Brivaracetam: a new drug in development for epilepsy and neuropathic pain

Background: Epilepsy is a neurological disorder with a worldwide prevalence estimated to be 0.5 – 1.0% of the population. Many potent antiepileptic drugs (AED) have been used for treatment but still about 30% of patients are resistant to current AEDs. Some AEDs are also used for the treatment of neuropathic pain. Objective: The aim of this report is to present preclinical and clinical studies of brivaracetam (UCB-34714), a new drug developed by UCB Pharma. Methods: Published results of preclinical studies in several animal models of epilepsy, neuropathic pain, essential tremor and results of Phase I and II evaluations of brivaracetam have been analysed. Results/conclusion: Brivaracetam represents a new mechanism of action being a ligand of synaptic vesicle protein 2A. It is undergoing Phase III evaluation after a successful Phase II programme in which was effective as an adjunctive treatment in partial-onset epilepsy (50 mg/day). It is well tolerated, without serious adverse side effects.     

SV_(40)LT抗原基因肝细胞——理想的肝细胞来源

目的制备并初步评估一种理想的肝细胞来源—SV40LT抗原基因永生化肝细胞。方法将SV40LT抗原基因在逆转录病毒介导下转入原代培养的大鼠肝细胞,获得能在体外增殖的肝细胞。通过绘制生长曲线了解转染肝细胞的体外生长特性,细胞冻存复苏试验评估转染肝细胞的冻存价值并与原代肝细胞和大鼠肝癌细胞CBRH7919比较。结果SV40LT抗原基因转入原代培养的大鼠肝细胞能在体外增殖。SV40LT抗原基因转染肝细胞比原代肝细胞生长速度快(P<0.05),与肿瘤细胞相比生长曲线差异无显著性(P>0.05)。复苏后冻存的SV40LT抗原转染的肝细胞的细胞活率为(74±4)%,原代肝细胞的细胞活率为(72±6)%。两者差异无显著性(P>0.05)。结论肝细胞经SV40LT抗原基因转染后获得永生化特性,冻存复苏后获得满意的细胞活率,是一种理想的肝细胞来源。     

Immortalized chromaffin cells disimmortalized with Cre/lox site-directed recombination for use in cell therapy for pain after partial nerve injury

To prepare immortalized adrenal chromaffin cells for eventual clinical use, the immortalizing oncogene must be removed. We have utilized a Cre-mediated excision of a loxP-flanked Tag sequence to test whether immortalized chromaffin cells could be disimmortalized by this method. Cultures of embryonic rat adrenal cells were immortalized with the tsA-TN retroviral vector encoding the loxP-flanked temperature-sensitive allele of SV40 large T antigen (tsA-TN) and a positive/negative neo/HSV-TK sequence for selection with either G418 or gancyclovir, respectively. These cells were then infected with the 1710-CrePR1 bicistronic retroviral vector coding for a form of Cre modulatable by the synthetic steroid RU486. These immortalized loxTsTag/CrePR1/RAD cells expressed immunoreactivities (ir) for all the catecholamine enzymes: tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), and phenylethanolamine-N-methyltransferase (PNMT). After initial incubation at 37 degrees C with RU486 for 3 days, followed by the addition of gancyclovir for 7 days, Tag-ir was not detectable in most of the surviving chromaffin cells, compared to 100% expression in immortalized loxTsTag/CreR1/RAD cells not treated with RU486 and gancyclovir. The expression of TH, DbetaH, and PNMT was increased after disimmortalization and the ability of disimmortalized cells to synthesize norepinephrine was also significantly increased compared to immortalized cells. When both types of chromaffin cells were transplanted in a model of neuropathic pain and partial nerve injury, both cell grafts were equally able to reverse the behavioral hypersensitivity induced by the injury. The use of Cre/lox site-directed disimmortalization of chromaffin cells that are able to deliver neuroactive molecules offers a novel approach to cell therapy.     

应用神经网络和遗传算法优化利福霉素B发酵培养基

对培养基进行优化时，会获得大量的实验数据，但这些实验数据往往不能被进一步利用。如果使用一些不同的方法对历史数据进一步挖掘就可能得出额外的规律。本文使用神经网络对历史数据进行处理，得到了利福霉素B培养基成份和发酵效价之间的关系；再以这个关系作为遗传算法的适应度函数，在一个相对大的空间内快速搜索最优解。优化的培养基使摇瓶发酵效价提高了17．9％，说明所建立的模型能够实现培养基优化的目的并具有数据挖掘的功能。     

耳穴贴压配合丹栀逍遥散治疗视神经萎缩

目的：观察治疗视神经萎缩的临床疗效。方法；对用耳穴贴压法配合丹栀逍遥散内服治疗组51例（58眼）和单纯服用西药对照组43例（49眼）的视力，视野进行观察，共3个疗程。结果：视力变化，治疗组有效率79．3％，对照组44．9％，视野变化，治疗组有效率59．2％，对照组22．6％，治疗组疗效优于对照组。结论：耳穴贴压配合丹栀逍遥散内服对增进视力，改善视功能有较好的作用。     

耳穴疗法在Doula式分娩中的应用

目的：探讨帮助产妇安全顺利分娩，减轻宫缩痛，减少产后出血量的方法，方法：将60例产妇随机分为治疗组与对照组各30例，治疗组采用耳穴贴压法，在子宫，神门，下腹等耳穴上用电刺激后，再贴压王不留行籽，同时对产妇实行一对一护理，采用Doula式分娩照顾，对照组只采用Doula式分娩照顾，结果：采用耳穴贴压方法止痛效果好，产程明显缩短，产后出血量少（P＜0．01），结论：耳穴贴压法有助于产妇安全顺利分娩。     

Unitary giant synapses embracing a single neuron at the convergent site of time-coding pathways of an electric fish, Gymnarchus niloticus

Phase-locking neurons in the electrosensory lateral line lobe (ELL) of a weakly electric fish, Gymnarchus niloticus, fire an action potential in response to each cycle of the sinusoidal electrosensory signal (350-500 Hz) created by the fish's own electric organ. The exact firing times of the phase-locking neurons are altered (time-shifted) by capacitance of electrolocation objects or by electric organ discharges of other individuals. The magnitude of the time shifts depends on the location of the neurons' receptive field on the skin; thus, time disparities arise between the firing of phase-locking neurons. To compute these disparities, there should be a site where these phase-locking neurons converge. In this study we morphologically identified a novel cell type, which we named the "ovoidal cell", that receives the convergent projections of phase-locking neurons in the inner cell layer (ICL) of the ELL. We labeled these neurons with biocytin and examined them by light and electron microscopy. The giant cells and the S-type primary afferents, two types of phase-locking neurons, respectively terminate on the soma via chemical synapses and on the dendrite of the ovoidal cells via mixed synapses. Each terminal of the giant cells embraces the soma of an ovoidal cell, covering as much as 84% of the somatic membrane. The giant cell terminals and ovoidal cell somata were immunoreactive to SV2, a synaptic vesicle protein, but the S-afferent terminals were not, even though they contain numerous synaptic vesicles. The dendrite of the ovoidal cells also contacts the pyramidal cells of the ICL, which are known to be sensitive to time disparities. The anatomical connections of the phase-locking neurons to the ovoidal cells strongly suggest that they are involved in computing time disparity.