多发性硬化患者周围血IFN-γ和IL-10分泌细胞数的改变

目的:观察多发性硬化(MS)患者分泌γ-干扰素(IFN-γ)及白介素-10(IL-10)的细胞数的变化。方法:采用酶联免疫斑点技术比较MS患者、其他神经疾病患者和健康对照组外周血中髓鞘碱性蛋白(MBP)、乙酰胆碱受体(AChR)、植物血凝素(PHA)反应性及自发性分泌IFN-γ和IL-10的细胞数。结果:MS患者周围血单个核细胞中自发性分泌IFN-γ的细胞数和自发性分泌IL-10的细胞数多于其他神经系统疾病患者和健康对照组。经过MBP刺激后,MS患者分泌IFN-γ和IL-10的细胞数明显多于其他神经系统疾病患者和健康对照组。MS患者周围血细胞对MBP存在特异性反应。MS患者分泌IFN-γ的细胞数多于分泌IL-10的细胞数。结论:Th1类细胞因子(IFN-γ)分泌大于Th2类细胞因子(IL-10)与MS活动密切相关。MS患者的淋巴细胞对MBP存在特异性反应。     

地塞米松对MS的IFN-γ-10分泌性T细胞的影响

目的检测多发性硬化(MS)患者外周血单个核细胞在地塞米松(Dex)影响下的IFN-γ和IL-10的分泌细胞水平.方法采用酶联免疫斑点技术(ELISPOT)检测体外培养的外周血单个核细胞(MNC)在CNS髓鞘素抗原MBP刺激下的地塞米松对照试验,检测IFN-γ和IL-10分泌性T细胞水平,并与其他神经疾病(OND)组及健康对照组的检测结果进行对比.结果显示MS患者IFN-γ分泌细胞水平高于对照组,Dex使MS患者IFN-γ分泌细胞减少,对IL-10分泌细胞无明显影响.结论MS患者存在Th1/Th2细胞因子的失衡,Dex能抑制MSTh1类细胞因子IFN-γ,其治疗作用可能与此有关.     

重症肌无力患者末梢血Th1和Th2细胞内细胞因子的变化及意义

目的研究重症肌无力(MG)患者末梢血细胞因子及抗乙酰胆碱受体抗体(AchRab)水平,探讨细胞因子在MG发病中的作用。方法研究对象为17例MG患者,分为急性期组10例,非急性期组7例,设健康对照组15例。应用流式细胞术(FCM)测定末梢血产生各型细胞因子(CK)的CD4+T细胞%,采用酶联免疫吸附法(ELISA)测定血清中抗乙酰胆碱受体抗体(AchRab)。结果⑴MG患者急性期组和非急性期组IFN-γ+IL-4-CD4+T细胞%及AchRab的含量比健康对照组显著增多(P<0.05和P<0.001);⑵急性期组和非急性期组IFN-γ-IL-4+和IL-13+CD4+T细胞%比健康对照组显著减少(P<0.05);⑶IL-10+CD4+T细胞%各组之间无显著性差异;⑷各组IFN-γ+IL-4-CD4+T细胞%与AchRab均呈正相关。结论MG患者Th1和Th2细胞因子的平衡紊乱,Th1细胞因子IFN-γ对MG患者自身抗体的产生有促进作用。     

地塞米松对多发性硬化细胞因子的影响

目的:多发性硬化(MS)是一种由Th1细胞介导的自身免疫性疾病,因而减少T细胞产生γ-干扰素(IFN-γ)或增加白细胞介素-10(IL-10)的产生将会达到治疗MS的目的。通过计数分泌细胞因子IFN-γ和IL一10,检测多发性硬化(MS)患者外周血单个核细胞在地塞米松(Dex)影响下的IFN-γ和IL-10的分泌细胞水平。方法:将外周血单个核细胞暴露于中枢神经系统髓鞘索抗原髓鞘碱性蛋白进行体外短时间培养,然后用Dex作对比试验,用酶联免疫斑点试验(ELISPOT)检测IL-10和IFN-γ分泌细胞,同时检测其它神经病组(OND)及健康对照组。结果:显示MS患者IFN-γ分泌细胞水平高于对照组,Dex使MS患者IFN-γ分泌细胞减少,对IL-10分泌细胞无明显影响。结论:MS患者存在Th1/Th2细胞因子的失衡,Dex能抑制MS Th1类细胞因子IFN-γ,恢复其两类细胞因子之间的平衡而对MS患者产生治疗作用。     

