脂质体在基因治疗中的应用

综述阴离子脂质体，ＰＨ敏感脂质体，免疫脂体，融合脂质体以及阳离子脂质体等多种脂质体在基因治疗中的应用。重点介绍阳离子脂质体的制轩及临床应用。     

热敏靶向脂质体在肿瘤治疗中的研究进展

介绍热敏靶向脂质体在肿瘤热疗中的应用以及国内外研究的现状，并介绍热敏长循环脂质、磁性热敏脂质体、免疫热敏脂质体和多聚物热敏脂质体等新型热敏靶向脂质体的特点和应用。     

脂质体递药系统的临床研究进展

本文将脂质体递药系统按结构、组成和功能分成普通脂质体、多囊脂质体、长循环脂质体、热敏脂质体和免疫脂质体5类，分别介绍其应用和临床研究进展。     

新型药物载体免疫脂质体的研究进展

介绍了免疫脂质体的分类,主要分为抗体介导型免疫脂质体和受体介导型免疫脂质体;作用特点主要有靶向性、缓释型和细胞亲和性;并介绍了抗体与脂质体的主要连接方法;实际应用主要为作为抗肿瘤药物的载体、基因治疗的载体以及治疗中枢神经系统疾病的药物载体。     

主动靶向脂质体在抗肿瘤治疗中的研究进展

主动靶向脂质体给药系统可使抗肿瘤药物与靶组织结合,将药物可控性地分布于靶组织并持续缓慢释药,在提高药物抗癌效果的同时,降低了其对正常组织的不良反应。本文主要介绍了免疫脂质体、受体介导的脂质体、糖基修饰的脂质体及多肽修饰的脂质体等主动靶向脂质体在抗肿瘤研究中的进展。主动靶向脂质体给药系统将会发展为抗肿瘤药物的理想剂型,具有很好的临床应用前景。     

载药脂质体的研究动态

载药脂质体的研究动态１０００８０中国科学院动物研究所生物膜与膜生物工程国家重点实验室丁友真脂质体作为药物载体的研究已有多年了。经过二十多年的探索、发现脂质体在抗血药物，抗菌药物等的包裹、投放、在免疫和临床诊断等方面是非常有应用价值的。六十年代Ｂａｎｇ...     

复方地塞米松霜的研制及临床应用

脂质体是由磷脂双分于层定向排列成的几毫微米至几微米的超细粒子.自从60年代问世后,70年代初便开始作为药物载体应用.最成功的便是1977年国外有人用脂质体包封抗肝利什曼原虫药物锑剂,结果药物在肝脏浓集200～700倍,治疗指数提高35～40倍.但随着脂质体应用、研究的深入,人们发现一般脂质体作为药物载体,其阿靶分布并不理想,贮存中稳定性也较差.近几年来为提高其靶向性和疗效,逐步开发、利用一些新型脂质体.现将温度敏感脂质体、pH敏感脂质体、免疫脂质体、聚合膜脂质体、前体脂质体等新型脂质体的研究概况介绍如下:     

大肠癌特异性卡莫氟免疫脂质体的体外抗癌活性研究

目的研制抗人体大肠癌的单克隆抗体的卡莫氟免疫脂质体 ,并对其体外抗癌活性进行了研究。方法由偶联剂将抗大肠癌的单抗与载药脂质体偶联制成免疫脂质体 ,并应用酶联免疫吸附法和MTT法分别测定其免疫活性和体外细胞毒毒性。结果脂质体稳定性良好 ,制成免疫脂质体后 ,单抗免疫活性不丧失 ;体外细胞毒实验结果显示 ,卡莫氟免疫脂质体对人大肠癌细胞的体外抗癌活性优于普通脂质体和游离药物 ,IC50 分别为两者的 1 0 6和 3 5 9倍 ,对非靶细胞的作用与普通脂质体相似。结论卡莫氟免疫脂质体对细胞生长的抑制作用有明显的靶向特异性     

抗体介导的免疫脂质体的研究进展

免疫脂质体作为靶向药物传递体系,以其增效减毒的特性在肿瘤诊断及治疗等领域具有独特的优势,相关研究也得到越来越多的重视.目前,免疫脂质体的制备工艺逐渐完善,选择合适的偶联方案对制剂的活性及稳定性至关重要.了解靶向分子结构及偶联反应机理有助于更好地选择修饰和连接技术,有效实现免疫脂质体靶向传递的作用.本文就免疫脂质体中抗体的类型、抗体和磷脂的修饰技术以及抗体偶联脂质体的方法进行综述.     

