Absorption,distribution, metabolism and excretion of novel phosphodiesterase type 4 inhibitor ASP3258 in rats

The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of ¹⁴C‐ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography‐nuclear magnetic resonance spectroscopy data revealed that O‐glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When ¹⁴C‐ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of ¹⁴C‐ASP3258 to bile‐cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258‐derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species. Copyright © 2014 John Wiley & Sons, Ltd.     

美国医疗机构抗菌药物临床应用管理策略及对我国的启示

抗菌药物管理计划的制定与实施是国外医疗机构提高抗菌药物合理使用水平的重要措施。在Pubmed等数据库文件检索的基础上,以美国疾病控制与预防中心开发的抗菌药物应用管理机制为主要研究对象,对国外医院抗菌药物管理项目及其相关评价研究从两方面进行归纳阐述,包括宏观层面管理和抗菌药物临床使用的细节管理。旨在通过借鉴国外经验,对我国医疗机构抗菌药物管理实践与研究的发展提出建议。     

Primary cutaneous neuroendocrine tumor (atypical carcinoid) expressing KIT and PDGFRA with myoepithelial differentiation: a case report with immunohistochemical and molecular genetic studies

Primary cutaneous neuroendocrine tumors (NET) except for Merkel cell carcinoma have rarely been reported. Herein reported is a very unique case of primary cutaneous NET with immunohistochemical markers of myoepitheliomas. A 47-year-old woman presented a tumor measuring 0.8x0.9x0.6 cm of the face. The tumor was excised completely with wide margins. Morphologically, the tumor was located in the dermis, and the tumor was composed of epithelioid cells arranged in trabecular, sinusoidal, rosette, ribbon-like, and cord-like patterns. Focal areas show tubular formations. The tumor cells were homogenous, and their nuclei showed hyperchromasia but no apparent histological features of malignancy were seen. The stroma was very scant. No invasive features were seen. Immunohistochemically, the tumor cells were strongly positive for cytokeratin (CK) 34BE12, CD5/6, CK14, NCAM (CD56), p63, and KIT (CD117), and moderately positive for CK AE1/3, p53, chromogranin, synaptophysin, neuron-specific enolase (NSE), PDGFRA, CA19-9, and Ki-67 antigen (labeling index=23%). The tumor cells were negative for CK CAM5.2, CK7, CK8, CK18,CK19,CK20, EMA, vimentin, CEA, HMB45, S100 protein, α-smooth muscle antigen, desmin, CD34, GFAP, neurofilaments, CD99 (MIC2), CD45, CD57, ErbB2, TTF-1, MUC1, MUC2, MUC5AC, and MUC6. Mucins examined by d-PAS and Alcian blue techniques were negative. A genetic analysis using PCR-direct sequencing method in paraffin sections identified no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. Imaging modalities including CT and MRI identified no tumor in the body. The clinicians thought that the tumor was cured. She was a sailor and immediately visited other countries; therefore the follow-up could not be done.     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

Clobenpropit,a histamine H3 receptor antagonist/inverse agonist,inhibits [3H]-dopamine uptake by human neuroblastoma SH-SY5Y cells and rat brain synaptosomes

Background

Clobenpropit, a potent antagonist/inverse agonist at the histamine H₃ receptor (H₃R), reduced the cytotoxic action of 6-hydroxydopamine (6-OHDA) in neuroblastoma SH-SY5Y cells transfected with the human H₃R. We therefore set out to study whether this effect involved a receptor-independent action on dopamine transport.

大型仪器设备共享平台的设计与实现

目的:设计并实现一个基于Web的大型仪器设备共享服务平台,提高大型仪器设备的使用和管理效率.方法:以SQL Server为后台数据库,使用ASP.NET和Ajax技术进行系统平台的构建和实现.结果:该平台已成功应用到大型仪器设备的管理和使用当中,取得了良好的实践效果.结论:大型仪器设备共享平台的投入使用,既提高了仪器设备的管理效率和使用效率,同时也为广大科研人员提供了一个高效的仪器预约使用平台.     

基于.NET的医院网络设备管理系统设计与应用

目的：开发设计一种远程网络设备管理软件,解决医院网络设备管理手段落后的问题.方法：采用模块化思想和可视化管理,应用.NET程序设计,基于telnet协议,利用网络设备固定命令,实现远程管理功能.结果：经在医院网络中测试运行,实现了网络交换机管理、备份和恢复配置程序、显示接口运行状态等服务,满足了网管人员的基本需求.结论：该系统平台为管理人员提供了方便快捷的可视化服务,同时,减少了维护人员的工作量,提升了工作效率,对医院网络管理智能化起到了推动作用,具有一定的应用和推广价值.     

Contribution of neutrophils in the pathogenesis of rheumatoid arthritis

Neutrophils are major innate immune effector cells for host defense and have been a topic of active research for their participation in the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis (RA) due to recently discovered neutrophil extracellular trap (NET) formation. NET formation and other mechanisms leading to the release of neutrophil nuclear and cytoplasmic contents are implicated as a source of citrullinated antigens in RA. Further investigations are required to delineate what factors diverge neutrophils from host defense to autoimmune response in RA.     

ASP．NET在医院图书馆网站开发中的应用

网络新形势下,传统图书馆在检索、借阅、浏览等方面显得力不从心.通过对图书馆的存在模式的新思考,ASP.NET技术使开发一套功能强大的动态网站变得简单、高效.本文分析了ASP.NET技术特点及其实现方式,并以"新书推荐"实例展示了ASP.NET技术在动态网站开发中的应用.