瘦素对MS患者外周血单个核细胞分泌细胞因子影响的研究

目的探讨外源性瘦素(leptin)对多发性硬化(MS)患者外周血单个核细胞分泌细胞因子的影响。方法采集31例活动期MS患者、22例缓解期MS患者和40名健康对照者外周静脉血,常规制备外周血单个核细胞(PBMC)悬液,分别在leptin、植物血凝素(phytohemagglutinin,PHA)l、eptin PHA的不同刺激条件下培养,72 h后收集培养上清液,于-20℃冻存,批量进行IL-4、INF-γ检测。结果活动期MS患者PBMC在leptin、PHAl、eptin PHA干预下其培养上清液INF-γI、L-4水平均明显高于缓解期MS组和对照组(均为P<0.01)。活动期MS患者PBMC在leptinl、eptin PHA干预下培养上清液INF-γ水平显著高于PHA干预培养上清液(P<0.01),而IL-4水平却明显降低(P<0.01)。干预条件对缓解期MS组和对照组培养上清液细胞因子水平无明显影响(P>0.05)。结论leptin能够影响MS患者PBMC分泌细胞因子,增加炎性细胞因子产生,抑制抗炎性细胞因子分泌,这可能与leptin增加MS的易感性相关。     

地塞米松对MS的IFN-γ及IL-10分泌性T细胞的影响

目的　检测多发性硬化 (MS)患者外周血单个核细胞在地塞米松 (Dex)影响下的 IFN- γ和 IL- 10的分泌细胞水平。方法　采用酶联免疫斑点技术 (EL ISPOT)检测体外培养的外周血单个核细胞 (MNC)在 CNS髓鞘素抗原 MBP刺激下的地塞米松对照试验 ,检测 IFN -γ和 IL - 10分泌性 T细胞水平 ,并与其他神经疾病 (OND)组及健康对照组的检测结果进行对比。结果　显示 MS患者 IFN- γ分泌细胞水平高于对照组 ,Dex使 MS患者 IFN- γ分泌细胞减少 ,对 IL- 10分泌细胞无明显影响。结论　MS患者存在 Th1/ Th2细胞因子的失衡 ,Dex能抑制 MS Th1类细胞因子 IFN- γ,其治疗作用可能与此有关。     

阿托伐他汀对实验性变态反应性脑脊髓炎T辅助细胞功能的影响

目的探讨阿托伐他汀对实验性变态反应性脑脊髓炎(EAE)豚鼠T辅助细胞功能的影响,探讨阿托伐他汀对EAE发病保护作用的免疫调节机制。方法皮下注射粗制碱性髓鞘蛋白(MBP)建立EAE模型。40只豚鼠分成4组:正常对照组、EAE对照组、EAE低剂量组和EAE高剂量组,每组10只,雌雄各半。ELISA法测定EAE发病高峰期外周血单个核细胞培养上清液的细胞因子INF-γ、IL-4水平。结果EAE对照组IL-4浓度低于正常对照组(P<0.01),EAE高、低剂量组IL-4浓度高于EAE对照组(P<0.01),EAE高剂量组IL-4浓度比EAE低剂量组高(P<0.01)。EAE对照组IFN-γ浓度高于正常对照组(P<0.01),EAE高、低剂量组IFN-γ浓度低于EAE对照组(P<0.01),EAE高剂量IFN-γ浓度比EAE低剂量组低(P<0.01)。结论EAE豚鼠存在Th1细胞的过度活化、Th2细胞分泌活性降低;阿托伐他汀能具有抑制Th1细胞活性、提高Th2细胞分泌能力,具有调节Th1/Th2失衡作用。     

