海洋源细菌素研究现状及展望

细菌素是细菌通过核糖体合成的抗菌肽,通常能抑制分类地位相近的其他细菌的生长。自20世纪20年代以来报道的陆地源细菌素已多达数千例。乳酸链球菌素是研究得最为透彻的陆地源细菌素,且被公认为安全有效的天然食品生物保鲜剂,在欧美的食品工业中具有广泛应用。与陆地源数以千计的细菌素相比,海洋环境中已发现的细菌素尚不足百种。但有些已发现的海洋源细菌素却表现出陆地源细菌素所不具备的独特活性以及较大的应用潜力,如一些海洋源细菌素具有的对革兰氏阴性耐药性菌的拮抗活性,显示出其成为一线抗革兰氏阴性药物多黏菌素替代品的潜在可能。海洋细菌素的研究正受到越来越多的关注。本文从产生菌、样品来源、结构特性等方面对2009年以来报道的海洋细菌素进行了回顾,对海洋细菌素的研究现状及新细菌素的发现手段进行了分析及讨论。展望未来海洋源细菌素的研究,相信随着深海采样技术、海洋细菌培养技术及细菌素研究技术的进步,越来越多的海洋细菌素产生菌将会进入研究视野,更多结构新颖、活性良好的海洋细菌素也将会被发现。     

我院2005年病原学检查及细菌耐药情况分析

目的 了解医院致病菌种类及其耐药情况，指导临床合理用药。方法 收集临床各科送检的标本，按常规方法培养，分离出致病菌株，采用K—B纸片扩散法进行药物敏感试验。结果 共分离出致病菌株603株，其中革兰氏阳性茵430株（71．3％），革兰氏阴性茵173株（28．6％）。结论 细菌对常用抗茵药物的耐药率总钵呈上升趋势，临床必须慎重、合理地应用抗茵药物，防止滥用。     

变异链球菌UA140产生的细菌素(mutacin和mutacin)

细菌素是由细菌核糖体合成的肽类抗生素。根据翻译后的修饰作用情况 ,将革兰氏阳性菌细菌素分为2类 : 类 ,修饰的细菌素 ,即 lanbiotic类 ; 类 ,未修饰的细菌素 ,即非 lanbiotic类。lanbiotic类为含羊毛硫氨酸的小肽抗生素 ,通过翻译后的修饰作用形成脱水氨基酸残基和硫脂桥。非 lanbiotic类细菌素可以分为 2类 :单肽细菌素和双肽细菌素。非 lanbiotic类细菌素的生物合成涉及一个前肽的合成 ,该前肽由一个在加工位点具有 2个甘氨酸的先导肽和成熟肽部分组成 ,在成熟过程中 ,通过 1个专门的蛋白酶在 2个甘氨酸后的区域切下先导肽 ,释放出成熟…     

细菌自溶素的研究进展

细菌自溶素参与细菌很多重要的生理活动，如细胞分裂、孢子形成等。综述了自溶素参与的细菌生理功能、调控网络，及其在病原菌检测、新型抗菌制剂开发等方面的应用。     

Cefepime对细菌调理素吞噬作用的影响

已经证明某些抗生素的亚-MIC对细菌的形态学及超微结构的特征有修饰作用。药物接触细菌,如用氯林霉素和单环β-内酰胺类抗生素的亚-MIC处理细菌,就可以导致多形核白细胞吞噬作用的增强。第四代头孢菌素Cefepime(BMY28142)对革兰氏阳性阴性菌具广谱抗菌作用。已有报道Cefepime对青霉素结合蛋白(PBP_s)2和3能发挥这种作用。PBP_s是肽聚糖生物合成最后阶段的催化酶,而由于它可导致细胞表层结构缺损,合成异常的肽聚糖,产生了PBP_s的抑制作用,这在宿主防御和细菌之间的相互作用方面,可能有着重要影响。作者用Cefepime的亚-MIC与革兰氏阴     

羊毛硫细菌素生物合成基因簇的遗传分析

羊毛硫细菌素是一类核糖体合成且经翻译后修饰的具有生物活性的小肽，通常含有羊毛硫氨酸及β-甲基羊毛硫氨酸等稀有氨基酸。近年来随着来源于乳酸乳球菌的nisin（乳链菌肽）被广泛地用作天然食品防腐剂和对其研究的不断深入，羊毛硫细菌素已引起研究者广泛关注。因其无耐药性，羊毛硫细菌素还极有可能替代传统抗生素应用于生物医药领域。羊毛硫细菌素的生物合成基因包括结构基因、修饰基因、加工基因、转运基因、免疫基因、调节基因，它们成簇排列于产生菌的染色体或质粒上，构成数个转录单元。本文综述了近年来羊毛硫细菌素生物合成基因簇遗传分析的研究进展。     

快速二步法从复合培养基内大量纯化片球菌素样细菌素及其它带正电荷的抗菌多肽

建立了一种适用于小量和大规模纯化片球菌素样细菌素及其它带正电荷的多肽的快速简单的二步法。第一步 ,将细菌培养物直接上样到阳离子交换柱 (1ml阳离子交换剂 /10 0 ml细胞培养物 ) ,细菌和带负电荷的化合物经柱流出 ,而带正电荷的细菌素随后用 1mol/ L Na Cl洗脱出来。第二步 ,将含细菌素的洗脱液上样到一个低压反相交换柱 ,然后用丙醇洗脱。培养物上清液中的初始活性在两个纯化步骤里都能回收 80 %以上 ,而且通过反相层析和毛细管电泳检测 ,最终得到的细菌素制品的纯度可达 90 %以上快速二步法从复合培养基内大量纯化片球菌素样细菌素…     

膀胱术后导尿管留置与尿路感染的病原菌分布及耐药性分析

目的：了解异物对尿道感染(Utlc)的致病菌谱，及对常用抗菌素药物的敏感性。方法:对1997年3月～2002年3月间．我院膀胱手术187例．留置导尿管引起尿路感染患者尿液行细菌学培养、分离的病原茵以Kirby—Bauer琼脂扩散法药敏检验。结果:留置导尿管患者187例．尿液标本分离的病原茵103株，阳性率55．08％；其中以革兰氏阴性细菌为主，约占52％；大肠埃希茵、变形杆菌、痢疾杆菌属占前三位；第三代头孢菌素对革兰氏阴性或阳性茵敏感明显优于第一、二代头孢菌素。喹诺酮类也有较好的效果。结论:留置导尿管是致尿路感染的致病原因．其致病菌以革兰氏阴性为主，多重感染且耐药，抗菌素治疗应交叉使用，必要时联合应用。     

细菌素nisin的检测方法

细菌素作为蛋白质 (多肽 )类抑菌物质近年来越来越受到人们的重视 ,其中乳链菌肽 (nisin)是目前研究最多的一种细菌素。本文主要概述了基于nisin抑菌活性、免疫学特性、自诱导作用的三类nisin的检测方法     

灯盏花素注射液的细菌内毒素检查

目的:建立灯盏花素注射液的细菌内毒素检查法.方法:按<中国药典>2000年版二部收载的细菌内毒素检查方法及指导原则进行实验.将灯盏花素注射液经240倍稀释,用标示灵敏度为0.25 EU·ml-1的鲎试剂检测其细菌内毒素.结果:灯盏花素注射液稀释240倍对鲎试剂无干扰作用.结论:可以用细菌内毒素检查法对灯盏花素注射液进行热原检查.     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.