藿香根的化学研究

从藿香(Agastache rugosa O.Kuntze)根中分离得到11个化合物,其中Ⅰ～Ⅷ分别鉴定为山楂酸(maslinic acid,Ⅰ),齐墩果(oleanolic acid,Ⅱ),3-乙酰基齐墩果醛(3-O-acetyl oleanolic aldehvde,Ⅲ),刺槐素(acacetin,Ⅳ),tilianin(Ⅴ).藿香甙(agastachoside,Ⅵ),胡萝卜甙(daucosterol,Ⅶ)和β-谷甾醇(β-Sitosterol,Ⅷ)。Ⅸ为一新的二萜成分,经光谱测定其结构为19(4→3)abeo-11,14-dihydroxy-12-methoxy-abieta-8。11,13,15-tetraen-7-one,命名为去氢藿香酚(dehydroagastol)。Ⅹ和Ⅺ的结构在继续研究中。     

左旋氧氟沙星对大鼠血胰屏障的通透性

目的 :研究左旋氧氟沙星对大鼠血胰屏障的通透性。方法 :经尾静脉推注左旋氧氟沙星 (2 0mg·kg 1体重 ) ,在规定的时间点取样 ,用高效液相色谱法 (HPLC)测定胰腺、肝脏组织和血清中药物的含量。结果 :在大鼠血清中的左旋氧氟沙星浓度在5min时最高 ,为 2 0 .2 47μg·mL 1,胰腺、肝脏组织都在 10min时最高分别 2 1.85 0 μg·g 1、30 .5 90 μg·g 1,然后持续下降 ;10min时胰组织的药物浓度开始高于血清 ,90min后两者浓度接近。药物对血胰屏障的通透率 (PR)在 5min时 0 .85 ,然后处于上升趋势 ,2 0min时最高达到 3 .82 ,然后下降 ,90min后接近 1。结论 :静脉推注左旋氧氟沙星后 ,药物对血胰屏障具有良好的通透性 ,值得向临床推荐预防和治疗胰腺感染。     

Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree

Diffuse palmoplantar keratoderma (DPPK) is an autosomal dominant genodermatosis characterized by uniform hyperkeratosis of the palm and sole epidermis. This disorder can be caused by mutations in the genes keratin 1 , keratin 9 , keratin 16 , desmoglein 1 and plakoglobin . Here we present a DPPK Chinese pedigree and identify the aetiology as a novel missense mutation, L437P, located in a highly conserved helix motif in domain 2B of KRT1. Functional analysis shows that overexpression of the L437P mutant in cultured cells leads to abnormal intermediate filament networks and filament aggregation. This gain-of-function mutation highlights the role of domain 2B in mediating filament assembly.

Conflicts of interest

The authors declare that they have no actual or potential conflicts of interest to disclose. Appropriate approval and procedures were used concerning human subjects.     

转化生长因子β1抗体复合缓释载体生物蛋白胶应用于鞘管区预防屈肌腱粘连的生物力学分析

目的:单纯生物蛋白胶是一种良好的缓释载体,拟通过与转化生长因子β1抗体复合应用于肌腱损伤局部,观察其对鞘管区屈肌腱粘连的预防作用和对肌腱愈合的影响。方法:实验于2003-01/04在解放军第四军医大学西京医院骨科研究所完成。①实验动物:将72只来亨鸡(leghorn)按随机化原则分为单纯转化生长因子β1抗体组、单纯生物蛋白胶组、转化生长因子β1抗体复合生物蛋白胶组及生理盐水组,每组18只。实验过程中对动物处置符合动物伦理学要求。②实验方法:分别将鸡左足第三、四趾趾深屈肌腱横断,作The 4-strand Cruciate repair缝合,然后按照分组,用1 mL无菌注射器,向鞘管区分别注入0.2 mL转化生长因子β1抗体(8 mg/L)和生理盐水,用生物蛋白胶专用注射器向鞘管区分别注入0.2 mL生物蛋白胶和转化生长因子β1抗体生物蛋白胶复合液。③实验评估:术后5 d行早期功能锻炼,在第1,3,8周麻醉后处死取材,第四趾标本分别行大体观察、组织学检查和缝合处粘连评分。第三趾在SHIMADZU SPL-10kN型材料实验机上进行生物力学测试。结果:转化生长因子β1抗体复合生物蛋白胶组术后3,8周,缝合处粘连程度评分、肌腱滑动距离、模拟主动屈曲度及屈曲功均优于其余3组,且差异有显著性意义(P<0.05)。4个处理组的最大抗断裂载荷差异无显著性意义(P>0.05)。结论:转化生长因子β1抗体复合缓释载体生物蛋白胶可以有效预防术后肌腱粘连,并且不影响肌腱的正常愈合进程。     

