大鼠脑胶质瘤细胞温热治疗的观察分析

目的温热疗法对大鼠脑胶质瘤细胞的杀伤效果。方法用Rat glioma cellC6,9L肿瘤细胞,37℃(对照组),42℃,43℃,44 ℃(治疗组)加温1 h,用WST-1 assay方法测定细胞生存率,分析杀肿瘤细胞效果。结果43℃,44℃加温1h,均取得了显著的杀肿瘤细胞效果。结论温热疗法对大鼠脑胶质瘤细胞杀伤效果是可靠的。     

大鼠脑胶质瘤细胞湿热治疗的观察分析

目的 温热疗法对大鼠脑胶质瘤细胞的杀伤效果。方法 用Rat glioma cellC6，9L肿瘤细胞，37℃（对照组），42℃，43℃，44℃（治疗组）加温1h，用WST-1assay方法测定细胞生存率，分析杀肿瘤细胞效果。结果 43℃,44℃加温1h，均取得了显著的杀肿瘤细胞效果。结论 温热疗法对大鼠脑胶质瘤细胞杀伤效果是可靠的。     

温热疗法对人脑胶质瘤细胞杀伤作用研究

目的温热疗法对人胶质瘤细胞的杀伤作用.方法用人胶质瘤细胞NP2, U251,行37℃(对照组),42℃,43℃,44℃(治疗组)加温1 h,用WST-1方法测定细胞生存率,分析肿瘤细胞杀伤效果.结果 43℃,44℃加温1 h,均取得了显著的肿瘤细胞杀伤效果.结论温热疗法作为脑胶质瘤新的临床治疗方法是可行的,可靠的.     

U-251人星形细胞瘤系的体外热化疗试验

目的 探讨热疗、化疗及两者序贯治疗对脑胶质瘤细胞增殖的影响.方法 体外传代培养的人星形细胞瘤系U-251细胞分别通过42℃、44℃高热环境和化疗药物顺铂、鬼臼噻吩甙在37℃恒温箱中孵育1 h;另取星形细胞瘤系U-251细胞同时行热疗和化疗联合应用1 h;再取星形细胞瘤系U-251细胞行序贯治疗,即先用1种处理方法,然后间隔1 h、4h,间隔期间在37℃恒温箱中孵育.治疗后采用MTT法测定肿瘤细胞增殖情况并进行统计学分析.结果 不同温度的热疗和不同种类的化疗药物对肿瘤细胞均可产生有效的杀伤作用,细胞增殖率明显下降.热化疗联合应用较单独应用能明显增加其抗肿瘤的效果,序贯治疗中可见44℃热疗+化疗组、44 ℃热疗后间隔1 h再行化疗组,其抗肿瘤的效果明显强于其他序贯处理组,差异有统计学意义(P＜0.05).结论 热化疗能有效杀伤肿瘤细胞,联合应用具有协同效应.两种治疗措施序贯治疗可见44 ℃高热预处理能提高肿瘤细胞对化疗药物的敏感性,但化疗药物的预处理效果相对较差,故该协同效应的机制可能是由于高热损伤了肿瘤细胞膜结构从而增加了药物的穿透所致.     

局部微波加温程度对裸小鼠脑胶质瘤生长影响的探讨

本文采用44℃、不同的加温时间(10、20、30和40分钟),对移植于裸小鼠的人脑恶性胶质瘤作局部微波加温治疗。通过光镜、甲基-3H 胸腺嘧啶核苷掺入法和观察加温后移植瘤生长曲线变化等方法发现:以44℃、加温20分钟已能达到满意的加温效果,再延长加温时间,并不能明显提高治疗效果。     

人IFN-β基因脂质体转染胶质瘤细胞及对其增殖的抑制作用

目的观察β-干扰素(IFN-β)基因脂质体pSV2IFN-β转染人胶质瘤细胞系SHG44及其对SHG44细胞增殖的影响.方法应用流式细胞仪、酶联免疫吸附试验(ELASA)及细胞免疫组织化学染色法检测脂质体pSV2IFN-β转染后,SHG44细胞IFN-β的表达情况;应用四唑盐比色试验(MTT)检测脂质体pSV2IFN-β转染后转染组与对照组SHG44细胞增殖的差异.结果 IFN-β基因脂质体pSV2IFN-β转染SHG44胶质瘤细胞系后4 d和6 d,对肿瘤细胞具有明显的增殖抑制作用,抑制率分别为16.7%和32.7%.ELASA及流式细胞仪蛋白检测均表明转染后胶质瘤细胞具有显著的IFN-β表达(P<0.01),其中在转染后72 h和96 h,IFN-β表达量分别为(35.4±2.7)U/ml和(40.3±3.2)U/ml.免疫组织细胞化学实验也表明转染后的细胞有明显的IFN-β的表达.结论 IFN-β基因脂质体pSV2IFN-β可转染SHG44胶质瘤细胞系,并对胶质瘤细胞的增殖具有显著的抑制作用.     

