加替沙星对社区获得性感染体外抗菌活性研究

目的 了解我院社区获得性呼吸道、泌尿道感染病原菌对加替沙星等抗菌药物的体外抗菌活性。方法 采用琼脂二倍稀释法测定加替沙星对303株临床分离致病菌体外抗菌活性，并与左氧氟沙星、司帕沙星、环丙沙星、头孢噻肟比较。结果试验结果表明，加替沙星具有强而广谱的体外抗菌活性。在革兰氏阳性菌中，加替沙星对金黄色葡萄球菌、溶血葡萄球菌及其它葡萄球菌的MIC50分别为≤0.03mg/L、0.25mg/L、≤0.03mg/L，MIC90分别为0.25mg/L、0.5mg/L及0.06mg/L；革兰氏阴性菌中，加替沙星对大肠埃希氏菌、肺炎克雷白氏菌、不动杆菌及铜绿假单胞菌的MIC50分别为≤0.12mg/L、≤0.03mg/L、≤0.03mg/L及0.12mg/L，MIC90分别为1mg/L、0.12mg/L、0.25mg/L及1mg/L。对链球菌、阴沟肠杆菌、流感嗜血杆菌、奇异变形杆菌、弗劳地枸橼酸杆菌及粘质沙雷氏菌，加替沙星亦有明显的抗菌活性。结论 加替沙星对社区获得性呼吸道、泌尿道感染常见病原菌的抗菌活性强，可用于敏感菌引起的各种社区获得性呼吸道及泌尿道的各种感染。     

司帕沙星和妥舒沙星的体内外抗菌作用研究

目的观察国产司帕沙星、妥舒沙星及其它四种氟喹诺酮类抗菌药对成都地区780株临床分离菌的体外抗菌活性，并比较司帕沙星、妥舒沙星和环丙沙星对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠的体内抗菌活性。方法用琼脂稀释法测定国产司帕沙星和妥舒沙星的MIC50和MIC90，并与其它四种氟喹诺酮类抗菌药进行了比较。本文还测定了抗菌药对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠治疗的ED50结果体外试验表明司帕沙星和妥舒沙星能有效抑制或杀灭革兰阳性、革兰阴性菌及厌氧菌，显示了广谱抗菌活性。司帕沙星和妥舒沙星对革兰阳性菌的抗菌活性是环丙沙星的2～8倍，氧氟沙星和氟罗沙星的4～16倍，是诺氟沙星的16～32倍。司帕沙星对MRSA的抗菌活性与妥舒沙星相似，但优于环丙沙星、氧氟沙星、氟罗沙星和诺氟沙星。司帕沙星对大多数革兰阴性菌的抗菌活性与环丙沙星和妥舒沙星相似，是氧氟沙星、氟罗沙星和诺氟沙星的2～8倍。两药对厌氧菌的抗菌活性也较环丙沙星强。口服或皮下注射司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。三种受试药对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于铜绿假单胞菌所致感染。结论司帕沙星和妥舒沙星对革兰阳性菌和厌氧菌的体外抗菌活性优于环丙沙星和其它药物，对大多数革兰阴性菌的抗菌活性与环丙沙星相似，但优于其它受试药。司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的体内保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。     

国产头孢他美酯、头孢他美体内外抗菌作用研究

采用琼脂二倍稀释法评价国产头孢他美酯(cefetametpivoxil)、头孢他美对临床分离的558株致病菌的体外抗菌作用及其对小鼠感染细菌的体内疗效,并与进口头孢他美酯、头孢克洛、头孢噻啶、头孢唑林、司帕沙星、环丙沙星进行比较.结果表明头孢他美酯体外抗菌活性弱,对所试多数革兰氏阳性、阴性细菌的MIC为4～>128mg/L,而其母体化合物头孢他美体外呈现出较强的抗菌活性,对所试表葡球菌、肺炎链球菌、溶血性链球菌的MIC50在0.06～8mg/L(其中包括产β-内酰胺酶菌株),对金葡球菌非产酶株和产酶株的MIC50各是32和64mg/L;对革兰氏阴性菌中的大肠埃希氏菌(包括产β-内酰胺酶菌株),肺炎克雷伯氏菌、伤寒杆菌、痢疾杆菌、变形杆菌、硝酸盐阴性不动杆菌、普鲁威登斯菌、阴沟肠杆菌、粘质沙雷氏菌及鲍氏不动杆菌等均敏感,MIC50在0.5～8mg/L;本品对铜绿假单胞菌无效.头孢他美对金葡球菌、表葡球菌的抗菌活力不如第一、二代头孢菌素,如头孢噻啶、头孢唑林、头孢克洛,但对肺炎链球菌、溶血性链球菌的活力比头孢克洛、头孢噻啶和头孢唑林强4～8倍,与司帕沙星、环丙沙星相近.头孢他美对革兰氏阴性杆菌的抗菌活力强于头孢克洛、头孢噻啶,头孢唑林2～64倍,比不上司帕沙星和环丙沙星.头孢他美对厌氧菌的抗菌活力较头孢克洛强,MIC50在16～32mg/L.头孢他美为杀菌剂,MBC浓度为MIC浓度的2～4倍.在2～4MIC浓度时呈现明显的杀菌效力.接种菌量、pH值改变、血清浓度变化对头孢他美和头孢他美酯的MIC值影响不显著.体内抗菌实验表明,头孢他美酯口服给药对金葡球菌、肺炎链球菌、大肠埃希氏菌、肺炎克雷伯氏菌感染小鼠呈现出较佳的体内疗效,比头孢克洛强2～20倍.本实验结果表明,国产头孢他美酯体内外抗菌作用与进口头孢他美酯基本一致.     