免疫脂质体作为靶向给药系统的研究进展

免疫脂质体是用抗体或其片段修饰的脂质体,能与靶细胞表面抗原或受体结合,从而对靶细胞具有分子水平上的识别能力。与游离药物、非特异抗体脂质体、单独单抗等相比,免疫脂质体有更好的选择性和更强的杀伤活性。在动物体内,免疫脂质体可使药物特异性分布在病灶部位,从而增强药物疗效、减轻不良反应,并且表面聚乙二醇化还增强了体内的循环时间。本文综述了用于修饰的不同种类抗体、抗体与免疫脂质体偶联方式,并总结了免疫脂质体在抗肿瘤药、基因治疗、活体成像技术以及在传染病、自身免疫和神经退行性疾病治疗方面的应用。     

Self-injection of barbiturates and benzodiazepines in baboons

Self-injection of three barbiturates, six benzodiazepines, and chlorpromazine was examined in baboons. Intravenous injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Prior to testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. Amobarbital, pentobarbital, and secobarbital maintained the highest levels of self-injection, which were similar to those maintained by cocaine. Clonazepam, clorazepate, diazepam, flurazepam, medazepam, and midazolam maintained relatively modest levels of self-injection, while chlorpromazine maintained only low levels, which were in the range of vehicle control. Of the six benzodiazepines, midazolam produced the highest levels of self-injection. At the highest self-injected doses, the barbiturates produced anesthesia in contrast to the benzodiazepines, which produced only sedation. None of the drugs affected food intake except for chlorpromazine, which produced dose-related decreases. The differences among the drug classes (i.e., barbiturate, benzodiazepine, phenothiazine) with respect to the maintenance of self-injection correspond well with the results of previous animal and human drug self-administration studies.     

基于HMGR、SQS1、β-AS基因CNVs的甘草道地性机制研究

本文利用real-time PCR方法对不同产地甘草的3-羟基-3-甲基戊二酰CoA还原酶 (3-hydroxy-3-methylglutaryl-CoA reductase, HMGR)、鲨稀合成酶1 (squalene synthetase 1, SQS1)、β-香树脂醇合成酶 (β-amyrin synthase, β-AS) 基因的拷贝数进行了研究, 发现不同产地的HMGR基因存在1～3个拷贝数变异, SQS1基因存在1～2个拷贝数变异, 未发现β-AS基因拷贝数变异。甘草HMGR、SQS1、β-AS基因拷贝数存在5种自然组合类型: A型 (2+1+1)、B型 (1+1+1)、C型 (3+2+1)、D型 (2+2+1) 和E型 (3+1+1), 其中内蒙古杭锦旗甘草存在A、B两种类型, A与B的比例为1∶1.3; 内蒙古赤峰甘草也存在A、B两种类型, 但A与B比例为3∶1; 宁夏盐池甘草存在A、B、C、D 4种类型, A/B/C/D比例为1∶5.1∶1∶2, A/B比例为1∶5.1; 甘肃民勤甘草存在A、B、E 3种类型, A/B/E比例为4.1∶2.1∶1, A/B比例为2∶1。本研究证明中药功能基因基因组拷贝数变异 (copy number variations, CNVs) 与产地具有相关性, 可能是道地药材形成的机制之一。     

Endocrine disruption mechanism of o,p'-DDT in mature male tilapia (Oreochromis niloticus)

The aim of the present study was to evaluate, in vivo, the potential of o,p'-DDT to disrupt the endocrine system of mature male tilapia. In particular, the possibility that o,p'-DDT effects were mediated directly via the estrogen receptor (ER). Compounds with known ability to bind to the ER were employed: estradiol to induce and tamoxifen to inhibit the estrogenic effects result of the activation of the ER. In addition, an aromatase inhibitor, 4-hydrxyandrostenedione (4-OHA), was used to assess the ability of o,p'-DDT to induce estrogenic effects in a surrounding of low estradiol concentration. The effects of estradiol and o,p'-DDT were studied alone or in the presence of tamoxifen or 4-OHA at the end of a 12-day period of exposure. The main endpoints measured were plasma alkaline-labile phosphorous (ALP; an indirect indicator of vitellogenin), estradiol, testosterone and o,p'-DDT. It was found that o,p'-DDT was able to induce the vitellogenesis (measured as plasma ALP increase) and decrease the circulating levels of estradiol and testosterone. Interestingly, o,p'-DDT kept this ability in whole fish with low concentrations of estradiol which would exclude endogenous estradiol as indirect mediator of the estrogenic effects induced by o,p'-DDT. In addition, the plasma concentration of o,p'-DDT, instead of that of estradiol, was closely related to the plasma ALP increase induced by o,p'-DDT. This indicates that o,p'-DDT could have directly activated the vitellogenesis. The antiestrogenic action of tamoxifen to inhibit the vitellogenesis and the decrease on plasma estradiol induced by o,p'-DDT indicates that o,p'-DDT can bind directly to the ER. In conclusion, this in vivo study shows that o,p'-DDT has the potential to disrupt the endocrine system and strongly supports that the estrogenic actions of o,p'-DDT involve binding to the ER.     