亚甲基二膦酸的合成

目的：改进工艺，合成药用原料亚甲基二膦酸。方法：以亚膦酸三异丙酯为原料，经取代、缩合、水解等反应而合成目标产物。结果：产物结构经红外光谱、核磁共振等分析确证；制成药盒符合中国药典2000年版标准。结论：此合成工艺实用可行。     

CDK4 inhibition and doxorubicin mediate breast cancer cell apoptosis through Smad3 and survivin

Cyclin D1/CDK4 activity is upregulated in up to 50% of breast cancers and CDK4-mediated phosphorylation negatively regulates the TGFβ superfamily member Smad3. We sought to determine if CDK4 inhibition and doxorubicin chemotherapy could impact Smad3-mediated cell/colony growth and apoptosis in breast cancer cells. Parental and cyclin D1-overexpressing MCF7 cells were treated with CDK4 inhibitor, doxorubicin, or combination therapy and cell proliferation, apoptosis, colony formation, and expression of apoptotic proteins were evaluated using an MTS assay, TUNEL staining, 3D Matrigel assay, and apoptosis array/immunoblotting. Study cells were also transduced with WT Smad3 or a Smad3 construct resistant to CDK4 phosphorylation (5M) and colony formation and expression of apoptotic proteins were assessed. Treatment with CDK4 inhibitor/doxorubicin combination therapy, or transduction with 5M Smad3, resulted in a similar decrease in colony formation. Treating cyclin D overexpressing breast cancer cells with combination therapy also resulted in the greatest increase in apoptosis, resulted in decreased expression of anti-apoptotic proteins survivin and XIAP, and impacted subcellular localization of pro-apoptotic Smac/DIABLO. Additionally, transduction of 5M Smad3 and doxorubicin treatment resulted in the greatest change in apoptotic protein expression. Collectively, this work showed the impact of CDK4 inhibitor-mediated, Smad3-regulated tumor suppression, which was augmented in doxorubicin-treated cyclin D-overexpressing study cells.     

甲醛存在下阿米卡星的单扫描示波极谱法测定

研究了在Britton-Robinson(pH8.0)介质中,阿米卡星(AMK)甲醛衍生物的单扫描示波极谱行为,并对其电极反应机理作了研究。在选定条件下,AMK浓度在6.0×10^-7～5.0×10^-5mol·L^-1范围内与峰电流呈线性,相关系数为0.9998,检测限为2.4×10^-7mol·L^-1。方法无需前处理即可用于针剂、尿及血清样品中痕量AMK测定,回收率90%～110%,相对标准偏差小于4.1%。     

棉酚衍生物和酚醛类化合物的合成及抗生育作用

合成了一批三羟基萘醛、多羟基联苯醛、多羟基联萘醛和一些棉酚衍生物,提供抗生育研究。     

天然有机化合物质谱研究——Ⅺ.苯丙型苷快原子轰击质谱MNa~+的MIKES谱

研究了六种苯丙型苷与Na~+加合离子的快原子轰击质谱(FAB—MS)和质量分离离子动能谱(MIKES)。结果表明:在FAB谱中[M+Na]~+加合离子的丰度要比[M+H]~+离子高得多。由此可给出糖苷的分子量信息,[M+Na]~+离子的MIKES谱可给出糖基序列信息。     

抗心肌缺血药2,6-二甲基-4-双取代苯基-1,4-二氢吡啶-3,5-二羧酸酯的合成

本文报道了9个新的2,6-二甲基-4-双取代苯基-1,4-二氢吡淀-3,5-二羧酸酯的合成。初步药理试验表明:化合物I_6具有较强的抑制KCl诱发兔主动脉条的收缩作用,增加冠脉血流量和心输出量,降低心肌耗氧量;增强小鼠抗缺氧能力;对大鼠心肌缺血有保护作用;能缩小兔缺血心肌再灌流引起的心肌梗塞范围。