新型双氯芬酸钠缓释片的人体相对生物利用度研究

８名健康男性志愿者单剂量交叉口服１００ｍｇ受试双氯芬酸钠缓释片、扶他林或ＶｏｌｔａｒｅｎＳＲ１００后,Ｔｍａｘ分别为２．４±１．０、２．１±０．５和４．４±１．８ｈ;Ｃｍａｘ分别为６０２．６±９２．８、３３３７．６±１０８８．２　７６１．０±３４２．０ｎｇ／ｍｌ;ＭＲＴ分别为１３．２±４．８、２．９±０．８和７．９±１．９ｈ;ＡＵＣ０分别为４８６６．２±６４４．６、５３１４．３±５３４．３和４８２９．１±５８２．８ｎｇ／（ｍｌ－１·ｈ）;双氯芬酸钠缓释片和ＶｏｌｔａｒｅｎＳＲ１００相对于扶他林的生物利用度分别为８８．３±１３．２％和８６．３±１２．６％。另８名志愿者交叉口服受试双氯芬酸钠缓释片（１００ｍｇ,ｐｄ）和扶他林（５０ｍｇ,ｂｉｄ〕,连服５天。Ｃｍａｘ分别为５９３．９±１３４．１、１２４７．８±５２７．５ｎｇ／ｍｌ,峰谷波动率（ＰＴＦ）分别为３．３±１．２、５．３±２．１。本研究将为新型双氯芬酸钠缓释片的临床应用提供依据。     

复方乳酸钠注射液的原子吸收光谱测定

采用原子吸收光谱法直接测定复方乳酸钠注射液的含量。加入１％ＣｓＣｌ可消除Ｋ＋、Ｎａ＋共存时的增感效应，使测定结果准确、可靠。本法回收率分别为：１０２．２±１．６％（Ｎａ＋），１０１．１±１．１％（Ｋ＋），１００．１±１．２％（Ｃａ＋＋）。     

毛细管气相色谱法测定撒烈痛片含量

本文采用毛细管气相色谱法测定撒烈痛片的含量。色谱柱：交联ＳＥ－５４弹性石英毛细管柱（０．２５ｍｍｉｄ×２５ｍ），氢火焰离子化检测器（ＦＩＤ），进样量在０．３ｍｇ－１．３ｍｇ内４种成分与峰面积比呈直线相关（非那西丁：ｙ＝２．９５５４ｘ－０．１２８１，ｒ＝０．９９９５；咖啡因：ｙ＝１．５５８４ｘ－０．０２５７，ｒ＝０．９９９４；氨基比林：ｙ＝１．１６５３ｘ－０．０８９３，ｒ＝０．９９９２；苯巴比妥：ｙ＝２．５３５ｘ－０．１７５４，ｒ＝０．９９９８）。平均回收率±标准差分别为１００．２％±１．１７％、９９．８％±１．９４％、１００．５％±１．４６％、９８．４％±１．８２％。     

紫外分光光度法测定痤疮搽剂中甲硝唑和氯霉素的含量

本文应用差示分光光度法和单波长分光光度法，在３２２ｎｍ和２７８ｎｍ波长处，测定痤疮搽剂中甲硝唑和氯霉素的含量。回收率分别为１００．５±０．７％和１００．４±１．３％。此法适宜于医院制剂分析。     

原子吸收光谱法测定乳酸钠林格氏液的含量

建立了用原子吸收光谱法直接测定乳酸钠林格氏液中Ｎａ＋、Ｋ＋、Ｃａ＋＋的含量的方法。在测定时加入１％ＣｓＣｌ可消除碱金属离子Ｋ＋、Ｎａ＋共存时的增感效应，使测定结果准确、可靠，方法回收率分别为：１０２．２％±１．６％（Ｎａ＋）、１０１．１％±１．１％（Ｋ＋），１００．１％±１．２％（ａ＋Ｃ＋）     

Effects of heparin on growth factor-induced mitogenic and proliferative responses of rat pulmonary a

目的：探讨肝素是否能抑制生长因子诱导的大鼠肺动脉平滑肌细胞（ＰＡＳＭＣ）分裂和增殖．方法：应用含１０％ＦＢＳ的Ｍ１９９培养液培养大鼠ＰＡＳＭＣ．细胞分裂及细胞增殖分别用［ｍｅｔｈｙｌ３Ｈ］ＴｄＲ和细胞计数监测．结果：ＦＢＳ（１０％），以及ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联合应用均能增加大鼠ＰＡＳＭＣ分裂．肝素（１００ｍｇ·Ｌ－１）抑制１０％ＦＢＳ诱导的大鼠ＰＡＳＭＣ增殖（２８％±６％）和胸腺嘧啶摄取反应（２７％±７％），抑制ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联用诱导的大鼠ＰＡＳＭＣ增殖（２５％±６％，２７％±７％，２０％±４％），以及胸腺嘧啶摄取反应（２３％±７％，２６％±６％，２０％±６％）．结论：肝素抑制生长因子诱导的大鼠ＰＡＳＭＣ的分裂与增殖．     

偏最小二乘法－紫外分光光度法同时快速测定多组分的含量

本文用偏最小二乘－紫外分光光度法同时测定复方水杨酸搽剂中水杨酸、间苯二酚和苯酚的含量。平均回收率分别为：１００．４±０．６％、１０１．５±０．８％和９９．５±１．０％（置信度９５％）。实测３批样品，结果准确、可靠。     

离子对液相色谱法测定活络灵胶囊中非那宗、维生素B_1和维生素B_6的含量

在μＢｏｎｄａｐａｋＣ１８柱上，乙腈—水相（取辛烷基磺酸钠０．３２ｇ、三乙胺２ｍＬ，冰醋酸１０ｍＬ，加水至１０００ｍＬ）（１３∶８７）为流动相，同时分离和测定活络灵胶囊中非那宗、维生素Ｂ１和维生素Ｂ６。检测波长２８０ｎｍ。三成分的线性关系良好，６次测定的回收率±ＲＳＤ分别为（１００．１７±０．０４）％、（９９．９０±０．２２）％、（１００．１７±０．６２）％。     

褶合光谱法测定复方雷琐辛醇溶液中三组分的含量

本文用褶合光谱法不经分离同时测定雷琐辛、苯酚、水杨酸的含量取得了较满意的结果。平均回收率（ＥＲ）和相对平均偏差（ＲＳＤ）分别为１００．４１％、１００．２２％、１００．１５％、１．０４％、１．７５％、１．５０％。     

人血白蛋白的两种低温乙醇工艺的比较

以正常人新鲜冰冻血浆作原料，采用低温乙醇Ｃｏｈｎ５法相６法进行对照性中量试生产。结果表明，Ｃｏｈｎ６法所得白蛋白半制品的３批收率平均为２．４４±０．１ｇ／１００ｍｌ血浆，纯度平均为９８．６±０．６％，分别比Ｃｏｈｎ５法提高０．１２ｇ／１００ｍｌ血浆和１％；就分离白蛋白而言，Ｃｏｈｎ６法较Ｃｏｈｎ５法更为理想。     

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.     

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.