盐酸反式曲马朵口服制剂中盐酸曲马朵立体异构体的分离与测定

目的 :建立盐酸反式曲马朵口服制剂中盐酸曲马朵 4种立体异构体的分离测定方法。方法 :采用高效毛细管电泳法 ,未涂层毛细管 75 μm× 37cm (有效长度 30cm) ;分离介质为 40mmol·L-1Tris缓冲液 (pH 2 5 ) ,内含 0 8mmol·L-1磺丁基 - β-环糊精 ;分离电压 15kV ,柱温 2 5℃ ,检测波长 2 14nm ;进样电压 10kV ,2 0s ,入口为阳极。 结果 :以 (- ) -氧去甲基曲马朵为内标 ,反式曲马朵、顺式曲马朵的对映体达到基线分离 ,( ) -盐酸反式曲马朵、 (- ) -反式曲马朵的线性浓度范围为 0 5～ 1 5 μg·mL-1;4种制剂中 ( ) -盐酸反式曲马朵和 (- ) -盐酸曲马朵平均回收率 96 87%～10 2 4%和 96 2 8%～ 10 1 3 % ,RSD <5 % ,n =5 ;盐酸曲马朵 4种立体异构体的最低检测浓度为 5ng·mL-1;4种盐酸反式曲马朵口服制剂中盐酸顺式曲马朵各对映体含量不超过 0 12 % ,盐酸反式曲马朵各对映体的含量为标示量的 45 5 8%～5 0 93 %。结论 :本方法可用于盐酸反式曲马朵口服制剂中盐酸顺式曲马朵对映体的限量检查和盐酸反式曲马朵对映体的含量测定     

反相高效液相色谱法同时测定人血浆中对乙酰氨基酚/曲马朵及其代谢物的含量

目的:建立一种用高效液相色谱法(HPLC)同时测定人血浆中对乙酰氨基酚/曲马朵及其代谢物氧去甲基曲马朵(M1)浓度的方法。方法:以间乙酰氨基酚为内标,血浆样品经碱化后,用乙酸乙酯提取。HPLC-UV测定采用DiamonsilTM C18色谱柱(250mm×4.6mm),流动相为0.01mol·L-1磷酸二氢钾缓冲液(含三乙胺0.005mol·L-1,磷酸调pH3.0)-乙腈(79:21),流速:1.0ml·min-1,紫外检测波长:218nm。结果:本实验条件下各物质分离良好,对乙酰氨基酚在0.2-21.6μg·ml-1范围呈线性,曲马朵及其代谢物M1分别在10-720和5-160ng·ml-1范围呈线性。对乙酰氨基酚的最低检测限为0.2μg·ml-1,曲马朵和M1的最低检测限分别为10和5ng·ml-1。三种物质的方法回收率均在80%-120%范围内,提取回收率均在75%以上。结论:本法简单、快速,可用于人血浆中对乙酰氨基酚/曲马朵及M1的同时检测。     

曲马朵急性戒断反应诱导小鼠大脑皮层μ受体mRNA表达增加

目的 :从分子水平探讨曲马朵急性戒断机理及 5 -羟色胺酸、育亨宾对曲马朵急性戒断反应的影响。方法 :利用RT -PCR技术研究小鼠大脑皮层 μ受体mRNA表达的变化。 结果 :曲马朵急性戒断小鼠 μ受体mRNA的表达明显升高 ,增加了 15 3.3% ,而育亨宾和 5 -HTP可抑制曲马朵急性戒断诱导的 μ受体mRNA改变。 结论 :中枢 5 -羟色胺系统和去甲肾上腺素系统对曲马朵急性戒断诱导的小鼠大脑皮层 μ受体mRNA高表达具有调节作用     

曲马朵对吗啡所致小鼠僵住症的影响

目的　观察曲马朵是否对吗啡所致小鼠僵住症产生影响及其作用机制。方法　采用“抓棒”实验测定小鼠的僵住持续时间。结果　①曲马朵在10～ 90mg·kg- 1范围内不能诱发小鼠产生僵住症 ,但呈剂量依赖性抑制 4 0mg·kg- 1吗啡诱发的小鼠僵住症 ;②氟西汀 (2 0 ,30和 4 0mg·kg- 1)、吗氯贝胺(12 .5 ,2 5 ,5 0mg·kg- 1)、5 羟色氨酸 (12 .5 ,2 5和 5 0mg·kg- 1)增强曲马朵抑制吗啡所致小鼠僵住症的作用 ;③对氯苯丙氨酸 (30 0和 35 0mg·kg- 1)拮抗曲马朵对吗啡所致小鼠僵住症的抑制作用。结论中枢 5 HT能神经系统参与曲马朵对吗啡所致小鼠僵住症的抑制作用。     

盐酸曲马朵滴剂的HPLC测定

以ＨｙｐｅｒｓｉｌＯＤＳ为色谱柱、乙腈－二乙胺缓冲液（２０８０）为流动相，采用ＲＰ－ＨＰＬＣ法测定盐酸曲马朵滴剂的含量。曲马朵与其顺式异构体、辅料中抗氧剂成分能完全分离。平均回收率为１００．８５％，ＲＳＤ为０．８０％。     

