哌拉西林／他唑巴坦对656株临床分离致病菌的体外抗菌作用研究

研究比较了国产哌拉西林／他佐巴坦及哌拉西林和其它联合制剂对６５６株临床分离菌的体外抗菌作用，结果表明，对大多数革兰氏阴性杆菌哌拉西林／他唑巴坦联合制剂与哌拉西林相比显示出了较强的抗菌活性，对大肠埃希氏菌、耐药粘质沙雷氏菌和铜绿假单胞菌，哌拉西林／他唑巴坦ＭＩＣ９０是哌拉西林的ＭＩＣ９０１／１６～１／３２。哌拉西林／他唑巴坦与其他酶抑制剂联合制剂抗菌活性比较表明，哌拉西林／他唑巴坦对大肠埃希氏菌、粘质沙雷氏菌、铜绿假单胞菌、变形杆菌和福氏痢疾杆菌抗菌活性比氨苄西林／舒巴坦、阿莫西林／克拉维酸和替卡西林／克拉维酸联合制剂强４～１６倍。对革兰氏阳性及革兰氏阴性球菌，哌拉西林／他唑巴坦联合制剂对肺炎链球菌、甲氧西林敏感的金葡球菌以及淋病奈瑟氏球菌的ＭＩＣ９０与哌拉西林ＭＩＣ９０相似，但对表葡球菌、其他金葡球菌和化脓性链球菌，哌拉西林／他唑巴坦联合制剂的ＭＩＣ９０是哌拉西林的１／８，而且，哌拉西林／他唑巴坦联合制剂的抗菌活性较其他酶抑制剂联合制剂强４～１６倍。对脆弱拟杆菌，哌拉西林／他唑巴坦ＭＩＣ９０是哌拉西林的１／８。     

国产氟罗沙星体外抗菌活性研究

测定国产氟罗沙星对４９３株临床分离细菌的最低抑菌浓度（ＭＩＣ），并与氧氟沙星、洛美沙星、环丙沙星和几种头孢菌素、氨基糖苷类抗生素作了比较。结果表明：氟罗沙星对革兰氏阴性细菌有强大抗菌活性，对肠杆菌科细菌的ＭＩＣ９０≤１μｇ／ｍｌ。对铜绿假单胞菌亦有较强抗菌活性，其ＭＩＣ５０、ＭＩＣ９０分别为２和４μｇ／ｍｌ。金葡球菌（含ＭＲＳＡ菌株）对氟罗沙星亦很敏感，ＭＩＣ９０≤１μｇ／ｍｌ。链球菌属对其基本耐药，ＭＩＣ９０为８～１６μｇ／ｍｌ。对大多数常见致病菌，氟罗沙星体外抗菌活性与氧氟沙星、洛美沙星相近，稍逊于环丙沙星。对革兰氏阴性菌，氟罗沙星与头孢噻肟、头孢他啶、阿米卡星相当，优于头孢唑林、氨苄西林、哌拉西林、庆大霉素。耐庆大霉素、头孢菌素菌株对氟罗沙星仍敏感。细菌对氟罗沙星单步自发耐药突变频率极低，但通过连续传代培养可以培育出对氟罗沙星高度耐药菌株。     

亚胺培南／西司他丁等对MRSA和MSSA的体外抗菌活性研究

用琼脂稀释法对亚胺培南／西司他丁等７种抗生素进行了对临床分离的１０４株耐甲氧西林金葡球菌（ＭＲＳＡ）和１２０株甲氧西林敏感的金葡球菌（ＭＳＳＡ）的体外抗菌活性比较，结果表明亚胺培南／西司他丁和去甲万古霉素的抗菌活性最强，对ＭＲＳＡ的ＭＩＣ＿（９０）分别为４和２μｇ／ｍｌ，对ＭＳＳＡ的ＭＩＣ＿（９０）为１和２μｇ／ｍｌ。其它５种抗生素对ＭＲＳＡ的抑菌作用均较差。但其中的头孢唑林和头孢拉定对ＭＳＳＡ的抑菌作用较好，１２０株ＭＳＳＡ对两者的敏感率分别为９０％和７４．１７％。     

