Quantitative Prediction of Oral Bioavailability of a Lipophilic Antineoplastic Drug Bexarotene Administered in Lipidic Formulation Using a Combined In Vitro Lipolysis/Microsomal Metabolism Approach

For performance assessment of the lipid-based drug delivery systems (LBDDSs), in vitro lipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilization processes. Much of previous research on in vitro lipolysis has mostly focused on rank-ordering formulations for their predicted performances. In this study, we have incorporated in vitro lipolysis with microsomal stability to quantitatively predict the oral bioavailability of a lipophilic antineoplastic drug bexarotene (BEX) administered in LBDDS. Two types of LBDDS were applied: lipid solution and lipid suspension. The predicted oral bioavailability values of BEX from linking in vitro lipolysis with microsomal stability for lipid solution and lipid suspension were 34.2 ± 1.6% and 36.2 ± 2.6%, respectively, whereas the in vivo oral bioavailability of BEX was tested as 31.5 ± 13.4% and 31.4 ± 5.2%, respectively. The predicted oral bioavailability corresponded well with the oral bioavailability for both formulations, demonstrating that the combination of in vitro lipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivo intestinal lymphatic uptake was also assessed for the formulations and resulted in <1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability.     

下颈椎前路椎弓根螺钉固定系统与普通前路椎体螺钉固定系统的静力学比较

目的：比较下颈椎前路椎弓根螺钉（ATPS）锁定固定系统和普通前路椎体螺钉（VBS）锁定固定系统的静力学特性。方法：采集新鲜颈椎标本16具,分解为C3.,4,C4,5,C5,6,C6,7共32个运动节段（functionalspinalunit,FSU）,其中C3,4,C4,5,C5,6,C6,7各8个。将其按照不同节段随机分成A、B两组,对所获标本椎间盘切除后模拟植骨,分别植入自行设计生产的下颈椎前路椎弓根螺钉配套钢板系统和普通颈椎前路椎体螺钉钢板系统。在生物力学试验机上行钢板的垂直拔出强度试验。结果：下颈椎前路椎弓根螺钉的最大轴向拔出力为（604．68±48．76）N,椎体螺钉为（488．24±32．42）N,两者比较差异有统计学意义（t=2．147,P〈0．05）,前路椎弓根螺钉固定系统与椎体螺钉固定系统在各FSU间差异无统计学意义（A组和B组的F值分别为2．27、2．05,P〉0．05）。结论：下颈椎前路椎弓根螺钉钢板系统的拔出力明显优于普通前路椎体螺钉钢板系统,从生物力学角度上来看具有应用可行性。     

表面处理及不同水门汀材料对纤维桩粘固性能影响的研究

目的：评价酸蚀一喷砂处理以及4种不同水门汀材料Fuji I（FUI）、Fuji Cem（FUC）、RelyX Unicem（RX—U）、RelyXARC（RXA））对纤维桩粘固性能的影响。方法：选取80颗无龋坏单根管人前磨牙,根据对应纤维桩表面处理与否随机分为2组,进而根据粘接材料的不同分为4个亚组。常规根管充填和桩道预备后,分别选用4种水门汀材料将表面处理前后的玻璃纤维桩粘接到预备根管内;观察纤维桩表面及每组试件粘接界面扫描电镜（SEM）下微观形貌,测试即刻拉出强度（pull—outtest）。结果：表面处理前后纤维桩的各水门汀材料拉出强度以RXA组最高,随后依次为RXU、FUC、FUI组,且各组间均相差显著（P〈0．05）;纤维桩表面处理后与各水门汀材料的拉出强度较之处理前均显著提高（P〈0．05）：SEM观察显示：表面处理后纤维桩的表面粗糙度纤维暴露数量均有明显增加;表面处理前后各组粘接界面微观形貌存在差异,各组的粘接界面均较处理前更致密。结论：酸蚀一喷砂处理纤维桩表面后可以提高其与不同水门汀材料的粘接固位力。     

Probing the weak interaction of proteins with neutral and zwitterionic antifouling polymers

Protein–polymer interactions are of great interest in a wide range of scientific and technological applications. Neutral poly(ethylene glycol) (PEG) and zwitterionic poly(sulfobetaine methacrylate) (pSBMA) are two well-known nonfouling materials that exhibit strong surface resistance to proteins. However, it still remains unclear or unexplored how PEG and pSBMA interact with proteins in solution. In this work, we examine the interactions between two model proteins (bovine serum albumin and lysozyme) and two typical antifouling polymers of PEG and pSBMA in aqueous solution using fluorescence spectroscopy, atomic force microscopy and nuclear magnetic resonance. The effect of protein:polymer mass ratios on the interactions is also examined. Collective data clearly demonstrate the existence of weak hydrophobic interactions between PEG and proteins, while there are no detectable interactions between pSBMA and proteins. The elimination of protein interaction with pSBMA could be due to an enhanced surface hydration of zwitterionic groups in pSBMA. New evidence is given to demonstrate the interactions between PEG and proteins, which are often neglected in the literature because the PEG–protein interactions are weak and reversible, as well as the structural change caused by hydrophobic interaction. This work provides a better fundamental understanding of the intrinsic structure–activity relationship of polymers underlying polymer–protein interactions, which are important for designing new biomaterials for biosensor, medical diagnostics and drug delivery applications.     

