RP-HPLC测定血浆中6种苯二氮芏卓类药物的浓度

目的: 建立人血浆中6种苯二氮(艹卓)类药物浓度的RP-HPLC测定方法. 方法: 采用KF-C18色谱柱,甲醇-水-乙腈(55∶37∶8,V/V)为流动相,紫外检测波长为240 nm.结果: 6种苯二氮(艹卓)类药物分离良好,浓度在0.10～20.0 μg·ml-1范围内线性关系良好;最低检测浓度为10.0～20.0 ng·ml-1(S/N≥3);回收率为(90.3%～102.4%);日内和日间精密度RSD均小于5.0%. 结论: 本方法简便快速,准确可靠,适用于血药浓度的常规监测和药物中毒病人的急救诊断.     

RP-HPLC同时测定血浆中8种苯二氮(艹卓)类药物

目的 采用HPLC法建立同时测定血浆中8种苯二氮(艹卓)类药物(氯硝西泮、艾司唑仑、阿普唑仑、三唑仑、澳沙西泮、替马西泮、氯氮(艹卓)和地西泮)的方法.方法 血浆样品经正己烷-二氯甲烷(5:3)提取.选用Diamonsil Rp-C18柱(250 mm×4.6mm,5μm);甲醇-25 mmol.L-1醋酸铵溶液(63:37)作流动相,流速1.0 mL·min-1,检测波长230 nm.结果 氯硝西泮、三唑仑、澳沙西泮、氯氮(艹卓)、地西泮的最低检测浓度为8μg·L-1,艾司唑仑、阿普唑仑、替马西泮的最低检测浓度为5μg·L-1;方法回收率接近100%;提取回收率大于70%,日内、日间精密度小于6%;艾司唑仑、阿普唑仑和替马西泮10～1.5×103μg·L-1的线性关系良好,其余5种药物的线性范围为20～1.5×103μg·L-1(r＞0.999).结论 所建方法操作简便、快速、准确、灵敏度高、重复性好,适用于临床上人血浆中8种苯二氮(艹卓)类药物的同时定性、定量检测.     

精神病专科医院300例住院患者中应用苯二氮（艹卓）类药物情况分析

目的：探讨精神病专科医院住院患者应用苯二氮(艹卓)类药物的使用情况。方法：随机选取我院300例住院患者作为研究对象,通过住院精神病患者调查表分析住院精神病患者使用苯二氮(艹卓)类药物的整体情况。结果：我院精神病住院患者使用苯二氮(艹卓)类药物人数为110例、占比36.7%。药物共有4种,其中使用氯硝西洋的69例、占比62.7%;使用艾司唑仑的3例,占比2.7%;精神分裂症患者中使用苯二氮(艹卓)类药物83例,占比75.6%。结论：精神病专科医院住院患者应用苯二氮(艹卓)类药物能够起到一定作用,但不宜过度使用。     

门诊苯二氮（艹卓）类药物应用分析

目的 了解我院门诊苯二氮（艹卓）类药物（BZD）的使用情况,评价其合理性.方法 对我院2009年1月1日至12月31日使用苯二氮（艹卓）类药物的门诊处方共17 185张进行统计与分析.结果 苯二氮（艹卓）类药物广泛应用于精神科和心理科门诊,主要联合用药处方有苯二氮（艹卓）类与抗抑郁药7011张（40.80%）,苯二氮（艹卓）类与抗精神病药物6149张（35.78%）,不合理用药处方占所统计总处方数的1.32%.结论 苯二氮（艹卓）类药物在我院门诊的使用是基本合理的,但亦存在少数不合理用药现象,是造成苯二氮（艹卓）类药物滥用的主要原因.     

半个世纪的争议——苯二氮()类药物临床应用50年

上个世纪50年代,苯二氮(艹卓)类药物进入临床使用,由于此类药物高效、安全、耐受性良好,目前苯二氮(艹卓)类药物已成为抗焦虑和失眠领域应用最广泛的药物。根据统计,全球有超过5000万人服用苯二氮(艹卓)类药物。苯二氮(艹卓)类药物目前仍是失眠和抗焦虑的一线治疗药物。 然而,由于许多原因,苯二氮(艹卓)类药物只是用于短期的抗焦虑及失眠的治疗,这是因为人们担心长期使用     

纳洛酮治疗60例苯二氮类药物中毒临床分析

目的观察纳洛酮治疗苯二氮(艹卓)类药物中毒的临床疗效.方法选用60例苯二氮(艹卓)类药物中毒患者,入院后采取常规洗胃利尿排泄、输液等治疗外,主要用纳洛酮治疗.观察疗效并进行统计学分析.结果疗效较好,全部60例患者除一例死亡外,其余59例均治愈出院,成功率为98.3%.结论纳洛酮治疗苯二氮(艹卓)类药物中毒见效快,简便,价格便宜,疗效确切,副作用少.     

