卡马西平和左乙拉西坦单药治疗儿童部分发作性癫痫的对照研究

目的:比较卡马西平和左乙拉西坦单药治疗儿童部分发作性癫痫的疗效.方法:53例在我院新诊断的部分发作性癫痫儿童,根据就诊顺序按单双号顺序分成两组,分别给予卡马西平和左乙拉西坦单药治疗,左乙拉西坦起始剂量10 mg/(kg·d),每周加量一次,逐渐加量至20～30 mg/(kg·d),最大剂量40 mg/(kg·d);卡马西平起始剂量5 mg/(kg·d),每周增加5 mg/(kg·d),逐渐增加剂量至10～20 mg/(kg·d).血药浓度6～10 mg/L.随访6月后评价疗效及不良反应.结果:53例全部完成观察和随访,卡马西平组26例,左乙拉西坦组27例.卡马西平组15例完全控制发作(57.7%),4例部分控制(15.4%),总有效率为73.1%;左乙拉西坦组10例完全控制发作(37.0%),5例部分控制(18.5%),总有效率为55.5%.两组总有效率比较差异无统计学意义(P>0.05).两组均未见严重不良反应.结论:左乙拉西坦和卡马西平单药治疗儿童部分发作性癫痫均有很好疗效和耐受性.     

卡马西平联合左乙拉西坦或托吡酯治疗儿童难治性部分性发作癫痫的疗效比较

目的:探究卡马西平联合左乙拉西坦或托吡酯治疗儿童难治性部分性发作癫痫的临床疗效。方法:选取2015年7月—2016年7月进行治疗的儿童难治性部分癫痫患者80例,随机分为A组和B组,每组40例。A组采用卡马西平联合左乙拉西坦治疗,B组采用卡马西平联合托吡酯治疗。对两组临床治疗有效率、平均癫痫发作次数及不良反应发生情况进行对比。结果:A组治疗总有效率(95%)高于B组(75%)(P<0.05)。A组治疗1个月、2个月后癫痫发作次数与B组相比差异无统计学意义(P>0.05);治疗4个月后,A组发作次数明显少于B组(P<0.05)。A组不良反应发生率与B组相比差异无统计学意义(P>0.05)。结论:卡马西平联合左乙拉西坦或托吡酯治疗儿童难治性部分性发作癫痫临床疗效显著,但与托吡酯相比,卡马西平联合左乙拉西坦治疗可在提高治疗效果的同时,使癫痫发作次数明显减少,且不良反应发生率较低。     

丙戊酸钠、奥卡西平与左乙拉西坦分别治疗小儿癫痫的疗效及对认知功能的影响

目的 探讨丙戊酸钠、奥卡西平与左乙拉西坦分别治疗小儿癫痫的疗效及对小儿认知功能的影响。方法 收取2011年4月—2016年1月于渭南市妇幼保健院进行治疗的癫痫患儿96例作为研究对象,根据随机数字表法将其分为A、B、C组,每组各32例,分别使用丙戊酸钠、奥卡西平或左乙拉西坦进行治疗,3组患儿均治疗16周。对3组患儿临床疗效、脑电变化情况、认知功能变化情况以及用药安全性进行观察与比较。结果 A、B、C组治疗总有效率分别为71.88%、78.13%、90.63%,C组高于A、B组,但三组间比较无统计学差异。随治疗时间延长,3组患儿痫样放电好转率逐渐升高。C组好转率高于B组更高于A组,组间比较差异均有统计学意义（P＜0.05）。3组患儿治疗前语言智商（VIQ）、操作智商（PIQ）及总智商（FIQ）均无显著差异,治疗后B、C两组均较治疗前得分显著升高,且高于同期A组得分,差异有统计学意义（P＜0.05）。A组不良反应发生率为28.13%,B组为12.50%,C组为3.13%,3组间比较差异显著（P＜0.05）。结论 丙戊酸钠、奥卡西平与左乙拉西坦单药治疗小儿癫痫疗效相当,但奥卡西平与左乙拉西坦对脑电功能及小儿认知功能改善具有更加积极的意义,且以左乙拉西坦的安全性更高,具有更好的应用价值。     

