三氧化二砷脂质体治疗大鼠_6脑胶质瘤的实验研究

目的研究三氧化二砷(As_2O_3)脂质体对荷瘤大鼠血脑屏障(BBB)的透过率及其对大鼠脑胶质瘤的生长抑制作用。方法应用超声薄膜分散法制备As_2O_3脂质体,检测其包封率;建立大鼠脑胶质瘤模型,分别给予As_2O_3脂质体和As_2O_3,应用原子荧光法检测给药后大鼠脑组织中的砷浓度,以判定其对血脑屏障的透过性,并与给予生理盐水的对照组相比,从电镜、TUNNEL、MRI影像及大鼠的生存状态等方面研究As_2O_3脂质体对C_6胶质瘤的影响。结果 As_2O_3脂质体组砷的血脑屏障透过性明显提高,电镜及TUNEL法检测示肿瘤细胞凋亡率(20.03%)高于其他2组(3.92%、4.09%);大鼠中位生存时间(70d)优于生理盐水组(21d)和As_2O_3组(23d)。结论 As_2O_3脂质体可以明显提高鼠脑内As_2O_3浓度,并能诱导胶质瘤细胞的凋亡,抑制大鼠脑胶质瘤的生长,从而延长荷瘤大鼠的生存时间。     

冷冻治疗大鼠C6脑胶质瘤的实验研究

目的研究冷冻治疗对大鼠C6脑胶质瘤的增殖抑制作用及其机制。方法建立大鼠C6脑胶质瘤模型，60只载瘤大鼠随机均分为对照组和治疗组。治疗组实施冷冻治疗后免疫组化检测P27Kipl蛋白的表达，磁共振检测肿瘤体积变化，并观察动物生存期。对照组未实施冷冻治疗。结果与对照组比较，冷冻治疗可上调P27Kip1蛋白的表达，对照组为（4.81±0.72）％，治疗组为（28.84±3.56）％，P〈0.05；缩小肿瘤体积，对照组为（292.97±19.13）mm^3，治疗组为（76.37±10.22）mm^3，P〈0.05；延长动物生存期，对照组为（37.00±1.55）d。治疗组为（57.00±3.16）d，P〈0.05。P27Kip1蛋白阳性表达率和荷瘤鼠生存期呈正相关（r=0.836，P〈0.05）；同体积呈负相关（r=-0.696，P〈0.05）。结论冷冻治疗可抑制大鼠C6脑胶质瘤的增殖，延长动物生存期，其机制同上调P27Kip1蛋白的表达有关。     

三氧化二砷诱导9L胶质瘤细胞凋亡的实验研究

目的研究三氧化二砷（As2O3）对鼠胶质瘤生长的影响及其机制。方法应用不同浓度As2O3,分别处理9L胶质瘤细胞株不同时间,采用四甲基噻唑蓝比色（MTT）法观察As2O3对9L胶质瘤细胞生长的影响,以透射电镜、Hoechst 33342/PI双染荧光及流式细胞仪检测9L胶质瘤细胞凋亡。结果不同浓度的As2O3均可显著抑制9L胶质瘤细胞株的生长。As2O3作用可引起9L胶质瘤细胞的凋亡,且随As2O3浓度的增大和作用时间的延长,9L胶质瘤细胞的凋亡率明显上升。结论As2O3在体外可显著抑制9L胶质瘤细胞生长,其机制与诱导肿瘤细胞凋亡有关,且其凋亡率随As2O3作用的时间延长和剂量的增加而增加。     

三氧化二砷对正常星形胶质细胞的影响

本实验研究了三氧化二砷(As2O3)对大鼠正常神经胶质细胞的生长抑制作用,并与其对9L胶质瘤细胞的抑制作用进行对比,以明确As3O3在诱导9L胶质瘤细胞凋亡的同时,是否会对正常神经细胞产生影响,从而为临床应用As2O3治疗脑胶质瘤提供实验依据.     

