托吡酯与丙戊酸钠缓释片治疗难治性癫痫疗效比较

目的 :比较托吡酯与丙戊酸钠缓释片治疗难治性癫痫的疗效。方法 :托吡酯组 39例 ,丙戊酸钠组 4 1例 ,托吡酯成人及儿童剂量在约 2mo中逐渐增至 2 0 0mg·d- 1及 4mg·kg·d- 1左右 ,po ,bid。丙戊酸钠缓释片成人剂量 0 .5～ 1.0 g·d- 1,儿童剂量逐增至总量 15～ 30mg·kg·d- 1,为每日清晨或早晨、中午 2次服用。治疗 4mo及 6mo后评定疗效。结果 :托吡酯组治疗 6mo的继发性全身发作 ,简单及复杂性部分发作有效例数优于丙戊酸钠组 ,4例在加药期快时出现疲劳、嗜睡、注意力不集中等。丙戊酸钠组 1例发生骨髓造血功能严重低下。结论 :托吡酯治疗难治性癫痫简单及复杂部分性发作伴或不伴继发性全身发作疗效优于丙戊酸钠 ,无骨髓抑制 ,也无肝、肾功能损伤     

丙戊酸托吡酯治疗儿童特发性全身性癫痫疗效比较研究

目的：评价丙戊酸和托吡酯治疗儿童特发性全身性癫痫的疗效及耐受性。方法：对1999年10月至2003年4月来我院的152例首诊特发性全身性癫痫并接受丙戊酸或/和托吡酯治疗的病人进行随访。并对结果进行分析。结果：丙戊酸单药治疗完全控制率为63．41％。托吡酯单药治疗完全控制率40．00％,二者有显著差异;丙戊酸部分控制者添加托吡酯治疗31．25％完全控制,托吡酯治疗部分控制者添加丙戊酸后36．84％发作停止。无显著差异。两种药物的不良反应均较轻且耐受性较好。结论：丙戊酸是治疗儿童特发性全身性癫痫的最有效药物之一。如丙戊酸未能完全控制发作。添加托吡酯治疗疗效好。     

托吡酯、卡马西平与丙戊酸钠治疗脑炎继发癫痫的效果观察

目的分析托吡酯、卡马西平与丙戊酸钠治疗脑炎继发癫痫效果。方法选取我院在2014年2月至2016年2月期间收治的150例脑炎继发癫痫患者为本次研究对象,并根据用药的不同分成3组,托吡酯组、卡马西平组以及丙戊酸钠组,每组患者各50例。托吡酯组给予托吡酯药物的口服治疗、卡马西平组给予卡马西平药物的口服治疗、丙戊酸钠组给予丙戊酸钠药物的口服治疗。分析三组患者的治疗效果以及不良反应发生情况,并进行对比。结果托吡酯组的有效率为82%;卡马西平组有效率为78%;戊酸钠组有效率为80%,三组患者的总有效率差异不显著,无统计学意义(P>0.05);托吡酯组、卡马西平组以及丙戊酸钠组患者的不良反应发生率分别为6.0%、20%、12%,卡马西平组不良反应发生率明显高于丙戊酸钠组和托吡酯组,丙戊酸钠组患者的不良反应发生率明显高于托吡酯组,三组差异对比有统计学意义(P<0.05)。结论对于脑炎继发癫痫患者的治疗而言,采用托吡酯、卡马西平以及丙戊酸钠均可达到理想的临床疗效,但卡马西平药物以及丙戊酸钠药物的不良反应发生率较高,托吡酯药物药物不良反应发生率较低,可以有效提升患者的安全性,应用价值较高。     

观察卡马西平和托吡酯与丙戊酸钠治疗脑炎继发癫痫的临床效果

目的 观察卡马西平、托吡酯、丙戊酸钠治疗脑炎继发癫痫的临床效果.方法 选取2010年1月-2012年1月灌云县人民医院接受治疗的108例脑炎继发癫痫患者作为研究对象,将其随机分为卡马西平组、托吡酯组和丙戊酸钠组,各36例.观察3组患者的临床疗效.结果 治疗后卡马西平组、丙戊酸钠组和托吡酯组总有效率分别为75.63%（25/36）、77.78%（28/36）和79.63%（29/36）,3组间比较差异无统计学意义（P＞0.05）.结论 卡马西平、托吡酯、丙戊酸钠治疗脑炎继发癫痫的疗效相当;对脑炎继发癫痫患者采取单药治疗时,卡马西平对部分性发作有较好疗效,托吡酯与丙戊酸钠适宜治疗各种类型脑炎继发癫痫患者,同时托吡酯具有较少不良反应.     

