Evaluation of Drugs for Treating Obesity

Criteria for the evaluation of new drugs to treat obesity are important as guides for designing clinical trials to test these agents. These criteria must be developed in relation to the realities of obesity, which is a chronic disease associated with morbidity and mortality that is increased by visceral fat deposits. The observation that patients regain weight after stopping drug treatment for obesity argues for the proposition that drugs work only when taken and NOT that the drugs are ineffective. The analogy between the development of treatments for obesity to those for the treatment of hypertension is used to highlight potential areas for new developments. Several features of an ideal drug for the treatment of obesity are suggested. Criteria for evaluating new drugs include both primary and secondary endpoints. The primary endpoint for an anti-obesity drug should be weight loss, possibly by category of success. Losses of total body fat or visceral fat might be alternative primary endpoints. Secondary endpoints include reduction in risk factors for associated diseases and improvement in the quality of life. In trials where vigorous placebo designs including highly aggressive behavior modification or very-low-calorie diets were used, it may be difficult or impossible to detect a response to a drug.     

Synapto-Protective Drugs Evaluation in Reconstructed Neuronal Network

Chronic neurodegenerative syndromes such as Alzheimer’s and Parkinson’s diseases, or acute syndromes such as ischemic stroke or traumatic brain injuries are characterized by early synaptic collapse which precedes axonal and neuronal cell body degeneration and promotes early cognitive impairment in patients. Until now, neuroprotective strategies have failed to impede the progression of neurodegenerative syndromes. Drugs preventing the loss of cell body do not prevent the cognitive decline, probably because they lack synapto-protective effects. The absence of physiologically realistic neuronal network models which can be easily handled has hindered the development of synapto-protective drugs suitable for therapies. Here we describe a new microfluidic platform which makes it possible to study the consequences of axonal trauma of reconstructed oriented mouse neuronal networks. Each neuronal population and sub-compartment can be chemically addressed individually. The somatic, mid axon, presynaptic and postsynaptic effects of local pathological stresses or putative protective molecules can thus be evaluated with the help of this versatile “brain on chip” platform. We show that presynaptic loss is the earliest event observed following axotomy of cortical fibers, before any sign of axonal fragmentation or post-synaptic spine alteration. This platform can be used to screen and evaluate the synapto-protective potential of several drugs. For instance, NAD⁺ and the Rho-kinase inhibitor Y27632 can efficiently prevent synaptic disconnection, whereas the broad-spectrum caspase inhibitor zVAD-fmk and the stilbenoid resveratrol do not prevent presynaptic degeneration. Hence, this platform is a promising tool for fundamental research in the field of developmental and neurodegenerative neurosciences, and also offers the opportunity to set up pharmacological screening of axon-protective and synapto-protective drugs.     

药物安全性评价中的实验动物福利

开展实验动物福利工作不论对于实验动物自身,还是科学研究都具有重要意义。本文对实践中如何开展实验动物福利工作,以及其中存在的问题进行了初步探讨。     

Evaluation of Spontaneous Reports of Adverse Reactions to Drugs

An adverse drug-reaction monitoring system based on spontaneous reporting to a central register of adverse reactions has been in operation for eight years. As a test of the validity of the reports and of the probability of causal relationship between drug and reaction a random sample of 82 cases were followed up in detail. The sample included 17 deaths, 26 serious reactions, and 39 reactions of moderate or only minor severity. Altogether 78% of the reactions were considered to be “probably” drug related and 13% “possibly” drug related. It is concluded that the reports are of value in the detection and evaluation of drug safety.     

药物经济学在仿制药一致性评价中的运用

药物经济学评价作为新兴学科,在目前如火如荼的仿制药一致性评价中得到广泛关注。文章在简介药物经济学评价基本方法的基础 上,对制药企业在仿制药一致性评价过程中的经济学问题及对策进行了探讨。     

嘧啶核苷磷酸化酶与抗癌药物治疗效果的评价

嘧啶核苷磷酸化酶(PyNPase)是嘧啶核苷补救代谢途径中的关键酶,广泛分布于微生物及动物组织细胞中。近几年来,很多学者对PyNPase在抗癌药物合成和癌症治疗方面的作用及其临床应用进行了广泛的研究。本文综述了PyNPase与肿瘤患者临床病理特征、抗癌药物评价等之间的关系。     

基于一致性评价导向的国家基本药物口服制剂信息集萃

初步整理了国家基本药物口服制剂信息,包括药物疾病分类、中英文通用名、剂型、规格、国产批文数量、原研公司、原研商品名、 原研剂型、原研规格、BCS分类等,旨在为仿制药一致性评价工作提供借鉴。     

The Practising Physician's Approach to the Evaluation of New Drugs

Physicians have the difficult task of locating and evaluating information about the numerous new drugs that continually appear on the market, and this difficulty is magnified by the massive promotional efforts of pharmaceutical manufacturers. Doctors should use all possible sources of information, but the varied (and often subtle) forms of advertising must be recognized for what they are. Physicians also need to develop skill in interpreting clinical papers and in understanding a little of the uses and meanings of statistics. Most of all, they should have sufficient self-confidence to refrain from using any new drug until scientific evidence of its efficacy and safety is available.     

