牡荆素鼠李糖苷的大鼠在体肠吸收动力学

目的 研究牡荆素鼠李糖苷(RHV)的大鼠在体肠吸收动力学特征.方法 采用HPLC法测定RHV在肠循环液中的药物浓度;采用UV法测定肠循环液中酚红浓度;以大鼠原位灌注模型考查RHV的肠吸收动力学情况.结果 RHV 浓度为20、10、5μg·ml-1的吸收速率常数(Ka)分别为0.0416、0.0478、0.0312 h-1;肠循环液pH4、6、8时RHV的Ka分别为0.0253、0.0478、0.0588 h-1;RHV在十二指肠、空肠、回肠和结肠时的Ka分别为0.0479、0.0308、0.0322、0.0305 h-1.结论 RHV 浓度对RHV的Ka无显著性影响;在pH4～8时,随肠循环液pH的增大,RHV的Ka增加;RHV在大鼠十二指肠、空肠、回肠和结肠的吸收无显著性差异(P＞0.05);RHV在大鼠肠道的吸收呈一级动力学过程,吸收机制为被动扩散.     

数种因子对人胎肺细胞分泌t─PA的影响

原代人胎肺细胞培养２０ｄ后，更换１％ＢＳ培养基，细胞生长停止，ｔ－ＰＡ分泌量低；在１％ＢＳ培养基中使Ｃａ２＋浓度增加到３．５ｍｍｏｌ／Ｌ，ＬＨ浓度增加到１％，细胞表现较高ｔ－ＰＡ分泌活性，与１％ＢＳ组差异显著。以此配方为基础培养基，再分别补充以下因子：５μｇ／ｍｌ转铁蛋白，５ｍｇ／ｍｌ白蛋白，２．５ｍｇ／ｍｌ葡萄糖，１ｍｇ／ｍｌ甘露糖，１μｇ／ｍｌ氢化可的松，２Ｕ／ｍｌ胰岛素，２ｍｍｏｌ／Ｌ谷氨酰胺，２０ｎｍｏｌ／Ｌ亚硒酸钠。除谷氨酰胺和甘露糖外，其他因子均显著提高肺细胞的ｔ－ＰＡ分泌活性（Ｐ＜０．０５）     

Tolerability,pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody,in Chinese healthy volunteers and psoriatic patients

Aim:

To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.

Methods:

Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0 or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks.

Results:

CMAB001 was well tolerated in the single- and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the C_max increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection.

Conclusion:

CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.     

Radioiodinated progesterone derivative for progesterone receptor targeting with enhanced nucleus uptake via phenylboronic acid conjugation

A novel ¹³¹I‐radiolabeled probe with aromatic boronate motif (¹³¹I‐EIPBA) was designed to target progesterone receptor (PR)–positive breast cancer with enhanced nucleus uptake. Acetylene progesterone was conjugated with pegylated phenylboronic acid via click reaction and radiolabeled with ¹³¹I to afford ¹³¹I‐EIPBA. Meanwhile, ¹³¹I‐EIPB without boronate was prepared as control agent. After determination of the lipophilicity and stability of these tracers, in vitro cell uptake studies and in vivo biodistribution in rats were performed to verify the enhanced nucleus uptake and PR targeting ability of ¹³¹I‐EIPBA. ¹³¹I‐EIPBA was obtained with moderate radiochemical yield (40.35 ± 3.52%) and high radiochemical purity (>98%). As expected, the high binding affinity (39.58 nM) of ¹³¹I‐EIPBA for PR was determined by cell binding assay. The internalization ratio of ¹³¹I‐EIPBA was remarkably higher than that of ¹³¹I‐EIPB in PR‐positive MCF‐7 cells. Furthermore, the enhanced nucleus uptake of ¹³¹I‐EIPBA (0.59 ± 0.02%) was found to be significantly higher than that of ¹³¹I‐EIPB (0.13 ± 0.01%) in MCF‐7 cells. A novel ¹³¹I‐EIPBA compound was developed for PR targeting with improved cellular nucleus uptake. Furthermore, the introduction of aromatic boronate motif provides a worthwhile strategy for enhancing the nuclear receptor targeting of tracers.     

