论医院药学服务的有效开展

目的：探讨对药学服务的性质,明确药学服务的涵义,促进我国医院药学服务工作的有效开展.方法：对与药学服务密切相关的各学科分别加以分析.结果：在我国目前特定的条件下,医院药学服务工作能否有效开展并不单单取决于临床药师,而是更多地取决于医院管理层对医院药学服务的认识程度和重视程度,取决于医院开展药学服务的管理体制和管理机制.结论：多学科支撑性是医院药学服务的基本特性,这一性质决定了医院药学服务的有效开展需要多种技术人才的通力协作.     

放线菌药物资源开发面临的问题与对策

放线菌药物的开发已取得了极其辉煌的成就,对医疗事业的发展和人类健康做出了重大贡献.然而,随着放线菌药物资源的长期开发和利用,也面临诸多问题.如:包袱沉重,去重复难度极大,因而投资周期长、耗资巨,风险大;药物开发赶不上病原菌抗药性的增加及不断出现的新疾病;虽然未知放线菌甚多,但发现难度大.为此,提出了从化学、菌种和基因三方面开展放线菌药物研究的应对策略,以解决限制放线菌药物资源持续利用和发展的瓶颈.     

NMD resulting from encephalomyocarditis virus IRES-directed translation initiation seems to be restricted to CBP80/20-bound mRNA

Nonsense-mediated messenger RNA decay (NMD) generally degrades mRNAs that prematurely terminate translation as a means of quality control. NMD in mammalian cells targets newly spliced mRNA that is bound by the cap-binding protein heterodimer CBP80/20 and one or more post-splicing exon junction complexes during a pioneer round of translation. NMD targets mRNA that initiates translation using the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES), therefore NMD might target not only CBP80/20-bound mRNA but also its remodelled product, eIF4E-bound mRNA. Here, we provide evidence that NMD triggered by translation initiation at the EMCV IRES, similar to NMD triggered by translation initiation at an mRNA cap, targets CBP80/20-bound mRNA but does not detectably target eIF4E-bound mRNA. We show that EMCV IRES-initiated translation undergoes a CBP80/20-associated pioneer round of translation that results in CBP80/20-dependent and Upf factor-dependent NMD when translation terminates prematurely.     

BiHC,a T-Cell–Engaging Bispecific Recombinant Antibody,Has Potent Cytotoxic Activity Against Her2 Tumor Cells

Among different cancer immunotherapy approaches, bispecific antibodies (BsAbs) are of great interest due to their ability to recruit immune cells to kill tumor cells directly. Various BsAbs against Her2 tumor cells have been proposed with potent cytotoxic activities. However, most of these formats require extensive processing to obtain heterodimeric bispecific antibodies. In this study, we describe a bispecific antibody, BiHC (bispecific Her2-CD3 antibody), constructed with a single-domain anti-Her2 and a single-chain Fv (variable fragment) of anti-CD3 in an IgG-like format. In contrast to most IgG-like BsAbs, the two arms in BiHC have different molecular weights, making it easier to separate hetero- or homodimers. BiHC can be expressed in Escherichia coli and purified via Protein A affinity chromatography. The purified BiHC can recruit T cells and induce specific cytotoxicity of Her2-expressing tumor cells in vitro. The BiHC can also efficiently inhibit the tumor growth in vivo. Thus, BiHC is a promising candidate for the treatment of Her2-positive cancers.     

Practical considerations for pharmaceutical antibody production in different crop systems

The potential of plant cells to produce functional recombinantantibodies has been demonstrated in a number of different plant systems. Wepresent a comparative study of a well-defined target protein, a single chain Fvantibody, in different transgenic crop species and cultured tissues. The effectof different regulatory elements and signals for subcellular targeting areconsidered. Practical considerations for the choice of a particular cropsystem,such as yield, storage, distribution and containment properties are discussed.     

The inhibition and reactivation of human maternal and fetal plasma cholinesterase following exposure to the organophosphate, dichlorvos.

Spontaneous and chemically-induced reactivation of organophosphate-inhibited cholinesterase were studied using as an enzyme source plasma obtained from non-pregnant females, pregnant females at term and their respective neonates, sampled immediately following delivery. Aliquots of plasma were incubated with dichlorvos (10^?6M) for 5 min at 37°C resulting in a 96 percent inhibition of cholinesterase activity in all three groups at which time either pralidoxime chloride (10^?3M) or an equivalent volume of saline was added to the reaction flask and the restoration of cholinesterase activity was monitored over the next 120 min. Pralidoxime-mediated cholinesterase reactivation in ‘non-pregnancy’ plasma was significantly greater than that observed in either ‘maternal’ or ‘fetal’ plasma, however, no significant difference was noted in reactivation rates for these latter two groups. Significant differences were also observed in the rates of spontaneous reactivation, however, after correcting for this, there were still significant differences in the rates of pralidoxime-mediated reactivation (non-pregnant > pregnant ≥ fetal).     

Seasonal plasticity in telencephalon mass of a benthic fish

To gain a deeper understanding of how environmental conditions affect brain plasticity, brain size was explored across different seasons using the invasive round goby Neogobius melanostomus. The results show that N. melanostomus had heavier telencephalon in the spring compared to the autumn across the two years of study. Furthermore, fish in reproductive condition had heavier telencephala, indicating that tissue investment and brain plasticity may be related to reproductive needs in N. melanostomus.     

Horseradish peroxidase covalent grafting onto screen-printed carbon electrodes for levetiracetam chronoamperometric determination

A new enzymatic electrochemical biosensor based on disposable transducers, namely screen-printed carbon electrodes, has been developed for the determination of the antiepileptic drug levetiracetam. Horseradish peroxidase was immobilized onto the carbon working electrode previously modified by an aryl diazonium salt. The formation of amide bonds between the amino and carboxylic groups of the enzyme surface, catalyzed by hydroxysuccinimide and carbodiimide, leads to the electrode functionalization. This orientated enzymatic modification results in high reproducibility, with an associated relative standard deviation of 6.21% for the slopes of several calibration curves in the calibration range from 0.10 to 0.83 mM. Experimental variables that can affect levetiracetam chronoamperometric response, such as hydrogen peroxide concentration, pH, and applied potential, were optimized to perform a selective determination. An average limit of detection of 1.75 × 10⁻⁵ M (α = β = 0.05) was obtained. The biosensors were finally applied to the determination of levetiracetam in complex matrices such as pharmaceutical drugs, yielding successful results.     

Features of biology of the round goby <Emphasis Type="Italic">Neogobius melanostomus</Emphasis> (Perciformes,Gobiidae) in waters of Kuibyshev Reservoir

Based on materials of 2003–2005, the size-age composition, dates of reproduction, distribution, as well the qualitative and quantitative composition of the food of the round goby Neogobius melanostomus in the coastal part of Kuibyshev Reservoir are considered. It is shown that the round goby prefers coastal parts of the reservoir with depths to 10 m and rocky grounds and that its main food are mollusks of the genus Dreissena.