大环内酯类抗生素的研究新进展

大环内酯类抗生素在呼吸道感染的治疗上起着十分重要的作用。目前上市的治疗呼吸道感染的药物都存在着不同程度的局限性,故随着新耐药菌的不断出现,研制出新型大环内酯类抗生素迫在眉睫。近年来大环内酯类抗生素的研究重点主要集中在通过对高活性化合物进行结构修饰、改善药学活性及改变剂型、提高生物利用度等几个方面。本文就近10年来大环内酯类抗生素研究上的新进展作一简要综述,包括新型大环内酯类抗生素——酮内酯类、2001年上市的泰利霉素及各候选药物:可利霉素、cethromycin、solithromycin和modithromycin。其中solithromycin为第四代大环内酯类即氟酮内酯类抗生素,modithromycin为双环内酯类抗生素。     

阿奇霉素的药动力学特点及临床应用

阿奇霉素(azithromycm，AZM)是一种氮环内酯类抗生素，其化学结构为—个甲基取代的氮原子加入红霉素内酯环中所成的15元环大环内酯类。目前，该药物在临床应用日前日益广泛，下面就其药动学特点及临床应用作一介绍。     

新大环内酯类抗生素的体外抗菌作用研究

以琼脂对倍稀释法测定新大环内酯类抗生素（ａｚｉｔｈｒｏｍｙｃｉｎ、ｃｌａｒｉｔｈｒｏｍｙｃｉｎ及罗红霉素）等抗菌药对２０２株临床分离菌的最低抑菌浓度。结果，新大环内酯类抗生素对流感杆菌及副流感杆菌的抗菌活性高，明显优于红霉素等沿用大环内酯类抗生素；对肺炎球菌、Ａ及Ｂ组链球菌的抗菌作用与其它大环内酯类抗生素相仿，对Ｄ组链球菌和金葡球菌的作用较差。以上结果显示，新大环内酯类抗生素对院外获得性呼吸道感染常见病原菌具良好抗菌作用，其中对嗜血杆菌属的抗菌作用明显优于沿用大环内酯类抗生素，因此新大环内酯类抗生素为院外呼吸道感染的适宜选用药物。     

大环内酯类抗生素研究的新进展

对大环内酯类抗生素抗菌以外的作用和新大环内酯的品种进行了综述.大环内酯类抗生素对心血管疾病、闭塞性支气管炎、大泡性肺气肿、腹部手术、慢性便秘、免疫炎症等有一定的防治作用,还可利用其对细胞的穿透作用增强其他药物的作用.新大环内酯的品种有酮内酯、酰内酯、氨基甲酸酯和脱水内酯四类.     

大环内酯类抗生素研究的新进展

对大环内酯类抗生素抗菌以外的作用和新大环内酯的品种进行了综述。大环内酯类抗生素对心血管疾病、闭塞性支气管炎、大泡性肺气肿、腹部手术、慢性便秘、免疫炎症等有一定的防治作用，还可利用其对细胞的穿透作用增强其他药物的作用。新大环内酯的品种有酮内酯、酰内酯、氨基甲酸酯和脱水内酯四类。     

Azithromycin及其相关化合物的分析

azithromycin(CP-62993,XZ-450,AM)是具有15元的氮杂内酯(azalactone)环的半合成大环内酯类抗生素。化学结构上系在红霉素A内酯环的9a位内插一个含有取代甲基的氮原子,成为氮杂类(azalids)化合物。修饰后的产物即azithromycin,较母体化合物红霉素扩大了抗菌谱,提高了抗菌活力和对酸性环境的稳定性。口服后生物利用度高,半衰期较长,具有更高的组织浓度。1993年已收入美国药典Ⅹ Ⅹ Ⅱ版第8补编内。本文介绍AM的有关化学、酸稳定性研究、产品质     

酮内酯类抗生素的结构修饰研究进展

近年来,发现了一类新的大环内酯类抗生素-酮内酯,它的结构特征为在C-3位酮基取代,C-11和C-12位形成环状碳酸酯,并在环状碳酸酯的氮原子上连接杂环.本文综述了近年来酮内酯类的半合成改造研究进展.     

大环内酯类抗生素研究的新进展

对大环内酯类抗生素抗菌以外的作用和新大环内酯的品种进行了综述.大环内酯类抗生素对心血管疾病、闭塞性支气管炎、大泡性肺气肿、腹部手术、慢性便秘、免疫炎症等有一定的防治作用,还可利用其对细胞的穿透作用增强其他药物的作用.新大环内酯的品种有酮内酯、酰内酯、氨基甲酸酯和脱水内酯四类.     

