新喹诺酮类药在呼吸道感染中的临床应用进展

呼吸道感染是呼吸科的常见病、多发病,肺炎链球菌、流感嗜血杆菌和卡他莫拉菌是引起社区获得性肺炎最为重要的细菌,但是,近年来,包括肺炎支原体、肺炎衣原体和军团菌等在内的非典型病原体的感染比例在增加,来自世界不同地区,较大系列的报道,非典型病原体高达40%,其中肺炎支原体、肺炎衣原体和军团菌分别为1%～36%,3%～22%和1%～16%,这些非典型病原体可以是社区获得性肺炎(CAP)的单一病原体,但有1/3～1/2与CAP的主要病原菌肺炎链球菌合并存在,并促使病情加重,尤其是肺炎衣原体。研究表明,肺炎链球菌对左氧氟沙星、莫西沙星等呼吸喹诺酮类药物的耐药率<1.0%。且喹诺酮类药对突变的肺炎支原体依然保持着高敏感性,肺炎链球菌对青霉素高度耐药,对大环内酯类耐药率超过50%。流感嗜血杆菌及卡他莫拉菌对β内酰胺类联合酶抑制剂的复合制剂和喹诺酮类均敏感。于是中国《社区获得性肺炎诊断和治疗指南》中将呼吸喹诺酮药物列为了一线治疗用药。在新的治疗策略中,更为合理的是早期使用覆盖常见病原菌的强效抗生素及更合理的疗程。     

慢性阻塞性肺疾病伴社区获得性肺炎60例病原菌及其耐药性分析

目的 对COPD伴社区获得性肺炎病原菌和耐药情况进行分析,为临床合理用药提供依据.方法 对60例COPD伴社区获得性肺炎患者的痰液标本进行病原菌检测和药敏性试验.结果 病原菌以肺炎链球菌为主24例（40％）,其次为肺炎克雷伯菌10例（13.3％）、流感嗜血杆菌8例（16.7％）、肺炎支原体6例（8.3％）、甲型溶血性链球菌5例（6.7％）、金黄色葡萄球菌4例（3.3％）、嗜肺军团菌2例（3.3％）、其它1例（1.67％）;药敏试验显示革兰阴性菌具有较高的耐药率.流感嗜血杆菌、肺炎链球菌、嗜肺军团菌体对青霉素具有较高的耐药率.肺炎支原体、肺炎克雷伯菌对阿奇霉素表现出一定的耐药率.金黄色葡萄球菌、甲型溶血性链球菌对头孢噻吩表现出耐药性.结论 COPD伴社区获得性肺炎患者感染病菌情况主要以革兰阴性菌抗生素耐药较为严重.在之后的临床使用抗生素选择其它类的抗生素,提高临床药物抗菌疗效.     

82例社区获得性肺炎病原体调查分析

目的调查社区获得性肺炎（CAP）的病原体分布,为本社区CAP的经验性治疗提供依据。方法收集2006年1月～2008年1月CAP患者共82例,分别留取呼吸道分泌物进行细菌培养,应用常规方法分离鉴定细菌,同时检测患者急性期和恢复期肺炎支原体、肺炎衣原体、嗜肺军团菌血清抗体。结果82例CAP患者48例（58．5％）病原学检查阳性。检出肺炎支原体14例;肺炎衣原体5例;嗜肺军团菌3例。分离出流感嗜血杆菌15例;肺炎链球菌10例;卡他莫拉菌5例;肺炎克雷伯杆菌2例;金黄色葡萄球菌2例。14例为混合感染。结论流感嗜血杆菌和肺炎链球菌仍是CAP的主要致病菌。非典型病原体在CAP中占有重要地位,且多为混合感染。     

阿奇霉素治疗社区获得性肺炎的临床效果

社区获得性肺炎(Community acquired pneumonia，CAP)是指在医院外罹患的感染性肺实质(含肺泡壁即广义上的肺间质)炎症，包括具有明确潜伏期的病原体感染而在入院后平均潜伏期内发病的肺炎。社区获得性肺炎最常见的病原体是：肺炎链球菌、流感嗜血杆菌、卡他莫拉氏菌及肺炎支原体、肺炎衣原体和嗜肺军团菌等非典型病原体。患者初始治疗时致病菌尚不清楚，因而采用经验性治疗方案，其中包括第二代头孢菌素单用或联合大环内酯类或单用新大环内酯类，阿奇霉素是新一代的大环内酯类抗生素，其抗菌广，     

