to the variability of postsynaptic currents and render the mean-variance nonstationary analysis unreliable, even when all receptors see on average the same glutamate concentration. Firstly, the variability of the instantaneous cleft concentration of glutamate, unlike the mean concentration, first rapidly decreases before slowly increasing; the variability is greater for fewer molecules in the cleft and is spatially nonuniform. Secondly, the efficacy with which glutamate produces a response changes with time. Understanding the factors that determine the time course of vesicular content release as well as the spatiotemporal changes of glutamate concentration in the cleft is crucial for understanding the mechanism that generates postsynaptic currents. Received: 28 May 1998 / Received after revision: 17 August 1998 / Accepted: 3 September 1998     

An algorithm accounting for plating efficiency in estimating spontaneous mutation rates

An algorithm is described for calculating the probability distribution of the number of mutant colonies arising in a Luria-Delbrück fluctuation experiment subject to a plating efficiency of less than 100%. A table is constructed to facilitate the estimation of spontaneous mutation rates taking into account the plating efficiency.     

The fluctuation in recovery following whiplash injury 7.5-year prospective review

Forty-two patients with a whiplash injury were assessed at the time of injury, after 3 months, 2 years and a mean of 7.5 years. The range of neck movement, pain, its effect on lifestyle, and psychometric testing were determined in each of the patients. Between 2 and 7.5 years, 5 (12%) described improved symptoms, 12 (29%) complained of continuing pain and 14 (33%) reported increased severity of symptoms since the accident. Neck pain was the commonest complaint in 23 (55%) and low back pain in 18 (43%). Radiation of pain was more common in the severely symptomatic patients. There was no significant difference in either the ages or sex of the patients between the symptomatic and asymptomatic groups. Anxiety and depression correlated well with symptom severity. None of the asymptomatic patients revealed any degree of psychological disturbance compared with 30 (77%) in the symptomatic groups. Symptoms largely stabilised within 3 months but there was significant fluctuation in symptom severity between 3 months and 2 years. This suggests that outcome cannot be accurately assessed during this time. In order to effectively manage those most severely affected by whiplash, patients should be identified within the first 12 weeks following injury if the outcome of their injury is to be modified.     

Chaos attractors of ventricular elastance to evaluate cardiac performance

Quantitative evaluation of cardiac function is very important in the clinical application of a ventricular assist device. This article reports a new evaluating method of E max, which is the most reliable parameter to evaluate cardiac function. Fluctuation in the E max time series data was evaluated by the nonlinear mathematical analyzing method including chaos and fractal theory. Experimental goats were anesthetized with halothane inhalation, and left ventricular volume and pressure were measured with other hemodynamic parameters to evaluate E max during various drug administrations. E max was evaluated by two methods. One was the conventional pressure volume loop evaluation and the other was the parameter optimization method without left ventricular volume data. As a result, E max evaluated by the parameter optimization method correlated well with the E max with conventional PV curve. Furthermore, interesting results were obtained. There were rhythmical fluctuations in the E max time series data. By the methodology of Takens, E max time series data was embedded into the phase space and a strange attractor was observed. These results may be important when considering E max evaluation during left ventricular assistance.     

Modifications of the bacterial reverse mutation test reveals mutagenicity of TiO2 nanoparticles and byproducts from a sunscreen TiO2-based nanocomposite

The bacterial reverse mutation test, recommended by the Organization for Economic Co-operation and Development (OECD) to determine genotoxicity of chemical compounds, has been recently used by several authors to investigate nanoparticles. Surprisingly, test results have been negative, whereas in vitro mammalian cell tests often give positive genotoxic responses. In the present study, we used the fluctuation test procedure with the Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 to determine the mutagenic potential of TiO₂ nanoparticles (NP-TiO₂) and showed that, when it is used conventionally, this test is not suitable for nanoparticle genotoxicity assessment. Indeed, the medium used during exposure prevents electrostatic interactions between bacterial cells and nanoparticles, leading to false-negative responses. We showed that a simple pre-exposure of bacteria to NP-TiO₂ in a low ionic strength solution (NaCl 10 mM) at a pH below the nanoparticle isoelectric points (pH 5.5) can strongly improve the accuracy of the test. Thus, based on these improvements, we have demonstrated the genotoxicity of the engineered NP-TiO₂ tested and a NP-TiO₂ byproduct from a sunscreen nanocomposite. It was also shown that strain TA102 is more sensitive than the other strains, suggesting an oxidative stress-mediated mechanism of genotoxicity.     

江苏省江滩地区感染性钉螺动态观察

目的 掌握江苏省江滩地区感染性钉螺(以下简称阳性钉螺)的现状分布和消长规律，为控制成批急性血吸虫感染(以下简称急感)的发生提供科学依据。方法以县(市、区)为单位，随机抽检5—10个有螺滩，每滩采样5—10个点，每点捕捉钉螺50--100只，然后由专业人员采用解剖镜检法检测钉螺的自然感染情况，同时对查出的阳性钉螺滩块及螺点即时进行药物杀灭。结果 5年共检测沿江有螺滩467个(条块)，捕捉钉螺169 200只，检出阳性螺滩(条块)102个和阳性钉螺433只，覆盖于12个县(市、区)，已占全省沿江县(市、区)的75．0％(12／16)。结论 经连续5年的观察，江滩阳性钉螺面积和阳性钉螺的螺口数呈逐年增长态势，存在着发生成批急感的潜在威胁。因此，加强江滩和通江河道的治理，提高阳性滩地的灭螺覆盖率和灭螺质量以及反复查治江滩散养畜牧的是今后工作的关键。     

低频振幅联合功能连接对原发性失眠的研究

目的 低频振幅(ALFF)联合功能连接探讨原发性失眠患者脑功能及网络改变.方法 64名原发性失眠患者(患者组)和59名健康对照者(对照组)进行静息态功能磁共振扫描,然后对两组间的ALFF值以及ALFF值差异脑区的功能连接进行独立样本t检验分析.结果 患者组ALFF增高的脑区为右侧颞中回、右侧补充运动区、右侧额上回内侧、...     

血液病患者激素治疗后的血糖变化特点及意义

目的：观察不同血糖基础的血液病患者使用糖皮质激素（GC）治疗前后的血糖变化特点,探讨其临床意义。方法：65例血液病患者按OGTT分组为糖调节正常（NGT）、糖耐量异常（IGT）和糖尿病（DM）三组,观察各组患者使用GC治疗前后的血糖变化特点。结果：GC治疗后所有患者日平均血糖升高,且餐后血糖升高明显,GC治疗后三组间三餐前后各点血糖值比较差异有统计学意义（P<0.05）。结论：GC治疗后大部分患者的血糖都会升高,且GC所致血糖变化具有其自身特点,大部分患者表现为午后至睡前严重高血糖,部分患者可出现夜间低血糖。