酮内酯类抗生素的研究进展（上）

几十年来大环内酯类抗生素在临床上的广泛应用取得了很好的疗效，但随着大环内酯类抗生素临床应用的增加，细菌对其耐药性也不断上升，促使人们加快对大环内酯类抗生素构效关系研究，从而来开发更有效更具潜力的药物；近年来国外在对红霉素的构效关系的深入研究中，开发出了同时对耐药茵有效的酮内酯大环内酯类药物，如泰利霉素，噻霉素；本文简要对大环内酯酮内酯类药物的研究开发状况作一介绍一     

酮内酯类抗生素的研究进展

几十年来大环内酯类抗生素在临床上的广泛应用取得了很好的疗效。但随着大环内酯类抗生素临床应用的增加 ,细菌对其耐药性也不断上升 ,促使人们加快对大环内酯类抗生素构效关系研究 ,从而开发更有效更具潜力的药物。近年来国外在对红霉素的构效关系的深入研究中 ,开发出了同时对耐药菌有效的酮内酯类药物 ,如泰利霉素 ,噻霉素。对酮内酯类药物的研究开发状况作一介绍     

甲基黄酮醇胺盐对大鼠学习记忆的促进作用与其抗氧化作用的关系

目的研究甲基黄酮醇胺盐对大鼠学习记忆的影响，分析该药影响学习记忆与其影响脑内自由基反应的关系。方法ｉｐ甲基黄酮醇胺盐５，１０ｍｇ·ｋｇ－１共７ｄ后，采用Ｍｏｒ－ｒｉｓ水迷宫测试大鼠的学习记忆能力，同时测定训练ｄ５和休息３０ｄ后大鼠脑内过氧化脂质（ＬＰＯ）含量和超氧化歧化酶（ＳＯＤ）活性。结果甲基黄酮醇胺盐两种剂量均可提高大鼠获取空间定位信息能力和信息贮存能力并增强记忆保持和再现过程。用药大鼠脑内ＬＰＯ含量明显低于对照组，与其记忆成绩呈正相关性。而脑内ＳＯＤ活性则高于对照组，与其记忆成绩呈负相关性。结论甲基黄酮醇胺盐对大鼠的学习记忆机能具有促进作用，而它的抗氧化作用可能为其促进学习记忆的作用机制。     

舒芬太尼复合咪达唑仑在乳腺癌手术麻醉苏醒中的应用

目的研究舒芬太尼+咪达唑仑在乳腺癌手术麻醉复苏中的应用,术后麻醉苏醒情况及拔管时血流动力学变化。方法选取ASAⅠ级,临床诊断为乳腺癌,拟行乳腺癌改良根治术患者60例,随机分为三组,每组20例,三组均采用气管内插管全身麻醉方式,以维库溴铵诱导插管,1组(F)以芬太尼+异丙酚+咪达唑仑维持麻醉,2组(S)以舒芬太尼+丙泊酚+咪达唑仑维持麻醉,3组(T)以舒芬太尼+丙泊酚+咪达唑仑维持麻醉,于术毕前10min停止丙泊酚输注,追加舒芬太尼+咪达唑仑,观察记录手术结束,取吸痰时,拔管时及拔管后MAP,HR,与基础值进行比较,记录呼患者睁眼时间,拔除气管导管时间和OAA/S评分。结果与术毕时比,F组和S组的MAP和HR在吸痰、拔管时均明显增高(P<0.05)。在睁眼时间、拔管时间两项观察指标中,各组之间差异有统计学意义,T组患者睁眼时间及拔管时间最短,S组次之,F组最慢,OAA/S评分T组评分较F组和S组明显升高(P<0.05)。结论舒芬太尼联合咪达唑仑用于乳腺癌手术患者,能保证很好的麻醉深度,术毕前10min追加舒芬太尼+咪达唑仑,拔管时心血管反应轻,术毕苏醒时间快,清醒状况良好,值得临床推广。     

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.     

《儿科阿奇霉素注射使用的快速建议指南》临床问题与结局指标的调查分析

目的:通过总结《儿科阿奇霉素注射使用的快速建议指南》临床问题与结局指标的前期调查结果,与指南专家评估结果进行对比,探讨开展该工作的意义。方法:通过电子问卷,对临床一线医务人员进行调查,调查内容主要包括参与者的基本信息、对指南拟纳入的临床问题(5分制)和结局指标(9分制)进行重要程度评分以及补充。计算各题平均分,采用变异系数表示一致性,采用Wilcoxon秩和检验,对比参与者和专家评估结果,对补充的内容进行描述性分析。结果:共纳入155位参与者的调查结果,各年龄段、文化程度和职称等均有分布。结果显示,注射用阿奇霉素的用法用量(4.56分)和有效性指标(7.28分)最受关注,特殊人群用药(42.71%)和安全性(34.52%)的一致性较差;与专家评估对比分析显示,对于大部分问题和指标,前期调研和专家评估的评分差异无显著性,专家评估的变异系数更低;共收集有效补充15条,最终将新生儿的使用问题纳入。结论:在指南制订前期,有必要对临床问题和结局指标进行广泛调查,收集并分析评估和补充意见,这对指南专家组的评估具有一定的参考意义。     

Lipophilicity of kinetically labile metal complexes through the example of antidiabetic Zn(II) and VO(IV) compounds

