Recombinant human antithrombin III: rhATIII

GTC Biotherapeutics (formerly Genzyme Transgenics Corporation) is developing a transgenic form of antithrombin III known as recombinant human antithrombin III [rhATIII]. It is produced by inserting human DNA into the cells of goats so that the targeted protein is excreted in the milk of the female offspring. The transgenic goats have been cloned in collaboration with the Louisiana State University Agriculture Center. GTC Biotherapeutics is conducting clinical trials of rhATIII in coagulation disorders. rhATIII is believed to be both safer and more cost-effective than the currently available plasma-derived product. rhATIII is also being investigated in cancer and acute lung injury. Genzyme Transgenics Corporation, originally a subsidiary of Genzyme Corporation, changed its name to GTC Biotherapeutics in June 2002; it is no longer a subsidiary of Genzyme Corporation. GTC Biotherapeutics is seeking partners for the commercialisation of rhATIII. Restructuring of GTC Biotherapeutics to support its commercialisation programmes was announced in February 2004. Genzyme Transgenics Corporation was developing rhATIII in association with Genzyme General (Genzyme Corporation) in the ATIII LLC joint venture, but in November 2000 a letter of intent was signed for the reacquisition of the rights by Genzyme Transgenics Corporation. It was announced in February 2001 that this reacquisition was not going to be completed and that the development of rhATIII was to continue with ATIII LLC. However, in July 2001, Genzyme Transgenics Corporation reacquired all the rights in the transgenic antithrombin III programme. SMI Genzyme Ltd, a joint venture between Sumitomo Metal Industries, Japan, and Genzyme Transgenics Corporation, USA, was set up to fund development of transgenic antithrombin III in Asia. However, in October 2000, Genzyme Transgenics Corporation reacquired, from Sumitomo Metal Industries, the rights to its technology for production of medicines from milk in 18 Asian countries, including Japan. The 10-year-old joint venture, SMI Genzyme Ltd, was dissolved. In June 2002, GTC Biotherapeutics estimated the current market size for plasma ATIII products to be approximately $US250 million - of which sales in Europe amounted to $US110 million, Japan $US130 million and the US $US10 million.     

The parents' experience: coping with drug use in the family

The families of drug users are often overlooked in the planning and delivery of services. This paper is based on interviews with parents of heroin users and staff from a support agency that worked with families affected by drug use. Findings highlight the devastation parents experienced in learning that their child was using heroin, and the subsequent impact that this had on their lives. Accessing support from a specialist agency provided tangible benefits for parents. These included a reduced sense of isolation, an increased knowledge of drugs and drug-related issues, and greater empathy for their son or daughter. This resulted in an improved support network for the drug user. However, parents faced many obstacles in accessing support, not least a lack of awareness of their needs amongst appropriate agencies. The paper concludes by highlighting the need to develop further tailored interventions to support families affected by drug use, and to improve the knowledge and awareness of the issue among treatment agencies and a range of other relevant organizations.     

Developing guidelines for thrombolytic therapy

The development and implementation of guidelines for the use of thrombolytic therapy at a 1000-bed community hospital are described. A thrombolytic therapy committee composed of two physicians, a nurse, and a pharmacist was established to develop the guidelines. The committee outlined goals for the guidelines, developed a format, and defined individual responsibilities. Indications, absolute requirements for use, contraindications, administration procedures, necessary tests before and during infusion, and recommendations for the use of anticoagulant therapy following thrombolytic therapy were listed. All of the committee members participated in educating the hospital staff involved with thrombolytic therapy. The pharmacist served as a liaison with the laboratory and used a flow sheet to monitor all patients receiving thrombolytic therapy. Two years after the guidelines were implemented an evaluation of physician compliance and adverse effects secondary to thrombolytic therapy showed excellent compliance (97-100% on all criteria listed) and an incidence of bleeding comparable with the values reported in the literature for heparin. The guidelines are reviewed annually by the committee and revised when necessary. The use of thrombolytic guidelines has minimized adverse effects and the misuse of laboratory tests, assisted with proper patient selection, and united several disciplines in a collaborative fashion toward a common goal.     

