EMA对药用辅料右旋糖酐新的安全性评价

欧洲药品局（EMA）于2018年11月发布了"人用药品辅料右旋糖酐的包装说明书资料"，该文件引用大量文献全面评价了右旋糖酐的安全性，特别指出含有右旋糖酐辅料的注射和吸入制剂的疫苗与药品，应在说明书中描述有关其过敏反应信息的新要求。介绍该文件的主要内容，期望对我国这类药品说明书的撰写和监管有所帮助。     

我国血吸虫对吡喹酮抗药性研究之概要

血吸虫病是一种严重危害人类健康、影响社会经济发展的重大传染病,为全球公共卫生负担和危害最严重的被忽视的热带病之一。吡喹酮是20世纪70年代研制出的一种高效、低毒、价廉的广谱抗蠕虫口服药,为世界卫生组织（WHO）推荐的抗血吸虫的首选药物。吡喹酮在血吸虫病流行区现场大规模反复使用已超过40年,血吸虫是否会对吡喹酮产生抗药性引起国际社会极大担忧,为学术界关注的热点科学问题。针对血吸虫病防治中这一重大需求,自1996年起, 在国家科技支撑计划、国家自然科学基金、江苏省自然科学基金等项目基金资助下,我们在血吸虫病流行区现场和实验室,对血吸虫在吡喹酮药物的压力是否会产生抗药性、抗性虫株的生物学特性、抗性的检测、吡喹酮抗性的交叉抗药性及抗药性的预防和控制等科学问题进行较为系统的研究,本文就其研究及其意义作一概述。     

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.     

OTC drug advertising in Japan: the role of need for cognition and celebrity endorser credibility

Abstract

This research explores how the level of consumers’ need for cognition (NFC) is associated with celebrity endorser credibility and examines its effects on advertising-related attitudes. A 3 (endorser types: actor/actress, athlete, TV personality/talent) × 2 (endorser’s gender) factorial experiment with 435 Japanese consumers was conducted. Concerning Japanese OTC drug advertising, lower NFC individuals perceived celebrity endorsers as more credible in comparison to higher NFC individuals. The main effects of NFC and endorser type on endorser credibility existed; however, no interaction between the two variables was found. The endorser type had an influence on attitudes toward ads and the advertised brand.     

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

神经外科重症监护病房常见病原菌的分布与耐药性研究

目的调查珠江医院神经外科重症监护病房(ICU)病原菌的分布与耐药情况,分析ICU院内感染的发生原因,探讨防治对策。方法应用法国VITEKⅡ全自动细菌鉴定仪鉴定病原菌,用纸片扩散法检测药敏结果。结果神经外科ICU菌群主要以革兰阴性杆菌(71.6%)为主,鲍曼不动杆菌占16.7%,大肠埃希菌占15.7%,铜绿假单胞菌占13.7%,肺炎克雷伯菌占13.7%等。但葡萄球菌、粪肠球菌等阳性球菌(28.4%)也有增加的趋势。亚胺培南和头孢哌酮/舒巴坦仍保持最高抗菌活性,细菌的耐药率分别为15.3%和30.6%。结论我院神经外科ICU感染主要病原菌是革兰阴性杆菌,对常用抗菌药物耐药性较高,但革兰阳性球菌所占比例呈增高趋势。控制第二、三代头孢菌素以及制酸剂(质子泵抑制剂)的预防性用药,减少耐药菌株的产生,有针对性地使用抗生素是控制危重病人感染的有效措施。     

Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Wound Botulism Associated with Black Tar Heroin

The incidence of wound botulism is increasing and the epidemiology of the disease is changing. The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin. This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism. In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness. For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness. This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism. To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early.