儿童误服药(毒)物中毒87例分析

目的:研究探讨儿童因误服药(毒)物中毒的情况以及加强家庭安全用药管理的对策。方法:选择2013年1月至2016年1月在我院进行诊治的误服药(毒)物中毒的患儿87例为研究对象,在对患儿进行救治后,对患儿及其家长进行调查,通过患儿病情的一般情况、实验室检查等分析儿童误服药(毒)物中毒的年龄分布以及误服药(毒)物的类别,并根据患儿的发病趋势分析家庭安全用药管理对策。结果:>2岁~4岁组患儿误服药(毒)物中毒的发生率(45.98%)明显高于其他年龄组。除药物外,误服农药也需引起重视。因误服药(毒)物中毒而导致住院治疗的患儿平均住院时间为5.54d。平均住院费用为8 269.8元。结论:儿童常由于误服药(毒)物而造成意外中毒,尤以>2岁~4岁的儿童发生率较高。家长需加强对家庭中常用药(毒)物的管理,降低患儿意外误服药(毒)物的发生率,减少患儿意外伤害事件的发生。     

前体对多拉菌素生物合成的影响

目的 通过研究前体对多拉菌素生物合成的影响,寻找提高多拉菌素发酵产量的有效方法.方法 本文主要考察了不同前体对多拉菌素生物合成的作用,以及有效前体的最佳添加浓度和添加时间.结果 丙酸钠是多拉菌素合成的最佳前体,在发酵96h时添加0.1％的丙酸钠,多拉菌素产量达139.89μg/mL,比对照组提高了38.2％.结论 前体的供给能显著影响多拉菌素的生物合成,补加丙酸钠能有效提高多拉菌素的发酵产量.     

国外药物相互作用信息的介绍与分析

本文简要介绍了药物相互作用的定义、分类以及研究药物相互作用信息的目的和意义.并对国外目前应用较广泛、具有较大影响力的几个药物相互作用数据库的结构、内容及特点进行了介绍和分析,以期为国内医药专业人员学习、研究及利用药物相互作用信息提供一些参考.     

中波段紫外线对角质形成细胞凋亡的诱导和钙信号的影响

目的　观察中波段紫外线 (UVB)照射诱导人永生化角质形成细胞 (HaCaT细胞 )的凋亡和对细胞静息Ca2 + 及thapsigargin和adrenaline引起的Ca2 + 运动影响。方法　采用四甲基偶氮唑盐 (MTT)染色法分析受UVB照射后细胞存活率的变化 ,用流式细胞术、琼脂糖凝胶电泳和Hoechst332 5 8核染色法观察UVB对HaCaT细胞凋亡的影响 ,采用Fura 2 /AM荧光分光光度法测定胞浆游离Ca2 + 浓度的变化。结果　在 1 2 5～ 6 2 5J·m-2 的UVB照射剂量之间和照射后培养时间 2 4h内的条件下 ,UVB照射以剂量和时间依赖的方式抑制细胞的存活率 ;在照射后培养时间 1 8h内以剂量依赖的方式诱导细胞凋亡 ;2 5 0J·m-2 UVB照射后 ,细胞的静息钙迅速下降 ,在照射后第 6h静息钙降至最低 ,且thapsigargin(1 0μmol·L-1 )和adrenaline(1 0 μmol·L-1 )所引起的钙释放及由此产生的钙内流也随照射后培养时间的延长而逐渐减少。结论　UVB照射可诱导HaCaT细胞的凋亡及引起细胞钙稳态的失衡。     

Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro

Aim:

To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro.

Methods:

The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and phosphorylated kinases was detected using Western blotting.

Results:

Treatment of U251 and U87 cells with anisomycin (0.01–8 μmol/L) inhibited the cell growth in time- and concentration-dependent manners (the IC₅₀ values at 48 h were 0.233±0.021 and 0.192±0.018 μmol/L, respectively). Anisomycin (4 μmol/L) caused 21.5%±2.2% and 25.3%±3.1% of apoptosis proportion, respectively, in U251 and U87 cells. In the two cell lines, anisomycin (4 μmol/L) activated p38 MAPK and JNK, and inactivated ERK1/2. However, neither the p38 MAPK inhibitor SB203580 (10 μmol/L) nor the JNK inhibitor SP600125 (10 μmol/L) prevented anisomycin-induced cell death. On the other hand, anisomycin (4 μmol/L) reduced the level of PP2A/C subunit (catalytic subunit) in a time-dependent manner in the two cell lines. Treatment of the two cell lines with the PP2A inhibitor okadaic acid (100 nmol/L) caused marked cell death.

Conclusion:

Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit. The regulation of PP2A/C exression by anisomycin provides a clue to further study on its role in glioma therapy.