头孢硫脒与6种抗菌药物联用对金葡球菌的体外抗菌活性

目的:评价头孢硫脒分别与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星和加替沙星6种抗菌药物联合用药,对于临床分离的金葡球菌(SA)的体外联合抗菌效应.方法:经VITEK鉴定临床分离致病菌,采用棋盘法设计,微量肉汤稀释法测定6组抗菌药物对SA及耐甲氧西林金葡球菌(MRSA)的最低抑菌浓度,并计算部分抑菌指数(FIC指数). 结果:头孢硫脒与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星、加替沙星联合应用后,MIC50,MIC90明显降低,FIC指数<0.5占60%～90%,0.5～1占10%～30%,1～2占0～13.3%,>2为0.结论:头孢硫脒与6种抗菌药物联合应用后,对SA基本表现为协同和相加作用,说明联合用药的疗效要高于两药单独使用.     

头孢硫脒与加替沙星对革兰阳性球菌的联合药敏研究

目的:评价头孢硫脒与加替沙星联合用药,对临床分离的G 球菌的体外联合抗菌效应.方法:采用棋盘法设计,微量肉汤稀释法测定头孢硫脒与加替沙星对90株临床分离的G 球菌的MIC,并计算FIC指数判定联合效应.结果:头孢硫脒与加替沙星联合应用后,其MIC50显著降低.FIC指数分布:FIC≤0.5占60%～86.7%;0.5＜FIC≤1占13.3%～26.7%;1＜FIC≤2占0～13.3%;FIC＞2为0.结论:加替沙星与头孢硫脒联合用药后,对G 球菌主要表现为协同作用和相加作用,并以协同作用为主,无关作用较少,无拮抗作用.     

头孢硫脒与其他6种抗菌药物对表皮葡萄球菌体外联合药敏的研究

目的 :评价头孢硫脒分别与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧沙星和加替沙星等 6种抗菌药物联合用药 ,对于表皮葡萄球菌 (Staphylo coccusepidermidis ,SE)的体外联合抗菌效应。方法 :采用棋盘法设计 ,微量肉汤稀释法测定不同浓度组合的 6组抗菌药物对 30株临床分离的表皮葡萄球菌的最低抑菌浓度 (MIC) ,并计算部分抑菌指数 (FIC指数 )。结果 :头孢硫脒对表皮葡萄球菌的MIC50 、MIC90 为 1、6 4mg·L-1;与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧沙星、加替沙星联合应用后 ,其MIC50 分别降低至 0 .12 5、0 .12 5、0 .12 5、0 .12 5、0 .2 5、0 .12 5mg·L-1,MIC90 分别降低至 1、1、1、2、1、1mg·L-1。结论 :6种抗菌药物与头孢硫脒联合用药后 ,对表皮葡萄球菌球菌基本表现为协同或相加作用 ,并以协同作用为主 ,无关作用较少 ,无拮抗作用。     

头孢硫脒与奈替米星对90株革兰阳性球菌联合药敏研究

目的评价头孢硫脒与奈替米星对90株G+球菌体外联合抗菌效应.方法采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的三组抗菌药物对90株临床分离的G+球菌的最低抑菌浓度,并计算FIC指数.结果头孢硫脒对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌的MIC50分别为16mg/L、1mg/L、2mg/L,与奈替米星联合应用后,其MIC50分别显著的降低至0.5mg/L、0.125mg/L、0.25mg/L.FIC指数结果表明头孢硫脒与奈替米星抗菌药物联合应用,对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌多数呈协同和相加作用,并以协同作用为主(66.7%～90%),无关作用较少(0～6.6%),无拮抗作用.结论头孢硫脒与奈替米星联合应用对90株G+球菌呈基本协同或相加作用.     

头孢硫脒与奈替米星对90株革兰阳性球菌联合药敏研究

目的:评价头孢硫脒与奈替米星对90株G+球菌体外联合抗菌效应.方法:采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的三组抗菌药物对90株临床分离的G+球菌的最低抑菌浓度,并计算FIC指数.结果:头孢硫脒对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌的MIC50分别为16mg/L、1mg/L、2mg/L,与奈替米星联合应用后,其MIC50分别显著的降低至0.5mg/L、0.125mg/L、0.25mg/L.FIC指数结果表明头孢硫脒与奈替米星抗菌药物联合应用,对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌多数呈协同和相加作用,并以协同作用为主(66.7%～90%),无关作用较少(0～6.6%),无拮抗作用.结论:头孢硫脒与奈替米星联合应用对90株G+球菌呈基本协同或相加作用.     

