乙型脑炎疫苗研究进展

乙型脑炎（乙脑）的流行是世界性的公共卫生问题之一,其流行范围正逐步扩大。目前对于乙脑尚无特效治疗手段,因此预防乙脑的发生尤为重要。随着对日本脑炎病毒研究的深入,利用基因工程技术研制新型候选疫苗已成为预防乙脑新的发展方向。我们简要综述了乙型脑炎病毒的基因组结构及其蛋白功能,以及国内外乙型脑炎疫苗研发的新进展。     

乙型脑炎病毒研究进展

从病毒的分类地位、病毒的生物学特性、病毒粒子的形态结构、病毒基因组结构与功能、病毒感染与复制、病毒致病机制及病毒引起的疾病诸方面对乙型脑炎病毒的研究进展作了综合评述,并对该领域的研究热点和方向作了探讨。     

乙型脑炎病毒的分子生物学研究进展

日本脑炎病毒(Japanese Encephalitis Virus,JEV)也称乙型脑炎病毒或简称乙脑病毒,主要引起中枢神经系统损害,属人畜共患的自然疫源性传染病,传播地域广,病死率高,常留有后遗症。目前尚无特效治疗药物,虽有疫苗,但不够理想。     

持续性植物状态患者血浆、脑脊液中氨基酸水平的变化

目的：探讨持续性植物状态(PVS)患者脑眷液(CSF)和血浆中氨基酸类物质水平与PVS发病的关系。方法：采用高压液相色谱(HPLC)方法测定。结果:PVS患者血浆中较对照组显著升高的氨基酸有：谷氨酸(Glu)、精氨酸(Arg)。脑眷液中较对照组显著升高的氨基酸有：γ-氨基丁酸(GABA)、丝氨酸(Ser)、酪氨酸(Tyr)、色氨酸(Trp)、赖氨酸(Lys)、胍氨酸(Cit);较对照组显著降低的氨基酸有：胱氨酸(CysT)。结论：CSF中的γ-氨基丁酸、丝氨酸、酪氨酸、色氨酸和赖氨酸等的升高,胱氨酸的降低以及血浆中的谷氨酸、精氨酸的升高可能与PVS的发生和发展过程有关。     

纯化乙型脑炎疫苗的研制

将乙脑P3毒株接种地鼠肾细胞,制备病毒原液,经灭活、浓缩、层析纯化后收集抗原,再经除菌、配制,制备乙脑纯化疫苗。结果表明：病毒浓缩液经纯化后,杂蛋白去除率大于99％,牛血清蛋白残留量也明显降低;纯化疫苗主要指标检定均达到预期效果;效力试验结果显示当纯化原液蛋白含量稀释至15μg/ml时,疫苗效力符合要求。     

乙型脑炎患者脑脊液游离氨基酸的改变

<正> 乙型脑炎是夏季蚊虫叮咬以后,传播的一种病毒性脑炎。据文献报导脑炎和脑膜炎均能导致脑脊液中游离氨基酸(FreeAminoAcid,FAA)的组成和含量的改变,而且这些改变常与疾病性质、严重程度有着密切的关系。本文采用简便、快速、经济和灵敏的DNS-C1(Dimethy1 Amino-Naphthalene-5-Sulfony1 Chloride,丹     

乙型脑炎病毒的研究进展

本文根据国内外最新资料,对乙型脑炎病毒基因和蛋白的结构和功能、病毒的分型和变异、及其致病机理进行了综述。     

乙型脑炎病毒及其疫苗的研究进展

流行性乙型脑炎是由乙型脑炎病毒引起的、经蚊虫传播的严重危害中枢神经系统的人畜共患急性传染病,其重症病死率高,易造成永久性的神经系统后遗症,严重威胁着人类的健康。目前尚无特效的治疗流行性乙型脑炎的方法,控制蚊虫传播和免疫接种是当前的主要防御手段。简要综述了乙型脑炎病毒的基因组结构、结构蛋白与非结构蛋白功能、基因分型,以及流行性乙型脑炎疫苗的研究进展。     