白细胞介素抑制剂类生物制剂治疗斑块状银屑病的文献可视化分析

目的 分析白细胞介素（IL）抑制剂类生物制剂在斑块状银屑病治疗中的研究现状及热点。方法 检索2011年1月1日至2022年4月30日在Web of Science核心合集数据库发表的IL抑制剂类生物制剂在斑块状银屑病治疗方面的相关研究，利用CiteSpace5.8.R3软件进行文献的可视化分析，从发文量、国家/地区、机构、作者、期刊等文献关键特征分析该领域的研究现状，通过文献共被引、关键词共现、聚类及突现分析该领域的知识基础、研究热点及前沿。结果 共纳入文献2 056篇，近10年发文量呈逐年递增趋势，共计104个国家/地区的545个机构参与了IL抑制剂类药物治疗斑块状银屑病的研究，其中美国发文量805篇，占总发文量的39.15%居首位，且与德国、英国、瑞士、加拿大等有密切合作，发文最多的机构是瑞士诺华制药，发文最多的作者是德国汉堡艾本多夫医学中心的Reich K，被引频次第一的作者是加拿大Prob Med公司的Papp KA，被引频次最高的期刊为British Journal of Dermatology；该领域的研究热点主要为生物制剂治疗斑块状银屑病的作用机制、疗效及安全性研究，研究...     

紫花丹参不同部位微量元素含量的分析比较

目的分析比较紫花丹参不同部位微量元素含量。方法用电感耦合等离子发射光谱法分别测定紫花丹参根、茎、叶、花4个部位17种微量元素的含量,对不同部位微量元素含量进行分析比较。结果紫花丹参根中镁元素含量最高,茎中钡和锶含量高,叶中硼和铜含量高,而花中铁元素含量分别是根、茎、叶的2.5、4和10倍,另外,花中的钛、锰、镍、钒、锡、铅、钴、铬、镉、锂、锌等11种微量元素含量也均高于其它3个部位。结论从微量元素角度分析,丹参的花也具有一定的药用价值。     

Comparison of the gastrointestinal anatomy,physiology, and biochemistry of humans and commonly used laboratory animals

In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route. Among the physiological factors, pH, bile, pancreatic juice, and mucus and fluid volume and content can modify dissolution rates, solubility, transit times, and membrane transport of drug molecules. The microbial content of the G.I. tract can significantly affect the reductive metabolism and enterohepatic circulation of drugs and colonic delivery of formulations. The transit time of dosage forms can be significantly different between species due to different dimensions and propulsive activities of the G.I. tract. The lipid/protein composition of the enterocyte membrane along the G.I. tract can alter binding and passive, active, and carrier-mediated transport of drugs. The location and number of Peyer's patches can also be important in the absorption of large molecules and particulate matter. While small animals, rats, mice, guinea pigs, and rabbits, are most suitable for determining the mechanism of drug absorption and bioavailability values from powder or solution formulations, larger animals, dogs, pigs, and monkeys, are used to assess absorption from formulations. The understanding of physiological, anatomical, and biochemical differences between the G.I. tracts of different animal species can lead to the selection of the correct animal model to mimic the bioavailability of compounds in the human. This article reviews the anatomical, physiological, and biochemical differences between the G.I. tracts of humans and commonly used laboratory animals.     

改良早期预警评分对重症胰腺炎患者预后的预测价值研究

目的探讨改良早期预警评分(MEWS)应用于重症胰腺炎(SAP)患者预后预测的价值和可行性。方法 63例患者按临床结果分为存活组42例和死亡组21例。以确诊为SAP时作为观察起点,同时采集相关数据,对每位患者分别进行MEWS及APACHE-O评分;以1个月后作为观察终点,比较2种评分系统对预后的预测价值。结果 存活组MEWS和APACHE-O评分均低于死亡组,差异均有统计学意义(P<0.05和P<0.01)。2种评分系统均以死亡为预测指标,MEWS评分界值为7分,灵敏度(Sen)为76.19%,特异度(Spe)为85.71%,ROC曲线下面积Az=0.8741,U=8.3958,P=0.0000,均有较强的预测价值。APACHE-O评分界值为21分,Sen为85.71%,Spe为88.10%;ROC曲线下面积Az=0.9138,U=11.2608,P=0.0000。结论 MEWS和APACHE-O评分对SAP患者预后具有同等预测价值,但MEWS评分系统结构简单,获取数据方便,既省时又节省费用,可用于对SAP患者预后的预测。     