反义AKT2 cDNA治疗C6胶质瘤的体内外实验研究

目的研究反义AKT2(antisense AKT2，AS—AKT2)cDNA对鼠脑胶质瘤细胞系C6的生长抑制作用。方法将AS—AKT2 cDNA构建体转染鼠脑胶质瘤细胞系C6，原位杂交和蛋白印迹鉴定后，应用PCNA阳性率和MTT法检测细胞增殖能力，TUNEL法计算凋亡指数。应用立体定向技术将C6细胞和转染反义AKT2 cDNA的C6细胞种植到SD大鼠的右侧尾状核作为对照组和转染组；并对颅内已经形成C6胶质瘤的大鼠进行脂质体包裹的AS—AKT2 cDNA和空载体治疗；MRI动态监测大鼠颅内肿瘤生长情况，并检测标本AKT2和PCNA表达以及细胞的凋亡情况。结果转染AS—AKT2 cDNA后C6细胞AKT2表达显著抑制，增殖减慢，凋亡指数增加。反义治疗组和转染组大鼠生存时间明显延长；转染组和治疗组肿瘤标本AKT2表达下降或消失，PCNA阳性率降低，可见大量凋亡细胞，而对照组和空载组标本几乎没有凋亡细胞。结论体内外实验证明AS—AKT2 cDNA可以抑制肿瘤细胞增殖、诱导凋亡，AKT2可作为基因治疗胶质瘤的重要优选靶的。     

三氧化二砷诱导C6胶质瘤细胞凋亡实验研究

目的：研究三氧化二砷（As2O3）在体外是否具有抗鼠胶质瘤作用,并对其作用机制进行初步探讨。方法：应用不同浓度As2O3,且在不同时间点分别处理C6胶质瘤细胞株及原代培养的正常鼠神经胶质细胞,采用甲基噻唑基四唑（MTT）法,观察As2O3对C6胶质瘤细胞株及正常鼠神经胶质细胞生长的影响,以透射电镜、Hoechst33342和碘化丙啶（PI）双重荧光染色检测两种细胞凋亡的形态变化,并用异硫氰酸荧光素（FITC）标记的Annexin-V和PI双标记法通过流式细胞仪检测细胞凋亡率。结果：MTT法发现,As2O30.5～8.0μmol/L的浓度均可显著抑制C6胶质瘤细胞株的生长,而对正常原代神经胶质细胞株的抑制作用较弱。经As2O3作用后,透射电镜、Hoechst33342/PI双染荧光均观察到C6胶质瘤细胞发生了显著的凋亡形态改变;运用Annexin-V-FITC/PI双标记法在流式细胞仪检测显示,随As2O3浓度的增大和时间的延长,C6胶质瘤细胞株的凋亡率明显上升,而正常神经胶质细胞的凋亡率要明显小于C6胶质瘤细胞株。结论：As2O3在体外可显著抑制C6胶质瘤细胞株生长,其机制与诱导肿瘤细胞凋亡有关,且凋亡率随As2O3作用的时间和剂量的增加而增加。但As2O3对正常神经胶质细胞生长的抑制作用较弱,提示As2O3抑制细胞生长的作用具有一定的选择性。     

放线菌素D和VM-26对大鼠胶质瘤细胞增殖的影响的体内实验研究

目的研究放线菌素D(ACTD)、替尼泊甙(VM-26)对大鼠胶质瘤细胞增殖的体内治疗效果。方法将C6大鼠胶质瘤细胞接种于鼠脑右侧尾状核,并对鼠脑内已形成的C6胶质瘤分别用ACTD及VM-26抗瘤缓释剂瘤区原位注射。观察大鼠的一般情况、生存期、肿瘤病理学和磁共振成像(MRI)动态改变,采用PCNA计数、TUNEL法检测肿瘤细胞增殖活性及凋亡。结果对照组及空载组大鼠平均生存期为19.3d,ACTD组6只及VM-26组3只大鼠生存期明显延长,存活期超过200d;除因病理检查人为处死各2只外,ACTD组治疗后4周内死亡2只,VM-26组5只。MRI检查对照组脑内有明显瘤灶,治疗组脑内瘤灶治疗后明显减少或消失,治疗组C6细胞增殖活性降低,大量细胞凋亡,ACTD组较VM-26组显著。结论ACTD可望成为体内局部应用治疗胶质瘤的优选化疗药物。     

三氧化二砷对人脑SHG-44胶质瘤细胞作用的体外实验研究

目的 探讨三氧化二砷(As2O3)对人脑SHG-44胶质瘤细胞株的增殖抑制及诱导凋亡机制.方法 将不同浓度的As2O3与体外培养的SHG-44胶质瘤细胞相互作用后,采用MTT比色法检测As2O3对胶质瘤细胞的增殖抑制;倒置显微镜、荧光显微镜下观察吉姆萨及Hochest33258染色后细胞凋亡的形态学改变;流式细胞仪检测细胞凋亡及对SHG-44胶质瘤细胞周期影响.结果 MTT比色法检测到As2O3对SHG-44胶质瘤细胞增殖具有明显的抑制作用,并呈剂量依赖性和时间依赖性;倒置显微镜及荧光显微镜下可观察到给药组细胞生长密度低以及出现细胞凋亡的特征性改变;流式细胞仪检测到给药组细胞凋亡比率明显高于空白对照组(P＜0.05),并具有剂量依赖性及时间依赖性,同时将胶质瘤细胞阻滞在S期,抑制了细胞周期的进程.结论 As2O3对SHG-44胶质瘤细胞增殖具有明显的抑制作用、可诱导SHG-44胶质瘤细胞的凋亡,并抑制细胞周期进程.     

二氮嗪对大鼠脑缺血再灌注细胞凋亡的影响

目的研究二氮嗪开放线粒体ATP敏感性钾通道对大鼠脑缺血再灌注细胞凋亡的影响。方法采用线栓法建立大鼠局灶性脑缺血再灌注损伤模型,将20只大鼠随机分成4组,假手术组、缺血组、缺血＋二氮嗪治疗组和缺血＋二氮嚷＋MitoK（ATP）通道特异性抑制剂5-HD组。观察各组凋亡细胞数和凋亡相关蛋白Bcl-2、Bax的变化。结果与缺血组比较,二氮嗪使凋亡细胞数明显减少（83．2±9．04 vs 123．96±13．45）,Bcl-2表达增高（0．17±0．01 vs 0．13±0．01）,Bax表达下降（0．15±0．02 vs 0．20±0．03）,差异具有显著性（P＜0．05）。5-HD能取消这些作用（P＜0．05）。结论局灶性脑缺血再灌注损伤时,二氮嗪能通过上调半暗带区Bcl-2蛋白表达,下调Bax蛋白表达,减少神经元凋亡,对脑缺血损伤起保护作用。     

局灶性脑缺血对细胞周期蛋白D1/CDK4基因表达的影响

目的观察脑缺血后细胞周期蛋白（cyclin）D1和它的酶CDK4基因表达，以及这种表达的改变是否影响神经细胞凋亡。方法成年雄性SD大鼠32只随机分为假手术组（n=4）和实验组（n=28），实验组再进一步分为7个亚组（再灌注2h，6h，12h，1d，3d，7d和14d，每组n=4）。应用线栓法建立SD大鼠大脑中动脉阻塞／再灌注模型．TUNEL法检测神经细胞凋亡。原位杂交检测cyclinD1和CDK4mRNA的表达。结果CyclinD1mRNA和CDK4mRNA的表达与凋亡细胞的区域基本相同。再灌注2h脑组织即开始出现神经细胞凋亡，并于1d分别在皮层区和纹状体区达高峰（分别为72．80±4．66和87．75±0．85）。神经细胞cyclinD1mRNA和CDK4mRNA的表达分别于再灌注2h和6h开始逐渐增强，并于12h和1d达高峰（皮质区分别为94．50±2．75和85．75±3．73，纹状体区分别为88．25±5．06和89．80±2．93）。结论CyclinD1和CDK4选择性地在形态学完整或已经有改变的缺血侧神经元和少突胶质细胞内表达。CyclinD1／CD1（4mRNA表达可能是诱导细胞凋亡的重要因素之一。     

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.     

