具抗凝血作用的铁、铜三元配合物与人血清白蛋白的相互作用

采用光度法研究了具抗凝血作用的过渡金属铁和铜的华法灵、水杨酸三元配合物与人血清白蛋白的相互作用, 观察到铁、铜三元配合物使人血清白蛋白荧光产生猝灭现象, 猝灭方式为静态猝灭, 并计算了配合物与人血清白蛋白的结合常数和结合位点数. 根据不同温度下的热力学函数, 确定了配合物与人血清白蛋白的作用力类型. 并且发现三元配合物的存在明显改变人血清白蛋白的构象. 并讨论了配合物使人血清白蛋白构象发生变化的可能原因.     

Use of measurement uncertainty analysis to assess accuracy of carbon mass balance closure for a cellulase production process

Closing carbon mass balances is a critical and necessary step for verifying the performance of any conversion process. We developed a methodology for calculating carbon mass balance closures for a cellulase production process and then applied measurement uncertainty analysis to calculate 95% confidence limits to assess the accuracy of the results. Cellulase production experiments were conducted in 7-L fermentors using Trichoderma reesei grown on pure cellulose (Solka-floc), glucose, or lactose. All input and output carbon-containing streams were measured and carbon dioxide in the exhaust gas was quantified using a mass spectrometer. On Solka-floc, carbon mass balances ranged from 90 to 100% closure for the first 48 h but increased to 101 to 135% closure from 72 h to the end of the cultivation at 168 h. Carbon mass balance closures for soluble sugar substrates ranged from 92 to 127% over the entire course of the cultivations. The 95% confidence intervals (CIs) for carbon mass balance closure were typically ±11 to 12 percentage points after 48 h of cultivation. Many of the carbon mass balance results did not bracket 100% closure within the 95% CIs. These results suggest that measurement problems with the experimental or analytical methods may exist. This work shows that uncertainty analysis can be a useful diagnostic tool for identifying measurement problems in complex biochemical systems.     

纳米二氧化硅影响人肺癌细胞的定量糖蛋白质组学研究

纳米二氧化硅(纳米SiO₂)是一种正在规模化生产的纳米材料, 无定型纳米SiO₂因其吸入和口服对生命体不会造成直接的危害被认为是生物安全的纳米材料, 已被广泛用于疾病诊断、生物分析和成像、药物载体等的研究中, 导致其进入人体的方式日益增多, 因此它对人体健康影响的研究对于其作为生物材料真正实现广泛应用尤为重要. 本文采用肼化学方法为基础的定量蛋白质组学对无定型纳米SiO₂进入人肺癌细胞后产生的影响进行了分析, 结果表明其进入细胞后, 导致细胞内的平衡状态发生变化, 从而影响了细胞内许多重要的蛋白质的表达水平. 部分跨膜蛋白质表达的变化对纳米SiO₂进入细胞的途径的阐明有一定的指导意义.     

人体胎盘合体滋养细胞质膜的脂肪酸组成分析

用Ｗｈｉｔｓｅｔｔ法提取１８只正常足月妊娠分娩的胎盘合体滋养细胞质膜（ＳＰＭ）,采用Ｌａｎｄｏｎ法提取脂质,使用气相色谱法和丁二酸二乙二醇酯（ＤＥＧＳ）填充柱分离测定ＳＰＭ的脂肪酸,结合气相色谱／质谱定性,将１３种碳数大于１４的脂肪酸进行了定性和定量。定量出的脂肪酸占出峰物质总量的７４．１％,其中饱和脂肪酸为３０．６４％,不饱和脂肪酸为４３．４６％。     

Model of full-length HIV-1 integrase complexed with viral DNA as template for anti-HIV drug design

Summary We report structural models of the full-length integrase enzyme (IN) of the human immunodeficiency virus type 1 (HIV-1) and its complex with viral and human DNA. These were developed by means of molecular modeling techniques using all available experimental evidence, including X-ray crystallographic and NMR structures of portions of the full-length protein. Special emphasis was placed on obtaining a model of the enzyme’s active site with the viral DNA apposed to it, based on the hypothesis that such a model would allow structure-based design of inhibitors that retain activity in vivo. This was because bound DNA might be present in vivo after 3’-processing but before strand transfer. These structural models were used to study the potential binding modes of various diketo-acid HIV-1 IN inhibitors (many of them preferentially inhibiting strand transfer) for which no experimentally derived complexed structures are available. The results indicate that the diketo-acid IN inhibitors probably chelate the metal ion in the catalytic site and also prevent the exposure of the 3’-processed end of the viral DNA to human DNA.     

Competing binding of metal ions with protein studied by microdialysis

A method has been established to study the competing binding of metal ions with protein by a combined technique of microdialysis with high performance liquid chromatography (HPLC). Ni2+, Cd2+, Zn2+, Cu2+ and human serum albumin (HSA) were chosen as model metal ions and protein. The experimental results show that Ni2+ and Cu2+ share a common primary binding site on HSA, and Zn2+ and Cd2+ share a different common primary binding site from them, but there is a common multi-metal binding site for all of those four metal ions. This method show advantages of fast sampling, easily to be operated and especially to be useful when ideal spectroscopic probes are not available for the study of interaction between protein and metal ions.     