托吡酯联合丙戊酸钠治疗难治性癫痫临床观察

目的：探讨托吡酯联合丙戊酸钠治疗难治性癫痫的临床疗效。方法将我院收治的135例难治性癫痫患者按治疗方法的不同分为治疗组46例,对照组1组45例,对照2组44例。三组均采用抗癫痫药（AED）治疗。治疗组口服托吡酯片、丙戊酸钠片,对照1组仅口服托吡酯片,对照2组仅口服丙戊酸钠片。治疗1个疗程后,比较三组疗效、不良反应及治疗前后发作频率的变化。结果治疗后,治疗组的总有效率均高于对照1组和对照2组,差异有统计学意义;治疗后治疗组的癫痫发作频率均明显低于对照1组和对照2组,差异有统计学意义;三组不良反应发生率比较差异无统计学意义,症状均较轻微,停药后可自行消失。结论托吡酯联合丙戊酸钠治疗难治性癫痫临床疗效良好,结论值得进一步研究。     

托吡酯治疗小儿癫痫

目的 :评价托吡酯治疗小儿癫痫的疗效和安全性。方法 :3 1例癫痫病儿 (男性 2 1例 ,女性 10例 ,年龄 6a±s 4a)口服托吡酯 ,起始剂量为 1～ 2mg·kg- 1·d- 1,qd ;目标剂量为 4～ 10mg·kg- 1·d- 1,bid。随访时间为 3～ 8mo。结果 :托吡酯总有效率为 69% ,单药治疗与添加治疗的疗效比较差异无显著意义 (P >0 .0 5 ) ,其不良反应较轻。结论 :托吡酯对于小儿癫痫有较好的疗效 ,单药与添加治疗的疗效近似 ,病儿对其有较好的耐受性。     

老年癫痫患者丙戊酸钠血药浓度监测及个体化用药

目的:探讨丙戊酸钠(VPA)治疗老年癫痫患者药物剂量与血药浓度之间的关系,为老年患者丙戊酸钠合理用药提供参考。方法:选择使用丙戊酸钠治疗的老年癫痫患者30例,连续服药1周以上,于早晨服药前抽取静脉血3 mL,HPLC法测定浓度。结果:每天剂量<0.8 g组,平均浓度为(41.1±5.6)mg·(-1);每天0.8 g组,平均浓度为(60.5±14.3)mg·L~(-1),每天剂量>0.8 g组浓度为(72.2±26.4)mg·L~(-1)。结论:老年患者丙戊酸钠血药浓度监测对临床治疗很有意义,但个体差异大,影响因素多,个体化给药必须综合考虑各方面的因素。     

丙戊酸钠与托吡酯治疗初诊癫痫患者效果对比

目的 比较丙戊酸钠与托吡酯治疗初诊癫痫患者的效果.方法 选择2014年1月至2015年12月收治的90例初诊癫痫患者为研究对象,采用随机数字法将本研究入组患者分为A组和B组,A组给予丙戊酸钠治疗,B组给予托吡酯治疗,观察记录两组患者的临床疗效和药物不良反应.结果 B组治疗总有效率为95.56％,高于A组治疗总有效率,差异有统计学意义(P＜0.05).B组药物不良反应发生率为4.44％,A组药物不良反应发生率为20.00％,差异有统计学意义(P＜0.05).结论 丙戊酸钠与托吡酯治疗初诊癫痫患者都有很好的效果,但是较丙戊酸钠而言,托吡酯效果要好一些,且托吡酯的安全性要高于丙戊酸钠.     

托吡酯联合丙戊酸钠治疗难治性癫痫的临床价值

目的:研究托吡酯联合丙戊酸钠治疗难治性癫痫的临床疗效。方法:选取收治的难治性癫痫患者101例,随机分为对照组50例与观察组51例。对照组采用托吡酯治疗,观察组在此基础上添加丙戊酸钠联合治疗。结果:用药后两组患者癫痫发作次数较用药前均有所改善,且观察组改善情况明显优于对照组;两组患者用药后不良反应发生率差异均无统计学意义;观察组治疗总有效率为92.16%,明显高于对照组(72.00%)。结论:托吡酯联合丙戊酸钠对难治性癫痫患者的临床治疗效果非常显著,可有效减少癫痫发作次数,提高治疗效果,且未增加不良反应。     

伴中央-颞区棘波儿童良性癫痫患者首次治疗分别使用丙戊酸钠、卡马西平、托吡酯的疗效比较

目的：比较丙戊酸钠、卡马西平、托吡酯作为伴中央-颞区棘波儿童良性癫痫（benign epilepsy with centro-temporal spikes,BECT）患儿首次治疗用药的疗效。方法：回顾性选取2019年2月—2022年2月本院收治的BECT患儿100例,依据用药方法不同分为丙戊酸钠组（40例）、卡马西平组（30例）、托吡酯组（30例）。比较各组临床疗效、认知功能、生活质量、首药治疗失败时间、药物不良反应事件发生情况、家长满意度。结果：三组总有效率、操作智商、语言智商、总智商评分、生活质量评分、家长满意度比较,差异无统计学意义（P>0.05）;卡马西平组首药治疗失败时间晚于丙戊酸钠组、托吡酯组（P<0.05）,且丙戊酸钠组患儿的首药治疗失败时间晚于托吡酯组（P<0.05）;丙戊酸钠组、卡马西平组药物不良反应事件发生率低于托吡酯组（P<0.05）,但丙戊酸钠组、卡马西平组药物不良反应事件发生率比较,差异无统计学意义（P>0.05）。结论：卡马西平、丙戊酸钠、托吡酯治疗BECT的疗效相当,均能够提升患者认知功能、生活质量、家长满意度,但与托吡酯相...     

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.

---

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.     

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.     

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.