合肥地区社区获得性肺炎154例病原学调查

目的了解合肥地区本院CAP患者病原体分布,分析各种病原体的构成。方法对2005年1月~2007年3月间本院154例CAP患者进行病原体检测,病原体确定诊断阳性判断标准:合格标本培养出病原体;间隔2~4周,非典型病原体抗体滴度呈现大于或等于4倍增高。应用PCR分别扩增肺炎支原体16SrRNA,肺炎衣原体主要外膜蛋白基因和军团菌主要外膜蛋白porin基因。结果154例标本进行了细菌培养和血清学检测和DNA检测,其中肺炎链球菌是最为常见的病原菌,占23.8%,流感嗜血杆菌占5.2%,化脓链球菌占5.2%,肺炎克雷伯菌和不动杆菌各占1.9%;在非典型病原体中,肺炎支原体占13.6%,肺炎衣原体占1.9%,嗜肺军团菌占0.6%。其中,单一病原体感染占57.1%,二重病原体混合感染占15.6%,三重占2.6%,混合感染病原体中肺炎支原体最为多见占52.4%。结论合肥地区本院CAP病原体最为常见的是肺炎链球菌,非典型病原体中以肺炎支原体最为多见,混合感染中以肺炎支原体最为多见,占52.4%。     

北京东南部地区成人社区获得性肺炎620例病原学分析

目的 了解北京东南部地区成人社区获得性肺炎（CAP）的病原学分布特点,为CAP经验性治疗提供依据。方法回顾性分析2016年10月1日至2020年4月30日北京市垂杨柳医院620例CAP患者的病原学分布特点。结果 非典型病原体阳性率为40.8%,肺炎支原体占39.4%;细菌检测阳性率为56.8%,肺炎链球菌占35.8%,流感嗜血杆菌占19.0%;病毒检测阳性率为19.7%,甲型流感占5.6%,副流感占5.6%。混合感染率为43.5%,肺炎链球菌合并肺炎支原体最常见。结论 肺炎支原体为北京东南部地区成人CAP的首位病原体,肺炎链球菌、流感嗜血杆菌次之,甲型流感病毒及副流感病毒是最常见的病毒病原。且本地区CAP混合感染率高。本研究初步揭示了该地区成人CAP的病原学分布特点,为经验性治疗提供病原学依据。     

太原地区成人及儿童社区获得性肺炎非典型病原体流行病学调查

目的对引起社区获得性肺炎(CAP)的病原体进行流行病学调查,以了解非典型病原体感染的状况并分析其感染的流行病学特征。方法收集2005年12月至2006年12月CAP成人患者86例,儿童患者375例。取患者急性期痰标本进行细菌培养,应用常规方法分离鉴定细菌。应用被动凝集法检测血清肺炎支原体抗体,应用间接免疫荧光(IIF)法检测血清肺炎衣原体抗体,应用聚合酶链反应(PCR)扩增痰中军团菌属特异性16SrRNA基因,应用酶联免疫吸附试验(ELISA)检测患儿血清中呼吸道合胞病毒,腺病毒,流感病毒A型、B型,副流感病毒1、3型等6种病毒抗体。结果86例成人CAP患者,病原体检出率为64.0%,其中17例(19.8%)检出肺炎支原体,16例(18.6%)检出军团菌,2例(2.3%)检出肺炎衣原体,14例(16.3%)分离出肺炎链球菌,4例(4.6%)为肺炎克雷伯菌,2例(2.3%)流感嗜血杆菌,19例(22.1%)患者存在混合感染,混合感染者中10例为肺炎支原体混合其他病原体。375例患儿中,痰培养360例,其中细菌培养阳性者148例(41.1%);在同时进行痰培养和血清学检测的350例患儿中,254例(72.6%)检测到病原体,其中细菌感染138例(39.4%),病毒感染133例(38.0%),肺炎支原体感染77例(22.0%),肺炎衣原体感染8例(2.3%),军团菌感染7例(2.03%),混合感染112例(32.0%)。成人患者,≤25岁组肺炎支原体感染率高于>25岁组,无基础疾病组肺炎支原体感染率高于有基础疾病组,冬季肺炎支原体感染率高于其他季节;儿童肺炎支原体感染以1～7岁为主。结论非典型病原体尤其是肺炎支原体感染在CAP中占据重要地位。     

