我院静脉药物配置中心不合理医嘱分析

目的:统计并分析楚雄州医院静脉药物配置中心常见的不合理医嘱信息,规范临床合理用药,确保患者静脉用药安全、经济、有效。方法:对静脉药物配置中心审核的711 428条医嘱中遇到的不合理医嘱进行统计归类分析。结果:静脉药物配置中心的药师通过审核医嘱,及时发现并纠正临床用药中存在的问题,有效控制并减少了因不合理用药引起的各类不良事件。结论:通过药师审核医嘱,以确保临床用药安全、有效。     

国际抗肿瘤药物市场趋势

抗肿瘤药已成为全球医药市场中最大的产品单元,进入快速发展期。本文从肿瘤类疾病流行病学情况、全球抗肿瘤市场状况和主要跨国医药企业该类产品的发展等对抗肿瘤药市场趋势进行了综合分析,并对近年抗肿瘤药制剂技术的进展进行了简要介绍,以期为我国抗肿瘤药物的发展提供参考依据。     

Genetic control of hippocampal cholinergic and dynorphinergic mechanisms regulating novelty-induced exploratory behavior in house mice

Summary Neurobehavioral genetics endeavors to trace the pathways from genetic and eenvironmental determinants to neuroanatomical and neurophysiological systems and, thence, to behavior. Exploiting genetic variation as a tool, the behavioral sequelae of manipulating these neuronal systems by drugs and antisera are analyzed. Apart from research in rats, this paper deals mainly with the genetically-influenced regulation in mice of exploratory behaviors that are adaptive in novel surroundings and are hippocampally-mediated. Special attention is paid to neuropeptidergic, GABAergic, and cholinergic synaptic functions in the mouse hippocampus.The behaviorally different inbred mouse strains C57BL/6 and DBA/2 show opposite reactions (reductions and increases, respectively, in exploration rates) to peripheral and intrahippocampal injections with agents that interfere with peptidergic, cholinergic, and GABAergic neurotransmission. These findings can be explained by an interdependent over-release of opioids, arrested GABA release, and excess acetylcholine in the hippocampal neuronal network of DBA/2 mice, as compared to C57BL/6 mice where these systems are functionally well balanced. Very similar results have been obtained with the lines SRH and SRL, derived from C57BL/6 and DBA/2, and genetically selected for rearing behavior. Most probably, the opioids act to disinhibit exploratory responses. An additional genetic approach is mentioned, in which four inbred mouse strains and one derived heterogeneous stock are used for estimating genetic correlations between structural properties of the hippocampal mossy fibers and levels of hippocampal dynorphin B, on the one hand, and frequencies of exploratory responses to environmental novelty, on the other.     

魔芋根腐病化学防治药剂筛选试验

为寻求经济、有效的防治魔芋根腐病的方法，本试验选7种杀菌剂对引起魔芋根腐病的病原菌（Alternar-ia）分别采用孢子萌发抑制法和菌饼法来进行室内毒力测定。结果表明，较为理想的化学防治药剂为绿亨二号、霜霸、达科宁，这3种药剂具有成本低廉，操作方便等优点，在生产上有很高的应用价值。     

Mechanism-based targeting of NMDA receptor functions

NMDA receptors (NRs) are key signaling proteins in the central nervous system and represent important targets for drug development in several neurologic disorders. They are critically involved with fundamental brain processes, and thus indiscriminate pharmacological suppression of NR currents has seen only modest therapeutic success so far. Targeting harmful NR receptor activities while sparing the receptor’s vital functions requires a better understanding of the complexity of NR activation reaction; of the range of mechanisms that modulate discrete receptor activities; and of the consequences of this modulation on specific receptor functions. A quantitative account of the NR activation pathway was recently proposed and validated. It describes the gating reaction as a sequential, multi-step process rather than a binary, on-off switch. Alongside isoform-specific modulators, state-specific modulators may represent sophisticated interventions with high potential for narrow, functional specifi city. Here I review physiologic mechanisms that control NR responses; the salient features of the NR activation reaction; and discuss the model’s validity and its implications for drug development and characterization.Submitted 25 May 2005; accepted 29 June 2005     

β2-integrins mediate a novel form of chemoresistance in cycloheximide-induced U937 apoptosis

