Speech-induced aphasic seizures in epilepsy caused by LGI1 mutation

Summary:  Purpose: Patients with autosomal dominant lateral temporal lobe epilepsy (ADTLE) may have seizures precipitated by sound or speech. We have examined a patient with speech-induced seizures caused by an LGI1 mutation (C46R).
Methods: A clinical study and a video-EEG recording using interrogative speech as the activation procedure was performed in a 23-year-old man.
Results: He had experienced short episodes of sensory aphasia in situations in which he was suddenly verbally addressed. Voices became distorted, and he could not comprehend despite hearing words. The day after a late party, his girlfriend unexpectedly spoke to him. Her speech became unintelligible to him. He did not reply and had a generalized tonic–clonic (GTC) seizure. During an EEG, he was suddenly asked for the names of his siblings. He answered, but lost understanding of the further conversation and described how syllables floated together with an echoing character. With a versive movement to the right, another GTC occurred. In the EEG, rhythmic 6-Hz activity built up in the frontotemporal areas starting on the left side with bilateral and posterior spreading. Postictal slowing was symmetrical, and no aphasia was noted on awakening.
Conclusions: To our knowledge, this is the first video-EEG recorded seizure in LGI1 -caused ADTLE. This peculiar seizure semiology and precipitating effect of speech may serve as a marker for identifying further individuals with this particular phenotype and genotype and may indicate that the LGI1 gene may have a physiologic function connected to the human capacity for speech and language.     

泻下药和解表药的现代药理解释

 目的在中药现代化的进程中,对中医药体系中的传统药效的现代药理学解释是一项有深远意义的工作。本实验设计了3种方法,在总体上对中药的传统药效与中药的现代药理活性进行对比分析,从中发现规律,对被研究的中药药效给出言之有据的解释。方法收集大量中药传统药效、中药现代药理活性和中药所含活性化合物现代药理活性数据,通过统计方法寻找特定中药药效类别(泻下和解表)的现代药理学的特征,从而得到其现代药理学解释。结果使用的3种方法都能够给出与2种药效相关的现代药理活性。汇总3种结果得到,泻下与导泄、兴奋胃肠平滑肌、止血和利尿4种药理活性相关;解表与抗凝血/抗血栓、止痛、解热3种药理作用相关。3种方法比较,共有化合物方法结果比较好。结论对大量中药的传统药效和它们的现代药理活性数据进行比对分析,可以得到中药药效的现代药理解释。这种方法可以推广到对其他中药传统药效的研究中,对中医药的现代化进程起到推动作用。     

Precipitation of the Renin Inhibitor Ditekiren Upon iv Infusion; in Vitro Studies and Their Relationship to in Vivo Precipitation in the Cynomolgus Monkey

Ditekiren is a pseudo-octapeptide being developed as an inhibitor of human renin. Preclinical drug safety studies with this drug involved continuous iv infusions through indwelling catheters in the right internal jugular vein of the cynomolgus monkey for up to 30 days. The following physicochemical properties of ditekiren make it susceptible to intravascular precipitation immediately following iv infusion: (1) the water solubility of ditekiren is high at acidic pH where the drug is formulated (pH 4) but low at physiologic pH, and (2) the water solubility of ditekiren decreases by roughly 50% from room temperature (25°C) to physiologic temperature (37°C). Studies of 28-and 30-day infusion durations revealed intravascular precipitation in monkeys using drug solutions and rates of infusion that were expected to be precipitation-free, based on the solubility of ditekiren and assumptions about blood flow in the monkey right internal jugular vein. Therefore, an in vitro apparatus was used to study the relationship among the drug concentration in the infusate, the rate of infusion, and the occurrence of precipitation in a fluid stream of phosphate-buffered bovine serum albumin solution (a facsimile of plasma). Maximum rates of infusion without precipitation were determined for a range of concentrations of drug in two separate formulations. Infusion conditions identified by the in vitro method as precipitation-free were then tried in a definitive 14-day monkey study. Of 24 monkeys infused with solutions of ditekiren, none showed evidence of intravascular precipitation. This study demonstrates that the in vitro precipitation system is useful in establishing drug concentrations and rates of injection which avoid the problem of intravascular precipitation in preclinical animal studies.     

滤液法和沉淀法测定地骨皮醇提物中的甜菜碱含量

目的建立地骨皮醇提物中甜菜碱的含量测定方法。方法基于甜菜碱与雷氏盐的反应 ,采用分光光度法测定地骨皮醇提物中甜菜碱含量。结果沉淀法与滤液法的平均回收率分别为 98.4 0 %与 98.2 1% ,RSD分别为0 .97%与 1.0 4 % (n =6 )。结论滤液法与沉淀法用于甜菜碱的含量测定 ,所得结果基本一致 ,滤液法操作相对简便     

Methods for the Preparation and Manufacture of Polymeric Nanoparticles

This review summarizes the different methods of preparation of polymer nanoparticles including nanospheres and nanocapsules. The first part summarizes the basic principle of each method of nanoparticle preparation. It presents the most recent innovations and progresses obtained over the last decade and which were not included in previous reviews on the subject. Strategies for the obtaining of nanoparticles with controlled in vivo fate are described in the second part of the review. A paragraph summarizing scaling up of nanoparticle production and presenting corresponding pilot set-up is considered in the third part of the review. Treatments of nanoparticles, applied after the synthesis, are described in the next part including purification, sterilization, lyophilization and concentration. Finally, methods to obtain labelled nanoparticles for in vitro and in vivo investigations are described in the last part of this review.     