甲磺酸加替沙星与其他4种氟喹诺酮类药物对临床分离菌的体外抗菌活性比较

目的 :比较甲磺酸加替沙星与氧氟沙星、左氧沙星、环丙沙星、司帕沙星对 182株临床分离菌的体外抗菌活性。方法 :采用琼脂平板二倍稀释法测定加替沙星等 5种氟喹诺酮类药物对 182株临床试验分离菌株的最低抑菌浓度 (MIC)。结果 :加替沙星对葡萄球菌属的MIC90 比其他 4种氟喹诺酮类药物低。葡萄球菌属对加替沙星的敏感率显著高于其他4种氟喹诺酮类药物 ;对其他G 球菌的MICR 也较其他氟喹诺酮类药物低。G-杆菌中埃希菌属、肠杆菌属对加替沙星的敏感率明显高于其他 4种氟喹诺酮类药物 ,加替沙星对埃希菌属、肠杆菌属的MIC90比左氧沙星低 2倍 ,比其他 3种抗菌药物低 8倍 ;假单胞菌属、克雷伯菌属和其他G-杆菌对加替沙星的敏感率与左氧沙星的差异无统计学意义 ,与其他 3种氟喹诺酮类药物的差异有统计学意义。结论 :甲磺酸加替沙星具有广谱而强大的体外抗菌活性。     

帕珠沙星对临床分离致病菌的体外抗菌活性研究

目的评价帕珠沙星的体外抗菌活性。方法采用琼脂二倍稀释法，测定帕珠沙星与左氧氟沙星对342株临床分离菌株的最低抑菌浓度（MIC）。结果帕珠沙星对革兰阴性菌和革兰阳性菌的MIC90分别为0．06～4和1～16μg／ml。对大肠埃希菌、阴沟肠杆菌、变形菌、铜绿假单胞菌、不动杆菌和链球菌的MIC90为0．06～4μg／ml，是左氧氟沙星的1／2～1／8;对肺炎克雷伯菌、金葡菌和表葡菌与左氧氟沙星抗菌作用相当，MIC90分别为0．5、1、1μg／ml；对流感嗜血杆菌、黏膜炎莫拉菌和粪肠球菌的MIC90为0．5、1、16μg／ml，高于左氧氟沙星（0．25、0．5、8μg／ml）。结论帕珠沙星对革兰阴性菌和革兰阳性菌均具有广谱的抗菌作用，对革兰阴性菌的抗菌活性优于革兰阳性菌。     

美罗培南对临床分离致病菌的体外抗菌活性研究

目的评价美罗培南的体外抗菌活性方法采用琼脂二倍稀释法测定美罗培南及对照药亚胺培南、头孢吡肟、头孢他啶、头孢哌酮／舒巴坦、环内沙星对412株临床分离致病菌的体外抗菌活性。结果显示，对多种革兰氏阴性菌，美罗培南均有较强的抗菌作用，其抗菌作用强于对照药亚胺培南、头孢吡肟、头孢他啶、环丙沙星、奈替米星；对大肠埃希氏菌、克雷泊氏菌属、产气肠杆菌、志贺氏菌属、沙门氏菌属、柠檬酸菌属、变形菌属、沙雷氏菌属MIC90≤0．008～0．25mg/L，是亚胺培南MIC9o的1／4～1／16，对阴沟肠杆菌、不动杆菌属与亚胺培南的抗菌作用相当，分别为0．25、0．5mg／L：对流感嗜血杆菌美罗培南的MIC90为0．125mg／L，是亚胺培南的1／16，是第四代头孢菌素头孢吡肟的1/4：对铜绿假单孢菌美罗培南的MIC90为4mg／L，低于亚胺培南8mg／L。对革兰氏阳性菌作用稍差于亚胺培南，优予其他4种对照药。     

盐酸左氧氟沙星对325株分离细菌的体外抗菌活性研究

目的：研究左氧氟沙星的体外抗菌活性作用。方法：采用平板双倍稀释法测定盐酸左氧氟沙星的体外抗菌活性,并与其它2种常用氟喹诺酮类抗菌药物进行比较。结果：结果表明：盐酸左氧氟沙星的抗菌活性强,抗菌谱广。对金葡球菌、表葡球菌和肺炎链球菌的MIC90值分别为16mg/L,32mg/L,2mg/L,是氧氟沙星和环丙沙星的1／2－1／4,抑菌率为82．5％－94．7％;对大肠埃希氏菌、铜绿假单孢菌等革兰氏阴性菌的MIC50值为＜0．03mg/L-0.25mg/L,是氧氟沙星和环丙沙星的1／2－1／4,抑菌率为92．9％－100％。结论：盐酸左氧氟沙星是一种广谱菌药物。     

