气相色谱——质谱法测定人血中丁螺环酮浓度

建立了血浆样品中盐酸丁螺环酮的气相色谱－质谱（ＧＣ－ＭＳ）联用的定量分析方法，血浆样品用二氯甲烷提取，采用ＧＣ－ＭＳ选择离子和辅助定量离子监测，方法的线性范围为０．５～５０ｎｇ／ｍｌ，回收率达８１％以上，并具有较好的准确度和精密度，该方法应用于盐酸相螺环酮临床药代动力学试验中血药浓度的测定，获得了准确，可靠的数据。     

盐酸丁螺环酮合成工序改进

盐酸丁螺环酮合成工序改进粱毅恒，徐燕，谢安云（湖南医药工业研究所，长沙４１００１４）ＩＭＰＲＯＶＥＤＳＹＮＴＨＥＳＩＳＯＦＢＵＳＰＩＲＯＮＥＨＹＤＲＯＣＨＬＯＲＩＤＥ￥ＬＩＡＮＧＹｉ－Ｈｅｎｇ；ＸＵＹａｎ；ＸＩＥＡｎ－Ｙｕｎ（ＨｕｎａｎＩｎｓｔｉｔｕ...     

盐酸丁螺环酮片的溶出度研究

盐酸丁螺环酮片的溶出度研究湖南医药工业研究所４１００１４何燕，刘晓莉盐酸丁螺环酮是抗抑郁的二类新药，副作用小，口服后吸收迅速。为了全面考察其片剂的质量，而进行了溶出度测定方法的研究。一、仪器与试药岛津ＵＶ－３０００分光光度计；天津大学无线电厂ＲＣ－Ⅱ...     

认知行为疗法联合盐酸丁螺环酮片治疗广泛性焦虑患者的临床效果研究

目的探讨认知行为疗法联合盐酸丁螺环酮片治疗广泛性焦虑患者的临床效果。方法 84例广泛性焦虑患者,采用随机数字表法分为盐酸丁螺环酮片治疗组和认知行为疗法联合盐酸丁螺环酮片治疗组,每组42例。盐酸丁螺环酮片治疗组患者采取盐酸丁螺环酮片治疗,认知行为疗法联合盐酸丁螺环酮片治疗组患者则采取盐酸丁螺环酮片联合认知行为疗法治疗。比较两组患者临床疗效;广泛性焦虑症状缓解时间、住院时间;治疗前后焦虑自评量表评分、生活质量评分、汉密尔顿焦虑量表评分;不良反应发生情况。结果认知行为疗法联合盐酸丁螺环酮片治疗组患者的临床总有效率100.00%显著高于盐酸丁螺环酮片治疗组的71.43%,差异具有统计学意义(P<0.05)。治疗后,两组患者的焦虑自评量表评分、汉密尔顿焦虑量表评分、生活质量评分均优于治疗前,且认知行为疗法联合盐酸丁螺环酮片治疗组优于盐酸丁螺环酮片治疗组,差异均具有统计学意义(P<0.05)。认知行为疗法联合盐酸丁螺环酮片治疗组患者的广泛性焦虑症状缓解时间、住院时间分别为(5.35±1.21)、(13.25±2.11)d,短于盐酸丁螺环酮片治疗组患者的(9.73±2.27)、(21.78±5.29)d,差异均具有统计学意义(P<0.05)。两组患者的不良反应发生率比较,差异无统计学意义(P>0.05)。结论盐酸丁螺环酮片联合认知行为疗法治疗广泛性焦虑的效果理想,可进一步改善广泛性焦虑患者的认知功能以及焦虑症状,缓解广泛性焦虑患者的不良情绪。     

