噁唑烷酮类抗菌药物的研究

噁唑烷酮类化合物是新一代全合成的抗菌药物，有着全新的结构和独特的作用机制。此类药物可阻止细菌蛋白质的早期合成反应，与其他蛋白质合成抑制剂类抗菌药物无交叉耐药性，体内外对许多临床耐药菌有强烈的抗菌活性。本文主要介绍口恶唑烷酮类作用机制、体内外抗菌活性及药效方面的研究情况。     

抗菌药物的作用机制及细菌耐药性机制的研究进展

抗菌药物为人类的健康生存和发展作出了巨大的贡献。而细菌耐药性问题近年来已经发展到了非常严重的地步。深入了解药物的作用机制及其相关的耐药机制对研制新的有效抗菌药物是非常必需的。近年来对临床常用的抗菌药物β－内酰胺类、氨基糖苷类、喹诺酮类的作用机制和耐药机制进行了研究。其耐药机制涉及多个方面，主要有：酶对药物进行水解、酰化、磷酸化及核苷化；改变修饰药物的靶位；通过改变细胞膜的通透性或增加药物外排而降低细胞体内药物的浓度以及细菌固有的一些特性，如铜绿假单胞菌的生物被膜等，每类药物各有其侧重点。     

抗菌药物主要作用靶点的研究进展

抗菌药物是指能够杀灭细菌或者对细菌活性产生抑制作用的一类药物,主要包括抗生素类、磺胺类、咪唑类、硝基咪唑类、喹诺酮类等在内的化学合成药物。该类药物一般是由细菌、放线菌、真菌等微生物经过培养获取的产物,或者是采用化学半合成法制造的相同或相似的物质,经过化学反应合成。当前,医疗技术在不断的发展与完善,针对预防和治疗细菌感染所研制的抗菌药物日益增多,造成耐药菌株也同步增多,细菌对抗菌药物的耐药性在不断升级强化并且在病原微生物中得到广泛传播。抗菌药物的不合理使用或滥用所带来的一系列药物不良反应的同时,也致使抗细菌感染治疗所面临的挑战更加严峻。因此,不断研发新型高效的抗菌药物的同时,在解决因不断加剧的耐药性而产生的无药可用的问题中具有十分重要的临床意义,并且基于新的作用靶点而进行的新型抗菌药物的研发是一个新的方向。基于此,本研究主要综述抗菌药物作用靶点的研究进展文献,并对研究进展做了分析,以供同行业学者借鉴。     

吗啉硝唑临床应用的研究进展

从结构特点、抗菌机制、抗菌活性、药动学、药物相互作用及临床应用等方面全面介绍吗啉硝唑的研究进展,为深入研究提供参考。吗啉硝唑作为新型硝基咪唑类抗菌药,抗菌活性强,不易产生耐药性,临床应用日益增多。多项研究证实吗啉硝唑疗效显著,安全性高。吗啉硝唑具有科研和临床应用价值,值得深入研究。     

新大环内酯Flurithromycin的抗菌作用

Furithromycin是一种新的大环内酯类抗生素.与同类其它品种相比,其抗菌谱及抗菌作用与红霉素相似,但对酸更稳定,血清半衰期更长,组织浓度更高.本文对该品的抗菌作用,抗生素后效应(PAE)以及与其他抗生素的相互作用进行了较详细的研究.     

抗菌药物不良反应分析

抗菌药为选择性高、副作用较少的药物，在日常诊疗中，抗菌药物为使用率最高的一大类药物。抗菌药的不良反应主要来源于抗菌作用（如林可霉素引起的伪膜性肠炎）、化学结构（氨基糖苷类引起的肾、神经毒性）、某化学基团作用（N．甲四唑硫甲基引起的出血性倾向等）、抗菌之外作用（喹诺酮类诱发的痉挛等）及药物相互作用（红毒素引起特非那定的严重心律失常）等。笔者针对这些抗菌药物引起肝损害的不同机制和程度予以分述。     

喹诺酮类抗菌药物的抗肿瘤作用

喹诺酮类抗菌药物以4 -喹诺酮母核作为基本结构 ,对细菌DNA回旋酶具有选择性抑制作用 ,目前作为一种常用的抗菌药物广泛应用于临床。其抗菌谱广 ,对革兰阴性菌、金黄色葡萄球菌有良好的抗菌作用。近年来的研究表明 ,某些喹诺酮衍生物还具有抗肿瘤作用。1化学结构与抗肿瘤作用的关系1 1喹诺酮类药物的基本结构目前常用的喹诺酮类药物多为第3代 ,即氟喹诺酮类。它通过对喹诺酮母核化学结构的修饰出现一系列新型氟取代的4 -喹诺酮衍生物。在化学结构上 ,基本母环的3位有1个羧基 ,6位通常有氟取代 ,多数7位有1个哌嗪环 ,有的在8位引入第2个氟…     

药物蛋白质组学研究进展

药物蛋白质组学是基因组和药物发现之间的桥梁,目前已广泛应用于临床和生物医学的各个领域.其研究内容在临床前包括:构建分子药理筛选模型、筛选药物作用靶点、研究药物作用机制和毒理机制等;临床研究包括:利用疾病特异性蛋白质作为疾病分类分型和诊断的标志,还用于评价疗效和预测疾病的预后和转归等.     

细菌耐药机制与临床治疗对策

由于广谱抗菌药的滥用以及细菌间耐药基因的转导，细菌对常用抗菌药物耐药的发展成为人类健康事业面临的严重问题之一。细菌主要通过产生灭活酶或钝化酶，改变抗菌药物作用靶位，改变细菌细胞壁的通透性、主动外排作用以及形成细菌生物被膜而对抗菌药物耐药，这些耐药机制不是相互孤立存在的，两个或更多种不同的机制相互作用决定一种细菌对一种抗菌药物的耐药水平。本文介绍了临床常见致病菌对各类抗菌药物主要的耐药机制及耐药基因，并总结了针对常见细菌耐药的合理用药及相关防治对策，以期为临床常见致病菌耐药提供解决方案。     

1例病毒性脑炎癫痫发作后肺部感染患儿的药学监护

目的:从病毒性脑炎癫痫发作后肺部感染患儿1例的药学监护谈抗菌药物选择与使用,探讨临床药师在临床疾病治疗中的作用.方法:临床药师参与1例病毒性脑炎癫痫发作后肺部感染患儿的药物治疗过程,提供药物相互作用相关知识及抗菌药物选择建议.结果:医师部分采纳临床药师建议,修正用药方案,避免滥用抗菌药物.结论:临床药师参与临床治疗取得较好效果.减轻患者经济负担,避免药物相互作用以及抗菌药物滥用,提升合理用药水平.     

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.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.