A Neuropharmacological Evaluation of Felbamate as a Novel Anticonvulsant

Felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM) was subjected to a series of carefully selected in vivo and in vitro tests to provide additional insight into mechanism of action, margin of safety, and clinical potential. FBM was effective against intracerebroventricular (i.c.v.) N-methyl-D-aspartate (NMDA)-induced clonus and i.c.v. NMDA- and quisqualic acid (quis)-induced forelimb tonic extension in mice and ineffective against i.c.v. quis-induced clonus in mice. FBM was also effective in preventing the expression of Stage 5 kindled seizures in corneal-kindled rats. The calculated protective indices (rotorod median toxic dose divided by anticonvulsant median effective dose) ranged from 28 to 146 for those tests in which FBM displayed activity. With the in vitro tests, FBM did not significantly displace [3H]MK-801 from its binding site. In contrast, FBM was effective in blocking sustained repetitive firing in mouse spinal cord neurons grown in tissue culture (median inhibitory concentration 67 micrograms/ml). This effect on repetitive firing suggests indirectly that FBM modulates sodium channel conductance. The results, when compared to similar data for phenytoin, carbamazepine, valproate, and ethosuximide, support the concept that FBM is a relatively nontoxic agent with a unique profile of anticonvulsant action, a broad margin of safety, and a clinical potential that includes at least generalized tonic-clonic and complex partial seizures.     

工业毒物与肝脏混合功能氧化酶的相互影响

为探讨工业毒物与肝脏混合功能氧化酶（ＭＦＯ）的相互影响规律，从中寻找对人体影响的监测依据，进行了实验研究与现场研究。结果发现：在各种实验染毒条件下，不同毒物可导致ＭＦＯ活力的多样化改变：诱导或抑制、单相或双相反应等，毒物毒性可随之改变；ＭＦＯ还参与多种毒物代谢，与多种肝毒机制有关，如脂质过氧化作用、肾上腺皮质功能改变及肝细胞大分子共价结合作用等，其中人体ＭＦＯ对毒物的反应规律，有望提供肝脏毒物对人体影响的监测指标。     

大学生应对方式的若干影响因素研究

目的：探讨大学生所采用的应对方式的影响因素。方法：运用应对方式问卷、SCL－90、父母养育方式问卷、16PF和多维度－多归因因果量表对182名大学生进行测试，在SPSS支持下作相关分析和多元逐步回归分析。结果：大学生所采用的心理健康密切相关的应对方式受父母养育方式、个性特质和心理控制源的影响。结论：在大学生心理卫生工作中应加强健康个性的培养和内控性归因指导，此外，还应重视对父母进行养育方式的指导。     

Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.

We describe a family with adult neuronal ceroid lipofuscinosis, with apparent autosomal dominant inheritance, observed in six affected individuals in three generations. Disease onset was usually in the fifth decade, but was earlier in the youngest generation. Early symptoms consisted of myoclonus in face and arms, epilepsy, auditory symptoms, cognitive decline, or depression. Parkinsonism occurred a few years after disease onset, with stooped posture, shuffling gait, bradykinesia, and mask face. Four subjects deteriorated to a state of severe handicap, with severe dementia, contractures, dysphagia, and dysarthria. Leg weakness evolved to flaccid paraparesis in two patients. Diagnosis was confirmed by brain biopsy in one patient and full autopsy in two patients. Abundant intraneuronal storage of autofluorescent material was found throughout the brain. Electron microscopy showed granular osmiophilic deposits and scarce fingerprint profiles. Striking loss of neurons in the substantia nigra pars compacta and reticulata was found. (123)I-IBZM Single photon emission computed tomography in two patients showed loss of postsynaptic D2 receptor binding in the striatum. We conclude that parkinsonism in ANCL is likely to be caused by both presynaptic nigral cell loss and postsynaptic striatal degeneration.     

