41株金黄色葡萄球菌耐药性分析及PVL基因检测

目的了解临床分离金葡菌对常用抗生素的耐药性和杀白细胞毒素(PVL)基因携带情况。方法采用头孢西丁纸片扩散法检测耐甲氧西林金黄色葡萄球菌(MRSA),K-B法检测临床分离的41株金葡菌对常用抗生素的敏感性,PCR法检测mecA基因和PVL基因携带情况。结果 41株金葡菌中MRSA占51.2%,MRSA对克林霉素、红霉素、氨基糖苷类和喹诺酮类耐药率明显高于甲氧西林敏感金黄色葡萄球菌(MSSA),MRSA和MSSA对复方新诺明敏感率分别为90.5%和95%,未发现对万古霉素、替考拉林和利奈唑胺耐药株。21株MRSA mecA基因均阳性,41株金葡菌中共检出2株携带PVL基因,MRSA与MSSA各占1株,均分离自骨科病房。结论该院临床分离MRSA耐药率高,应规范临床用药,加强MRSA耐药性监测,加强PVL基因的检测,防止此类菌株的播散。     

重症监护病房耐甲氧西林金黄色葡萄球菌及其肠毒素的检测和耐药性分析

目的评价乳胶结合实验检测重症监护病房（ICU）耐甲氧西林金葡菌（MRSA）及金葡菌肠毒素，并进行耐药性分析。方法收集130株金葡菌临床分离株，通过药敏试验将其分为耐甲氧西林金葡菌和甲氧西林敏感金葡菌（MSSA）．用反向间接血凝试验（RPHA）检测金葡菌肠毒素。结果MRSA产肠毒素为67株．MSSA产肠毒素为19株，MRSA产肠毒素率为100％，MSSA产肠毒素率为30％。结论重症监护病房应重视MRSA的检测和金葡菌肠毒素的检测。合理使用广谱抗生素。     

长春市金葡菌耐药状况及耐甲氧西林金葡菌基因分型

目的调查长春地区临床分离金葡菌的耐药状况及Panton—Valentine杀白细胞素（PVL）分布情况；确定耐甲氧西林金葡菌（MRSA）染色体及葡萄球菌me~盒式染色体（SCCmec）基因分型。方法琼脂稀释法测定苯唑西林等17种抗菌药物对2004年6月～2005年1月长春市3家教学医院临床标本分离的83株金葡菌的最低抑菌浓度（MIC）；聚合酶链式反应（PCR）进行金葡菌的PVL基因检测；脉冲场凝胶电泳（PFGE）对MRSA菌株作染色体同源性分析。多重PCR方法检测MRSA的SCCmec基因分型。结果83株金葡菌中MRSA12株（占14．5％）；金葡菌PVL的基因阳性7株（占8．4％）。MRSA对β-内酰胺类、红霉素、克林霉素、庆大霉素、四环素、氟喹诺酮类耐药率均超过90％，对氯霉素、利福平耐药率分别为8．3％、58．3％。未发现对糖肽类及复方磺胺甲嗯唑耐药的MRSA。甲氧西林敏感金葡菌（MSSA）对青霉素G、红霉素、克林霉素、四环素、庆大霉素耐药率分别为95．8％、67．6％、49．3％、45．1％、26．8％，对头孢菌素、氯霉素、利福平、氟喹诺酮类、复方磺胺甲曙唑耐药率均低于20％。MRSA的PFGE显示为A、B两种类型，以A型为主，占92％（11／12），三家医院均有分布。MRSA的SCCmec分型．Ⅲ型为主75％（9／12）。结论长春市MRSA发生率低于国内报道平均水平；MRSA为两种不同类型克隆株，在不同医院间存在克隆传播；未发现社区获得性MRSA菌株。     

新生儿重症监护室金黄色葡萄球菌定植菌株的耐药性及生物膜形成能力研究

摘要：目的 研究北京儿童医院新生儿重症监护病房(NICU)患儿鼻前庭金黄色葡萄球菌(简称金葡菌)的定植情况及定植菌 株的药物敏感性、生物膜形成能力。方法 前瞻性收集2015年5月至2016年3月于北京儿童医院NICU住院患儿鼻前庭分离出的 金葡菌,前期已进行分子分型,本次实验利用E-test 法检测金葡菌对临床常用抗菌药物的药物敏感性,结晶紫染色实验检测定 植菌株的生物膜形成能力。结果 536例鼻拭子分离出96株金葡菌,定植率为17.9%。其中,耐甲氧西林金葡菌(MRSA) 28株, 甲氧西林敏感金葡菌(MSSA)有68株。MRSA菌株对青霉素、苯唑西林、头孢曲松、红霉素和夫西地酸耐药率分别为100%、 57.1%、78.6%、92.9%和3.6%。MSSA菌株对青霉素、头孢曲松、红霉素、庆大霉素的耐药率分别为82.4%、8.8%、47.1%和 16.2%。MRSA中有14.3%苯唑西林敏感甲氧西林耐药金葡菌(OS-MRSA)。定植菌株的生物膜阳性率91.7%,MRSA和MSSA在生 物膜形成能力方面没有显著差异,不同ST型菌株生物膜形成能力存在差异(P=0.0276),产膜菌株与非产膜菌株的药物敏感性无 明显差异。结论 定植的金葡菌常对青霉素、红霉素耐药,对其他临床常用抗菌药物敏感性较好,有一定比例OS-MRSA。定 植菌株生物膜阳性率高,不同分型菌株生物膜形成能力不同。     

