萘丁美酮代谢物MNAA对人尿褪黑素水平的影响

采用高效液相荧光法（ｅｘλ＝２９５ｕｍ，ｅｍλ＝３４０ｎｍ）同步检测人尿中萘丁美酮（ＮＡＢ）的主要代谢物６－甲氧基－２－萘乙酸（ＭＮＡＡ）及褪黑素（ＭＴ）。５名男性志愿者于１８点口服５００ｍｇＮＡＢ后，尿中ＭＴ累积量仍呈昼夜变化节律，其累积量分别从未服药前的每１２小时２７４．０±５８ｐｍｏｌ（夜晚）和７７．６±２５ｐｍｏｌ（白天）减少至１４５．６±３２ｐｍｏｌ（夜晚）和５０．３±１２ｐｍｏｌ（白天）（Ｐ值均小于０．０１）。依照尿中的ＭＮＡＡ消除速率对中点时间作曲线，求得ＭＮＡＡＴ为２２．５ｈ，ＴＰＫ为１４．２ｈ，与已知报告的血浆中数值相近。相关分析证明，ＭＴ累积量抑制与ＭＮＡＡ消除速率相关（ｒ＝０．９６４４，Ｐ＜０．０５）。ＭＮＡＡ在尿中９６ｈ的累积量仅占口服５００ｍｇＮＡＢ的３．５％，高于ＨａｄｄｏｃｋＲＥ采用同位素得出１％的结论。     

年龄对萘丁美酮胶囊药物动力学的影响

萘丁美酮为一新型非甾体抗炎药物，具有药效强、毒副作用小、半衰期长等优点，是一个大有发展前途的药物。本文研究了年龄对萘丁美酮胶囊剂的药物动力学的影响，对青年和中年受试者单剂量口服萘丁美酮胶囊剂１０００ｍｇ后，６－ＭＮＡ的药物动力学参数用ｔ检验进行比较。结果表明：全部药物动力学参数无显著性差异（ｐ＞０．０５）．通过本实验的结果可以看出：萘丁美酮在中青年受试者中的药物动力学无明显的差异。     

NO对去甲吗啡在离体豚鼠回肠上依赖性耐受性产生的作用

目的观察 ＮＯ合酶（ ＮＯ ｓｙｎｔｈａｓｅ,ＮＯＳ）抑制剂左旋硝基精氨酸（ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ,ＮＯＡｒｇ）和 ＮＯ合成前体左旋精氨酸（Ｌ－ａｒｇｉｎｉｎｅ,Ｌ－Ａｒｇ）对去甲吗啡（ｎｏｒｍｏｒｐｈｉｎｅ,ＮＭ）在离体豚鼠回肠上依赖性耐受性产生的影响,研究ＮＯ在阿片类药物依赖性耐受性产生中的作用。方法以离休豚鼠回肠为实验对象,４℃孵育６ ｈ, ２４ ｈ后,分别测定纳洛酮（ｎａｌｏｘｏｎｅ,Ｎｘ）与氯化乙酰胆碱（ａｃｅｔｙｌｃｈｏｌｉｎｅ,Ａｃｈ）引起的收缩高度比值,作为依赖性产生的指标。在耐受性产生实验中,分别测定回肠空白组和药物组４℃孵育３ｈ后对ＮＭ抑制电刺激收缩的剂量反应曲线。结果回肠分别经ＮＭ,ＮＭ加ＮＯＡｒｇ,ＮＭ加Ｌ－Ａｒｇ中孵育６ｈ后,纳洛酮均可使其产生戒断收缩,且两组与Ａｃｈ的收缩高度比值差异无显著性（ｎ＝６）, Ｐ＞０．０５。而孵育２４ ｈ后,ＮＭ,ＮＭ加 Ｌ－Ａｒｇ组收缩高度比值分别为 ０． ８９±０． ０２, ０． ９０±０． ０２, Ｐ＞ ０． ０５,而ＮＭ加ＮＯＡｒｇ药物组对纳洛酮的戒断收缩反应明显减弱,收缩高度比值为 ０．４７± ０．０５（ｎ＝ ６, Ｐ＜ ０．０１）。可见ＮＭ加ＮＯＡ?     

亚硫酸氢钠裂解6－甲氧基－2－萘乙酮肟

亚硫酸氢钠裂解６－甲氧基－２－萘乙酮肟赵文超，沙耀武（清华大学化学系，北京１０００８４）ＣＬＥＡＶＡＧＥＯＦ６－ＭＥＴＨＯＸＹ－２－ＡＣＥＴＯＮＡＰＨＴＨＯＮＯＸＩＭＥＢＹＳＯＤＩＵＭＢＩＳＵＬＦＩＴＥ￥ＺＨＡＯＷｅｎ－Ｃｈａｏ；ＳＨＡＹａｏ－Ｗｕ（...     