高效液相色谱法同时测定人血清中4种苯二氮(艹卓)类药物浓度

目的 　建立用高效液相色谱法同时测定人血清中 4种苯二氮 艹卓 类药物浓度的方法。方法 　以氯霉素为内标 ,经乙醚提取后于Techsphere-ODS色谱柱分离 ,甲醇 -水 ( 63 .5∶ 3 6.5 ,V/V)为流动相 ,流速为 1.0 m L· min- 1 ,检测波长为 2 5 4nm,采用保留时间和最大吸收波长同时定性 ,在线扫描范围 2 0 0～ 40 0 nm,扫描速度 4nm· s- 1。 结果 　全部样品洗脱时间不超过 15 min,药物之间达完全分离。 4种药物平均回收率均在 95 %以上 ,样品在各自拟定的浓度范围内呈良好的线性关系 ,最大日内差和日间差分别为 3 .77%和 5 .60 %。结论 　本法提取简单 ,数据可靠 ,干扰少 ,非常适用于苯二氮 艹卓 类药血药浓度检测和中毒病人的急诊诊断。     

催眠药研究进展

失眠是指正常睡眠被扰乱,并对患者白天活动有明显不良影响的一种生理现象.长期失眠损害人的恩维能力,甚至会影响人的免疫系统.根据流行病学调查,失眠者的患病率为30%～35%,长期失眠者的严重意外事故和外伤发生率明显较正常人高.许多药物可以催眠,如巴比妥类、非巴比妥类(如水合氯醛、利马扎封等)、苯二氮(艹卓)类和非苯二氮(艹卓)类(如唑吡坦、佐匹克隆等).过去常用的巴比妥类和非巴比妥类药物现在逐渐被苯二氮(艹卓)类和非苯二氮(艹卓)类药物替代,因为后者使用比较安全,成瘾性也较小.中医中药是人们研究的热点之一,许多中药成分具有良好镇静催眠作用,且不良反应较少,具有广阔的应用前景.1 人工合成催眠药物1.1 苯二氮(艹卓)(BZ_s)类 主要有氟西泮(flu-razepam)、夸西泮(quazepam)、艾司唑仑     

米氮平与苯二氮(艹卓)类药物合并美沙酮对海洛因脱毒的对照研究

目的:比较米氮平与苯二氮(艹卓)类药物合并美沙酮治疗对海洛因依赖者脱毒疗效.方法:比较了美沙酮合并米氮平组(37例)和美沙酮合并苯二氮(艹卓)类药物组(37例)在脱毒治疗后一周、治疗后二周戒断症状量表评分、HAMD焦虑量表评分及睡眠障碍的变化情况.结果:两组海洛因依赖者的戒断反应、焦虑症状在脱毒治疗后均显著减轻,米氮平合并美沙酮治疗比苯二氮(艹卓)类药物合并美沙酮治疗对戒断症状和焦虑减轻更明显,并明显改善入睡困难和睡眠浅.结论:米氮平合并美沙酮治疗和苯二氮(艹卓)类药物合并美沙酮治疗均可有效减轻海洛因依赖者的戒断症状,米氮平合并美沙酮的疗效更明显,并可明显改善睡眠障碍.     

β-咔咻-3-羧酸酯的合成

苯二氮(艹卓)(Ⅰ)的药理作用是通过中枢神经系统特殊的结合部位传递的。“苯二氮(艹卓)受体”对于药理和临床上具有活性的苯二氮(艹卓)类药物有很高的专一性。和Ⅰ不同而能与那些受体结合的一组化合物是β-咔啉类化合物。其中β-咔啉-3-羧酸酯类比母体酸的亲合力大三个数量级(低纳摩尔范围),使得β-咔啉衍生物成为研究苯二氮(艹卓)受体机能的重要工具。再者其结构能成为设计苯二氮(艹卓)类新药的重要基础。     

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.     

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.     

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.