耐甲氧西林金葡菌的头孢西丁检测法与耐药性分析

目的评价头孢西丁纸片扩散法检测耐甲氧西林金葡菌（MRSA）的效果．了解MRSA的耐药状况。方法用头孢西丁及苯唑西林纸片扩散法、mecA基因聚合酶链反应（PCR）检测MRSA．并以mecA基因PCR法为参考方法与头孢西丁及苯唑西林纸片扩散法检测MRSA进行比较分析。按CLSI（原NCCLS）规定的标准测定MRSA对青霉素等10种抗生素的耐药率（KB法）。结果95株金葡菌（SA）中mecA基因阳性株42株。头孢西丁纸片法筛选出40株MRSA，其中39株mecA基因阳性，方法特异性为97．5％，灵敏度92．9％；苯唑西林纸片法筛选出44株MRSA，其中36株mecA基因阳性．方法特异性为81．8％．灵敏度85．7％。MRSA对青霉素、苯唑西林100％耐药，对万古霉素全部敏感．对红霉素、头孢唑林、克林霉素、氨苄西林／舒巴坦、头孢呋辛、左氧氟沙星、奈替米星呈不同程度耐药。结论头孢西丁纸片扩散法检测MRSA特异性和灵敏度优于苯唑西林纸片扩散法。MRSA具有多重耐药性．须加强其对抗生素的耐药性监测。     

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。     

苯唑西林和万古霉素对金葡菌儿童株和成人株的体外抗菌活性差异

目的 分析苯唑西林和万古霉素对金葡菌儿童株和成人株的体外抗菌活性差异。方法用纸片扩散法检测苯唑西林和万古霉素对金葡菌的抑菌圈直径，用E-test法检测最低抑菌浓度（MIC），比较两种抗生素对金葡菌儿童株和成人株的抗菌活性。结果 纸片扩散法和E-test法检测金葡菌的药敏结果基本一致，E—test法结果显示儿童临床分离株对苯唑西林的敏感、中介和耐药率分别为88．2％、3．2％和8．6％，MIC50和MIC90分别为0．75和3．0μg／ml，成人临床分离株的敏感、中介和耐药率分别为28．2％、2．6％和69．2％。MIC50和MIC60均〉256ug／ml，成人株对苯唑西林的耐药率显著高于儿童株（r=107．1，P〈0．001）。所有菌株均对万古霉素敏感，其中儿童临床分离株的MIC50和MIC60分别为1．5和2．0μg／ml，成人临床分离株的MIC50和MIC60均为4．0μg／ml。结论 金葡菌成人株对万古霉索和苯唑西林的耐药性高于儿童株，临床应根据药敏试验结果合理选择抗生素，避免抗生素滥用。     

注射用法罗培南钠对金葡菌的体内外抗菌活性研究

目的研究注射用法罗培南钠对临床分离的金葡菌的体内外抗菌活性。方法用头孢西丁纸片法在近年来本室保存的临床分离金葡菌中筛选耐甲氧西林的金葡菌（methicillin resistant staphylococcus aureus，MRSA），用琼脂平板稀释法测定法罗培南和万古霉素对甲氧西林敏感的金葡菌（methicillin sensitive staphylococcus aureus，MSSA）和MRSA菌株的最低抑菌浓度（minimal inhibitory concentration．MIC）。根据MIC选择对法罗培南敏感、中度和高度耐药的MRSA菌株及1株MSSA建立小鼠腹膜炎模型，以注射用法罗培南钠及万古霉素通过静脉注射进行感染动物的治疗，评价对感染小鼠的保护作用。结果151株金葡菌中共分离出65株MRSA．阳性率为43％；体外试验法罗培南和万古霉素对86株MSSA均敏感。65株MRSA对法罗培南敏感者10株，其余均耐药；对万古霉素均敏感。注射用法罗培南钠对4株菌的ED50分别为38．3、38．6、71．9和7．07mg／kg；万古霉素则为2．25、10．18、20．85和1．77mg／kg。结论注射用法罗培南钠对MSSA有良好的体内和体外抗菌活性；注射用法罗培南钠对MRSA无效．即使体外敏感。     

MRSA表面标志物PBP2a的检出与苯唑西林MIC的相关性分析

目的研究MRSA表面标志物PBP2a与苯唑西林MIC的相关性。方法收集62株金黄色葡萄球菌临床分离株,通过乳胶凝集试验和全自动细菌分析仪分别检测青霉素结合蛋白2a(PBP2a)和苯唑西林MIC值。结果62株金葡中32株PBP2a检测阳性,30株PBP2a检测阴性。苯唑西林MIC≥4μg/ml31株,苯唑西林MIC≤2μg/ml31株。在苯唑西林MIC≥4μg/ml的31株MRSA中30株PBP2a检测均为阳性。结论金黄色葡萄球菌耐苯唑西林的耐药水平与PBA2a的检出有较好的相关性。     

171株金黄色葡萄球菌的分布与耐药性分析

目的：分析苏州大学附属第一医院金黄色葡萄球菌（金葡菌）的分布与耐药情况。方法：将该院2005年5月-2007年5月间分离的171株金葡茵采用K-B扩散法,并按美国临床实验室标准委员会（NCCLS）标准（2004版）进行耐药性分析。结果：金葡菌主要来源于患者耳脓液、脓液和痰液标本,占91．22％,其对除万古霉素外的9种抗菌药物均具有耐药性,并呈逐年升高趋势。结论：该院未发现对万古霉素耐药的金葡菌,除了万古霉素外,耐甲氧西林金葡菌（MRSA）的耐药率明显高于敏感甲氧西林金葡菌（MSSA）,而MRSA呈多重耐药性,MSSA对大部分抗菌药物均具有敏感性。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

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.