不同晶型甘氨酸在水中溶解度的测定与关联

不同晶型甘氨酸溶解度的测定对研究甘氨酸结晶及多晶型现象具有重要意义。采用激光动态法测定了15~80℃范围内α型和γ型甘氨酸在纯水中的溶解度数据,并且采用Apelb lat溶解度经验方程对实验数据进行了关联,回归了溶解度经验方程的参数,关联效果令人满意。实验结果表明,在水中α和γ甘氨酸溶解度均随温度升高而变大;在相同温度下,热力学亚稳的α型甘氨酸比稳态的γ型甘氨酸溶解度大。     

宠物化学药物研究

为正确导向宠物化学药物的发展,提高研制水平,避免＂超级细菌＂的产生,保护人类医疗资源,本文简述了宠物化学药物的研究现状,剖析了宠物化学药物的研究过程中存在的问题,提出了我国宠物化学药物创新发展战略,并展望了宠物化学药物的发展前景。科学使用宠物专用化学药物不仅促进宠物产业乃至整个畜牧业的健康发展,而且对降低耐药性产生,保护人类健康也具有重要的公共卫生学意义。     

固体分散技术增溶的新工艺研究进展

增加难溶性药物的溶出是药剂学设计的重点.提高难溶性药物溶出的途径包括应用混合溶剂、加入助溶剂、固体分散技术、超微粉碎技术等.本文就应用固体分散技术提高难溶性药物的研究做一综述,重点介绍了近年来制备固体分散体的新工艺.     

基于基因功能的创新药物研究

现代医药产业是一项重要的高新技术产业,对国家的经济发展和社会进步具有重要的影响。创新药物的研究与开发,集中体现了生命科学和生物技术领域前沿的新成就和新突破,是新世纪科技和经济国际竞争的战略制高点之一。针对严重影响我国人民身体健康的重大疾病,研究优良创新药物,对实现我国人口与健康领域的国家目标具有重要意义;现代医药产业的发展将成为推动我国21世纪经济发展的支柱产业和新的增长点。然而,当前我国药物研究与医药产业面临的形势与挑战十分严峻,“中国人21世纪吃什么药”的问题尚未真正解决。     

双载体制备青蒿素速释型固体分散体工艺优化研究

对载体类型影响青蒿素固体分散体中药物溶出度进行研究及优化制备工艺。以大豆卵磷脂与PEG 6000或聚乙烯吡咯烷酮为双分散载体,采用溶剂法制备青蒿素速释型固体分散体,以溶出度为考察指标,单因素试验筛选载体类型及最佳制备工艺;并采用红外吸收光谱法(IR)、差示扫描量热法(DSC)进行物相表征,明确载体-药物存在状态。结果表明在50 min内卵磷脂-PVP K30双载体比卵磷脂-PEG 6000药物溶出度更高,制备固体分散体为速释型,50 min内总溶出度87%以上,显著高于原料药和物理混合物,且优化最佳工艺条件为卵磷脂与PVP K30比为1∶7,搅拌时间30 min,无水乙醇用量20 mL。IR及DSC结果显示在固体分散体中药物可能以无定型状态存在。双载体制备青蒿素速释型固体分散体工艺简单可行,可显著提高药物溶出度,为提高青蒿素疗效奠定重要基础。     

中华眼镜蛇毒组份的抗肿瘤研究进展

药物治疗是肿瘤治疗的一个重要组成部分,对抗肿瘤药物疗效的筛选评价是肿瘤基础和临床研究的重点之一。中华眼镜蛇毒（Naja Naia Actra Venom,N．N．A．V）一直是国内外抗肿瘤药物研究中的重点生物源毒素之一。本文作者就中华眼镜蛇毒组份抗肿瘤的研究,作一综述。     

综述——纳米材料与药物输递：基于聚合物的环境敏感型纳米抗肿瘤药物传输系统的研究

环境敏感型聚合物纳米抗肿瘤药物传递系统能够响应外界环境的微小刺激,引起自身结构的变化,释放出药物,在肿瘤治疗方面具长效低毒、可控及高载药量等优势,已被广泛应用于生物医学领域．本文介绍了聚合物环境响应型纳米药物传输系统的发展近况,并从pH 值敏感型、温度敏感型、氧化还原敏感型、酶敏感型以及其他敏感型给药系统角度,阐述了环境敏感型药物传输系统在抗肿瘤领域的研究现状及未来展望．     

中药内的生物制药——固体发酵工程系列及其真菌药物

概述了我国古今中药内的生物制药工程中唯一的固体发酵生产真菌药物的情况,以神曲、猴头菌及槐耳菌质等为代表说明由"制曲工艺"、"固体培养"到固体发酵的理念与工艺的变化与发展,从"普通型固体发酵"发展到"双向型固体发酵"的范例可推断分析古代制曲工艺在基质中应用中药材的作用,说明其貌似粗糙而可能有潜在深刻的内涵亟待整理发掘。现已存在建立固体发酵系列工程的可能性,更显示了中药宝库的丰富内容和菌物药的价值,对指导研发新真菌药物有一定理论与实际意义。     

长效重组药物研究进展

生物重组药物半衰期的长短显著影响药物在使用时的剂量以及治疗的效果,所以延长其在体内的生物半衰期,防止药物在体内迅速降解成为现在药物研究的重要方向之一.针对目前较为广泛使用的几种重组药物长效化方法.如定点突变、化学修饰、基因融合、药物剂型和给药方式的改变等,结合目前已经上市的和正在研发中的长效重组药物进行了综述.     