Stability, distribution and use of antivenoms for snakebite envenomation in Latin America: Report of a workshop

The issues of antivenom stability and distribution, and the training of health staff in the correct use of antivenoms in Latin America were discussed in a workshop held at Instituto Clodomiro Picado, Costa Rica, in September 16-19, 2008, under the auspices of the program CYTED. Participants from public antivenom production laboratories of the region, together with representatives of the Ministries of Health, from Argentina, Paraguay, Brazil, Bolivia, Perú, Ecuador, Colombia, Venezuela, Panamá, Costa Rica and Nicaragua participated in the event. Technical advances in the study of antivenom stability and in the design of novel formulations aimed at generating products of higher stability were presented. In addition, antivenom acquisition and distribution systems in every country were presented and discussed, together with novel tools that could be useful for improving antivenom distribution, such as the software SIGEpi, developed by the Pan American Health Organization. The issue of the cold chain, as well as the most frequent causes of misuse of antivenoms in the region, were also analyzed. Finally, the experiences of training programs for health staff on the correct use of antivenoms in snakebite envenomation treatment in Latin America were presented. It was concluded that, in addition to the fostering of antivenom production and quality control, renewed efforts should be implemented at improving the stability, distribution and correct use of antivenoms in the region.     

Tissue-specific regulation of insulin-like growth factors and insulin-like growth factor binding proteins in male diabetic rats in vivo and in vitro

1. Insulin-like growth factors (IGFs) are associated with the development of diabetes mellitus. The liver, kidney and heart have been implicated as important organs in the onset of diabetes mellitus. However, the effect of diabetes on the IGF system in these organs has not been fully described. Thus, we investigated changes in IGF-I, IGF-II and IGF binding proteins (IGFBPs) in male steptozotocin-induced diabetic rats, as well as in a high glucose-induced in vitro model. 2. Serum levels of IGF-I were decreased, but the levels of IGF-II were increased, in diabetic rats compared with controls. The expression of IGFBP-3 in the serum was markedly decreased; in contrast, the expression of IGFBP-1 and -2 was increased in diabetic rats. The expression of IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4 in the liver of the diabetic group was similar to that in the serum of diabetic rats. 3. In heart tissue of the diabetic group, IGF-I levels were decreased, but IGF-II levels were increased. In addition, the expression of IGFBP-3, IGFBP-1 and IGFBP-2 was decreased in diabetic rats. 4. In the kidney of the diabetic group, IGF-I and IGF-II levels were increased. There was only slight expression of IGFBP-3 in the kidney and this was not altered in diabetic rats. Levels of IGFBP-1 and -2 were markedly increased in the kidney of diabetic rats. 5. Insulin treatment recovered the changes in expression of IGF-I, IGF-II and IGFBPs in the serum, liver, heart and kidney. In the liver, heart and kidney, the expression of the insulin receptor was increased in male diabetic rats. 6. In conclusion, diabetes tissue-specifically alters the IGF system in the liver, heart and kidney in rats; this effect can be recovered by insulin treatment.     

185例新生儿PICC常见并发症的临床护理研究

目的研究新生儿PICC导管的临床护理方法,减少并发症的发生,延长PICC导管使用时间。方法总结2007年1月至2008年8月185例新生儿PICC导管的临床护理。结果穿刺成功182例,成功率为98.38%。一次穿刺置管152例,二次穿刺置管17例,三次穿刺置管13例。166例好转或治愈出院拔管,7例放弃治疗拔管,1例感染拔管,2例堵管拔管,1例导管脱出拔管,1例出现静脉炎拔管,2例导管断裂拔管,2例导管移位拔管。最长保留时间46d,最短保留时间1d（堵管）,平均20.13d。经摄取胸片确认导管顶端位置：173例位于右上腔静脉,5例位于锁骨下静脉,2例位于右心房,2例位于颈静脉。结论PICC导管为输液治疗提供了一条安全、方便的通道,减少了反复穿刺给患儿带来的痛苦,避免了高渗药物对患儿血管的刺激,减轻了恶性刺激对患儿心灵的创伤和护理工作量。而对PICC导管的正确护理,是延长导管使用寿命的关键所在,临床护士应该熟练掌握。