豆鼠对流行性乙型脑炎病毒和圣路易脑炎病毒感受性的比较研究

圣路易脑炎与流行性乙型脑炎(以下简称乙型脑炎),在临床、传播媒介、流行季节和病毒性质上都很类似。在免疫血清学上虽有一定区别,但对实验室常用的动物中,主要只有小白鼠有高度的易感性,而在易感程度、感受途径和症状上,两者都没有显著区别。在免疫血清学方面,不仅操作比较麻烦,并且二者的抗原构造也有相似的部分,出现某种程度的交叉反应。因此,我们认为进一步寻找对这两型病毒在易感性上有区别的动物种,对病毒生物学性质的研究以及实际应用都是必要的。     

新生儿缺氧缺血脑病体液中游离氨基酸的改变

新生儿缺氧缺血脑病 ( hypoxic- ischem ic encephalapothy,HIE)是引起新生儿死亡及影响新生儿发育成长的一种常见病。使用丹酰氯反应 ,聚酰胺薄层析方法 ,分析了新生儿 HIE体液 (脑脊液及血液 )中 9种游离氨基酸水平的改变 ,以此探讨新生儿 HIE的发病机理 ,诊断依据以及治疗效果     

Plasma and Cerebrospinal Fluid Amino Acids in Epileptic Patients

Altered plasma and cerebrospinal fluid amino acid levels may be associated with human epilepsy. We studied three groups of patients, those with a generalized epileptic syndrome, juvenile myoclonic epilepsy, patients with refractory localization-related epilepsies, and patients with acute seizures (within 24 h). Plasma levels of amino acids were studied in all patient groups, as were those in the cerebrospinal fluid (CSF) of patients with acute seizures. After acute seizures, the amino acid changes in the CSF were limited to a reduction in the level of taurine, whereas the levels of most amino acids in plasma were decreased. On the other hand, levels of the excitatory amino acids glutamate and aspartate were increased. The most notable finding in the juvenile myoclonic epilepsy patients was an increase in glutamate level in the plasma. Our study supports the conception of an altered metabolism of glutamate in generalized epilepsies.     

犬肠缺血─再灌流诱发MSOF时血浆游离氨基酸变化

我们用饲菌加肠缺血的动物模型,测定了缺血─再灌流诱发ＭＳＯＦ的９只犬血浆游离氨基酸的浓度,结果表明,伤后含硫、支链和芳香族氨基酸有不同程度的升高,发生ＭＳＯＦ时显著升高（Ｐ＜０．００１）;总氨基酸升高显著（Ｐ＜０．０５）;必需氨基酸升高了５０％。     

冬虫夏草及人工虫草菌丝体的氨基酸营养

本文研究了天然虫草菌与人工虫草菌的氨基酸含量。结果表明,天然虫草菌、人工虫草菌的总氨基酸含量稍有差异,但中性、酸性、碱性氨基酸和必需氨基酸在总氨基酸中所占百分比的高低基本一致。     

Amino Acids and Biogenic Amines in Cerebrospinal Fluid of Patients with Parkinson's Disease

To study changes in amino acid metabolism and biogenic amines in Parkinson's disease, we set up a prospective study and measured biogenic amines, their main metabolites, and 22 different amino acids, in cerebrospinal fluid of Parkinson's disease patients (n = 24) and age-matched controls (n = 30). A trend toward higher dopamine levels in Parkinson's disease patients was interpreted as an effect of treatment with levodopa and/or selegiline. Significantly lower concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the Parkinson's disease group might reflect dopaminergic cell loss. Our results revealed decreased serotonin catabolism that was interpreted as an effect of treatment with selegiline. Whereas all amino acid levels were unchanged, taurine was significantly lower in Parkinson's disease patients. Studies showed that taurine exerts a trophic action on the central nervous system. In this view, decreased taurine in a neurodegenerative disorder as Parkinson's disease deserves attention.     

Amino Acids in Plasma and CSF and Monoamine Metabolites in CSF: Interrelationship in Healthy Subjects

Plasma and cerebrospinal fluid (CSF) concentrations of amino acids were measured in 65 healthy volunteers (50 men and 15 women). The CSF levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), and 5-hydroxyindoleacetic acid (5-HIAA) were also determined. Sex differences were observed in both plasma and CSF amino acid levels as well as in the relationship between these concentrations. No significant correlations were observed between the CSF levels of HVA and 5-HIAA, and the concentrations of their precursor amino acids in either plasma or CSF. The MOPEG level in CSF correlated positively with the plasma concentrations of several amino acids.     

结核性脑膜炎颅神经损害与脑脊液特点的关系研究

目的:探讨结核性脑膜炎颅神经损害与脑脊液特点的关系。方法:回顾性收集我院神经内科确诊的173例结核性脑膜炎患者临床资料,将所有患者分为伴颅神经损害和不伴颅神经损害两组,对其临床特点及脑脊液外观、压力及细胞学、生化、免疫球蛋白结果进行统计学分析。结果:颅神经损害者占所有病人的22.5%(39/173),视神经损害占61.5%(24/39),外展神经损害占53.8%(21/39),动眼神经损害占15.4%(6/39),听神经损害占15.4%(6/39);颅神经损伤组较无颅神经损伤组脑脊液压力、蛋白质及Ig G、Ig M、Alb明显升高(P0.01或0.001),且颅神经损害者头颅MRI脑膜强化较无颅神经损害者差异有统计学意义(P0.001),而脑脊液外观、白细胞计数及比例两组间并无发现显著差异。结论:结核性脑膜炎患者伴颅神经损害时,脑脊液压力、蛋白质及部分免疫球蛋白较无颅神经损害者明显升高,这将有助于结核性脑膜炎合并颅神经损害的临床诊断,对于有颅神经损害的结核性脑膜膜炎患者加强并早期启动抗结核治疗,以减少蛋白质沉积,从而降低颅神经损害的发生率。     

Ischemia-Induced Accumulation of Extracellular Amino Acids in Cerebral Cortex, White Matter, and Cerebrospinal Fluid

Abstract: In a global model of brain ischemia, accumulation of amino acids was studied in the extracellular space of the auditory cortex and the internal capsule using microdialysis, and in CSF of halothane anesthetized cats. In both brain regions, blood flow determined by hydrogen clearance decreased below 10 ml/100 g/min after extracranial multiple-vessel occlusion, and extracellular potassium activity ( K _e) measured in the dialysate increased significantly. A delayed rise in K _e was observed in CSF. In contrast, ischemic amino acid accumulation differed markedly between the two brain regions investigated. In cortex, transmitter amino acids glutamate, aspartate, and γ-aminobutyric acid (GABA) rose almost immediately after onset of ischemia, and increased 30-, 25-, and 250-fold, respectively, after 2 h of ischemia. The nontransmitter amino acids taurine, alanine, and serine increased 10-, seven-, and fourfold, respectively, whereas glutamine and essential amino acids (valine, phenylalanine, isoleucine, and leucine) increased only 1.5-fold. In the internal capsule, increases in amino acids, if any, were delayed and much smaller than in cortex. The largest alteration was a fivefold elevation of GABA. In CSF, changes in amino acids were small and comparable to those in the internal capsule. Our results demonstrate that ischemia-induced extracellular amino acid accumulation is a well localized phenomenon restricted to gray matter structures that possess release and reuptake systems for these substances. We assume that amino acids diffuse slowly into adjacent white matter structures, and into CSF.     

Three Dimensional Modeling of the Cerebrospinal Fluid Dynamics and Brain Interactions in the Aqueduct of Sylvius

A computational fluid dynamics (CFD) method is presented to investigate the flow of cerebro-spinal fluid (CSF) in the cerebral aqueduct. In addition to former approaches exhibiting a rigid geometry, we propose a model which includes a deformable membrane as the wall of this flow channel. An anatomical shape of the aqueduct was computed from magnetic resonance images (MRI) and the resulting meshing was immersed in a marker-and-cell (MAC) staggered grid for to take into account fluid–structure interactions. The time derivatives were digitized using the Crank–Nicolson scheme. The equation of continuity was modified by introducing an artificial compressibility and digitized by a finite difference scheme.

Calculations were validated with the simulation of laminar flow in a rigid tube. Then, comparisons were made between simulations of a rigid aqueduct and a deformable one. We found that the deformability of the walls has a strong influence on the pressure drop for a given flow.     

癫痫患者血浆中游离氨基酸水平分析

对７１例癫痫患者血浆中１８种游离氢基酸与３６例正常人血浆中游离氨基酸的水平对照。分析表明,抑制性氨基酸（γ－氨基丁酸、甘氨酸）水平明显升高的癫痫患者,其它氨基酸水平绝大多数低于正常人;兴奋性氨基酸（谷氨酸、天门冬氨酸、丙氨酸、谷氨酰胺）水平明显升高的癫痫患者,其它氨基酸水平低于正常人。