甲氧西林耐药金葡球菌（MRSA）耐药机制的研究

用北京地区综合医院中分离的１９０株金葡球菌进行耐药机制研究。按照ＮＣＣＬＳ发表的ＭＲＳＡ标准，采用琼脂稀释敏感试验并以多聚酶链反应（ＰＣＲ）技术检测ｍｅｃＡ基因。１９０株金葡球菌中，８８株耐甲氧西林（ＭＩＣ≥１６ｍｇ／Ｌ），９１株耐苯唑西林（ＭＩＣ≥４ｍｇ／Ｌ），全部甲氧西林耐药金葡球菌和９８．８９％苯唑西林耐药金葡球菌为ｍｅｃＡ基因阳性。有１１株ｍｅｃＡ基因阳性金葡球菌对甲氧西林敏感，９株ｍｅｃＡ基因阳性金葡球菌对苯唑西林敏感。在８８株ＭＲＳＡ菌株中，７３．６３％为β－内酰胺酶产生菌，但克拉维酸只对低度耐药的ＭＲＳＡ菌株有影响，高度耐药的ＭＲＳＡ其ＭＩＣ值则不受克拉维酸的影响。这表明高度耐药ＭＲＳＡ所产生的β－内酰胺酶的作用还不清楚。群体分析结果发现所测试的全部菌株的耐药类型均为异质性耐药菌株。以上结果表明，我国临床分离的ＭＲＳＡ，其耐药机制主要是ｍｅｃＡ基因介异的。     

国产米诺环素对耐甲氧西林金葡球菌的体外抗菌活性观察

用琼脂稀释法进行国产米诺环素对１０４株耐甲氧西林金葡球菌（ＭＲＳＡ）和１２０株甲氧西林敏感金葡球菌（ＭＳＳＡ）的抗菌活性研究，并与日本产米诺环素等进行了抗菌作用比较。结果表明国产米诺环素对ＭＲＳＡ和ＭＳＳＡ的抑菌效果，与日本产米诺环素基本一致。对ＭＲＳＡ的ＭＩＣ５０和ＭＩＣ９０前者分别为２和８ｍｇ／Ｌ，而后者分别为２和４ｍｇ／Ｌ。两者对ＭＳＳＡ的ＭＩＣ５０和ＭＩＣ９０均为０．５和４ｍｇ／Ｌ。国产米诺环素与其它６种抗生素比较，除去甲万古霉素外，其对ＭＲＳＡ和ＭＳＳＡ的抗菌效果，均优于头孢唑林等抗生素     

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。     

高产AmpC酶肠杆菌科细菌对12种常用抗生素的耐药性分析

目的检测肠杆菌科细菌产AmpC酶和超广谱β-内酰胺酶（ESBLs）并对其耐药性进行分析。方法氯唑西林增效试验测定AmpC酶。采用双纸片确诊试验测定ESBLs，用最小抑菌浓度法（MIC法）检测12种抗生素对这些菌株的体外抗菌活性。结果64株受检菌中共检出高产AmpC酶菌29株，产ESBLs菌32株，阳性率分别为45．3％、50％。高产AmpC酶组菌株对氨曲南、头孢曲松、哌拉西林、哌拉西林／三唑巴坦均存在不同程度的耐药（45．2％～68，5％），其耐药率明显高于非高产AmpC酶组菌株，两者相比有显著性差异（P〈0.05）。高产AmpC酶组菌株和非高产AmpC酶组菌株对氨苄西林、氨苄西林／舒巴坦、环丙沙星，头孢唑林、头孢吡肟的耐药率均较高（41．3％-94，2％），对阿米卡星、亚胺堵南、头孢哌酮／舒巴坦的耐药率均较低（0～34．6％），两者相比无显著性差异（P〉0．05）。结论肠杆菌科细菌中AmpC酶的检出率较高，高产AmpC酶细菌多呈多重耐药。临床可采用碳青霉烯类抗生素治疗高产AmpC酶的细菌感染，也可根据药敏试验结果选用头孢哌酮／舒巴坦、第四代头孢菌素或阿米卡星等抗生素治疗。     