Multiple system atrophy: α‐synuclein and neuronal degeneration

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy–Drager syndrome (SDS). The histopathological hallmark is the formation of α‐synuclein‐positive glial cytoplasmic inclusions (GCIs) in oligodendroglia. α‐synuclein aggregation is also found in glial nuclear inclusions, neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurites. We evaluated the pathological features of 102 MSA cases, and presented the pathological spectrum of MSA and initial features of α‐synuclein accumulation. We found that 39% of the 102 cases showed equivalent SND and OPCA pathologies, 33% showed OPCA‐ and 22% showed SND‐predominant pathology, whereas 6% showed extremely mild changes. Our pathological analysis indicated that OPCA‐type was relatively more frequent and SND‐type was less frequent in Japanese MSA cases, compared to the relatively high frequency of SND‐type in Western countries, suggesting that different phenotypic patterns of MSA may exist between races. In the early stage, in addition to GCIs, NNIs and diffuse homogenous α‐synuclein staining in neuronal nuclei and cytoplasm were observed in lesions in the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic spinal cord, lower motor neurons and cortical pyramidal neurons. A subgroup of MSA cases with severe temporal atrophy showed numerous NCIs, particularly in the limbic system. These findings suggest that primary non‐fibrillar and fibrillar α‐synuclein aggregation also occur in neurons. The oligo‐myelin‐axon‐neuron complex mechanism, along with the direct involvement of neurons themselves, may synergistically accelerate the degenerative process of MSA.     

神经元移行异常与癫痫

目的：探讨常见神经元移行异常的MRI表现与临床症状。资料与方法：搜集14例各种神经元移行异常的病例，分析其MRI表现与相应临床症状。结果：14例神经元移行异常者中灰质异位9例，其中皮层下灰质异位1例，皮层下带状灰质异位1例，室管膜下灰质异位7例；无脑回－巨脑回畸形5例，其中弥漫性4例，局限性1例。各种神经元移行异常病变的临床症状以癫痫最常见，临床表现一般与病变的范围和位置有关。结论：神经元移行异常虽然并不常见，但在癫痫的病因中起重要的作用，应引起人们的重视。     

Psychosocial Factors in the Use of Smokeless Tobacco and Their Implications for P.L. 99-252

This article briefly reviews the prevalence of smokeless tobacco use by males in the United States, the relationship of smokeless tobacco use to cigarette use, and patterns of use that include dosage, topography, products, and function of use. The primary focus of the article is to describe the concurrent and predictive factors associated with onset, use, and cessation of smokeless tobacco. The implications of P.L. 99-252, the Comprehensive Smokeless Tobacco Act of 1986, are discussed in the context of what is known about the psychosocial variables associated with the use of smokeless tobacco.     

Expression of transfected genes by differentiated, postmitotic neurons and photoreceptors in primary cell cultures

We report here that differentiated, primary, postmitotic neurons and photoreceptors in cultures obtained from embryonic chicks can express foreign genes after transfection by the calcium phosphate method. A variety of viral promoters were tested by using either beta-galactosidase or chloramphenicol acetyltransferase as reporter genes. Histochemical and immunocytochemical analysis showed beta-galactosidase expression by both neurons and photoreceptors. As commonly observed with dividing cells, transfection efficiencies showed inter-experimental variability, with efficiencies ranging from 2% to 20% using the same plasmid. On the other hand, intra-experimental variability between replicate dishes was much smaller. Analysis using the highly sensitive enzymatic assay for chloramphenicol acetyl transferase (CAT) showed that all of the promoter/enhancers-CAT constructs tested, with the exception of a construct containing the Maloney sarcoma virus promoter, led to the expression of detectable activity when transfected into cultured retinal cells. The calcium phosphate treatment used for cell transfection did not show detectable effects on overall cell survival, although it caused selective decreases in some metabolic activities of the cells. The studies demonstrate that it is possible to obtain expression of genes transfected into primary, postmitotic neuronal cells.     

两个地理株周期型马来丝虫成虫蛋白和同工酶电泳比较分析

本文应用圆盘电泳对我国湖北谷城和浙江安吉两个地理株的周期型马来丝虫成虫的蛋白和七种酶进行了区带分析和比较,结果显示两个株的蛋白、GPI、PGM 和 PO 同工酶电泳型没有差异;而 MDH 的同工酶电泳型则不相同,出现了两种类型;G_6PD、EST 和 LDH 则没有区带出现。