医疗机构合理用药评价模型的构建研究

目的 针对医疗机构的合理用药水平进行评价研究。方法 根据医疗机构合理用药的具体要求,构建医疗机构合理用药评价指标体系,采用基于模糊群决策的方法和多指标评价分析法构建医疗机构合理用药评价模型。结果 构建了基于模糊群决策的医疗机构合理用药评价模型,并通过实例分析证明了评价模型的可行性。结论 建立的基于模糊群决策的医疗机构合理用药评价模型能够对医疗机构的合理用药水平进行科学评价,为提高医疗机构合理用药水平奠定基础。     

三种药物联合治疗假丝酵母菌性阴道炎的临床疗效评价

目的:研究克霉唑阴道片、硝夫太尔制霉素阴道软胶囊联合定君生栓治疗复发性假丝酵母菌性阴道炎的临床疗效,为临床治疗提供依据。方法:选取2014年9月到2015年6月我院就诊的复发性假丝酵母菌性阴道炎患者60例,按照随机数字表法将患者分为实验组和对照组,每组30例,实验组给予克霉唑阴道片、硝夫太尔制霉素阴道软胶囊联合定君生栓治疗,对照组给予克霉唑阴道片和定君生栓治疗,治疗前检测所有患者病原菌分布情况,治疗后随访3个月,分析两组临床疗效和不良反应。结果:细菌培养结果共分离出158株假丝酵母菌,其中白色假丝酵母菌最多,占66.46%;实验组总有效率为93.33%,显著高于对照组的76.67%,两组比较差异具有统计学意义(P0.05);两组不良反应发生率比较无统计学意义(P0.05)。结论:克霉唑阴道片、硝夫太尔制霉素阴道软胶囊联合定君生栓治疗复发性假丝酵母菌性阴道炎具有较好的临床疗效,且无明显不良反应。     

Gender Differences in Subjective Time Evaluation and Sensitivity to Antianxiety Drugs

Differences in subjective time evaluation were found between young women and men. The women displayed a shorter individual minute (IM), which decreased in the evening as compared to the morning. The antianxiety drugs valerian and Grandaxin increased the IM at different times of the day irrespective of the gender of the subjects, which coincided with their antianxiety effect.     

斑马鱼胚胎和肿瘤细胞评价细胞毒药物活性比较研究*

目的:比较斑马鱼胚胎和肿瘤细胞作为药物筛选模型的优缺点.方法:采用MTT法检测顺铂、紫杉醇、阿霉素、5-氟尿嘧啶四种药物对HL-60和Hela细胞的增殖影响;同时,观察药物对斑马鱼胚胎发育的影响.结果:阿霉素、顺铂及紫杉醇作用于HL-60及Hela细胞的IC50均显著高于作用于斑马鱼胚胎的LD50;而5-FU作用于肿瘤细胞和斑马鱼胚胎的结果与其它药物相反;四种抗肿瘤药物对斑马鱼胚胎的生长发育均有致畸作用.结论:斑马鱼胚胎作为细胞毒类药物筛选模型,对于抗微管类药物较为敏感,但对于抗代谢药敏感性较肿瘤细胞差.     

Evaluation of Multi-Target and Single-Target Liposomal Drugs for the Treatment of Gastric Cancer

We studied the effects of multi- and single-target liposomal drugs on human gastric cancer cell AGS both in vitro and in vivo. The cytotoxic effect of dihydrotanshinone I was significantly enhanced by treatment with octreotide-polyethylene glycol(PEG)-liposome, Arg-Gly-Asp(RGD)-PEG-liposome, and RGD/octreotide-PEG-liposome encapsulated with 0.5 μg/ml of dihydrotanshinone I to AGS cell for 24 h, compared to control. Furthermore, the AGS cell survival rate for multi-target versus single target liposomal drugs was significantly suppressed. Microsocpic examination revealed that significant cell death occurred in the multi- and single-target liposomal encapsulated drug groups. Significant suppression of tumor growth in AGS cell xenograft nude mice given octreotide-PEG-liposome, RGD/octreotide-PEG-liposome encapsulated drug, versus those given a free drug was noted after 13 d of experimentation with the multi-targeted liposome: up to 60.75% and 41.2% reduction of tumor volume as compared to dimethylsulfoxide (DMSO) control and the free drug groups respectively. The treated animals showed no gross signs of toxicity. The results have potential clinical application.     

仿制药一致性评价中有关物质研究的思考

有关物质是药品的关键质量属性之一,也是仿制药一致性评价的重要内容,其涉及药品的安全性及其质量的可控性。文章梳理了 仿制药有关物质的来源及研究重点,评估仿制药有关物质的文献分析方法,总结归纳仿制药与被仿制药实际样品的杂质谱分析比较及其 意义,探讨杂质限度的确定原则与方法。