药物类新污染物的微生物降解机制研究进展

环境微生物作为自然界中主要的分解者蕴含着丰富的遗传和代谢多样性,在有机污染物降解中发挥着重要作用。药物被持续不断地释放到环境中,其环境暴露、环境风险和对人体健康的潜在影响已得到广泛关注。研究药物在环境中的微生物降解过程对于药物的环境命运、药物的环境风险评估和药物污染去除技术的开发等具有重要价值。本文重点综述了目前环境中常检出药物的微生物降解途径及其分子机理,总结了目前药物微生物降解研究领域的进展,最后探讨了药物的微生物降解领域未来的研究趋势。     

Analysis of disease-causing genes and DNA-based drugs by capillary electrophoresis towards DNA diagnosis and gene therapy for human diseases

Rapid progress in the Human Genome Project has stimulated investigations for gene therapy and DNA diagnosis of human diseases through mutation or polymorphism analysis of disease-causing genes and has resulted in a new class of drugs, i.e., DNA-based drugs, including human gene, disease-causing gene, antisene DNA, DNA vaccine, triplex-forming oligonucleotide, protein-binding oligonucleotides, and ribozyme. The recent development of capillary electrophoresis technologies has facilitated the application of capillary electrophoresis to the analysis of DNA-based drugs and the detection of mutations and polymorphism on human genes towards DNA diagnosis and gene therapy for human diseases. In this article the present state of studies on the analysis of DNA-based drugs and disease-causing genes by capillary electrophoresis is reviewed. The paper gives an overview of recent progress in the Human Genome Project and the fundamental aspects of polymerase chain reaction-based technologies for the detection of mutations and polymorphism on human genes and capillary electrophoresis techniques. Attention is mainly paid to the application of capillary electrophoresis to polymerase chain reaction analysis, restriction fragment length polymorphism, single strand conformational polymorphism, variable number of tandem repeat, microsatellite analysis, hybridization technique, and monitoring of DNA-based drugs. Possible future trends are also discussed.     

Advances in Molecular Modeling of Human Cytochrome P450 Polymorphism

Cytochrome P450 (CYP) is a supergene family of metabolizing enzymes involved in the phase I metabolism of drugs and endogenous compounds. CYP oxidation often leads to inactive drug metabolites or to highly toxic or carcinogenic metabolites involved in adverse drug reactions (ADR). During the last decade, the impact of CYP polymorphism in various drug responses and ADR has been demonstrated. Of the drugs involved in ADR, 56% are metabolized by polymorphic phase I metabolizing enzymes, 86% among them being CYP. Here, we review the major CYP polymorphic forms, their impact for drug response and current advances in molecular modeling of CYP polymorphism. We focus on recent studies exploring CYP polymorphism performed by the use of sequence-based and/or protein-structure-based computational approaches. The importance of understanding the molecular mechanisms related to CYP polymorphism and drug response at the atomic level is outlined.     

IL-8与胃癌关系的研究进展

IL-8是趋化性细胞因子,可以促进炎症细胞趋化和诱导细胞增殖,在胃癌组织中高表达。影响IL-8在胃癌组织中表达水平的因素包括幽门螺杆菌感染、NF-κB的干预、IL-8的基因多态性、表皮生长因子（EGF）的水平。IL-8主要参与胃癌的血管形成、促进金属蛋白酶的表达、影响E-cad和ICAM-1的水平、促进细胞有丝分裂、促使肿瘤转移等,对胃癌的发生、发展、预后均起重要的作用。选择性阻断IL-8及其受体具有抑癌作用,有望成为胃癌治疗的基础药物之一。     

Molecular genetics and epigenetics of the cytochrome P450 gene family and its relevance for cancer risk and treatment

The cytochromes P450 (CYPs) are very efficient catalysts of foreign compound metabolism and are responsible for the major part of metabolism of clinically important drugs. The enzymes are important in cancer since they (a) activate dietary and environmental components to ultimate carcinogens, (b) activate or inactivate drugs used for cancer treatment, and (c) are potential targets for anticancer therapy. The genes encoding the CYP enzymes active in drug metabolism are highly polymorphic, whereas those encoding metabolism of precarcinogens are relatively conserved. A vast amount of literature is present where investigators have tried to link genetic polymorphism in CYPs to cancer susceptibility, although not much conclusive data have hitherto been obtained, with exception of CYP2A6 polymorphism and tobacco induced cancer, to a great extent because of lack of important functional polymorphisms in the genes studied. With respect to anticancer treatment, the genetic CYP polymorphism is of greater importance, where treatment with tamoxifen, but also with cyclophosphamide and maybe thalidomide is influenced by CYP genetic variants. In the present review we present updates on CYP genetics, cancer risk and treatment and also epigenetic aspects of interindividual variability in CYP expression and the use of these enzymes as targets for cancer therapy. We conclude that the CYP polymorphism does not predict cancer susceptibility to any large extent but that this polymorphism might be an important factor for optimal cancer therapy using selected anticancer agents.     