In this study with cycloheximide (CHX, an inhibitor of protein synthesis) and the human leukaemic cell line U937, a novel form of chemoresistance, which we termed sudden drug resistance (SDR), was identified using Hoechst33258 staining, Western blott and DNA Ladder. CHX^high (10–100 g/ml)-induced apoptosis can spontaneously subside after 4–6 h or can be inhibited by short-term preincubation with CHXlow (2.5 g/ml). Unlike typical multidrug resistance, SDR is not caused by reduced drug accumulation or altered protein expression, and may be associated with a non-P-glycoprotein mechanism. To uncover this underlying mechanism, we focused on U937 cell aggregation promoted by CHX, because cell adhesion has been suggested to influence cell survival and prevent apoptosis. EDTA, or anti-CD18 monoclonal antibody, but not EGTA, acetylsalicylic acid or RGDS tetrapeptide, abrogated this homotypic aggregation and greatly increased CHX-induced apoptosis in a time-dependent manner, while fibrinogen and soluble intercellular adhesion molecule-1 exerted opposite effects. These results establish that ₂-integrin engagement is a key mediator of SDR, although it may be non-exclusive. This finding supplements the classical basis of chemoresistance and may provide another opportunity for improved leukemia therapy.Received 15 April 2004; received after revision 18 May 2004; accepted 21 June 2004     

What’s new in the renin-angiotensin system?

Angiotensin-converting enzyme (ACE) is a zinc- and chloride-dependent metallopeptidase that plays a vital role in the metabolism of biologically active peptides. Until recently, much of the inhibitor design and mechanism of action of this ubiquitous enzyme was based on the structures of carboxypeptidase A and thermolysin. When compared to the recently solved structures of the testis isoform of ACE (tACE) and its Drosophila homologue (AnCE), carboxypeptidase A showed little structural homology outside of the active site, while thermolysin revealed significant but less marked overall similarity. The ellipsoid-shaped structure of tACE, which has a preponderance of -helices, is characterised by a core channel that has a constriction approximately 10 Å from its opening where the zinc-binding active site is located. Comparison of the native protein with the inhibitor-bound form (lisinopril-tACE) does not reveal any striking differences in the conformation of the inhibitor binding site, disfavouring an open and closed configuration. However, the inhibitor complex does provide insights into the network of hydrogen-bonding and ionic interactions in the active site as well as the mechanism of ACE substrate hydrolysis. The three-dimensional structure of ACE now paves the way for the rational design of a new generation of domain-selective ACE inhibitors.     

壳聚糖负载利福平微囊的制备及其性能研究

采用溶剂挥发-乳化分散交联法制备利福平/壳聚糖微囊,借助红外光谱仪分析了REP/CS微囊的结构,使用扫描电子显微镜和光学显微镜观测微囊的形态、粒径及分布,紫外分光光度法测定载药量和包封率,考察微囊的体外释药性能,探讨影响制备利福平/壳聚糖微囊的主要因素.结果表明:微囊平均粒径为5.04±2.04μm,成球性良好,搅拌速度和油水比对微囊粒径以及球形影响最大;微囊的包封率达42.67%,主要受壳聚糖质量分数、mCS:mREP的影响;微囊在碱性条件下比在酸性条件下释药较快,具有明显的缓释作用.     

Preparation of two kinds of superparamagnetic carriers-supported cis-platinum complexes and the comparison of their characteristics

Nasopharyngeal carcinoma (NPC) is one of the most common types of malignant tumors in South China. In the past, radiation therapy is almost the only treatment for the patients. Recent decade researches suggested that chemotherapy also shows effectiveness …     

Preparation and Characterization of Nimodipine-loaded Methoxy Poly （ethylene glycol） -poly （lactic acid） Diblock Copolymer Nanoparticles

Amphiphilic diblock copolymers, methoxy poly （ ethylene glycol）-poly（lactic acid） （MePEG-PLA）, were synthesized from monomers of DL-lactide and methoxy poly （ethylene glycol） by a ring opening bulk polymerizatiou in the presence of stannous octoate. Their chemical structure and physical properties were investigated using FTIR, NMR, GPC, and fluorescence spectroscopy. To estimate the feasibility as colloidal drug carrier, nimodipine （ND） was loaded into MePEG-PLA block copolymer nanoparticles by phaseseparation/dialysis method. The mean diameter and drug loading efficiency of ND-loaded MePEG-PLA copolymer nanoparticles depended ou PLA/MePEG block composition of the copolymer and drug/polymer feed ratio in preparatiou. NMR study confirmed that nimodipine was entrapped into the hydrophobic inner core of MePEG-PLA copolymer nanoparticles and hydrophilic PEG chains were located ou the surface of the drug-loaded polymer nanoparticles. In vitro release experiments exhibited the sustained release behavior of nimodipine from MePEG-PLA copolymer nanoparticles, without any burst effect.