离子对RP-HPLC测定盐酸丁螺环酮缓释片中主药的含量

目的　测定盐酸丁螺环酮缓释片中盐酸丁螺环酮的含量。方法　采用离子对反相高效液相色谱法。Nova PakC18色谱柱 ,流动相为甲醇 -乙腈 -离子溶液 (十二烷基硫酸钠 2 5g ,二乙胺 1ml,加水至 10 0 0ml,冰醋酸调pH 3 0 ) (10∶5 0∶4 0 ) ,检测波长为 2 6 5nm。结果　盐酸丁螺环酮的含量在 0 32～ 1 6 μg·ml-1浓度范围内线性关系良好 (r =0 9999)。平均回收率 97 5 6 %(n =5 )RSD =1.13%。结论　所用方法简便、快速、准确。     

SPE结合GC—TID和GC—MS分析血浆中氨基甲酸酯类杀虫剂

目的：建立血浆中氨基甲酸酯类杀剂ＳＰＥ结合ＧＣ－ＦＩＤ和ＧＣ－ＭＳ的系统分析方法。方法：用ＳＰＥＣ Ｍｕｌｔｉ－Ｍｏｄａｌ混合相固相萃取柱建立血浆中５种氨基甲酸酯类杀虫剂的固相萃取方法;采用ＧＣ－ＭＳ作为定性分析工具,将保留时间、特征离子和谱库检索相结合实行多指标定性。结果：５种杀虫剂的绝对回收率在６０％～９６％之间,相对标准偏差小于９％（ｎ＝５）。结论：方法系统性好、快速、准确。     

盐酸丁螺环酮对动物口腔粘膜的渗透性及其机理

目的　研究盐酸丁螺环酮对动物口腔粘膜的渗透性及渗透机理。方法　采用离体动物口腔粘膜的体外渗透试验方法,比较盐酸丁螺环酮对家兔、豚鼠、猪、羊和牛的口腔粘膜渗透性,考察药物浓度及溶液pH值的影响。结果　盐酸丁螺环酮对家兔口腔粘膜的渗透性最大,渗透速率随溶液pH值升高而增大,与药物浓度成正比。结论盐酸丁螺环酮通过口腔粘膜转运的方式为被动扩散,转运途径为穿过细胞途径     

血浆α1—酸性糖蛋白的分离与精制

应用ＤＥＡＥ和ＣＭ纤维素柱在ＨＰＬＣ上进行了多样本血浆中同时对α１－酸性糖蛋白分离和精制的研究，通过将血浆透析，上ＤＥＡＥ和ＣＭ纤维素柱，在ＵＶ检测下收集样品，并真空冷冻干燥使ＡＡＧ得到分离和精制，经ＳＤＳ－ＰＡＧＥ检查，纯度呈单一区带。     

人血中盐酸苯环壬酯的GC－MS／SIM定量测定

建立了血中盐酸苯环壬酯的ＧＣ－ＭＳ／ＳＩＭ的定量分析方法。采用同位素标记物［２Ｈ３］盐酸苯环壬酯为内标，以ｍ／ｚ１３８和ｍ／ｚ１４１为盐酸苯环壬酯和［２Ｈ３］盐酸苯环壬酯的检测离子；方法线性度、回收率、相对标准偏差以及仪器的稳定性均达到定量测定的要求。其最低检测限为２５ｐｇ·ｍｌ－１血浆。该法应用于盐酸苯环壬酯Ⅰ期临床实验中的血药浓度测定，得到了准确、可靠的药代动力学和相对生物利用度数据，为盐酸苯环壬酯的新药报批提供了依据。     

盐酸丁螺环酮的围产期毒性作用

盐酸丁螺环酮是一种具有较强抗焦虑作用的新药，大鼠围产期及哺乳期毒性试验结果表明。本品对Ｃｒｉ：ＣＤ大鼠无致畸胎作用，剂量高于１２ｍｇ／ｋｇ时对母鼠及胎仔有一定的性作用，其无作用剂量为每天给药２ｍｇ／ｋｇ，该剂量相当于人临床用量的３倍，提示就生殖一毒性而言，盐酸丁螺环酮在人临床用量的剂量范围内使用是比较安全的。     

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.     

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.     

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.