淋球菌对氟喹诺酮类药物的耐药性研究

为了解淋球菌对氟喹诺酮类药的耐药性,用琼脂稀释法和纸片扩散法分别对１９８～１９９９年间广东省湛江地区分离出的９８株洒球菌流行株进行了药物敏感性测定。测定了流行株对诺氟沙星、依诺沙星、环丙沙星、氧氟沙星和洛美沙星５种氟喹诺酮类药物的最小抑菌浓度（ＭＩＣ）和抑菌圈直径（ｍｍ）,根据ＮＣＣＬＳ标准判定敏感与耐药。结果表明,纸片扩散法测定淋球菌对这５种抗生纱的耐药百分率分别为９１．８４％、９７．９６％、８     

三种氟喹诺酮类抗菌药的药物动力学研究

本文报道氟喹诺酮类药物诺氟沙星、依诺沙星和氧氟沙星的药物动力学研究结果。健康志愿者空腹口服单剂４００ｍｇ的诺氟沙星、依诺沙星和氧氟沙星后，采用微生物法测定其血、尿浓度，氧氟沙星的体内过程符合二室模型，依诺沙星和诺氟沙星符合一室模型，口服诺氟星、依诺沙星和氧氟沙星的消除半衰期分别为３．５、４．８和５．４ｈ，平均血峰浓度各为１．２、３．１和５．８ｍｇ／Ｌ，达峰时间各为１．６、１．２和１．１ｈ，ＡＵＣ分     

北京地区志贺菌8年来耐药趋势

为探讨北京地区志贺菌耐药趋势，对1994－2001年327株志贺菌对30种抗生素做药敏实验，结果8年来耐氟喹诺酮类菌株逐渐增多，1997－1998耐诺氟沙星菌株达11．6％，耐环丙沙星菌株达16．3％，均比1994显著增加（P＜0．001），3从1994－1998志贺菌对氟喹诺酮类中敏菌株也渐增加，且1999－2001增加迅速，是否预示今后几年氟喹诺酮类耐药株会迅速增加，应引起注意，氟喹诺酮类存在部分交叉耐药，耐5种氟喹诺酮类药物的菌株从1995逐渐上升，1999－2001耐药率达8．5％，8年来志贺菌对一代头孢，氨基糖甙类耐药相对稳定，仍可首选治疗急性菌痢，但丁胺卡那和几乎所有头孢类中敏菌株急剧增加，应引起重视。     

耐甲氧西林金黄色葡萄球菌对三种氟喹诺酮类药物的耐药分析

目的 了解目前广州市花都区中医院的耐甲氧西林金黄色葡萄球菌(MRSA)分布情况，及其对在临床上仍较常用的抗菌药—氟喹诺酮类药物的耐药现状。方法 使用了Autoscan-4型细菌鉴定仪对受试的94株金黄色葡萄球菌进行耐苯唑西林测定，并对青霉素G，头孢唑啉等14种抗生素进行了药敏试验。结果 在94株受试菌株中，共检出66株MRSA。全院的总检出率为70.2％，这些MRSA菌株对三种氟喹诺酮类药物的耐药率，而与对四环素等抗生素的耐药率相似，但却远远高于对万古霉素等抗生素的耐药率。结论 MRSA认对氟喹诺酮类药物有明显的交叉耐药性,且氛喹诺酮类药物虽然仍具备一定的抗MRSA活性．但作用并不明显．故不应成为治疗MRSA感染症的首选药。     

月桂氮卓酮对耐药性金黄色葡萄球菌体外抗菌活性研究

目的：研究月桂氮卓酮对酮对耐药性金黄色葡萄球菌的抑菌作用。方法：采用Ｋｉｂｙ－Ｂａｕｅｒ法。结果：抑菌圈６ｍｍ者３８株，占７３．１％；７ｍｍ者９株，占１７．３％；８ｍｍ者２株，占４．９％；〉１０ｍｍ者３株，占５．６％，标准株抑菌圈为１６．８ｍｍ。结论：对青霉素耐药的金黄色葡萄球菌，对月桂氮卓酮也表现出明显的耐药性。     