Visitors of the Dutch drug checking services: Profile and drug use experience

BackgroundDrug checking services (DCS) provide information about drug content and purity, alongside personalized feedback, to people who use drugs; however, the demographic and drug use characteristics of DCS clients are rarely reported. This paper describes these characteristics for clients of the Dutch DCS, the Drug Information and Monitoring System (DIMS).Methods1,530 participants completed a pen-and-paper questionnaire at one of eight participating DCS in the Netherlands in 2018.ResultsThe participants were mostly highly educated males in their twenties with no migration background. Experience with drugs prior to coming to the DCS was common. Only 0.7% indicated they had never used any of the twenty drugs studied. 93% of participants reported use of ecstasy or MDMA with an average of 6.3 years since first use.ConclusionsThese results indicate that drug checking can be a valuable tool for public health services as it facilitates access to more difficult-to-reach communities who use drugs. It is unlikely that DCS encourage drug initiation, since almost all people who visit the Dutch DCS already report experience with drugs. However, DCS should be aware that their services might not be easily accessible or attractive to all demographic groups.     

Clinical practice guidelines for the use of albumin: result of a drug use evaluation in a Paris Hospital

Chromatographic analysis of bisphosphonates in the past has been based primarily on reversedphase liquid chromatography (RPLC) and ionexchange chromatography. Gas chromatography (GC) and recently even capillary electrophoresis have also been employed. For bioanalysis, pretreatment of the sample is a major part of the analysis; protein precipitation, calcium precipitation, solidphase extraction (SPE) and derivatization have demonstrated to play an important role in bisphosphonate assays. For some of these treatments, for example SPE and derivatization, automation may be possible. Derivatization is a prerequisite for GC analysis of bisphosphonates; a volatile derivative has to be formed. For liquid chromatography, two types of derivatization are known for bisphosphonates. First, the bisphosphonate side chain can be modified by a chemical reaction to yield a derivative with advantageous chromatographic and spectroscopic properties. Secondly, by complexation of both phosphonate groups or of phosphate after decomposition of the analyte, a coloured complex can be formed. The most sensitive bioanalytical methods are based on RPLC and fluorescence detection, if necessary after derivatization. If low detection limits are not required, for example for analysis of pharmaceutical preparations, non-specific detection methods can be applied.     

网络药理学:药物发现的新思想

新药研发是医药产业发展的核心驱动力,也是社会发展的重要需求,但近年来,随着对药物研发要求的不断提高,新药研发正面临着巨大困难,单靶点高选择性的新药研发思想遇到了挑战,已经显示出发展的局限性。网络药理学是近年来在单靶点药物研究的基础上提出的新药发现新策略。本文围绕网络药理学的形成基础和目前研究现状,探讨网络药理学发展的方向和应用前景,同时分析网络药理学的局限性和存在的问题,并通过与传统中医药学理论和中药复方有效成分组学的思想相比较,探讨网络药理学在新药研发中的应用。     

Assessment of biotechnology products for therapeutic use

Biotechnology products for therapeutic use include a very diverse range of products, including growth factors, cytokines, hormones, receptors, enzymes, clotting factors, monoclonal antibodies, vaccines, DNA vaccines, gene transfer products, cell therapies and tissue/organ grafts. While some of these products are regulated as medicinal products, the regulatory status of others such as some cell therapies and tissue/organ-based products differs globally and falls within the borderline between the practice of medicine, medical devices and medicinal products. The unclear regulatory status of some products can add to the complexity of the safety assessment of such products. Conventional non-clinical testing paradigms and guidelines for small molecule development are often not relevant for biotechnology products. Guidelines relating to the non-clinical safety evaluation of biotechnology products, gene transfer products and cell therapy products are available and represent a set of general guiding principals to be applied on a case-by-case basis. The quality, safety and efficacy of biotechnology products for therapeutic use are intricately linked, far more so than for conventional medicinal products, leading to the need for increased communication between those responsible for ensuring product quality and those responsible for non-clinical safety testing. Safety issues include microbiological safety (due to the use of biological materials either during the manufacturing process or as an integral part of the products), pharmacological/ biological toxicity (due to excessive primary pharmacology or undesirable secondary pharmacology), immunogenicity and potential tumourigenicity (for example, for growth factors, immunosuppressive monoclonal antibodies and cell therapy products). Genotoxicity and intrinsic chemical toxicity are less of a problem for biotechnology products.     

