Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.     

硫酸铁铵催化合成乙酰乙酸乙酯乙二醇缩酮

采用正交试验优选出最佳条件为：当乙酰乙酸乙酯为0.2moL时，硫酸铁铵0.7g，环乙烷10mL。乙酰乙酸乙酯和惭二醇摩尔比为1：1.5，反应时间为5h。所得产率为59.2%。     

薄层扫描法测定复脉定冲剂中远志有效成分的含量

采用薄层扫描法对复脉定冲剂中远志有效成分３，４，５－三甲氧基反式肉桂酸乙酯的含量进行测定。方法简单、快速，结果可靠，可作为该制剂的质控标准。     

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.     

5-羟基-1H-吲哚-3-羧酸乙酯类化合物的合成及其抗流感病毒活性

目的设计合成5-羟基-1H-吲哚-3-羧酸乙酯类化合物,评价其抗流感病毒和抗呼吸道合胞病毒活性.方法经IR、1H-NMR和MS确证目标物结构,并经体外抗病毒试验进行活性筛选.结果与结论合成了9个5-羟基-1H-吲哚-3-羧酸乙酯类化合物,初步活性试验表明,具有一定的抑制流感病毒和呼吸道合胞病毒作用,其中,化合物Ⅷ1、Ⅷ2、Ⅷ5的抗病毒活性与利巴韦林和阿比朵尔相当.     

Convenient synthesis of D‐threo‐[dichloroacetyl 1–14C] chloramphenicol

A convenient synthesis of chloramphenicol labelled with carbon‐14 in the dichloroacetyl group at the 1 position is described. It was prepared as part of a 4‐step sequence from [1 ‐ ¹⁴C] glycine and the product was purified by preparative HPLC. A radiochemical yield of 47% was obtained based on [1 ‐ ¹⁴C] glycine and the product had a specific activity of 0.47 mCi/mmol. The procedure can be employed for the synthesis of high specific activity [¹⁴C] chloramphenicol, labelled at 1, 2 or both the positions of dichloroacetyl group. Copyright © 2005 John Wiley & Sons, Ltd.     

雷公藤提取物固体脂质纳米粒水分散体的制备及体外透皮吸收

制备雷公藤乙酸乙酯提取物固体脂质纳米粒水分散体,并初步研究了体外透皮行为.     

HPLC法同时测定不同产地大花红景天中6种活性成分

目的对青藏高原不同产地大花红景天Rhodiola crenulata中没食子酸、红景天苷、酪醇、儿茶素、没食子酸乙酯、对香豆酸进行分析研究,建立定量分析方法,为其进一步利用提供依据。方法采用30%乙醇提取样品;Diamonsil C18色谱柱(250 mm×4.6 mm,5μm);以乙腈-0.3%磷酸溶液为流动相进行梯度洗脱;检测波长275 nm,柱温25℃。结果没食子酸、红景天苷、酪醇、儿茶素、没食子酸乙酯、对香豆酸分别在38.2~382.0 ng/m L(r=0.999 8)、301.0~3 010.0μg/m L(r=0.999 9)、19.8~198.0 ng/m L(r=0.999 6)、17.1~171.0 ng/m L(r=0.999 6)、4.5~45.0 ng/m L(r=0.999 8)、6.38~63.80 ng/m L(r=0.999 4)呈良好的线性关系,加样回收率均符合定量测定要求。结论该方法简便,快速,准确,可用于同时对青藏高原大花红景天中6种活性成分的测定。     

黄连解毒汤联合氟康唑对耐药白念珠菌麦角甾醇的影响

目的:探讨黄连解毒汤乙酸乙酯提取物(ethyl acetate extract of Huanglian Jiedu decoction,EAHD)联合氟康唑(fluconazole,FLZ)对耐药白念珠菌生物膜麦角甾醇的影响。方法:采用CLSI M27-A3的微量稀释法测定EAHD与FLZ对白念珠菌FLZ耐药株的MIC与SMIC80;棋盘稀释法测定EAHD与FLZ联用对白念珠菌的协同效应;稀释涂布平板法考察EAHD与FLZ联用不同时间对菌体的杀伤作用;分别用HPLC和qRT-PCR法检测耐药白念珠菌生物膜麦角甾醇含量及相关基因的变化。结果:对于9株白念珠菌FLZ耐药株,EAHD对其MIC介于156~1 250 mg·L-1,FLZ对其MIC介于256~2 048 mg·L-1以上,二者联用后MIC显著降低,FICI(部分抑菌浓度指数)最低达0.066;EAHD单用对其SMIC80均高于1 250 mg·L-1,FLZ单用对其SMIC80均高于512 mg·L-1,最高可达2 048 mg·L-1以上,联用组除个别组具有相加作用外也均有协同效应。时间杀菌(time kill,TK)实验显示当作用12 h,二者联用杀菌效应最强。HPLC结果显示联用组、EAHD组与空白组麦角甾醇量相比,分别降低了近85%,50%。qRT-PCR检测FLZ组ERG1,ERG2,ERG6,ERG7,ERG11均上调,ACS1,ACS2,MET6均下调;EAHD组所有基因均下调;联用组ERG2,ERG6,ERG11均显著上调,ERG1,ERG7,ACS1,ACS2,MET6均显著下调。结论:EAHD协同FLZ抗白念珠菌耐药株,可能与抑制麦角甾醇合成相关基因的表达来降低麦角甾醇的合成有关,造成细胞膜损伤,抑制菌体生长。     

吴茱萸的化学成分

目的研究吴茱萸的有效成分。方法运用色谱法及重结晶法进行分离和纯化。结果从芸香科植物吴茱萸 (Evodiarutaecarpa (Juss .)Benth .)中分离得到 6个化合物 ,经综合分析分别鉴定为吴茱萸碱 (evodiamine ,Ⅰ )、去氢吴茱萸碱 (dehydroevodiamine ,Ⅱ )、吴茱萸内酯 (limonin ,Ⅲ )、对羟基苯甲酸乙酯 (p hydroxy benzoicacidethylester ,Ⅳ )、小檗碱 (berberine ,Ⅴ )、齐墩果酸 (oleanolicacid ,Ⅵ )。结论其中化合物Ⅳ、Ⅴ、Ⅵ首次从该属植物中分离得到