奥卡西平联合左乙拉西坦对颞叶癫痫患者认知功能的影响

目的探讨奥卡西平联合左乙拉西坦对颞叶癫痫患者认知功能的影响。方法84例颞叶癫痫患者,根据治疗方法不同分为研究组(44例)与对照组(40例)。研究组患者采用奥卡西平联合左乙拉西坦治疗,对照组患者采用奥卡西平单药治疗。比较两组临床疗效、治疗前后的认知功能评分、药物不良反应发生情况。结果研究组的总有效率88.6%高于对照组的70.0%,差异有统计学意义(P<0.05)。研究组治疗后的语言智商为(91.51±4.27)分,操作智商为(101.47±5.22)分,总智商为(103.31±4.83)分。对照组治疗后的语言智商为(87.27±4.88)分,操作智商为(96.52±4.81)分,总智商为(100.20±4.07)分。研究组的语言智商、操作智商、总智商评分均高于对照组,差异有统计学意义(P<0.05)。两组患者均无肝肾功能损害,心电图正常,不良反应发生率比较差异无统计学意义(P>0.05)。结论颞叶癫痫患者采用奥卡西平联合左乙拉西坦治疗,可获得更好的临床疗效,并对认知功能有改善作用,不良反应轻微。     

卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能和骨密度的影响分析

目的探究卡马西平与左乙拉西坦治疗成人癫痫的效果及对认知功能、骨密度的影响。方法92例成人癫痫患者作为研究对象,随机分为左乙拉西坦组与卡马西平组,各46例。左乙拉西坦组采用左乙拉西坦治疗,卡马西平组采用卡马西平治疗。比较两组患者治疗前及治疗6个月后认知功能[语言智商(VIQ)、操作智商(PIQ)、总智商(FIQ)]评分、骨密度(腰椎、股骨大转子、股骨颈)变化情况。结果治疗6个月后,两组患者VIQ、PIQ、FIQ评分均较治疗前显著提升,且左乙拉西坦组患者VIQ评分(101.2±3.1)分、PIQ评分(108.1±2.3)分、FIQ评分(105.2±1.8)分均明显高于卡马西平组的(95.1±2.8)、(94.1±2.0)、(93.5±1.6)分,差异有统计学意义(P<0.05)。治疗6个月后,卡马西平组患者腰椎、股骨大转子、股骨颈骨密度均较治疗前显著下降,且明显低于卡马西平组,差异有统计学意义(P<0.05);左乙拉西坦组治疗6个月后腰椎、股骨大转子、股骨颈骨密度与治疗前比较差异无统计学意义(P>0.05)。结论左乙拉西坦与卡马西平治疗成人癫痫,左乙拉西坦更能明显提升患者认知功能,且对患者骨密度无影响。     

左乙拉西坦联合奥卡西平治疗癫痫的临床效果

目的 观察左乙拉西坦联合奥卡西平治疗癫痫的临床效果。方法 回顾性分析2020年1—12月福建医科大学附一闽南医院收治的92例癫痫患者临床资料,根据是否联用药物治疗分为联合组和奥卡西平组,各46例。2组患者均予对症治疗,在此基础上,奥卡西平组予奥卡西平治疗,联合组在奥卡西平组基础上加用左乙拉西坦治疗,2组均以6个月为1个疗程。比较2组治疗效果、治疗前后癫痫发作情况(每年发作次数与单次发作持续时间)、脑电图指标(癫样放电与累及导联数)变化及不良反应。结果 联合组患者治疗总有效率为97.83%,高于奥卡西平组的73.91%(χ²=10.839,P=0.001);治疗后,2组每年发作次数、发作持续时间、癫样放电与累及导联数均较治疗前减少,且联合组减少的程度大于奥卡西平组(P均<0.01);联合组不良反应总发生率为4.35%,低于奥卡西平组的26.09%(χ²=8.425,P=0.004)。结论 左乙拉西坦联合奥卡西平治疗癫痫的临床效果显著且安全性高,能够减少患者癫痫发作次数以及发作时间,值得临床推广应用。     

