青霉烷酸二苯甲酯1β—氧化物的合成

６－ＡＰＡ经重氮化、溴化及在二苯腙存在下用过乙酸氧化得６，６－二溴青霉烷酸二苯甲酯１β－氧化物，后者经还原脱溴制得三唑巴坦中间体——青霉烷酸二苯甲酯１β－氧化物。     

含γ-苄谷氨酸的修饰性多肽作为药物载运平台

为研究修饰性多肽结构对药物释放的作用，合成了３种含γ－苄谷氨酸的修饰性多肽，分别为聚（γ－苄基－Ｌ－谷氨酸，ＰＢＬＧ）、聚（γ－苄基－Ｌ，Ｄ－谷氨酸，ＰＢＤＬＧ）及由ＰＢＬＧ（Ａ）和ＰＥＧ（Ｂ）聚合得到的三嵌段聚合物ＡＢＡ。对上述聚合物的理化性质进行考察后，着重研究了其作为药物载运平台对药物释放速率的影响。研究了自制的３种修饰性多肽的理化性质，包括粘度、分子量、转变温度、接触角、圆二色性及对苯甲酸扩散系数的影响。其中，ＡＢＡ分子量最小，仅为４１ｋｕ，而它却代表了目标单体（ＰＢＬＧ－ＰＥＧ－ＰＢＬ…     

多巴胺转运蛋白显像剂99mTc-TRODAT-1的合成

以可卡因为原料经水解、脱水、甲酯化、４－氯苯基经镁格氏反应、酯水解、酰氯化、等反应,合成了配体ＴＲＯＤＡＴ－１（２）。     

人大脑皮层膜谷氨酸受体的结合特性

用放射性配体受体结合实验研究了人大脑皮层膜与［３￣Ｈ］ＤＬ－谷氨酸结合的特性。人大脑皮层与谷氨酸特异性结合的最适条件是在４℃，ＨＥＰＥＳ缓冲液（ｐＨ６．４－８．６）中孵温３０－４０ｍｉｎ。结合实验前洗涤膜样品至为重要。人大脑皮层膜与谷氨酸特异性结合是可饱和的，其ＫＤ和Ｂｍａｘ值分别为１０３和１．６７ｎｍｏｌ·Ｌ－１蛋白，Ｈｉｌｌ系数１．０６．谷氨酸受体激动剂对人大脑皮层膜与谷氨酸结合的抑制强度依次为Ｌ－谷氨酸＞ＤＬ－谷氨酸＞红藻氨酸＞Ｎ－甲基－Ｄ－天冬氨酸（ＮＭＤＡ）＞Ｄ－谷氨酸。谷氨酸受体亚型拮抗剂２－氨基－５－磷酸基戊酸和６，７－二硝基唑喔啉－２，３－二酮（１ｎｍｏｌ·Ｌ－１）分别取代了５４％和５６％的特异性谷氨酸结合。１．２５ｎｍｏｌ·Ｌ－１镁离子抑制了５５％的特异性谷氨酸结合。人大脑皮层膜与谷氨酸的特异性结合不依赖钠离子，部分依赖于钙离子。人大脑皮层膜与谷氨酸特异性结合至少涉及到ＮＭＤＡ和红藻氨酸两个谷氨酸受体亚型。     

γ—亚麻酸甲酯乳剂小肠吸收动力学研究

本文采用大鼠在、离体小肠吸收实验，并结合体内法对γ－亚麻酸甲酯乳剂（γ－ＬＡＭＥ）的小肠吸收进行研究，γ－ＬＡＭＥ吸收率为８５％；胆管结扎与不结扎吸收率地显著性差异；其吸收机制属被动扩散，γ－ＬＡＭＥ大鼠幽门静脉及灌胃给药，其生物利用度分别为７４．４％及９２％．     

γ-亚麻酸甲酯乳剂小肠吸收动力学研究

本文采用大鼠在、离体小肠吸收实验，并结合体内法对γ－亚麻酸甲酯乳剂（γ－ＬＡＭＥ）的小肠吸收进行研究。γ－ＬＡＭＥ吸收率为８５％；胆管结扎与不结扎吸收率无显著性差异；其吸收机制属被动扩散．γ－ＬＡＭＥ大鼠幽门静脉及灌胃给药，其生物利用度分别为７４．４％及９２％．     

