替硝唑注射液体外抗厌氧菌作用的研究

报告替硝唑注射液对１６株厌氧菌参考株及１８６株临床厌氧菌分离株的体外抗菌作用，并与甲硝唑注射液比较。结果显示替硝唑对所有厌氧菌实验株均有抗菌活性，对１２５株革兰氏阴性厌氧杆菌有更强的抗菌活性，其ＭＩＣ９０为０．２～０．８ｍｇ／Ｌ；对３１株厌氧球菌的抗菌活性较强，其ＭＩＣ９０为０．８ｍｇ／Ｌ；对革兰氏阳性厌氧杆菌的抗菌作用较其它实验细菌稍差，其ＭＩＣ９０为１２．５～２５ｍｇ／Ｌ。与甲硝唑比较，替硝唑对厌氧菌的抗菌活性略优。     

替硝唑对厌氧菌体外抗菌活性的研究

测定了替硝唑对临床分离的１４８株厌氧菌和２株标准株的ＭＩＣ，确定替硝唑对革兰氏阴性厌氧菌活性最强，其ＭＩＣ为０．０６２～１ｍｇ／Ｌ，它们对梭菌的ＭＩＣ为０．２５～０．５ｍｇ／Ｌ，对革兰氏阳性无芽孢厌氧杆菌，除了真杆菌ＭＩＣ为４ｍｇ／Ｌ外，抗菌活性较低，其ＭＩＣ为大于６４ｍｇ／Ｌ，对厌氧球菌也有相当的活性，其ＭＩＣ为０．２５～１．０ｍｇ／Ｌ。     

国产克林霉素磷酸酯体外抗菌作用研究

国产、进口克林霉素磷酸酯与盐酸克林霉素对革兰氏阳性菌和阴性菌及厌氧菌具有相似的体外抗菌活性，克林霉素磷酸酯经碱性磷酸酯酶水解后，对金葡球菌、表葡球菌抗菌活性与红霉素及氯唑西林相似，ＭＩＣ＿（５０）分别为０．０６２和０．１２５ｍｇ／Ｌ，低于盐酸林可霉素。对一些红霉素耐药的金葡球菌、表葡球菌也有一定抗菌活性，最低ＭＩＣ＿（５０）分别为０．０６２和０．５ｍｇ／Ｌ，对肺炎链球菌、化脓性链球菌具有较好的抗菌活性，ＭＩＣ＿（５０）分别为０．０３１和０．０６２ｍｇ／Ｌ，对革兰氏阳性、阴性厌氧菌具有较强的抗菌活性，ＭＩＣ＿（５０）分别为０．０６２～０．５ｍｇ／Ｌ，ＭＩＣ＿（９０）为０．２５～４ｍｇ／Ｌ。结果表明，克林霉素磷酸酯对金葡球菌、表葡球菌、肺炎链球菌、化脓链球菌ＭＢＣ＿（５０）较其ＭＩＣ＿（５０）高１～４倍，其它结果显示克林霉素磷酸酯不受ｐＨ或接种量影响。     

5种抗菌药物对厌氧菌的体外抗菌活性研究

测定了罗红霉素、ａｚｉｔｈｒｏｍｙｃｉｎ、头孢西丁、托舒沙星对６０株厌氧菌的体外抗菌活性，并同甲硝唑比较，发现托舒沙星对厌氧菌的体外抗菌活性最好，ＭＩＣ_（５０）和ＭＩＣ_（９０）为０．１２５和２ｍｇ／Ｌ优于甲硝唑（０．２５和１６ｍｇ／Ｌ）；罗红霉素（０．５、１６ｍｇ／Ｌ）与甲硝唑相似，ａｚｉｔｈｒｏｍｙｃｉｎ、头孢西丁的体外抗菌活性比甲硝唑略差，ＭＩＣ_（５０）和ＭＩＣ_（９０）分别为４和３２、２和３２ｍｇ／Ｌ，它们对脆弱拟杆菌的体外抗菌活性优于对其它拟杆菌的体外抗菌活性，对短真杆菌、变形链球菌、普氏消化链球菌等也具有较好的体外抗菌活性。     

克林霉素体外抗菌活性研究

研究国产克林霉素对临床分离的７７株需氧菌和９９株厌氧菌的体外抗菌活性，并与林可霉素及其他抗菌药物进行了比较。结果表明：克林霉素对肺炎球菌的ＭＩＣ９０为０．０６ｍｇ／Ｌ，对溶血性链球菌的ＭＩＣ５０为０．０３ｍｇ／Ｌ，均强于林可霉素；对金葡球菌的ＭＩＣ５０为０．０３ｍｇ／Ｌ，强于林可霉素和青霉素Ｇ；对嗜血流感杆菌具中度活性，其ＭＩＣ５０为４ｍｇ／Ｌ；对Ｄ群链球菌作用较差，ＭＩＣ５０＞３２ｍｇ／Ｌ；对脆弱类杆菌的作用比林可霉素强４倍，ＭＩＣ９０分别为４和１６ｍｇ／Ｌ，但较甲硝唑作用稍差；对革兰氏阳性厌氧球菌，克林霉素与青霉素Ｇ的ＭＩＣ９０均≤０．０６ｍｇ／Ｌ，强于其他测试药物；对丙酸杆菌和真杆菌的ＭＩＣ９０分别为≤０．０６和０．１２５ｍｇ／Ｌ。     