Du6859a及其他新的氟喹诺酮类药物的体外抗菌活性

用琼脂稀释法测定Ｄｕ６８５９ａ对１２０６株临床分离菌的抗菌作用，并与其同类品种（司帕沙星、托舒沙星、诺氟沙星、氧氟沙星、左氟沙星、环丙沙星）比较。Ｄｕ６８５ｑａ对金葡球菌不产酶株、ＭＳＳＡ、ＭＲＳＡ、ＭＲＳＥ，溶血性链球菌和肺炎球菌的ＭＩＣ＿（９０）均为０．５ｍｇ／Ｌ；对肠球菌的ＭＩＣ＿（９０）为２ｍｇ／Ｌ，优于其同类品种。多数肠杆菌科细菌可为０．２５ｍｇ／Ｌ，铜绿假单胞菌可为０．５ｍｇ／Ｌ的本品所抑制，其抗菌活性与司帕沙星和托舒沙星相似。Ｄｕ６８５９ａ对各种厌氧菌亦具良好作用，多数菌株可为０．５ｍｇ／Ｌ的浓度抑制。因此认为本品具有良好的临床应用前景，值得进一步临床试验。     

新三代口服头孢菌素头孢布烯（ceftibuten）β—内酰胺酶稳定性研究

头孢布烯对２０株临床分离产酶耐药菌和８株标准产酶菌株以及２株产头孢菌素酶菌株β－内酰胺酶稳定性进行了研究,并与头孢唑林、头孢呋辛、头孢哌酮、头孢噻肟及头孢他啶等５个头孢菌素作了比较。结果表明头孢布烯具有很强的β－内酰胺酶稳定性,它不被ＴＥＭ－１、ＴＥＭ－２、ＯＸＡ－１、ＯＸＡ－２、ＯＸＡ－３、ＳＨＶ－１、Ｋ１、Ｄ３１ 等酶水解,其相对水解率（ＲｅｌａｔｉｖｅＨｙｄｒｏｌｙｓｉｓＲａｔｅ,ＲＨＲ）＜ ２％ 。在２０株临床分离产酶耐药菌所产β－内酰胺酶中,有３ 株可以缓慢水解头孢布烯,其ＲＨＲ分别为７．９％ 、６．８％ 和１１．１％ ．而另外１７ 株菌所产酶对头孢布烯的ＲＨＲ均＜ ２％ 。头孢布烯的相对水解率与头孢他啶相近,两者均为具有高度酶稳定性的头孢菌素,明显优于头孢唑林、头孢呋辛、头孢哌酮及头孢噻肟等其它４种头孢菌素。     

头孢吡肟与其它广谱β-内酰胺类抗生素体外抗菌活性比较

测定头孢吡肟对１００株临床分离菌的最低抑菌浓度（ＭＩＣ）,并与头孢他啶,头孢曲松,亚胺培南,头孢哌酮／舒巴坦等广谱β－内酰胺类抗生素体外抗菌活性进行比较。结果：头孢吡肟对革兰氏阴性杆菌有良好抗菌活性;对铜绿假单胞菌亦有较强的抗菌活性,其ＭＩＣ５０为３ｍｇ／Ｌ,和头孢他啶相当,苯唑青霉素敏感的葡萄球菌对头孢吡肟也较敏感,ＭＩＣ９０≤４ｍｇ／Ｌ。表明头孢吡肟较第三代头孢菌素抗菌谱更广,抗菌活性更强。     

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.