Universal monoclonal antibody-based influenza hemagglutinin quantitative enzyme-linked immunosorbent assay

Seasonal and pandemic influenza infections remain a serious public health concern. Many health authorities recommend annual vaccination as the most effective way to control influenza infection. Accordingly, regulatory guidelines ask vaccine manufacturers to determine vaccine potency at the time of release and throughout shelf-life to ensure vaccine quality. The potency of inactivated influenza vaccine is related to the quantity of hemagglutinin (HA). Since 1970s, single radial immunodiffusion (SRID) assay has been standardly used for the quantitation of HA in influenza vaccine. However, SRID is labor-intensive, inaccurate, and requires standard reference reagents that should be updated annually. Therefore, there have been extensive efforts to develop alternative potency assays. In this study, we developed and tested a new HA quantitative enzyme-linked immunosorbent assay (ELISA) using a universal monoclonal antibody that can bind to HAs from various subtypes in group 1 influenza A virus (IAV). We analyzed the conserved stalk domain of HA via a library approach to design a consensus HA antigen for group 1 IAV. The antigens were expressed as a soluble form in E. coli and were purified by Ni-affinity chromatography. When tested with variety of HAs from IAVs or influenza B viruses (IBVs), the mAbs exhibited specific binding to group 1 HAs, with potential exception to H9 subtype. Among various conditions of pH, urea, and reducing agents, pretreatment of HA at low pH exposing the conserved stalk domain was crucially important for optimal ELISA performance. Calibration curves for various HAs were generated to determine accuracy, specificity, sensitivity, and linear dynamic range. The ELISA method shows high sensitivity and accuracy compared with the SRID assay. The HA group specific universal mAbs against the consensus stalk domain of HA are conducive to establishing an ELISA-based standard procedure for the quantitation of HA antigens for annual vaccination against influenza infection.     

Volubility of the human infant: Effects of parental interaction (or lack of it)

Although parental volubility, or amount of talk, has received considerable recent attention, infant volubility has received comparatively little attention despite its potential significance for communicative risk status and later linguistic and cognitive outcomes. Volubility of 16 typically developing infants from 2 to 11 months of age was longitudinally investigated in the present study across three social circumstances: parent talking to infant, parent not talking to infant and parent talking to interviewer while the infant was in the room. Results indicated that volubility was least in the Interview circumstance. There were no significant differences in volubility between the parent Talk and No Talk circumstances. Volubility was found to reduce with age. These results suggest that infants vocalise in a variety of circumstances, even when no one talks to or interacts with them. The presence of a stranger or perhaps overhearing adults speaking to each other, however, may significantly reduce infant volubility.     

精氨酸加压素受体和催产素受体基因多态性与男性青少年暴力攻击行为的关联研究

目的:探讨精氨酸加压素受体(AVPR1A、AVPR1B)和催产素受体(OXTR)基因多态性在青少年男性暴力攻击行为发生中的作用,并进一步分析基因与基因的交互作用。方法:采用SNa Pshot基因分型技术对138名暴力攻击行为男性少教人员(暴力组)、98名非暴力男性少教人员(非暴力组)以及153名正常成年男性(正常组)的AVPR1A(rs1042615)、AVPR1B(rs28632197)、OXTR(rs13316193、rs2254298、rs53576、rs2268498、rs237885)进行基因分型检测,分析3组间的等位基因和基因型频率。采用多因子降维法(MDR)构建影响暴力攻击行为发生的基因-基因间交互作用模型。结果:暴力组AVPR1B基因rs28632197位点A等位基因频率明显高于非暴力组和正常组(P均0.017),OR值分别为2.24及2.63,95%CI分别为(1.45~3.47)和(1.78~3.88);暴力组与非暴力组及正常组在基因型分布差异有统计学意义(P0.05),暴力组含A等位基因的基因型(AA/AG)明显高于非暴力组和正常组(P0.017);其余位点组间差异无统计学意义。AVPR1B(rs28632197)与OXTR(rs53576)在暴力攻击行为的发生中存在基因间交互作用。结论:AVPR1B基因多态性可能与暴力攻击行为相关;AVPR1B与OXTR基因的交互作用可能增加暴力攻击行为的发生风险。     