卡培他滨超说明书用药治疗胰腺癌的指南质量评价

目的：使用指南研究与评价工具AGREEⅡ评价卡培他滨超说明书用药用于治疗胰腺癌的指南,为临床治疗胰腺癌提供相关依据。方法：制定卡培他滨治疗胰腺癌指南的纳入标准和检索策略,检索Epistemonikos、PubMed、Embase、Cochrane Library、美国国立指南文库（NGC）、CBM、万方和CNKI等数据库。按纳入标准纳入有关卡培他滨治疗胰腺癌的指南,提取和描述指南AGREEⅡ评价信息,使用AGREEⅡ评价纳入指南质量,使用组内相关系数（ICC）进行评价员间一致性检验。分析比较不同指南推荐内容的共识和差异。结果：共纳入6篇指南,分别来自美国、中国、欧洲、西班牙。检索时限为建库到2018年3月20日。指南质量经AGREEⅡ评价评分显示：6大领域（范围和目的、制定指南的参与人员、制定的严谨性、清晰性与可读性、应用性、编辑的独立性）的平均分分别为54%,22.67%,21.67%,55.5%,12.17%,27.33%。结论：纳入研究的卡培他滨治疗胰腺癌的超说明书用药相关指南证据等级较低,整体质量有待提高。不建议将卡培他滨用于胰腺癌的治疗,临床如需使用,建议签署知情同意书后使用。     

Yeast-inspired drug delivery: biotechnology meets bioengineering and synthetic biology

Introduction: Yeast-based drug delivery offers a promising platform for the treatment of various medical conditions. Even the most promising nanoparticulate delivery systems have challenges from gastrointestinal barriers. The novel approach using bio-inspired yeast microcapsule helps in the delivery of charged nanoparticles like quantum dots, iron oxide nanoparticle, and various fluorescent nanoparticles. The long-term administration has a good safety profile compared to other delivery systems. Particles can be incorporated into yeast microcapsule by electrostatic interaction, layer-by-layer approach, and surface derivatization.

Areas covered: The article highlights the various applications of yeast cells in drug delivery. The authors describe the mechanism of encapsulation into yeast cells. The authors discuss various methods used for cell wall preparation and mechanisms associated with the passage of yeast cell through the gastrointestinal tract. The authors also review the association of biotechnology with bioengineering and synthetic biology approaches in transforming yeast as a delivery vehicle.

Expert opinion: Yeast provides an opportunity to use the principles of biotechnology and bioengineering to tune it to an efficient drug delivery carrier. The applications of yeast microcapsule for oral and topical administration are noteworthy. It is proved that yeast microcapsules prepared from yeast cells are promising drug delivery carriers.     

: prevalence and association with drug use

In a cross-sectional study, we have investigated the prevalence of self-reported symptoms and their association with medicinal drug use in elderly people. Data from the Kungsholmen Project were used, a population-based study of elderly people aged 75 years and over in Stockholm, Sweden. The study sample comprised 1800 persons. Information on the occurrence of 22 different symptoms and the actual drug use was obtained at interviews with the participants. The relation of symptoms to age, gender and housing, and their association with drug use was analysed using logistic regression. The most commonly reported symptoms were pain and tiredness. In general, symptoms were more common in women and at higher ages. Many of the associations between symptoms and drug use reflected established treatments. However, some were suggestive of inappropriate treatment or dosage; for example, the association between tiredness and the use of anxiolytics and hypnotics-sedatives.     

Basic requirements for the use of terms for reporting adverse drug reactions (III)

This paper is the report of a meeting held in Geneva under the auspices of the Council for International Organizations of Medical Sciences (CIOMS) on 2–3 April, 1992. A third group of adverse drug reaction reporting terms is defined.     

神经精神药理学治疗药物监测共识指南:2017版

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗.TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能.在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童、孕妇、老年患者、智障患者、药物滥用者、涉法精神病患者、已知或怀...