Influence of Gypsum Waste Utilization on Properties and Leachability of Fired Clay Brick

Wastewater treatment activities in the chemical industry have generated abundant gypsum waste, classified as scheduled waste (SW205) under the Environmental Quality Regulations 2005. The waste needs to be disposed into a secure landfill due to the high heavy metals content which is becoming a threat to the environment. Hence, an alternative disposal method was evaluated by recycling the waste into fired clay brick. The brick samples were incorporated with different percentages of gypsum waste (0% as control, 10, 20, 30, 40 and 50%) and were fired at 1050 °C using 1 °C per minute heating rate. Shrinkage, dry density, initial rate of suction (IRS) and compressive strength tests were conducted to determine the physical and mechanical properties of the brick, while the synthetic precipitation leaching procedure (SPLP) was performed to scrutinize the leachability of heavy metals from the crushed brick samples. The results showed that the properties would decrease through the incorporation of gypsum waste and indicated the best result at 10% of waste utilization with 47.5% of shrinkage, 1.37% of dry density, 22.87% of IRS and 28.3% of compressive strength. In addition, the leachability test highlighted that the concentrations of Fe and Al was significantly reduced up to 100% from 4884 to 3.13 ppm (Fe) and from 16,134 to 0.81 ppm (Al), respectively. The heavy metals content in the bricks were oxidized during the firing process, which signified the successful remediation of heavy metals in the samples. Based on the permissible incorporation of gypsum waste into fired clay brick, this study promised a more green disposing method for gypsum waste, and insight as a potential towards achieving a sustainable end product.     

正寿王系列药物对抗吗啡依赖动物戒断症状的实验观察

目的·· :通过动物实验 ,观察正寿王1号及2号对吗啡依赖动物模型戒断症状的影响。方法·· :皮下注射吗啡 ,建立小鼠、大鼠及犬的依赖模型 ,每种动物分成正常对照组、吗啡依赖模型组、生理盐水模拟治疗组及药物治疗组 ,观察正寿王对7种指标的影响。结果·· :正寿王主要作用为 :明显减少吗啡依赖小鼠的跳跃鼠次 (1号 :P<0.01 ,2号 :P<0.001)及其它戒断症状;减少大鼠摇头次数 (P<0.01)和攻击行为 (P<0.01),对大鼠及犬体重影响不明显;此外能明显改善犬的戒断症状。结论·· :正寿王具有控制吗啡戒断症状的效能。     

醇沉浓度对心脉神口服液制备中多糖含量的影响

目的 :为比较、评价不同醇沉浓度对心脉神口服液中多糖含量的影响 ,进一步考查口服液制备工艺的合理性。方法 :以多糖作为指标性成分 ,以煎剂中的含量测定结果作为制剂的评价模式 ,设计了50%、60 %、70%、80 %的醇沉浓度 ,采用苯酚 -硫酸比色法测定多糖含量。结果 :不同醇沉浓度对多糖含量影响甚大 ,其多糖含量随乙醇用量的增加而降低 ,醇沉浓度达80%时 ,多糖含量损失近70%。结论 :多糖含量应作为该口服液制备工艺筛选时的考察指标之一     

Fast transmission of alterations in plasma phosphatidylcholine/sphingomyelin ratio and lyso phosphatidylcholine levels into changes of red blood cell membrane phospholipid composition after low density lipoprotein apheresis

Abstract. In order to evaluate whether changes in plasma phospholipid composition are rapidly transmitted to the red blood cell membrane (RBCM) under in vivo conditions, the levels of major phospholipids in plasma, low density and high density lipoproteins (LDL and HDL) as well as in RBCM were determined before (pre), directly after (post) and 2 days after (48 h post) LDL apheresis in six patients with severe hypercholesterolaemia. LDL apheresis induced a 30–70% decrease in plasma and LDL cholesterol and total phospholipid levels within 2–3 h. Concomitantly, the percentages of plasma phosphatidylcholine (PC) and the PC/sphingomyelin (SM) ratio were increased compared to initial values. The percentage of plasma lyso PC (LPC) determined before apheresis in the patients was 30% lower with respect to the mean level of LPC in a normolipidaemic control. For LPC of LDL no differences were observed between normolipidaemia and hypercholesterolaemia. LDL apheresis induced a rise by about one third in the percentage of plasma LPC. At 48 h post, plasma LPC levels reapproached pre-apher-esis levels, while the percentages of PC and the PC/SM ratio remained elevated. The pattern of changes induced by apheresis in plasma PC, SM and LPC levels was mimicked by changes in RBCM phospholipids. Strong positive relationships were noted for PC, SM and PC/SM as determined at pre, post and 48 h post between plasma and RBCM. In summary, changes in plasma PC, LPC, and PC/SM ratios as induced by LDL apheresis are rapidly transmitted to the RBCM under in vivo conditions, most probably as a result of phospholipid transfer between both compartments. In addition, the percentages of LPC in plasma and LDL particles of patients with severe hypercholesterolaemia are certainly below the levels of LPC reported to mediate biological effects of in vitro oxidized LDL.     

壳聚糖絮凝澄清工艺与醇沉工艺纯化乙肝宁复方水提液的对比

目的:探索壳聚糖絮凝澄清工艺与醇沉工艺对乙肝宁复方水提液的影响规律。方法:以干膏得率、药液澄明度、糖类及3种有效成分含量,浸膏吸湿率为评价指标,对上述2种纯化工艺进行对比考察。结果:2种纯化工艺的干膏得率相近;絮凝澄清工艺浸膏水溶液澄明度及其糖类、芍药苷的转移率均高于醇沉工艺,但其丹酚酸B和丹皮酚转移率均低于醇沉工艺。絮凝澄清工艺浸膏的吸湿性低于醇沉工艺浸膏。结论:为进一步研究中药浸膏固体制剂吸湿性机制与合理选择适宜纯化工艺用于中药制剂生产提供实验依据。