不同剂量曲马朵治疗全身麻醉术后寒战疗效比较

目的 比较不同剂量曲马朵治疗全身麻醉术后寒战的临床疗效以及不良反应发生情况,探讨曲马朵治疗全身麻醉术后寒战的适宜剂量.方法 选取进行全身麻醉腹部手术的患者87例,并按患者意愿分为五组.对照组17例不给予曲马朵治疗;观察1组17例静脉注射曲马朵0.5 mg/kg进行治疗;观察2组17例静脉注射曲马朵1.0 mg/kg进行治疗;观察3组18例静脉注射曲马朵1.5 mg/kg进行治疗;观察4组18例静脉注射曲马朵2.0 mg/kg进行治疗.治疗后,对发生寒战患者的寒战程度进行评分,观察五组患者治疗前后寒战评分的差异,比较不同剂量曲马朵治疗全身麻醉术后寒战的临床疗效以及不良反应发生情况.结果 使用曲马朵治疗可明显降低患者的寒战评分,提高疗效,各组不良反应发生率分别为0.00％、0.00％、0.00％、5.56％、61.11％,总有效率分别为11.76％、70.59％、100.00％、94.44％、77.78％.观察2组的临床疗效明显优于其他组,差异有统计学意义(x2 =9.85,P＜0.05).结论 曲马朵使用剂量为1.0 mg/kg或1.5 mg/kg,既能显著提高全身麻醉术后寒战的临床疗效,又能减少不良反应的发生,是临床上治疗该病的最佳剂量,值得在临床上推广使用.     

曲马朵预防术后早期疼痛的效果分析

目的 探讨曲马朵预防术后早期疼痛的效果.方法 采用回顾性分析的方法,分析择期手术患者300例临床资料,依据术后镇痛方式不同,分为曲马朵组150例和常规组150例,比较两组疼痛缓解情况.结果 曲马朵组患者疼痛缓解总有效率明显高于常规组(x2 =14.25,P＜0.05),曲马朵组患者术后恶心、呕吐、皮肤瘙痒、尿潴留等不良反应发生率明显低于常规组(x2 =6.93,6.93,2.02,2.02,均P＜0.05).结论 曲马朵预防术后早期疼痛的效果明显,安全性好,值得临床应用.     

盐酸曲马朵胶囊依赖1例

盐酸曲马朵胶囊作为一种镇痛药物,近几年来已广泛用于临床各科,尤其是在骨外科及戒毒临床使用更为普遍。本文报道１例严重的曲马朵胶囊依赖者。患者,女,３１ａ。１９９５年４月因车祸致使腰椎４、５、６椎骨粉碎性骨折,多处软组织受伤,昏迷８ｄ。２个月临床治愈后,智商、记忆力及精神症状都无明显影响,但因外伤处隐痛,开始每日服用盐酸曲马朵４片(每片５０ｍｇ)。持续服用近４个月后,感觉每日服用４片曲马朵胶囊,控制不了自己一种说不出的不适感觉。于是在以后的７个多月时间里,将曲马朵的用量逐渐增至每日６片、８片、１４片、２０片直至２…     

双氯芬酸栓与曲马朵用于下腹部手术后镇痛的疗效观察

下腹部手术后疼痛目前多采用哌替啶或曲马朵等针剂注射镇痛。2 0 0 1年 2月至 2 0 0 2年 2月 ,我们对 38例下腹部手术后疼痛病人采用双氯芬酸 (双氯灭痛 )栓直肠给药进行镇痛 ,并与肌注曲马朵镇痛对比 ,报告如下。1　资料与方法1.1　临床资料　双氯芬酸栓组 38例均为住院病人 ,男性 2 7例 ,女性 11例。年龄 (4 3± 5 )岁 (19～ 6 8岁 )。其中阑尾切除术 18例 (4 7.4 % ) ,腹股沟疝修补术 11例 (2 9.9% ) ,子宫切除术 2例(5 .3% ) ,卵巢囊肿摘除术 4例 (10 .5 % ) ,其他手术 3例 (占7.9% ) ,另有曲马朵组 38例 ,男性 2 9例 ,女性 9例。年龄 (…     

曲马朵的临床应用及不良反应发生的现状

目的：介绍镇痛药曲马朵的药理作用、临床应用和不良反应发生的现状。方法：从曲马朵的药理学特点,临床应用和收集近10年国内发生不良反应的文献资料,探讨曲马朵的镇痛疗效及不良反应的发生。结果：曲马朵具有镇痛作用较强,技术时间较长,依赖性潜力较低的特点,不能替代阿片类毒品起戒毒作用;曲马朵1次用量≥100mg的剂量及多次给药时,不仅有常见的,也可能出现严重的不良反应。结论：曲马朵可用于缓解临床各种中度至次重度疼痛,应加强管理,防止滥用。     

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.     

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.