Ceftibuten一个新的口服三代头孢菌素

Ｃｅｆｔｉｂｕｔｅｎ是一个口服三代头孢菌素，它对革兰氏阴性杆菌具有较强的抗菌活性，其ＭＩＣ５０为０．２５ｍｇ／Ｌ，ＭＩＣ９０为８ｍｇ／Ｌ。但对链球菌的抗菌活性弱，其ＭＩＣ５０为２ｍｇ／Ｌ，ＭＩＣ９０为４ｍｇ／Ｌ。Ｃｅｆｔｉｂｕｔｅｎ对ＴＥＭ型的超广谱β－内酰胺酰稳定。     

12种药物对临床分离厌氧菌的体外抗菌活性测定

测定了１２种药物对临床分离的３０株厌氧菌和３株标准菌株的ＭＩＣ，确定甲哨唑和ｃｌａｒｉｔｈｒｏｍｙｃｉｎ对革兰氏阴性厌氧菌的抗菌活性最强，其ＭＩＣ为０．５～１μｇ／ｍｌ．其次为大环内酯９４１和国产ｃｌａｒｉｔｈｒｏｍｙｃｉｎ（４μｇ／ｍｌ）及林可霉素和红霉素（８μｇ／ｍｌ），它们对于革兰氏阳性厌氧菌（包括梭菌）及消化链球菌也有相当的活性，而环丙氟啶酸、依诺沙星、头孢克罗、环丙沙星等抗厌氧菌拟杆菌活性较低；其ＭＩＣ为１６～６４μｇ／ｍｌ。     

新脂肽类抗生素达托霉素的抗菌活性及临床研究进展

在体外抗菌活性研究中,达托霉素（ｄａｐｔｏｍｙｃｉｎ）对革兰氏阳性菌耐药突变株表现出杰出的活性,其中对甲氧西林耐药性金黄色葡萄球菌（ＭＲＳＡ）的ＭＩＣ５０为０．１２５～２ｍｇ／Ｌ,对青霉素耐药性肺炎链球菌的ＭＩＣ５０＜０．０１～１ｍｇ／Ｌ,对万古霉素耐药性肠球菌（ＶＲＥ）的ＭＩＣ５０为０．５～２ｍｇ／Ｌ。一般而言,达托霉素的ＭＩＣ为万古霉素ＭＩＣ的１／２～１／４,并对ＭＲＳＡ和ＶＲＥ有杀菌活性。在各种革兰氏阳性菌中,对达托霉素的抗菌谱和药效学作了评价,达托霉素对所有测试菌的杀菌率都超过９９％,对…     

左氟沙星注射液药效学研究

目的：通过测定左氟沙星对常见感染性细菌的最低抑菌浓度（ＭＩＣｍｇ／Ｌ）和最低杀菌浓度（ＭＢＣｍｇ／Ｌ）以了解其体外抗菌作用。方法：采用平皿二倍稀释法测定ＭＩＣ;采用影印培养法测定ＭＢＣ;并测定条件因素对体外药效学的影响。结果：左氟沙星对革兰氏阳性球菌中的ＭＲＳＡ、ＭＳＳＡ、ＭＲＳＥ、ＭＳＳＥ的ＭＩＣ９０为４０,０５,８０,１０ｍｇ／Ｌ,对以大肠杆菌为代表的肠杆菌科细菌的ＭＩＣ低于２ｍｇ／Ｌ,对厌氧菌ＭＩＣ５０为２～４ｍｇ／Ｌ。结论：左氟沙星对绝大多数临床感染细菌具有极强抗菌作用,不仅能抑制需氧菌或兼性厌氧菌,对常见厌氧菌也有抗菌作用。     

司氟沙星的体外抗菌活性研究

采用试管双倍稀释法检测司氟沙星对临床分离的３７２株致病菌的体外抗菌活性,并与３种同类药物进行比较。结果表明司氟沙星对金葡球菌、表葡球菌和肺炎链球菌等革兰氏阳性菌有较强的抗菌活性,ＭＩＣ５０≤０．０３～０．０６ｍｇ／Ｌ,抑菌率７５％～９３．８％;对革兰氏阴性菌中的伤寒沙门氏菌、痢疾志贺氏菌亦有较强的抗菌作用,ＭＩＣ９００．０６～１．０ｍｇ／Ｌ,抑菌率９２．５％～１００％;除粘质沙雷氏菌和柠檬酸杆菌耐药率较高外,对多数肠杆菌科细菌亦有５３．１％～８５．７％的抑菌率。     

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.