The lipophilic character of several carrier ligands of antidiabetic Zn(II) and VO(IV) metal complexes were characterized by the traditional saturation shake flask method based on n-octanol/water partitioning. The transfer of the neutral ligand species to the organic phase was followed by UV spectrophotometry at various pH and the partition and distribution coefficients were calculated with the help of the proton dissociation constants and the spectra of the individual ligand species. Partition and distribution coefficients of the Zn(II) and VO(IV) complexes were determined by analysis of the metal ion content of the aqueous phases before and after separation by ICP-AES, their UV spectra and the corresponding concentration distribution curves. Results revealed the fairly hydrophilic character both the carrier ligands and their neutral Zn(II) and VO(IV) complexes. A quasi-linear relationship was found between logP of the ligands and that of the metal species in the case of the ligands studied with the exception of the picolinates. Importance of the knowledge of the chemical speciation (i.e. stoichiometry and stability constants) was also highlighted for the characterization of the lipophilic character of the kinetically labile metal complexes.     

不同统计方法对1998-2010年鲍曼不动杆菌耐药率与抗菌药物使用相关性研究

目的:研究1998-2010年13年间抗菌药的使用与鲍曼不动杆菌的耐药性水平变化之间的相关关系.方法:利用不同的统计方法,用SPSS 13.0统计软件统计抗菌药使用与细菌耐药之间的相关分析.结果:同期比较显示亚胺培南、头孢哌酮/舒巴坦、哌拉西林钠/他唑巴坦的DDDs与鲍曼不动杆菌对各自的耐药率之间存在正相关(P<0.05).非同期相关性统计结果显示,只有美洛培南的DDDs与其耐药率之间有正相关关系(P<0.05).鲍曼不动杆菌耐药率与不同类抗菌药物累计DDDs之间相关性分析,其中Bivariate 相关性统计结果显示,头孢类抗生素的使用对亚胺培南、头孢噻肟及哌拉西林钠/他唑巴坦的耐药率之间存在正相关关系(P<0.05).复方制剂的使用对头孢他啶、环丙沙星及头孢哌酮/舒巴坦存在正相关关系(P<0.05).碳青霉烯类抗生素的使用对亚胺培南、美洛培南、头孢噻肟及哌拉西林钠/他唑巴坦存在正相关关系(P<0.05).Panial相关性统计结果显示,复方制荆的使用对头孢他啶、头孢噻肟、氨曲南、环丙沙星、左氧氟沙星及头孢哌酮/舒巴坦存在正相关关系(P<0.05).碳青霉烯类抗生素的使用对亚胺培南的耐药率之间存在正相关关系(P<0.05).结论:不同的统计方法,相关关系结果有很大差异.     

Intraneuronal dopaminergic action of cocaine and some of its metabolites and analogs

The present study investigated the actions of cocaine and some of its metabolites and analogs upon the synaptosomal (P2) synthesis and release of dopamine appearing from [14C]phenylalanine. Also examined was the influence of reserpine upon these actions of cocaine. The P2 preparations from the rat caudate nucleus were incubated with the drugs for [14C]phenylalanine and, after filtration, the particulates and medium fractions were analyzed for [14C]dopamine and [14C]phenylalanine. Labelled dopamine in the medium was taken as a measure of its release by any addition of drug. Cocaine, norcocaine and the synthetic cocaine analogs WIN 35428 and WIN 35-065(2) each stimulated both the total (medium plus particulates) formation and the release of dopamine, while benzoylecgonine and ecgonine were without effect. Reserpine inhibited the synthesis and enhanced the release of dopamine. An addition of reserpine blocked the stimulating effect of cocaine, norcocaine, WIN 35428 and WIN 35-065(2) on synthesis and furthermore, these drugs had, in the same experiments, inhibitory effects on the synthesis, additive to the reserpine-induced inhibition. Benzoylecgonine and ecgonine were only weakly inhibitory in the presence of reserpine. Stimulation, rather than additive inhibition, by cocaine was observed in the presence of exogenous dopamine, and amphetamine increased the synthesis in the presence of either reserpine or added dopamine. Pretreatment of rats with reserpine also blocked the stimulation of synthesis by cocaine and WIN 35428. The uptake of labelled substrate was not affected by addition of drug, or by the pretreatment.     

Effects of chlordiazepoxide and of valproate on hyponeophagia in rats. Evidence for a mutual antagonism between their anxiolytic properties

The effects of chlordiazepoxide (0,2.5 and 7.5 mg/kg), of valproate (0,100 and 300 mg/kg), and of combinations of these drugs, on hyponeophagia in rats, were studied using a food preference test. Chlordiazepoxide alone reduced the latency for eating, and also enhanced the time of eating and the amount of familiar food eaten at the smaller dose, and of novel food eaten at the larger dose. Valproate alone reduced the latency of eating and enhanced time of eating and the amount of novel food eaten, especially at 300 mg/kg. However, valproate antagonised the effects of chlordiazepoxide on all behavioural measures. These findings are discussed in the context of the GABA hypothesis of the actions of benzodiazepines, with the conclusion that valproate has an atypical pharmacological profile amongst putative GABA agonists, and may have partial agonist activity at the proposed benzodiazepine/GABA receptor complex.