常用第一、二代头孢菌素注射剂体外抗菌活性研究

目的 评价目前临床常用第一、二代头孢菌素对近年临床常见分离菌的体外抗菌活性。方法 采用标准琼脂二倍稀 释法；对 760 株细菌进行了最低抑菌浓度 (MIC) 测定。结果 菌株主要来自 2015-2016 年间全国 18 个城市收集临床分离株。 对于革兰阴性菌，第二代头孢菌素抗菌作用优于第一代头孢菌素，但对于革兰阳性需氧或厌氧菌，则第一代头孢菌素抗菌作用 更优。第一代头孢菌素中，五水头孢唑林和头孢西酮抗菌作用最为全面，对甲氧西林敏感葡萄球菌、肺炎链球菌、革兰阳性菌 具有较好抗菌作用，其中对甲氧西林敏感葡萄球菌的 MIC90 值分别为≤ 1mg/L 和≤ 0.5mg/L，优于头孢拉定。对肠杆菌科细菌 中不产超广谱 β- 内酰胺酶 (ESBLs) 的大肠埃希菌、肺炎克雷伯菌以及嗜血菌、卡他莫拉菌，五水头孢唑林和头孢西酮也有很好 抗菌活性，MIC50 值≤ 4mg/L，MIC90 值分别为≤ 16mg/L 和≤ 32mg/L，优于头孢硫脒和头孢拉定。结论 第一、二代头孢菌素 各具特点，且同类药物中不同品种抗菌活性也不尽相同。其中五水头孢唑林抗菌作用较为全面，对革兰阳性、阴性菌均表现出 较好抗菌作用，是第一代头孢菌素中临床应用最广泛的品种之一。     

盐酸加替沙星（Gatifloxacin）体外抗菌作用

目的评价盐酸加替沙星(gatifloxacin)对临床分离的1 222株致病菌的体外抗菌作用,并与盐酸环丙沙星、氧氟沙星、司帕沙星等进行比较.结果盐酸加替沙星对大多数革兰阴性杆菌的MIC90值均低于0.5mg·L,抗菌作用与盐酸环丙沙星相似;对肺炎克雷伯杆菌、阴沟肠杆菌、变形杆菌、志贺菌的MIC90值分别为0.062,0.062,0.5,0.25mg·L-1;盐酸加替沙星对大肠杆菌的MIC90值为8mg·L-1,耐药率为58%,对盐酸环丙沙星耐药的大肠杆菌对盐酸加替沙星也耐药,存在着交叉耐药性.盐酸加替沙星对乙酸钙不动杆菌MIC90值为0.062mg·L-1,铜绿假单胞和窄食黄单胞菌的MIC90值分别为2和1mg·L-1,与盐酸环丙沙星相同.盐酸加替沙星对革兰阳性球菌的抗菌作用比盐酸环丙沙星与氧氟沙星增强,对甲氧西林敏感的金葡菌、化脓性链球菌和肺炎链球菌MIC.0值分别为0.125、0.1.25和0.5mg·L-1,与司帕沙星相同;对甲氧西林耐药的金葡菌盐酸加替沙星的MIC90值为4mg·L-1对表皮葡葡菌MIC90值0.5mg·L-1;流感嗜血杆菌对盐酸加替沙星高度敏感,MIC90值为0.016mg·L-4;盐酸加替沙星对厌氧菌脆弱拟杆菌MIC90值为1mg·     

安妥沙星琼脂稀释法体外抗菌活性测定临界浓度初步研究

目的 确定安妥沙星对葡萄球菌属、肠杆菌科、非发酵菌及嗜血菌属的琼脂稀释法体外抗菌活性测定临界浓度.方法 采用标准琼脂二倍稀释法测定安妥沙星对临床常见致病菌的最小抑菌浓度值,并与临床常用的氟喹诺酮类药物相比较分析,结合人体药代动力学参数,初步确定安妥沙星对常见细菌的临界浓度.结果 对临床分离致病菌的MIC测定值显示,安妥沙星的抗菌作用与左氧氟沙星接近,安妥沙星体外抗菌活性与左氧氟沙星相关性最好,安妥沙星一次口服300mg后药代动力学参数与左氧氟沙星一次口服400mg相似,综合PK/PD理论,初步设定安妥沙星琼脂稀释法体外抗菌活性测定的临界浓度为,嗜血菌敏感临界浓度为≤1,其它细菌敏感、中介与耐药临界浓度分别为≤2、4和≥8mg/L.结论 通过体外抗菌活性比较,结合药代动力学/药效学理论,初步确定了安妥沙星琼脂稀释法体外抗菌活性测定对常见细菌的临界浓度,供临床应用参考与验证.     

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.

---

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.     

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.