甲基强的松龙治疗实验性变态反应性脑脊髓炎的作用机制

目的:研究细胞因子、T细胞凋亡和淋巴细胞增殖在实验性变态反应性脑脊髓炎(EAE)形成中的作用及甲基强的松龙(MP)治疗EAE的作用机制。方法:采用人脑纯化的髓鞘碱性蛋白(MBP)与完全福氏佐剂免疫Lewis大鼠,建立EAE动物模型。用双抗体夹心ELISA法检测各组大鼠血清中IL-10、TNF-α、IFN-γ的含量:流式细胞仪检测外周血T细胞凋亡;3H-TdR释放法检测外周血淋巴细胞转化率。结果:与对照组比较,EAE组的外周血IFN-γ、TNF-α水平明显增高,IL-10水平明显降低,MP治疗后IFN-γ和TNF-α水平下降,IL-10浓度上调。MP还诱导外周血T细胞凋亡和抑制MBP致敏淋巴细胞增殖并呈剂量依赖性。结论:应用人MBP成功建立EAE大鼠模型,MP可能通过调节Th细胞因子格局、促进Th2细胞因子分泌、抑制MBP致敏淋巴细胞增殖及外周血T细胞凋亡而发挥治疗多发性硬化的作用。     

脑梗死髓鞘蛋白反应性IFN-γ的动态检测

目的了解脑梗死急性期和急性期后体内髓鞘蛋白反应性T淋巴细胞增殖的情况.方法用免疫酶点方法检测脑梗死发病后连续两个阶段外周血特异性MBP反应性IFN-γ酶点数.结果两个阶段酶点数均高于对照抗原,两个阶段之间差异无显著性.结论脑梗死后其外周血中髓鞘蛋白反应性T淋巴细胞增殖持续时间较长,这种现象可能代表与脑组织损伤或再生有关的免疫防御机制.     

病毒分子模拟介导多发性硬化发病机制的初步分析

目的 研究多发性硬化(MS)患者所具有的与人类疱疹病毒6型(HHV-6)病毒/人类疱疹病毒4型病毒(EBV)和髓鞘碱性蛋白(MBP)发生交叉反应的CD4+/CD8+T细胞,以及MS患者血清和脑脊液中MBP和抗病毒抗体表达状况,探讨MS发病与HHV-6/EBV感染的关系.方法 通过氚标记胸腺嘧啶核苷(3HTdR)掺人实验分析HHV-6/EBV病毒肽和MBP肽段诱导的MS患者CD4+和CD8+T细胞的应答反应,以高灵敏ELISA试剂盒检测MS患者脑脊液和血清中抗HHV-6/EBV抗体水平,并以引物序列特异的PCR(SSPPCR)技术分析MS患者HLA-II类分子DRBl的表达格局.结果 (1)MS患者HLA-Ⅱ类分子DRBl 04基因(41.7%)与健康对照组(18.7%)相比具有较高的检出率,但差异无统计学意义(P>0.05).(2)MS患者血清中存在高水平抗HHV-6抗体,同时亦可检测出抗EBV壳蛋白抗原(VCA)IgG抗体和EBV核抗原-1(EBNA-1)的IgG抗体.(3)3H-TdR掺入实验结果表明,MS患者的CD4+T细胞或CD8+T细胞对自身MBP肽段及合成的HHV-6/EBV肽段的诱导作用均存在交叉反应.结论 HHV-6/EBV与MS患者MBP自身抗原存在结构上的同源性.该同源性可诱发MS患者自身反应性CD4+/CD8+T细胞活化而导致MS患者免疫损伤,可能是MS的发病机制之一.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.