头孢硫脒与环丙沙星对革兰阳性球菌的联合药敏研究

目的　评价头孢硫脒 /环丙沙星对于临床分离的金黄色葡萄球菌(包括耐甲氧西林金葡菌)、表皮葡萄球菌 (包括耐甲氧西林表葡菌)、粪肠球菌的体外联合抗菌效应。方法采用棋盘法设计,微量肉汤稀释法测定。测定不同浓度组合的抗菌药物对 90株临床分离的革兰阳性球菌的最低抑菌浓度,并计算FIC指数判定联合效应。结果　头孢硫脒 /环丙沙星联合应用后,其MIC50明显降低。FIC≤0 5占 53 3% ~93 3%; 0 52为 0。结论　环丙沙星与头孢硫脒联合用药对革兰阳性球菌主要表现为协同作用。     

左氧氟沙星与头孢硫脒合用对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌体外抗菌活性研究

目的评价左氧氟沙星与头孢硫脒联合应用对金黄色葡萄球菌、表皮葡萄球菌和粪肠球菌的体外联合抗菌作用.方法采用棋盘法设计,微量肉汤稀释法测定其UIC值,计算FIC指数.结果左旋氧氟沙星与头孢硫脒联合应用后,左旋氧氟沙星对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、HRSA、NRSE的HIC50均有明显降低,同样头孢硫脒对金色葡萄球菌、表皮葡萄球菌、粪肠球菌、HRSA、HRSE的NICm亦显著下降.FIC指数范围主要在0～1.结论左氧氟沙星与头孢硫脒药物联合应用,对金黄色葡萄球菌、表皮葡萄球菌和粪肠球菌的体外联合抗菌作用以协同和相加为主.     

磷霉素与万古霉素对90株革兰阳性球菌的联合药敏研究

目的评价磷霉素与万古霉素对90株革兰阳性球菌30株粪肠球菌(Enterococcus faecalis,Ef)、30株金黄色葡萄球菌(Staphylococcus aureus,SA)、30株表皮葡萄球菌(Staphylococcus epidermidis,SE)的体外联合抗菌效应.方法采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的抗菌药物对90株临床分离的革兰阳性球菌的最低抑菌浓度,并计算FIC指数判定联合效应.FIC≤0.5为协同作用,0.5＜FIC≤1为相加作用,1＜FIC≤2为无关作用,FIC＞2为拮抗作用.结果磷霉素与万古霉素联合应用后,其MIC50显著降低.FIC指数分布FIC≤0.5占60%～93.3%;0.5＜FIC≤1占6.7%～40%;1＜FIC≤2占0;FIC＞2为0.结论磷霉素与万古霉素联合用药后,对革兰阳性球菌基本表现为协同作用和相加作用,并以协同作用为主,无关作用较少,无拮抗作用.     

磷霉素与万古霉素对90株革兰阳性球菌的联合药敏研究

目的:评价磷霉素与万古霉素对90株革兰阳性球菌:30株粪肠球菌(Enterococcus faecalis,Ef)、30株金黄色葡萄球菌(Staphylococcus aureus,SA)、30株表皮葡萄球菌(Staphylococcus epidermidis,SE)的体外联合抗菌效应.方法:采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的抗菌药物对90株临床分离的革兰阳性球菌的最低抑菌浓度,并计算FIC指数判定联合效应.FIC≤0.5为协同作用,0.5＜FIC≤1为相加作用,1＜FIC≤2为无关作用,FIC＞2为拮抗作用.结果:磷霉素与万古霉素联合应用后,其MIC50显著降低.FIC指数分布:FIC≤0.5占60%～93.3%;0.5＜FIC≤1占6.7%～40%;1＜FIC≤2占0;FIC＞2为0.结论:磷霉素与万古霉素联合用药后,对革兰阳性球菌基本表现为协同作用和相加作用,并以协同作用为主,无关作用较少,无拮抗作用.     

左氧氟沙星与头孢硫脒合用对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌体外抗菌活性研究

目的:评价左氧氟沙星与头孢硫脒联合应用对金黄色葡萄球菌、表皮葡萄球菌和粪肠球菌的体外联合抗菌作用.方法:采用棋盘法设计,微量肉汤稀释法测定其UIC值,计算FIC指数.结果:左旋氧氟沙星与头孢硫脒联合应用后,左旋氧氟沙星对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、HRSA、NRSE的HIC50均有明显降低,同样头孢硫脒对金色葡萄球菌、表皮葡萄球菌、粪肠球菌、HRSA、HRSE的NICm亦显著下降.FIC指数范围主要在0～1.结论:左氧氟沙星与头孢硫脒药物联合应用,对金黄色葡萄球菌、表皮葡萄球菌和粪肠球菌的体外联合抗菌作用以协同和相加为主.     

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.     

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.     

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.     

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.