雄激素和雄激素受体对肝癌细胞株PEG10表达的作用

目的 探讨雄激素和雄激素受体(AR)对肝癌细胞株PEG10表达的调控作用.方法 设计合成针对人ARsiRNA,并转染HepG2和7404肝癌细胞株.用双氢睾丸酮(DHT)干预HepG2细胞.Western Blot检测AR和PEG10表达水平.结果 从3对AR siRNA中筛选到1对siRNA(AR siRNA-3),它在2种肝癌细胞株中均可有效抑制AR的表达,其抑制作用呈剂量依赖关系.2种肝癌细胞株中,浓度为240 nmol/L的AR siRNA-3在转染后24 h,对AR抑制效率可达80%以上,且抑制效果可持续至72 h.AR siRNA-3转染24h后PEG10表达水平降低,转染48 h后,PEG10表达水平降低非常明显,72 h后PEG10表达有所上升.DHT可促进HepG2细胞PEG10的表达,呈剂量依赖关系.DHT对AR表达未见明显作用.结论 雄激素和AR参与了肝癌细胞株PEG10表达的调控.这可能是男性肝细胞癌发病率较高的原因之一.     

Silver-Russell syndrome in a girl born after <Emphasis Type="Italic">in vitro</Emphasis> fertilization: partial hypermethylation at the differentially methylated region of <Emphasis Type="Italic">PEG1</Emphasis>/<Emphasis Type="Italic">MEST</Emphasis>

Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART. Partial hypermethylation was identified at the differentially methylated region of paternally expressed PEG1/MEST in a girl with Silver-Russell syndrome born after in vitro fertilization.     

The Use of a PEG/Ascorbate Booster Following Standard Bowel Preparation Improves Visualization for Capsule Endoscopy in a Randomized,Controlled Study

Background Background/Aims: The increasing use of capsule endoscopy (CE) to examine the gastrointestinal tract highlights the need to establish intestinal preparations that ensure optimal visualization while maximizing patient adherence. Thus, we assessed whether bowel preparation involving dietary restriction and a booster regimen produces adequate CE visualization in a real-world clinical setting.Methods We conducted a randomized, double-blind, prospective study of CE procedures at 2 tertiary-care centers. Patients were allocated to 3 groups: group 1 followed a clear liquid diet and fasting-based bowel preparation for the exploration (n = 55); group 2 followed the same procedure as group 1 and then ingested 1 L of a polyethylene glycol (PEG)/ascorbic acid booster solution when the capsule reached the small intestine (n = 55); and group 3 followed the same procedure but ingesting only 0.5 L of the booster solution (n = 56). The quality of visualization and the average gastric, orocecal and small-bowel transit times were evaluated.Results A total of 166 patients participated in the study. Significantly higher quality of visualization (Park score) was obtained in group 3 (2.28 ± 0.59) than in group 1 (1.84 ± 0.54, P < .001), while there were no significant differences in the average gastric (range: 36.58-48.32 min, P = .277), orocecal (range: 322.58-289.45 min, P = .072), and small-bowel transit time (range: 280.71-249.95 min, P = .286) between the 3 groups.Conclusions Following a clear liquid diet and fasting-based bowel preparation for CE exploration, administering a booster solution of PEG/ascorbic acid after the capsule had reached the small intestine improves mucosal visualization and cleansing without affecting capsule transit times.     

聚乙二醇在聚砜膜上的接枝与表征

对用紫外辐照法在聚砜膜表面接枝的聚乙二醇作了初步的研究。通过静态水接触角测定、X射线-光电子能谱分析以及原子力学显微镜等测试手段，对接枝前后聚砜膜表面的性能进行了测定，证明采用同步接枝法和二步接枝法在聚砜材料表面接上了聚乙二醇，表面亲水性大大提高，两种接枝方法的接枝覆盖率分别为77．3％和41．9％，表面形貌、相位图等参数较接枝前变化明显，说明用同步法在聚砜膜表面产生了分枝的聚乙二醇层，而二步法在聚砜膜表面产生了薄煎饼状的聚乙二醇层。这一研究为下一步拟在聚砜中空纤维膜表面接上聚乙二醇刷分子层打下了基础。