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.     

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.     

Clobazam for Treatment of Intractable Epilepsy: A Critical Assessment

Summary: Clobazam (CLB), a 1,5-benzodiazepine, is a remarkably effective add-on drug for individual patients with refractory partial epilepsy. CLB has an excellent safety record. As with all benzodiazepines used for treating epilepsy, sedation and withdrawal effects, together with the development of tolerance, limit its usefulness. Recent efforts to prevent or reverse tolerance with intermittent administration of CLB or periodic injection of a benzodiazepine antagonist, flumazenil, are encouraging and justify further investigations.     

La passion de Torquemada et le terrorisme islamique : quelques points de comparaison

This original research compares the doctrinal, psychopathological and operational standpoints of the 15th century Spanish Inquisition (Torquemada) with those of radical Islamism from 1988 to 2005 (Al-Qaeda). The following are reviewed: (a) the main texts codifying the procedure for conducting the criminal investigation of a Holy Office trial (Directorium inquisitorum); (b) the life and work of the grand inquisitor Tomás de Torquemada (1420–1498); (c) the psychopathological relations between passion (passionate psychoses, passionate idealism, paranoid personality) and fanaticism; (d) “the madmen, the enlightened and the criminals” of Islamic terrorism; (e) the cognitive and emotional motives for engagement in the jihadist radicalization of young people; (f) the common principles of monotheistic fanaticism (Inquisition, Al-Qaeda) and the particular dogmas of Islamic terrorism in our time; (g) the operating modes of the Inquisition and the Jihadist holy war. The author concludes that the rigour and seriousness of the inquisitorial judicial procedure, which was precise, individual and personalized, contrasts with the revolutionary pamphlets of Al-Qaeda, which only provide broad guidelines for the modus operandi of the fight against infidels, who are usually random victims.     

Claustration et collectionnisme : réflexions à propos d’un cas de syndrome de Diogène avec vols kleptomaniaques et vengeurs

Social withdrawal is a pathognomonic behaviour that is consistently associated with mental illnesses. Compulsive hoarding can also be interpreted as a pathological behaviour, even when it does not involve kleptomania. Diogenes syndrome (DS) was first described in 1975, and is characterized by both behaviours - social withdrawal and compulsive hoarding. Even though it is often the manifestation of a psychiatric condition, its aetiology is diverse. The most frequent ones are however: dementia, schizophrenia and mental retardation. In this study, we describe an atypical case presenting with DS. Il consists of a young man, seen in a forensic setting, who had been diagnosed with kleptomania in the past, presents with compulsive hoarding, and whose recent thefts were fuelled by revenge. Finally, to our knowledge, the way social withdrawal is viewed is seldom taken into account. We analyse its implication on social withdrawal.     

Neurological soft signs and schizophrenia: a review of current knowledge

Schizophrenia is a frequent and disabling disorder emerging during adolescence or early adulthood. The identification of underlying processes has been hampered by the complex clinical expression and the probable etiological heterogeneity. The frequency of neurological soft signs (NSS) in patients with schizophrenia and their presence early in life (during the first two years) in high risk subjects support the hypothesis that schizophrenia is a "brain disease" reflecting pre- or perinatal insults during development. The growing interest for NSS has lead to multiple studies that are often difficult to compare. The objective of this review is to summarize the current knowledge on NSS, methodological issues and the future perspectives.     

Lacan, lecteur de Minkowski : l'approche structurale

The notion of structure occupies a predominant place in the theory of Lacan. He indicates that was developed from the work of Minkowski. In fact, through his phenomeno-structural approach, Minkowski does not limit himself to purely observable phenomena, but attempts to determine the underlying structure. He refers to the comprehensive phenomenology and psychopathology, and this method provides him with clinical finesse and another means of determining a diagnosis. Thus Lacan has used this as a basis for his approach to structure to develop a theory regarding the individual. This implies that the structure of the individual is based on his relation to language. From this concept, he then develops the clinical structures of neurosis, psychosis, and perversion. These structural landmarks also have an effect on the course of treatment.