奥卡西平与其他抗癫痫药联合治疗小儿癫痫的疗效和安全性

目的探讨奥卡西平(OXC)联合其他抗癫痫药物治疗小儿癫痫的临床疗效和安全性。方法 31例经小儿癫痫门诊诊治的局限性癫痫患儿,根据应用OXC的顺序分为A组和B组,A组23例,B组8例。对比两组患儿临床疗效、药物不良反应及患儿的耐受性。结果 A组23例,经OXC添加治疗完全控制发作者占43.5%,总有效率84.4%,OXC所用剂量为16.7~38.2 mg/(kg·d),平均26.80 mg/(kg·d),其中8例完全转换为OXC单药治疗无发作。B组OXC加左乙拉西坦治疗,发作频率减少均≥50%,疗效最高。结论 OXC联合用药治疗小儿癫痫安全、有效,有较好的依从性和耐受性,是适合于长期用的新型高效抗癫痫药物之一。     

左乙拉西坦治疗癫痫的临床效果观察

目的探讨左乙拉西坦对于癫痫的临床治疗效果。方法选取我院治疗的84例癫痫患者作为研究对象,随机分为实验组42例(左乙拉西坦治疗)和对照组42例(奥卡西平治疗),在治疗前后利用蒙特利尔认知评估量表(即MOCA)对认知功能进程评价,对比分析两组的认知功能评分变化和疗效。结果治疗后,实验组认知功能改善幅度[MOCA总分(22.9±3.7)分]显著高于对照组[MOCA总分(20.6±3.4)分],经统计学分析,P<0.05,差异均具有显著性,观察组临床治疗有效率(90.48%)与对照组(85.71%)无明显差异(P>0.05)。结论左乙拉西坦能够明显改善癫痫患者的认知功能,减少发作频率,提高临床疗效,值得临床推广。     

左乙拉西坦与卡马西平治疗高血压脑出血后癫痫的疗效对比分析

目的:通过对左乙拉西坦与卡马西平治疗高血压脑出血后癫痫的疗效对比分析,评价两者疗效的差异.方法:选取在本院门诊和住院部治疗的148例患者,分为左乙拉西坦组和卡马西平组,随访半年后观察两组癫痫发作控制情况;同时行动态脑电图检查了解放电情况.结果:左乙拉西坦组治疗总有效率为92.86%;卡马西平组治疗总有效率为80.77%,左乙拉西坦组治疗总有效率显著优于卡马西平组(X2=4.177,P=0.043,P<0.05);左乙拉西坦组动态脑电图检查异常率明显低于卡马西平组,差异有统计学意义(X2=4.255,P=0.041,P<0.05).结论:左乙拉西坦对于高血压脑出血后癫痫控制率明显高于卡马西平,治疗后异常放电率更低,值得临床推广.     

托吡酯联合丙戊酸钠治疗小儿癫疒间的临床观察

目的观察托吡酯联合丙戊酸钠治疗小儿癫疒间的临床疗效及安全性。方法选取76例小儿癫疒间患儿,按入院顺序随机分为2组,每组38例,观察组采用托吡酯联合丙戊酸钠治疗,对照组单独采用托吡酯治疗,其中托吡酯初始剂量为0.5¹.0 mg/(kg·d),逐渐增至维持量41.0 mg/(kg·d),逐渐增至维持量4⁸ mg/(kg·d),2次/d;丙戊酸钠口服液初始剂量为108 mg/(kg·d),2次/d;丙戊酸钠口服液初始剂量为10¹5 mg/(kg·d),逐渐增加至维持量2015 mg/(kg·d),逐渐增加至维持量20⁴0 mg/(kg·d),3次/d,两组患儿均连续治疗340 mg/(kg·d),3次/d,两组患儿均连续治疗3⁶个月。观察两组患儿癫疒间发作次数及发作频率,对两组患儿疗效进行评定并比较,治疗期间严密监测血常规、尿常规及肝肾功能等,仔细记录两组患儿不良反应发生情况。结果观察组完全控制率为42.11%,对照组为34.21%,两组比较差异无统计学意义(P>0.05);观察组总有效率为97.37%,对照组为84.21%,两组比较差异有统计学意义(P<0.05)。两组患儿治疗期间肝肾功能、血常规及尿常规等均无显著改变,不良反应主要表现为感觉异常、胃肠道反应、体重改变及嗜睡等轻微不良反应,其中观察组不良反应发生率为18.42%(7/38),对照组为10.53%(4/38),两组比较差异无统计学意义(P>0.05)。结论托吡酯联合丙戊酸钠治疗小儿癫疒间临床疗效优于单用托吡酯治疗,未明显增加不良反应发生率,患儿耐受性好,安全可行,值得推广应用。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.