乳糖酸红霉素细菌内毒素检查法研究

从乳糖酸红霉素细菌内毒素检查法的干扰实验入手,确定了方法的可行性。对全国九个主要生产厂各三批制品中的内源性细菌内毒素进行检测,23份样品中细菌内毒素含量低于或等于理论限值,4份样品超过理论限值,而家兔热原检查均视合格。文章表明:为了彻底解决乳糖酸红霉素热原检查中的家兔降温问题,可以采用细菌内毒素检查法,控制药品的热原指标。     

动态浊度法测定人参多糖注射液中细菌内毒素的含量

目的建立测定人参多糖注射液中细菌内毒素含量的方法。方法建立动态浊度法测定细菌内毒素标准曲线,通过测定供试液中外加内毒素的回收率进行干扰试验,确定样品检测浓度线性范围,并定量测定样品中的细菌内毒素。结果内毒素检测浓度线性范围为0.031 25².0 EU·mL-1(r=-0.998 9);样品在稀释36倍及以下时,对试验无干扰作用,细菌内毒素回收率在50%2.0 EU·mL-1(r=-0.998 9);样品在稀释36倍及以下时,对试验无干扰作用,细菌内毒素回收率在50%²00%范围内,样品中的内毒素含量可定量测定。结论动态浊度法可用于人参多糖注射液中细菌内毒素的定量检测。     

鲎试验检测甘氨酰谷氨酰胺中细菌内毒素的方法学研究

目的:确定甘氨酰谷氨酰胺细菌内毒素鲎试验检查法的可行性.方法:供试品干扰试验后,采用凝胶鲎试验对样品中的细菌内毒素进行检测.结果:三批样品稀释至20 mg/mL、10 mg/mL时,对细菌内毒素的检测均无干扰作用,样品中细菌内毒素的含量均小于0.025 EU/mg.结论:所建立方法检查甘氨酰谷氨酰胺的细菌内毒素可行.     

细菌内毒素定量测定法(动态比浊法)测定茵栀黄注射液中细菌内毒素含量

目的应用细菌内毒素定量测定法(动态比浊法)定量测定茵栀黄注射液中的细菌内毒素含量.方法通过对样品中定量添加标准内毒素的干扰试验,检测其回收率应在50%～200%范围.结果将样品进行1/30稀释可以有效地消除其对鲎试验的干扰.结论细菌内毒素定量测定法(动态比浊法)可以高效地测定样品中的细菌内毒素含量.     

细菌内毒素定量测定法(动态比浊法)测定茵栀黄注射液中细菌内毒素含量

目的:应用细菌内毒素定量测定法(动态比浊法)定量测定茵栀黄注射液中的细菌内毒素含量 .方法:通过对样品中定量添加标准内毒素的干扰试验,检测其回收率应在50%～200%范围 .结果:将样品进行1/30稀释可以有效地消除其对鲎试验的干扰.结论:细菌内毒素定量测定法(动态比浊法)可以高效地测定样品中的细菌内毒素含量.     

甲氨蝶呤冻干粉针剂细菌内毒素检查方法的研究

目的 探讨甲氨蝶呤冻干粉针剂进行细菌内毒素检查的可行性.方法 采用凝胶法鲎试验对样品中的细菌内毒素进行检测.结果 3批甲氨蝶呤冻干粉针剂在稀释成0.125 mg/ml浓度下对细菌内毒素检查均没有干扰作用;所测样品的细菌内毒素含量均小于2.4 EU/mg.结论 可建立甲氨蝶呤冻干粉针剂的细菌内毒素检查法,日常细菌内毒素检查时可将甲氨蝶呤在冻干粉针剂稀释成0.125mg/ml的水溶液以排除其干扰作用.     

采用鲎试剂检查低分子量肝素钙注射液中细菌内毒素的可行性研究

目的:探讨采用鲎试剂法对低分子量肝素钙注射液进行细菌内毒素检查的可行性。方法:采用动态浊度法和凝胶法,通过干扰试验,对样品中的细菌内毒素进行定性和定量检测。结果:将样品中低分子量肝素钙含量稀释至25I U/ml时对鲎试验检查有明显的干扰作用,而稀释至12·5I U/ml时则无干扰作用,样品中细菌内毒素的含量均小于0·01EU/I U。结论:本文建立的低分子量肝素钙注射液细菌内毒素检查法可行。     

动态比浊法定量测定维生素C注射液中细菌内毒素含量

目的:应用动态比浊法细菌内毒素试验定量测定维生素C注射液中的细菌内毒素含量。方法:通过对样品中定量添加标准内毒素的干扰试验,检测20倍稀释的样品液,其回收率在50％～200％范围。结果:维生素C注射液原液对本试验具干扰作用,而20倍稀释的样品液则无干扰作用。结论:应用动态比浊法细菌内毒素试验可以测定样品中的细菌内毒素含量。     

凝胶法鲎试验检测金纳多注射液中的细菌内毒素

目的应用凝胶法鲎试验检测金纳多注射液中的细菌内毒素含量.方法经干扰试验验证样品在若干稀释倍数下,对鲎试验无干扰作用.结果将样品进行1/6稀释可以有效地消除其对鲎试验的干扰.结论凝胶法鲎试验可以检测金纳多注射液中的细菌内毒素含量.     

动态浊度法测定注射用比阿培南细菌内毒素的含量

目的:建立测定注射用比阿培南细菌内毒素含量的方法。方法:采用动态浊度法,确定细菌内毒素检查的标准曲线及稀释倍数,通过干扰试验确定样品质量浓度测定范围,并对样品的细菌内毒素进行定量测定。结果:比阿培南质量浓度在0.062 5~0.25 mg/ml范围内对试验无干扰,细菌内毒素的回收率在50%~200%之间,比阿培南中的内毒素含量可定量测定。结论:动态浊度法可用于注射用比阿培南细菌内毒素的定量检测。     

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.