雌甾-3-甲氧基-2，5（10）-二烯-17-酮的合成研究

目的：研究雌甾-3-甲氧基-2,5（10）-二烯-17-酮（B）的最佳合成工艺。方法：以雌甾-3-甲氧基-2,5（10）-二烯-17-醇（A）为原料,分别运用沃氏氧化、活性二氧化锰和Collins试剂为氧化剂对其进行氧化反应,以得到标题化合物,并比较三种合成方法。结果与讨论：在以雌甾-3-甲氧基-2,5（10）-二烯-17-醇（A）为原料合成标题化合物的方法中,以沃氏氧化为最佳。     

Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection in hemodialysis patients

E.C. Seyhan, S. Sökücü, S. Altin, G. Günlüo?lu, S. Trablus, D. Yilmaz, O.K. Koksalan, H. Issever. Comparison of the QuantiFERON‐TB Gold In‐Tube test with the tuberculin skin test for detecting latent tuberculosis infection in hemodialysis patients.
Transpl Infect Dis 2010: 12: 98–105. All rights reserved Background and objectives. Hemodialysis (HD) patients are at increased risk of reactivation of latent tuberculosis (TB) infection (LTBI). LTBI screening of this population is recommended. The QuantiFERON‐TB Gold assay (QFT‐G) may be more accurate than the tuberculin skin test (TST) in the detection of LTBI. We prospectively compared the results of QFT‐G to TST in HD patients. Methods. We examined 100 patients and performed TST and QFT‐G tests. Data obtained from patients and medical records included medical history (past history of TB, Bacillus Calmette–Guerin [BCG] vaccination, history of contact with previous TB cases), radiography reports (chest x‐ray with changes consistent with old TB), and basic laboratory findings. Results. Forty‐three of 100 patients (43%) had a positive QFT‐G test result and 34 (34%) had a positive TST test result. Overall agreement between the QFT‐G and the TST was 65% (concordance [k]=0.26, P=0.01). Discordant test results were seen in 13 TST‐positive/QFT‐G‐negative patients and in 22 TST‐negative/QFT‐G‐positive patients. Before BCG vaccination and radiographic reports (of old TB changes) were associated with discordant test results. On multivariate analysis, a positive QFT‐G test was associated with contact with previous TB cases (P=0.026) and radiographic report (P=0.034), whereas a positive TST test also was associated with a history of BCG vaccination (P=0.015). Conclusions. QFT‐G test results were more closely associated with TB risk factors than were positive TST results. Additionally, the QFT‐G test was not affected by BCG vaccination. We concluded that QFT‐G test is a more useful diagnostic method than TST for detecting LTBI in HD patients.     

A new spectrophotometric method for the determination of methyldopa

A new, simple and low cost spectrophotometric method for the determination of methyldopa in pharmaceutical preparations was developed. The method was based on the coupling of methyldopa with 2,6-dichloroquinone-4-chlorimide (DCQ). The absorbance maximum (λ_max) of the resulted colored product was at 400 nm. Different buffers were used to determine the optimal pH for the reaction. About 1% w/v acetate buffer with pH 8.0 gave the optimal pH required for the reaction. Of the different solvents tried, water and ethanol were found to be the most suitable solvents. Beer’s law was obeyed in concentration range of 4–20 μg/ml methyldopa. The correlation coefficient was found to be (r = 0.9975). The limit of detection and limit of quantification were 1.1 μg/ml and 3.21 μg/ml, respectively. The reaction ratio between methyldopa and DCQ was studied and found to be 1:3. The work included the study of the possible interference of hydrochlorothiazide found in combination with methyldopa tablets. The method was validated and results obtained for the assay of two different brands of methyldopa tablets were compared with the BP method (colorimetric). The repeatability and reproducibility of the developed method were evaluated and the obtained results quoted. The derivative formed as a result of the reaction of methyldopa with DCQ was isolated and its possible mechanistic pathway was suggested.     

Evaluation of poly(d,l-lactide-co-glycolide) microspheres for the lung-targeting of yuanhuacine,a novel DNA topoisomerase I inhibitor

The present study was intended to develop poly(d,l-lactide-co-glycolide) (PLGA; 50:50, 0.15 dL/g) microspheres (MS) loaded with yuanhuacine (YHC) for passive targeting in lung as well as providing a simple evaluation method for the targeting efficiency of MS. A kind of photochromic spiropyran dye was applied to label MS to clearly demonstrate the in vivo distribution characteristics through intravenous injection into mice and rabbits. Sections of 10-μm thickness from different organs were cut using a microtome, and fluorescent microscopy was used to determine the biodistribution of the MS. The average particle size of MS was 9.0 μm, and the glass transition temperature was 37–40°C. In vitro, the cumulative release achieved 50.8% in 24 h. Histological sections from different organs indicated that the amount of MS in lung achieved maximum in 6 h, as about 8 times as in liver and 70 times higher than the average concentration of other organs. In vivo, MS were gradually swelled and drug concentration remained just 10% in 12 h, which would not result in long time embolization in the lung. This evaluation method supplies a simple and visualized channel in focus for the targeting efficiency of PLGA MS.     

Colloidal Gold: A Novel Nanoparticle Vector for Tumor Directed Drug Delivery

Colloidal gold, a sol comprised of nanoparticles of Au⁰, has been used as a therapeutic for the treatment of cancer as well as an indicator for immunodiagnostics. However, the use of these gold nanoparticles for in vivo drug delivery has never been described. This communication outlines the development of a colloidal gold (cAu) nanoparticle vector that targets the delivery of tumor necrosis factor (TNF) to a solid tumor growing in mice.

The optimal vector, designated PT-cAu-TNF, consists of molecules of thiol-derivatized PEG (PT) and recombinant human TNF that are directly bound onto the surface of the gold nanoparticles. Following intravenous administration, PT-cAu-TNF rapidly accumulates in MC-38 colon carcinoma tumors and shows little to no accumulation in the livers, spleens (i.e., the RES) or other healthy organs of the animals. The tumor accumulation was evidenced by a marked change in the color of the tumor as it acquired the bright red/purple color of the colloidal gold sol and was coincident with the active and tumor-specific sequestration of TNF. Finally, PT-cAu-TNF was less toxic and more effective in reducing tumor burden than native TNF since maximal antitumor responses were achieved at lower doses of drug.     

应用NCCLS EP10-A2文件对五种半胱氨酸蛋白酶抑制剂C试剂进行初步评价

目的 对五个厂家的半胱氨酸蛋白酶抑制剂C(胱抑素C)试剂检测性能进行初步评价.方法 按照美国临床实验室标准化委员会(NCCLS)EP10-A2文件,使用五种试剂分别对胱抑素C低值、中值、高值标本进行检测,计算偏倚、总不精密度及其截距、斜率、携带污染、非线性、漂移性,并判断其临床可接受性.结果 五个厂家的试剂总不精密度均在允许的范围内,截距、非线性、漂移性的差异无统计学意义;利德曼试剂测定值偏倚大于允许偏倚,其余四个厂家试剂偏倚在允许范围内;科华、景源、迈克、美康的试剂存在携带污染.结论 科华、景源、迈克、美康胱抑素C试剂合准确度和精密度良好,试剂稳定,性能指标基本符合临床要求,但携带污染还有待理一步改进.     

Stable isotope-resolved metabolomics and applications for drug development

Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response.In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality.