寡克隆区带及IgG指数在多发性硬化中的临床意义

目的研究寡克隆区带（OCB）和IgG指数在多发性硬化（MS）中的临床意义。方法收集MS患者54例和其他神经系统疾病（OND）患者271例,包括中枢神经系统感染性疾病62例及非感染性疾病209例的脑脊液和血清标本,分别进行OCB检测（聚丙烯酰胺凝胶电泳）和IgG指数的计算（免疫火箭电泳法）。结果MS组OCB阳性率为35.2%;OND组为8.9%,其中感染组为24.2%,非感染组为4.5%。MS与OND组整体比较OCB阳性率有显著性差异（P〈0.05）,但与感染组相比无显著性差异（P〉0.05）。MS组IgG指数阳性率为83.3%,OND组为78.2%（P〉0.05）。结论OCB对MS有一定的辅助诊断价值,但需除外CNS感染性疾病。IgG指数阳性可作为参考。     

糖尿病腹膜透析患者胰岛素治疗方案探讨

目的探讨糖尿病腹膜透析(CAPD)患者合理的胰岛素应用方法.方法采用横断面研究方法调查所有接受CAPD治疗至少6个月以上的糖尿病肾病患者的胰岛素使用方案及血糖控制情况.并在横断面研究的基础上,动态观察24例新收的糖尿病CAPD患者透析前、后胰岛素的使用方法、剂量调整方案及血糖控制情况.结果2002年6月至2002年12月间共25例2型糖尿病CAPD患者,其中腹腔内注射胰岛素(IP)6人,皮下注射胰岛素(SC)9人,腹腔和皮下联合应用(IP SC)7人.①空腹血糖、糖化血红蛋白、透析液糖总负荷量、透析液平均糖浓度、透析剂量在IP、SC、IP SC三组间差异均无显著性,(P＞0.05);②与IP及IP SC组相比,SC组胰岛素用量明显减少,(P＜0.05);③腹膜炎的总发生率为1次/每15患者月,明显高于同期非糖尿病腹膜透析患者的腹膜炎发生率(1次/每48患者月),(P＜0.01);④动态观察24例新收的糖尿病CAPD患者,胰岛素剂量较透析前平均增加了(0.33±0.23)倍.透析后调整的胰岛素实际增加量与理论预测增加量差异无显著性,(P＞0.05).患者血糖控制良好,平均为(5.81±1.22)mmol/L.结论皮下注射胰岛素是有效控制糖尿病CAPD患者血糖水平的适当途径.腹膜透析后,可在原有皮下应用胰岛素方案的基础上,参照糖吸收量计算需增加的胰岛素用量适当增减胰岛素,能有效控制血糖.     

β-N-Acetylhexosaminadases in human cerebrospinal fluid and serum of patients with multiple sclerosis

β-N-Acetylhexosaminidase activity and isoenzyme have been investigated in normal human cerebrospinal fluid and that of patients with multiple sclerosis. β-N-acetylhexosaminidase activity in normal cerebrospinal fluids has been resolved into five components. The major component was in a form that eluted from DEAE cellulose at the same salt concentration as hexosaminidase As, the isoenzyme previously identified in human serum. Cerebrospinal fluid from patients exhibited a different isoenzyme profile, showing a remarkable increase in a form having a pI which was more acidic than that of As. These changes have a potential use in the diagnosis and further biochemical characterization of multiple sclerosis.     

IgGs-Abzymes from the Sera of Patients with Multiple Sclerosis Recognize and Hydrolyze miRNAs

Autoantibodies-abzymes hydrolyzing DNA, myelin basic protein, and oligosaccharides have been revealed in the sera of patients with multiple sclerosis (MS). In MS, specific microRNAs are found in blood and cerebrospinal fluid, which are characterized by increased expression. Autoantibodies, specifically hydrolyzing four different miRNAs, were first detected in the blood of schizophrenia patients. Here, we present the first evidence that 23 IgG antibodies of MS patients effectively recognize and hydrolyze four neuroregulatory miRNAs (miR-137, miR-9-5p, miR-219-2-3p, and miR-219-5p) and four immunoregulatory miRNAs (miR-21-3p, miR-146a-3p, miR-155-5p, and miR-326). Several known criteria were checked to show that the recognition and hydrolysis of miRNAs is an intrinsic property of MS IgGs. The hydrolysis of all miRNAs is mostly site-specific. The major and moderate sites of the hydrolysis of each miRNA for most of the IgG preparations coincided; however, some of them showed other specific sites of splitting. Several individual IgGs hydrolyzed some miRNAs almost nonspecifically at nearly all internucleoside bonds or demonstrated a combination of site-specific and nonspecific splitting. Maximum average relative activity (RA) was observed in the hydrolysis of miR-155-5p for IgGs of patients of two types of MS—clinically isolated syndrome and relapsing-remitting MS—but was also high for patients with primary progressive and secondary progressive MS. Differences between RAs of IgGs of four groups of MS patients and healthy donors were statistically significant (p < 0.015). There was a tendency of decreasing efficiency of hydrolysis of all eight miRNAs during remission compared with the exacerbation of the disease.     

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.     

Regulation of proteins mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis

Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE-specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase-related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration.     

Magnetization transfer with echo planar imaging

The aim of magnetization transfer is to saturate the protons of the macromolecule pool with a radiofrequency (RF) pulse leading to differences in free water pool signal. Magnetization transfer (MT) contrast is difficult to achieve with the echo planar imaging (EPI) technique, although its short acquisition time would be most beneficial. Indeed, the RF saturation pulses can only be applied once before sampling the whole k-space in a single-short sequence. A possible solution to improve the sensitivity of EPI to magnetization transfer consists in applying a train of several saturation RF pulses before image acquisition. The different parameters of a RF pulse train and their influence on the MT rate have been tested to optimize an EPI clinical sequence. Our experimental procedure makes it possible to obtain a MT map in about 1 second. The technique is evaluated by multiple sclerosis lesion characterization. Supported by grants from the French research ministry and Siemens medical France.     

Memory for Visuospatial Location Following Selective Hippocampal Sclerosis: The Use of Different Coordinate Systems.

This study addressed the role of the medial temporal lobe regions and, more specifically, the contribution of the human hippocampus in memory for body-centered (egocentric) and environment-centered (allocentric) spatial location. Twenty-one patients with unilateral atrophy of the hippocampus secondary to long-standing epilepsy (left, n = 7; right, n = 14) and 15 normal control participants underwent 3 tasks measuring recall of egocentric or allocentric spatial location. Patients with left hippocampal sclerosis were consistently impaired in the allocentric conditions of all 3 tasks but not in the egocentric conditions. Patients with right hippocampal sclerosis were impaired to a lesser extent and in only 2 of the 3 tasks. It was concluded that hippocampal structures are crucial for allocentric, but not egocentric, spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Objective Measurement of Cognitive Fatigue in Multiple Sclerosis.

Objective: Objective examination of cognitive fatigue in persons with multiple sclerosis (MS). Participants: Fifty-six individuals with MS and 39 age- and education-matched healthy control subjects. Main Outcome Measures: Cognitive fatigue, operationalized as the failure to sustain effort over the course of a continuous working memory task; performance on the Paced Auditory Serial Addition Test was examined, with number of correct responses generated and responses produced under conditions of sustained central executive load as the dependent variables. Results: Cognitively impaired MS subjects produced significantly fewer correct responses than either nonimpaired MS subjects or healthy control subjects, who performed at a comparable level. Both MS groups, however, showed susceptibility to cognitive fatigue significantly earlier in time than the healthy group. Conclusions: Fatigue can influence performance even in the absence of cognitive impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)