特异性鲎试剂对利巴韦林葡萄糖注射液的细菌内毒素检查法的研究

目的：考察特异性鲎试剂对利巴韧林葡萄注射液的细菌内毒素的可行性。方法;采用干扰初筛实验、抑制增强实验,并特细菌内毒素检查法与家兔法检查法检测结果作经。结果：利巴韦林葡萄３糖注射液对特异性鲎试剂灵敏度无干扰。结论：选用特异性鲎试剂,可用鲎试剂法检查其热原。     

利巴韦林葡萄糖注射液细菌内毒素检测方法的研究

目的：建立利巴韦林葡萄糖注射液的细菌内毒素检查方法。方法：细菌内毒素检查法的干扰试验及对照试验。结果：样品无干扰作用，且与家兔法一致。结论：用鲎试剂检测利巴韦林葡萄糖注射液细菌内毒素是可行的。     

利巴韦林注射液细菌内毒素的检验

本文采用抑制增强试验的原理,对利巴韦林注射液的细菌内毒素检查进行考察,经对6批利巴韦林注射液的抑制增强试验研究。结果表明：细菌内毒素检查法对利巴韦林注射液8倍稀释液对灵敏度为0．25EU.ml^-1的鲎试剂反应没有出现抑制或增强作用。故本品适用于鲎试剂作细菌内毒素检查。     

利巴韦林葡萄糖注射液内毒素检测

探讨细菌内毒素检查法检测利巴韦林葡萄糖注射液中内毒素的可行性。结果：利巴韦林葡萄糖注射液经４倍稀释后对鲎试剂无干扰,可选用灵敏度为０．１２５Ｅｕ／ｍｌ的鲎试剂检测利巴韦林葡萄注射液的细菌内毒素。     

利巴韦林注射液细菌内毒素检测

目的:建立利巴韦林注射液细菌内毒素的检查方法.方法:用两个生产厂家的鲎试剂至5批样品,把中国药典2000年版二部附录ⅪE方法进行干扰试验考察.结果:利巴韦林注射液最大非干扰浓度为20mg·ml-1,其细菌内毒素限值可定为0.125EU·mg-1.因此可选用灵敏度(λ)为0.5EU·ml-1的鲎试剂,将样品稀释至4mg·ml-1后进行细菌内毒素检查.结论:可以用细菌内毒素检查法(凝胶法)代替家兔热原检查法控制其热原.     

利巴韦林葡萄糖注射液内毒素检测

探讨细菌内毒素检查法检测利巴韦林葡萄糖注射液中内毒素的可行性.结果:利巴韦林葡萄糖注射液经4倍稀释后对鲎试剂无干扰,可选用灵敏度为0.125Eu/ml的鲎试剂检测利巴韦林葡萄注射液的细菌内毒素.     

利巴韦林葡萄糖注射液内毒素检测

探讨细菌内毒素检查法检测利巴韦林葡萄糖注射液中内毒素的可行性.结果:利巴韦林葡萄糖注射液经4倍稀释后对鲎试剂无干扰,可选用灵敏度为0.125Eu/ml的鲎试剂检测利巴韦林葡萄注射液的细菌内毒素.     

氧氟沙星注射液细菌内毒素检查的研究

目的：探讨用鲎试剂检查氧氟沙星注射液细菌内毒素的可行性。方法：对家兔热原检查合格的氧氟沙星注射液作细菌内毒素检查的干扰试验。结果：氧氟沙星对鲎试剂的细菌内毒素检查无干扰.结论：鲎试剂可用于氧氟沙星注射液的细菌内毒素检查。     

细菌内毒素检测法用于奥硝唑注射液的可行性研究

目的：建立奥硝唑注射液的细菌内毒素检查方法。方法：采用细菌内毒素凝胶法,用不同生产厂家的鲎试剂对提供的奥硝唑注射液连续3批样品进行了干扰试验。结果：将奥硝唑注射液稀释至2mg·ml^-1,用灵敏度分别为0．25EU·ml^-1和0．125EU·ml^-1的鲎试剂检测细菌内毒素,无干扰因素影响。结论：奥硝唑注射液的细菌内毒素限值确定为0．3EU·mg^-1,可应用鲎试剂进行细菌内毒素法检查。     

痰热清注射液细菌内毒素检查

目的：建立痰热清注射液细菌内毒素的检查法。方法：用不同厂家、不同批号、不同灵敏度的鲎试剂对痰热清注射液进行干扰实验。结果：用标示灵敏度为0．25EU·ml^-1的鲎试剂,痰热清注射液稀释1：65倍数后,对细菌内毒素检查无干扰作用。结论：痰热清注射液可以用细菌内毒素检查法。     

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.     

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.     

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.