芪苈强心胶囊与西药联用治疗心衰的临床数据分析

目的:通过对北京医院(以下简称我院)芪苈强心胶囊的总体用药情况及其在治疗慢性心力衰竭方面与西药的联用情况进行回顾性分析,探讨中西药物联用对于治疗慢性心衰的临床价值和不良反应风险,促进药物的安全合理使用。方法:通过我院计算机系统,提取2011—2013年芪苈强心胶囊的用药人数、性别、年龄、用药科室、病种分布及与西药联用的数据,重点分析芪苈强心胶囊和西药强心药的相互作用,探讨中西药物之间是否有相互协同或是相互拮抗的作用关系。结果:芪苈强心胶囊从2011年开始在我院使用,用药人数、金额和频度在2012,2013年有较大增长。用药的大多为老年患者(80%在60岁以上),且以男性居多。用药数量最多为心血管内科,其次为中医科。临床主要用于治疗慢性心衰,并与多种西药联用,其中包括与地高辛等强心药的联用。结论:芪苈强心胶囊的使用主要以西医大夫为主,多用于慢性心衰的治疗,需要注重辨证用药;临床上发现将该药与地高辛联用会导致地高辛血药浓度升高,因此临床药师建议医生谨慎联用这两种药物,并在2013年杜绝了两药的联用。     

2013年北京医院门诊老年患者华法林处方不合理用药分析

目的:了解北京医院(以下简称"我院")华法林的使用情况,探讨其用药合理性。方法:从我院信息系统中筛选出2013年门诊60岁及以上患者使用华法林的处方1 621张,对处方用药的合理性进行点评、分析。结果:1 621张处方中,需要关注的问题处方有840张,占51.82%。其中,处方中存在药物不良相互作用的问题最为突出;其次为联合用药不适宜、用法与用量不适宜等。结论:应加强华法林在临床的合理应用,以提高治疗效果,减少不良反应的发生。     

质子泵抑制剂对华法林抗凝效果影响的研究进展

临床联用华法林与质子泵抑制剂的情况很多,鉴于华法林的治疗窗较窄,联用是否会影响华法林抗凝作用和增加出血风险,目前尚无定论。本文通过整合和分析国内外相关临床研究的证据,探讨各种质子泵抑制剂与华法林相互作用的机制和细胞色素P450（cytochrome P450）的CYP2C19基因多态性对两者相互作用的影响,发现华法林与泮托拉唑、雷贝拉唑联用相对较安全,但各研究对兰索拉唑、奥美拉唑、埃索美拉唑与华法林的相互作用是否具有临床意义仍存在争议,亟须进行前瞻性的多中心、随机、双盲、对照研究。     

Opioid receptor trafficking and interaction in nociceptors

Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

肠道微生态与炎症性肠病

炎症性肠病(inflammatory bowel disease,IBD)是一组病因未明、发病机制亦不明确的慢性肠道炎症性疾病,主要包括克罗恩病(Crohn's disease,CD)和溃疡性结肠炎(ulcerative colitis,UC)。近几十年的研究结果认为,其发病是环境、易感基因和肠道微生态3个要素相互作用的结果,且这些要素使IBD成为一种适合研究宿主与肠道微生物相互作用的高优先平台。最近,肠道菌群的图谱分析将IBD的发病机制与菌群各组成部分特征的改变相联系,进一步支持"肠道微生物和宿主相互作用的改变能形成IBD"这一观点。该文回顾性分析有关IBD患者体内微生物的研究文献,综述肠道微生态失衡对IBD的多方面影响,以动物模型和临床验证资料阐述不同的治疗方法改善肠道微生态变化的最新进展。