儿童苯巴比妥血药浓度与剂理疗效关系及临床意义

荧光偏振免疫分析法（ＴＤＸ仪）测定儿童苯巴比妥血药浓度３０８例，采用Ｆｏｘｂａｓｅ＾＋建立数据库辅助分析，结果表明不同年龄苯巴比妥的血药浓度与剂理比有一定差异；抗癫痫治疗浓度不必过份强调低限；苯巴比妥体内过程的个体差异较大，通过治疗药物监测有助于个体化给药，鉴别论断笔了解病人的依从性，以更好地发挥抗癫痫药的作用。     

4种抗癫痫类药血药浓度监测138例分析

本文对１９９７年４月至１９９９年１０胆应用荧光偏振免疫法测定苯妥英钠、苯巴比妥、卡马西平及丙酸钠４种抗癫痫炎药血药浓度的数据进行统计分析。发现超过一半的癫痫患者（尤其服用苯妥英钠者）服药后其血药浓度均不在有效治疗范围内、监测抗癫痫类药血药浓度具有临床意义。     

289例使用抗癫痫药患者的血药浓度分析

目的了解临床分别使用苯巴比妥、苯妥英钠、卡马西平3种抗癫痫药患者的血药浓度,指导临床合理用药。方法对289例分别使用抗癫痫药苯巴比妥、苯妥英钠、卡马西平的患者进行血药浓度测定结果的分析、评价。结果血药浓度在正常治疗浓度范围内的患者有167例（57.79%）,低于正常治疗浓度范围且疗效不佳的有99例（34.26%）,高于正常治疗浓度范围、怀疑中毒的有23例（8.21%）。结论对于癫痫患者,应重视血药浓度监测,及时调整用药方案,以达到安全、有效、合理用药。     

我院432例抗癫痫药血药浓度监测数据分析

目的:分析抗癫痫药血药浓度监测结果,为临床合理用药提供参考。方法:建立抗癫痫药Access数据库,对我院2001年1月～2009年6月4种常用抗癫痫药的血药浓度监测结果进行统计、分析。结果:我院抗癫痫药血药浓度监测例数大体呈逐年上升趋势,共监测432例/次;血药浓度在治疗窗内所占比例为48.6%;卡马西平、苯巴比妥、苯妥英钠、丙戊酸钠血药浓度在治疗窗内的有效率分别为91.3%、77.8%、62.5%、88.2%;儿童(0～10岁)与老人(>60岁)进行血药浓度监测例数占总监测例数的22.2%;有43例采用抗癫痫药联合给药方案,占总例数的10%,其中偏离正常治疗浓度范围的有27例,占62.8%。结论:血药浓度监测结果是指导临床用药的重要依据之一,结合其他临床指标综合分析,可最大限度地促进抗癫痫药合理应用。     

回顾性分析357例次小儿抗癫痫药物血药浓度

目的:回顾性分析4种常用抗癫痫药在儿童癫痫治疗中的血药浓度监测情况,以利指导合理用药。方法:采用HPLC法测定丙戊酸钠、卡马西平、苯巴比妥和苯妥英钠4种常用抗癫痫药物的血药浓度。结果:血药浓度在治疗窗内占47.1%,高于治疗窗占7.0%,低于治疗窗占45.9%。常规服药的患者有49.8%血药浓度在治疗窗内,联合用药致血药浓度偏离治疗窗达76.2%。结论:儿童使用抗癫痫药物监测血药浓度是指导临床用药的重要依据,特别是联合用药尤其应密切监测。     

我院抗癫痫药血药浓度监测情况分析

目的:为临床合理应用抗癫痫药提供参考。方法:采用回顾性方法,对我院2007年499例抗癫痫药治疗患者服用苯妥英钠、苯巴比妥、卡马西平和丙戊酸钠的血药浓度结果进行统计、分析。结果:单一用药患者中,血药浓度在正常治疗范围内者206例/次,占61.49%。联合用药患者中,血药浓度在正常治疗范围内者仅45例/次,占44.12%;服用中药治疗的患者中检出含有以上4种药物者占59.68%,服用中药治疗的患者中血药浓度在正常治疗范围内者占3.23%。结论:在应用抗癫痫药时,通过监测血药浓度,能更好地控制治疗浓度,避免多药联用,实现个体化给药。中药中是否含有化学合成药物成分也应引起重视。     

药学监护在癫痫疾病中应用的体会

目的：了解癫痫疾病的主要症状、后遗症及临床药学监护的重要意义，指导临床合理用药及更好发挥药物的疗效，提高患者的生活质量。方法：对我院2002～2005年主要抗癫痫药苯巴比妥、丙戊酸和卡马西平的血药浓度监测后，对所开展的具体工作进行总结。结果与结论：抗癫痫药治疗指数低，有效剂量个体差异大，血药浓度监测对调整给药剂量有指导意义，同时应高度重视药学监护，以保证临床治疗效果，减少不良反应。     

我院4种抗癫痫药物血药浓度监测结果回顾性分析

目的:提高临床对血药浓度监测工作的重视程度。方法:运用回顾性调查方法,对我院自1998年～2005年所监测的应用苯巴比妥、苯妥英钠、卡马西平、丙戊酸钠4种抗癫痫药治疗的1443例/次患者的血药浓度结果进行分析。结果:血药浓度在高、低及正常治疗浓度范围内的患者分别为10.40%、36.59%、53.01%。联合用药的患者中,血药浓度在正常治疗浓度范围内者为28.45%。结论:抗癫痫药的血药浓度监测对临床调整用药剂量有指导意义;及时监测血药浓度,实施个体化给药是确保临床治疗效果和用药安全的重要措施之一。     

111例抗癫痫药物血药浓度监测结果分析

目的 通过血药浓度监测了解苯妥英钠、卡马西平、苯巴比妥这3个抗癫痫药的血药浓度情况.方法 采用高效液相色谱法对111例分别口服苯妥英钠、卡马西平、苯巴比妥的患者进行血药浓度测定,并对结果进行分析、评价.结果 监测111例抗癫痫药血药浓度在有效血药浓度范围内的有57例,占51.4％,低于有效血药浓度范围30例,占27.0％,高于有效血药浓度范围的24例,占21.6％.结论 对于癫痫患者进行血药浓度监测,对临床及时调整用药方案,降低癫痫发作频率,减少药物不良反应具有重要意义.     

抗癫痫药物监测的规范化实践

目的：探讨抗癫痫药（AEDs）治疗监测的规范化体系。方法：对常用抗癫痫药卡马西平、苯妥因、苯巴比妥、扑米酮和丙戊酸的血药浓度开展规范化监测。结果：AEDs治疗监测应明确监测指征,做好样品的采集和血药浓度测定,及时报告监测结果,并给予简明的分析、解释及具体建议。结论：建立AEDs治疗监测的规范化质量保证体系,对抗癫痫治疗可起到积极的作用。     

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.

---

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.