萘丁美酮合成路线图解

萘丁美酮合成路线图解楼定忠，朱坡，刘泽贵（西南制药二厂，重庆６３００６１）ＧＲＡＰＨＩＣＡＬＳＹＮＴＨＥＴＩＣＲＯＵＴＥＳＯＦＮＡＢＵＭＥＴＯＮＥ￥ＬＯＵＤｉｎｇ－Ｚｈｏｎｇ；ＺＨＵＰｏ；ＬＩＵＺｅ－Ｇｕｉ（ＳｏｕｔｈｗｅｓｔＮｏ．２Ｐｈａｒｍａｃｅ...     

阿克拉霉素A毫微囊制备工艺及抑瘤试验

本文以氰基丙烯酸正丁酯（ＢＣＡ）为囊材制备了阿克拉霉素Ａ毫微囊（ＡＣＭ－Ａ－ＮＣ），利用均匀设计方案选出了较佳处方，加冻干赋型剂制得了阿克拉霉素Ａ毫微囊冻干品，冻干前后的平均粒经分别为（１２０±３４）ｎｍ和（１４６±３３）ｎｍ，应用凝胶过滤色谱法得阿克拉霉素Ａ的包封率为４７．６％，并进行了ＡＣＭ－Ａ－ＮＣ的ＬＤ５０测定以及对Ｓ１８０肉瘤，Ｐ３８８白血病的抑瘤实验，结果表明，ＡＣＮ－Ａ－ＮＣ降低了ＡＣＭ－Ａ的毒性，其抗癌活性也有所改善。     

2－（N－苄基－N－甲基）氨基乙醇的制备

２－（Ｎ－苄基－Ｎ－甲基）氨基乙醇的制备杜玉民，陈子明，鲍春和，耿惠琳（河北医学院药学系，石家庄０５００１７）ＰＲＥＰＡＲＡＴＩＯＮＯＦ２－（Ｎ－ＢＥＮＺＹＬ－Ｎ－ＭＥＴＨＹＬ）ＡＭＩＮＯＥＴＨＡＮＯＬ￥ＤＵＹｕ－Ｍｉｎ；ＣＨＥＮＺ１－Ｍｉｎｇ；ＢＡ...     

6－甲氧基－2－萘乙酮制备的改进

６－甲氧基－２－萘乙酮制备的改进南柱石（湖北制药厂药物研究所，襄樊４４１０２３）ＩＭＰＲＯＶＥＤＰＲＥＰＡＲＡＴＩＯＮＯＦ６－ＭＥＴＨＯＸＹ－２－ＡＣＥＴＯＮＡＰＨＴＨＯＮＥ￥ＮＡＮＺｈｕ－Ｓｈｉ（ＩｎｓｔｉｔｕｔｅｏｆＰｈａｒｍａｃｅｔｕｔｉｃｓ，...     

自体LAK细胞回输联合α－IFN或Ara－AMP治疗CHB疗效追踪观察

自体ＬＡＫ细胞回输联合α－ＩＦＮ或Ａｒａ－ＡＭＰ治疗ＣＨＢ疗效追踪观察中国人民解放军第１８０医院南京军区临床肝病研究中心周佳彦，王崇国近年来在寻找治疗慢性乙肝（ＣＨＢ）的理想药物中，我们试用重组α干扰素（ＩＦＮα－２ａ）或单磷酸阿糖腺苷（Ａｒａ－ＡＭ...     

阿克拉霉素A毫微囊制备工艺及抑瘤试验

本文以氰基丙烯酸正丁酯（ＢＣＡ）为囊材制备了阿克拉霉素Ａ毫微囊（ＡＣＭ－Ａ－ＮＣ），利用均匀设计方案选出了较佳处方，加冻干赋型剂制得了阿克拉霉素Ａ毫微囊冻干品，冻干前后的平均粒经分别为（１２０±３４）ｎｍ和（１４６±３３）ｎｍ，应用凝胶过滤色谱法得阿克拉霉素Ａ的包封率为４７．６％，并进行了ＡＣＭ－Ａ－ＮＣ的ＬＤ５０测定以及对Ｓ１８０肉瘤，Ｐ３８８白血病的抑瘤实验，结果表明，ＡＣＮ－Ａ－ＮＣ降低了Ａ     

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.     

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.     

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.