太原地区社区获得性肺炎病原学调查以及军团菌感染状况研究

目的①对太原地区社区获得性肺炎(CAP)病原学特征进行流行病学调查研究,以了解病原微生物的感染特点、流行的优势菌株等。②探讨CAP的流行规律及影响因素。③探讨军团菌实验室检测方法。方法收集符合CAP诊断标准,同时排除肺结核、肺部肿瘤、非感染性肺间质性疾病、肺水肿、肺不张、肺栓塞、肺嗜酸性粒细胞浸润症、肺血管炎等疾病的277例患者。取患者急性期痰标本(咽拭子)和尿进行检测,同时收集流行病学基线资料。①细菌学检测:取患者急性期痰标本或咽拭子标本进行细菌培养,分离鉴定细菌;②军团菌检测:应用聚合酶链反应(PCR)扩增军团菌特异基因16SrRNA和尿抗原检测。结果①按照患者的年龄和职业构成,太原地区成人CAP的发病人群主要以老年人(58.7%)、工人(28.1%)、干部职员(18.9%)为主。②共收集了194份新鲜痰液进行了痰(咽拭子)培养的患者中,细菌培养阳性者171例,其中单一感染者105例,2种以上混合感染23例。前3位病原体依次为:白色念珠菌(10.8%)、肺炎链球菌(5.6%)、流感嗜血杆菌(4.1%),混合感染检出率为12.2%。太原地区肺炎链球菌合并奈瑟菌为主要的混合感染(2.5%)。病原体的分布与年龄、季节和基础疾病无关(P>0.05)。③对100例CAP患者进行尿抗原检测,阳性者9例(9.0%);PCR检测阳性者3例(3.0%)。军团菌肺炎发病人群多在50～80岁,且大多数患者工作和生活环境中有密闭的空调系统或有冷却塔、热水系统等。结论近年来太原地区CAP细菌感染占据首要地位。细菌感染以真菌、肺炎链球菌最多。白色念珠菌和肺炎链球菌是CAP最重要的病原菌;CAP的混合感染不容忽视;革兰阴性杆菌感染增多。     

某县社区获得性肺炎病原学及耐药分析

目的回顾性分析怒江州人民医院呼吸科住院的成人社区获得性肺炎患者,以了解怒江州泸水县成人社区获得性肺炎(CAP)患者病原体分布及致病菌耐药情况,指导临床制定合理治疗方案。方法对2008年3月至2010年3月间怒江州人民医院呼吸科住院的怒江州泸水县207例成人CAP患者的痰培养结果、血清学检测结果及药物敏感试验结果进行回顾性分析。结果 142例患者的病原学检测阳性,占全部患者68.6%,其中痰培养阳性112例,占阳性患者的78.9%,其中革兰阴性菌感染率为47.9%。血清学检测肺炎支原体及衣原体抗体阳性30例,占阳性患者的21.1%。结论怒江州泸水县成人社区获得性肺炎病原体最为常见的是肺炎链球菌,其次是肺炎克雷伯菌,再次是卡他莫拉,非典型病原体中以肺炎支原体最为多见。而且CAP患者病原体耐药情况严峻,在临床选择抗菌药物时要予以充分考虑。     

社区获得性肺炎病原谱及药敏谱流行病学的调查

目的熟悉我省社区获得性肺炎（CAP）病原谱及药敏谱,为临床治疗CAP提供强有力的证据。方法细菌培养采用常规法．细菌鉴定大多数采用仪器法．小部分采用传统手工法,细菌药敏均采用琼脂稀释法。非典型病原体的肺炎支原体、肺炎衣原体、嗜肺军团菌均采用日本和美国进口试剂盒进行血清学检测、尿抗原采用酶免疫测定法（EIA）测定。结果人选病例121份,51～70岁患者是本项目的主要对象．占总数的78．5％;病例中（咳）痰标本占97％,其它方法采集的占3％,检出病原菌52例（42．9％）．其中肺炎链球菌13株（10．7％）,占细菌的第一位;药敏中阳性球菌、大多数阴性杆菌分别测14种抗生素,嗜血杆菌和莫拉菌测9种抗菌药物。非典型病原体共检测121例．阳性28例。检出率23．1％,其中肺炎支原体19例,肺炎衣原体6例,嗜肺军团菌3例。结论CAP是常见的社区感染,其病原谱和药敏谱的组成各地不尽相同;随着时间的推移和变迁,尤其是社会人口老龄化、免疫损害宿主的增加、病原体变化和抗生素耐药率上升等原因,CAP的诊治将面临许多新问题。     

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.