羧甲基茯苓多糖对人外周血淋巴细胞分泌IFN—α和IFN—γ的调 …

用羧甲基茯苓多糖（ＣＭＰ）预处理人外周血淋巴细胞（ＨＰＢＬ），经２００ＩＵ／ｍｌＩＦＮ－α启动后，加ＮＤＶ的促诱生的α－干扰素（ＩＦＮ－α）效价比无ＣＭＰ的常规诱生组高１．２倍，经ＰＨＡ和／或ＣｏｎＡ促诱生组成的γ－干扰素（ＩＦＮ－γ）产价比无ＣＭ宾ＰＨＡ和ＣｏｎＡ刺激常规诱生组高０．５倍尤以ＣＭＰ＋ＰＨＡ＋ＣｏｎＡ促诱生的ＩＦＮ－γ效果最佳。说明ＣＭＰ具有ＩＦＮ－α和ＩＦＮ－γ促诱生效应。用ＣＭ     

γ－氯丁酸甲酯的合成

γ－氯丁酸甲酯的合成宋慈媛，李正，李彦章，张肖瑜，张瑞兴（太原制药厂研究所，山西０３００２１）ＳＹＮＴＨＥＳＩＳＯＦＭＥＴＨＹＬγ－ＣＨＬＯＲＯＢＵＴＹＬＡＴＥ￥ＳＯＮＧＣｉ－Ｙｕａｎ；ＬＩＺｈｅｎｇ；ＬＩＹａｎ－Ｚｈａｎｇ；ＺＨＡＮＧＸｉａｏ－Ｙｕ...     

γ—亚麻酸甲酯乳剂代谢动力学

本文应用动物全血、组织匀浆体外保温实验和大鼠离体肝脏灌流技术研究了γ－亚麻酸甲酯乳剂的代谢动力学。γ－亚麻酸甲酯在全血中迅速水解；在肝、小肠和肾中也存在代谢；离体肝灌流液中γ－亚麻酸的浓度下降与时间关系经拟合符合单指数方程，消除半衰期为１３．２ｍｉｎ，肝固有消除率为２．４６ｍｌ／ｍｉｎ。     

绞股蓝皂甙XL Ⅲ对小鼠脑内谷氨酸和γ-氨基丁酸的影响

目的研究绞股蓝皂甙ＸＬⅢ（ｇｙｎｏｓａｐｏｎｉｎ，ＧｙｎＸＬⅢ）对小鼠学习记忆获得的影响和其作用机制—对小鼠脑内谷氨酸（Ｇｌｕ）／γ－氨基丁酸（ＧＡＢＡ）的影响。方法跳台法研究ＧｙｎＸＬⅢ对小鼠的学习记忆获得过程的影响；薄层层析法测试小鼠脑内谷氨酸和γ－氨基丁酸的含量。结果Ｇｙｎ－ＸＬⅢ１５ｍｇ·ｋｇ－１，ｉｐ对小鼠的学习记忆获得过程无影响（Ｐ＞０．０５），３０ｍｇ·ｋｇ－１可增强小鼠的学习记忆获得过程１９９７－０８－０６收稿，１９９７－１０－０５修回＊广东药学院科研基金资助课题，Ｎｏ９５１０３３作者简介：冯冰虹，男，３４岁，讲师；杜淇璋，男，６３岁，教授，中国药理学会理事，广东省药理学会专家委员会副主任（Ｐ＜０．０５），并显著提高脑内Ｇｌｕ水平（Ｐ＜０．０５），明显降低ＧＡＢＡ水平（Ｐ＜０．０５）；东莨菪碱（Ｓｃｏｐ）０．３ｍｇ·ｋｇ－１，ｉｐ的结果相反，显著降低Ｇｌｕ水平（Ｐ＜０．０１），提高ＧＡＢＡ水平（Ｐ＜０．０５）；预先ＧｙｎＸＬⅢ３０ｍｇ·ｋｇ－１，ｉｐ，５ｍｉｎ后ｉｐ东莨菪碱０．３ｍｇ·ｋｇ－１，结果显示，ＧｙｎＸＬⅢ扭转Ｓｃｏｐ的升高ＧＡＢＡ作用，使之显著下降（Ｐ＜０．０５），对Ｇｌｕ的影响?     

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.     

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.