药物基因组学相关P450和ABCB1多态性及SNP检测技术

药物基因组学（phamacogenomics）是临床检测遗传差异引起药物应答个体性差异的学科,它涉及药物代谢和有害的药物反应的预测等方面的内容。个性化药物和个性化治疗发展的关键条件是能够快速简便的检测出病人的遗传多态性。文章综述了药物基因相关问题,细胞色素酶1）450和ABCB1转运蛋白的遗传多态性以及检测遗传多态性的相关技术。     

Molecular biomonitoring of a population of nurses handling antineoplastic drugs

Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.     

Metabolism, Pharmacogenetics, and Metabolic Drug–Drug Interactions of Antipsychotic Drugs

1. Antipsychotic drugs are extensively metabolised by cytochrome P450 (CYP) enzymes.2. Dispositions of a number of antipsychotic drugs have been shown to cosegregate with polymorphism of CYP2D6.3. Metabolic drug–drug interactions have frequently been observed when antipsychotics are coadministered with other drugs.4. Many antipsychotic drugs are converted to active metabolites which can contribute to the therapeutic or side effects of the parent drug.5. Information concerning the individual CYP isoenzymes involved in the metabolism of antipsychotic drugs is important for the safe clinical use of this group of drugs.     

AFLP标记及在微生物和动物中的应用

AFLP是在PCR和RFLP基础上发展起来的新一代分子标记技术,具有稳定好、分辨率高和效率高等特点。AFLP技术现已广泛应用于微生物和动物方面的研究,在构造遗传图谱、遗传多态性研究、育种辅助选择等多领域中有着其它分子标记技术不可比拟的优势,广泛应用于微生物和动物的研究。     

Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals

Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-gp, MRP, BCRP in conjunction with metabolizing enzymes (CYPs) are major factors in such interactions. Most effective combination antiretrovirals (ARV) therapy includes a PI or a NNRTI or two NRTI. Coadministration of such ARV may induce efflux transporters and/or CYP3A4 resulting in sub-therapeutic blood levels and therapeutic failure due to reduced absorption and/or increased metabolism. A similar prognosis is true for ARV-compounds and drugs of abuse combinations. Morphine and nicotine enhance CYP3A4 and MDR1 expression in vitro. A 2.5 fold rise of cortisol metabolite was evident in smokers relative to nonsmokers. Altered functions of efflux transporters and CYPs in response to ARV and drugs of abuse may result in altered drug absorption and metabolism. Appropriate in vitro models can be employed to predict such interactions. Influence of genetic polymorphism, SNP and inter-individual variation in drug response has been discussed. Complexity underlying the relationship between efflux transporters and CYP makes it difficult to predict the outcome of HAART as such, particularly when HIV patients taking drugs of abuse do not adhere to HAART regimens. HIV(+) pregnant women on HAART medications, indulging in drugs of abuse, may develop higher viral load due to such interactions and lead to increase in mother to child transmission of HIV. A multidisciplinary approach with clear understanding of mechanism of interactions may allow proper selection of regimens so that desired therapeutic outcome of HAART can be reached without any side effects.     

Pharmacogenetically hazardous drugs: a proposed new scoring method.

Similar doses of a drug given to different individuals can result in widely disparate plasma concentrations and hence effects. Beside intraindividual differences also inter-ethnic differences of drug response must be taken into consideration. Both inter-individual and inter-ethnic variations of drug response are mostly related to genetic factors (polymorphism) involved in drug metabolism and kinetics. The farmacogenetic disorders involved clinically result in pharmacogenetic side effects. In order to avoid pharmacogenetic side effects, beside phenotyping of the patients, selection of drugs subjected to different pharmacogenetic disorders may be of great clinical importance. Therefore, a scoring method was carried out for the selection of pharmacogenetically hazardous drugs. With regard to both genetic and environmental factors influencing the drug response, 140 suspicious drugs were studied and classified with the method. Eighteen was the maximum point value for genetic and 12 for contributing factors involved, so 30 was the maximum point number in each drug studied. Out of 140 substances 50 drugs (qualified with 20 points or more) proved to be hazardous in different pharmacogenetic disorders, among them several widely used agents, e.g. Diazepam, Isoniazid, Phenytoin, Warfarin, Quinidine, Tolbutamide, etc. The article sums up the findings in a Table and comments them. This scoring method may be useful in drug safety and preventive medicine.