4种氟喹诺酮药物的耐药性

调查了４８８株常见致病菌对４种氟隆诺酮药物的耐药情况。结果：２６．８％对１种或多种氟喹诺酮药物耐药；革兰阳性球菌的耐药率为３５．１％，革兰阴性杆菌的耐药率为２３．７％。各菌株对诺氟沙星耐药率最高，对环丙沙星耐药率最低。造成耐药菌增多的原因与广泛和不合理用药有关。因此，氟喹诺酮药物在临床治疗中获得性耐药问题应引起重视。     

16种抗菌药物对来源于免疫功能低下患者的革兰氏阴性杆菌的体外抗菌活性比较

对从武汉地区免疫功能低下患者分离的１０６３株革兰氏阴性杆菌，用琼脂平皿稀释法测定１６种抗菌药物的最小抑菌浓度（ＭＩＣ）。用ＷＨＯＮＥＴ－３计算机软件完成数据分析。主要革兰氏阴性杆菌是铜绿假单胞菌（３２．５％）、大肠杆菌（２２．９％）、克雷伯氏菌属（１４．３％）、肠杆菌属（７．９％）、不动杆菌属（６．１％）和柠檬酸菌属（４．９％）。通过ＭＩＣ测定显示大部分菌株对１６种抗菌药物有不同程度的耐药性。４７．２％的菌株同时对５种以上抗菌药物耐药。１０６３株革兰氏阴性杆菌对亚胺培南／西司他丁最敏感，其次是对阿米卡星和头孢他啶，敏感率分别为９５％、８８％和８６％。亚胺培南／西司他丁的体外抗菌活性最高，ＭＩＣ５０和ＭＩＣ９０为０．５和２μｇ／ｍｌ，阿米卡星（ＭＩＣ５０和ＭＩＣ９０为２和６４μｇ／ｍｌ）及头孢他啶（ＭＩＣ５０和ＭＩＣ９０为２和３２μｇ／ｍｌ）次之。根据对１６种药物抗菌活性的比较，为正确合理使用抗菌药物治疗免疫功能低下者革兰氏阴性杆菌急危重症感染提供了依据     

肠杆菌科超广谱β-内酰胺酶检测及其临床应用

应用琼脂稀释法、Ｅｔｅｓｔ法分别测定了１６３株肠杆菌科细菌对１２种β－内酰酶胺类抗生素的最低抑菌浓度（ＭＩＣ）和超广谱β－内酰胺酶（ＥＳＢＬ），同时对含ＥＳＢＬ与不含ＥＳＢＬ菌株的药敏结果加以分析。结果：４．５％ 大肠埃希氏菌、１９．４％ 克雷伯氏菌、２３．１％ 沙雷氏菌、１０％ 弗氏柠檬酸杆菌和３３．３％ 阴沟肠杆菌ＥＳＢＬ阳性，总检出率为１１％ 。含ＥＳＢＬ菌株对１２ 种β－内酰胺类抗生素中的９ 种呈多重耐药，其耐药率３３．３％ ～１００％ ；而多数不含ＥＳＢＬ菌株仅对氨苄西林、羧苄西林和头孢唑林耐药，其耐药率５５．２％ ～８７．５％ 。应严格区分菌株是否含ＥＳＢＬ，并对含ＥＳＢＬ菌株的耐药性给予广泛关注。     

5种抗菌剂对淋病奈瑟氏球菌的抑菌效果研究

采用脂稀释法测定了５种抗菌剂对２０１株淋病奈瑟氏菌的最低抑菌浓度。结果检出４株为产β－内酰胺酶菌株，对青霉素和四环素的耐药率分别为５７．２％和８２．６％，其ＭＩＣ９０均已超过药界限。     

诺氟沙星耐药性初探

诺氟沙星耐药性初探李仲昆，赵云，林杉（昆明市延安医院，昆明６５００５１）从本院１９９３年５月１日至１２月３１日各科送检的标本中分离出２０４株致病菌，测定诺氟沙星的体外抗菌活性。结果：细菌耐药率为２４．５％，高于头孢噻肟（９．６％），低于庆大霉素（３５...     

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.