外源性IFN—β基因稳定转染对胶质瘤细胞凋亡的影响

目的研究外源性干扰素—β(IFN-β)基因对胶质瘤细胞系SHG-44的诱导凋亡作用，探索胶质瘤基因治疗的新途径。方法利用脂质体转染方法将IFN-β真核表达载体pSV2IFNβ导入人SHG44胶质瘤细胞。应用流式细胞仪和免疫荧光法检测IFN-β基因的稳定转染及表达，利用Hoechst染色、透射电镜观察细胞凋亡情况。结果IFN-β基因成功转染SHG44胶质瘤细胞并得以表达，并诱导SHG44胶质瘤细胞凋亡。结论IFN-β能够诱导入SHG44胶质瘤细胞凋亡，本实验为IFN-β基因治疗人脑胶质瘤的应用奠定了初步基础。     

白藜芦醇抑制SHG-44胶质瘤细胞生长实验研究

目的探讨白藜芦醇(Res)在体外诱导脑胶质瘤SHG-44细胞凋亡并抑制其生长的作用。方法四甲基偶氮唑蓝(MTT)比色法测量不同剂量的Res作用6h、24h和48h后对SHG-44胶质瘤细胞增殖的影响。HE染色、Hoechst33342荧光染色观察细胞形态改变,DNAladder检测细胞DNA裂解情况,流式细胞仪用异硫氰酸荧光素标记的膜联蛋白V(AnnexinV-FITC)和碘化丙啶(PI)双染检测凋亡率,并测定细胞周期的改变。结果Res明显抑制SHG-44细胞的生长和增殖(P<0.01),呈浓度及时间依赖性反应;Res所致的SHG-44胶质瘤细胞凋亡为浓度依赖关系,随着浓度的增高,凋亡更明显。此凋亡细胞周期主要发生G1期比例升高,S、G2期比例降低。结论Res明显抑制SHG-44细胞生长并诱导其发生凋亡和细胞周期改变,为Res用于治疗脑胶质细胞瘤提供了实验依据。     

苯乙酸钠对脑胶质瘤细胞诱导分化的实验研究

目的 用苯乙酸钠（NaPA)在体外处理P-168人胶质瘤细胞，观察其诱导分化治疗效果。并对其作用机制进行初步探讨。方法 对不同浓度NaPA处理后的P-168细胞进行四甲基偶氮唑盐比色法（MTT）分析及流式细胞仪检测，并观察肿瘤细胞的超微结构变化。结果 NaPA能明显抑制人胶质瘤细胞生长。呈现时间，浓度依赖性抑制作用，经流式细胞仪测定发现，NaPA处理的细胞S期为11.99%或13.17%，而未经处理的细胞S期为20.17%。电镜下显示NaPA处理后的胶质瘤细胞中线粒体，内质网，弹力丝丰富，而未经NaPA处理过的肿瘤细胞中有大量游离核糖体。结论 NaPA在体外不仅能够抑制人胶质瘤细胞的生长。而且对肿瘤细胞有明显的诱导分化作用。     

内皮抑素抑制胶质瘤多药耐药细胞株GL15细胞磷酸糖蛋白的表达及其意义

目的 研究内皮抑素对阿霉素(ADM)诱导的大鼠胶质瘤多药耐药细胞株GL15(GL15/ADM)细胞磷酸糖蛋白(P-gp)表达的抑制作用,探讨其对胶质瘤肿瘤耐药的影响.方法 将内皮抑素质粒转染胶质瘤耐药细胞,应用免疫印迹法、荧光分光光度计和流式细胞术分别检测转染后6,12,24,48 h不同时间段P-gp表达水平及天冬氨酸特异性半胱氨酸蛋白酶3(caspase-3)的活性和细胞凋亡率.结果 转染后6 h即可发现P-gp表达水平活性明显降低(P<0.05),且随转染后时间的延长而递减;转染后6h即可发现caspase-3活性明显上升(P<0.05),且随时间的延长而递增;转染后6、12、24、48 h肿瘤细胞凋亡率上升,并与非转染组间有极显著性差异(P<0.01).结论 内皮抑素能通过上调Caspase-3的活性,明显抑制胶质瘤耐药细胞中P-gp表达水平和促进肿瘤细胞凋亡,有助于提高胶质瘤的综合治疗效果.     

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.     

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.     

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.     

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.     

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.