亲和膜用于去除医药及人血清白蛋白溶液中的内毒素(英文)

 以纤维素膜为基质材料 ,制备了 3种用于去除内毒素的亲和膜 ,分别为壳聚糖亲和膜 (KFCC5 17) ,疏水阳离子亲和膜 (KFCG316 )和金属螯合物亲和膜 (KFCG40 2 )。研究了亲和膜对内毒素的吸附容量及在内毒素去除方面的应用 ,结果表明这 3种亲和膜都可以用于多种溶液中内毒素的去除。考察了离子强度、pH值以及流速对去除效果的影响 ,并分析了原因。KFCC5 17,KFCG316 ,KFCG40 2都可用于人血清白蛋白溶液中内毒素的去除 ,KFCC5 17还可用于医药制剂如氢化可的松、葛根素、盐酸丁卡因和右旋糖苷 40葡萄糖注射液中内毒素的去除。     

Liquid chromatography-tandem mass spectroscopic method for the determination of zerumbone in human plasma and its application to pharmacokinetics

A rapid, sensitive, specific and selective LC-MS/MS method for the determination of zerumbone (ZER) in human plasma using 2,4-diamino-6-(4-methoxyphenyl)-1,3,5-triazine (DMTZ) as an internal standard (IS) has been developed and validated. ZER was chromatographed on C8 column using a mobile phase of acetonitrile/water (80:20, v/v) at a flow rate of 0.25 ml min(-1) . Quantitation was achieved using ESI+ interface, employing multiple reaction monitoring (MRM) mode at m/z 219 > 81 and 218 > 134 for ZER and IS, respectively. The calibration standards were linear over a range of 5-3000 ng ml(-1) (r(2)=0.9994) with an LLOQ of 5 ng ml(-1) (RSD %; 11.4% and bias%; 9.5%). Intra- and inter-day precision of ZER assay ranged from 0.18 to 3.56% with accuracy (bias) that varied between -5.09 and 4.3%, demonstrating good precision and accuracy. Recoveries of ZER and the IS from human plasma were above 85%. The developed method was validated for the determination of ZER in rat plasma. Linearity, stability of ZER and the ME on rat plasma were discussed. The applicability of the developed method was demonstrated by measuring ZER in rat plasma samples following intravenous and intraperitoneal administration of ZER prepared in hydroxypropyl-β-cyclodextrin (HPβCD) and sodium carboxymethyl cellulose (CMC), respectively, in 20 mg kg(-1) and this study indicated a clear significant difference (p<0.05) in pharmacokinetic parameters of ZER in ZER/HPβCD complex compared with ZER in CMC preparation.     

Recent advancement and development of chitin and chitosan-based nanocomposite for drug delivery: Critical approach to clinical research

This review depicts the exposure of chitin and chitosan base multifunctional nanomaterial composites for promising applications in field of biomedical science structure, synthesis as well as potential application from a colossal angle. We elaborated critically each of the chitin and chitosan base nanomaterial with its potential application toward biomedical science. For different biomedical applications it use in form of hydrogels, microsphere, nanoparticles, aerogels, microsphere and in form of scaffold. Due to this it had been blended with different polymer such as starch, cellulose, alginate, lipid, hyaluronic acid, polyvinyl alcohol and caboxymethyl cellulose. In this review article, a comprehensive overview of combination of chitin and chitosan base nanomaterial with natural as well as synthetic polymers and their biomedical applications in biomedical field involving drug delivery system all the technical scientific issues have been addressed; highlighting the recent advancements.     

A simple HPLC method for the quantification of mizoribine in human serum: pharmacokinetic applications

A simple high-performance liquid chromatographic (HPLC) method was developed and validated for the quantification of mizoribine in human serum. After the addition of 70% perchloric acid and 3-methylxanthine (50 microg/mL, internal standard) to human serum, the samples were mixed and centrifuged at 12,000 rpm (1432 g) for 10 min. The supernatant was injected onto a C(18) column eluted with a mobile phase of 20 mm Na2HPO4 and methanol (93:7, v/v, pH 3) containing 0.04% octanesulfonic acid and detected utilizing an ultraviolet detector at 275 nm. The linear calibration curve was obtained in the concentration range of 0.1-4.0 microg/mL and the lower limit of quantification was 0.1 microg/mL. This method was validated with selectivity, linearity, precision and accuracy. In addition, the method was successfully applied to estimate the pharmacokinetic parameters of mizoribine in Korean subjects following an oral administration of 100 mg mizoribine (two Bredinine 50 mg tablets). The maximum serum concentration (C(max)) of 2.30 +/- 0.83 microg/mL was reached 2.27 +/- 0.66 h after an oral dose. The mean AUC(0-12 h) and the elimination half-life (t(1/2)) were 13.2 +/- 4.79 microg h/mL and 3.10 +/- 0.74 h, respectively.