儿茶素微囊剂对小鼠的免疫调节作用

目的:研究儿茶素微囊剂对小鼠的免疫调节作用。方法:环磷酰胺诱导小鼠免疫功能低下,予儿茶素微囊剂,观察小鼠耳片肿胀度、半数溶血值(HC50 )、碳粒廓清指数K、吞噬指数α等有关免疫指标的变化。结果: 儿茶素微囊剂高剂量组(500mg·kg-1·d-1 )小鼠的耳肿胀度为(36±7 )mg与生理盐水组(20±3)mg比较差异有非常显著意义(P<0. 05),碳粒廓清指数K和吞噬指数α分别提高为0. 053 3±0. 002 5, 7. 08±0. 03,与生理盐水组(0. 041 2±0. 002 8, 6. 16±0. 19 )相比差异有非常显著意义(P<0. 01 );环磷酰胺+儿茶素高剂量组小鼠耳片肿胀度为(19±3 )mg,与环磷酰胺组(9±4)mg比较差异有非常显著意义(P<0. 01 ),HC50增高至(223±15)与环磷酰胺组(193±18)比较差异有非常显著意义(P<0. 05 ),碳粒廓清指数K、吞噬指数α分别为0. 034 8±0. 002 8, 6. 01±0. 11,与环磷酰胺组(0. 024±0. 004, 5. 1±0. 6 )相比有一定的提高(P<0. 01 )。结论:儿茶素微囊剂对正常及免疫功能低下小鼠的细胞免疫和体液免疫均具有增强作用。     

RP-HPLC测定缓释膜剂中芬太尼的含量

目的　建立测定膜剂中枸橼酸芬太尼含量的方法。方法　采用RP -HPLC ,样品经超声处理过滤后采用C1 8Diamonsil色谱柱(4.6mm×2 5 0mm ,5 μm) ,以乙腈-pH 2 .5 0 .0 33mol·L-1 磷酸盐缓冲液(35∶6 5 )为流动相,检测波长2 2 0nm ,柱温为30℃。结果　枸橼酸芬太尼浓度在4 .0～4 0 .0 μg·ml-1 范围内线性关系良好(r =0 .9999,n =5 ) ,平均回收率为99.1 2 %,RSD =0 .6 6 %(n =3)。结论　该方法简便快速,结果准确,专属性强,可用于该制剂的质量控制。     

HPLC测定克林霉素搽剂的含量

目的　测定克林霉素搽剂的含量。方法　用HPLC法 ,C18色谱柱 ,以磷酸二氢铵溶液 (pH 3.0 ) -甲醇 (2 10∶30 0 )为流动相 ,检测波长 2 14nm。结果　线性范围为 0 .2～ 2 .0mg·ml-1,回归方程为 :Y =9.117× 10 5X +3 10 2× 10 4(r =0 .9999,n =5 )。回收率为 99 7% ,RSD =1 0 2 %。分析方法精密度RSD =1.34% (n =5 )。结论　方法简便、快速、准确。     

姜红止痛搽剂的质量标准

目的 建立姜红止痛搽剂的质量标准。方法 采用薄层色谱法(TLC)对制剂中的姜黄、红花、乳香、没药进行定性鉴别；采用高效液相色谱法(HPLC)测定制剂中姜黄素的含量。结果 TLC分离效果好，斑点清晰；姜黄素含量在0．07-0．35μg范围内，线性关系良好(r=0．9993)，平均回收率为99．92％，RSD=1．67％(n=5)。结论 所用方法专属性强、重复性好，可用于该制剂的质量控制。     

双氯芬酸钠脂质体凝胶剂的研制

目的 :研制双氯芬酸钠脂质体凝胶 ,并进行评价。方法 :运用薄膜蒸发法制备了双氯芬酸钠脂质体 ,然后用卡波姆 (Carbopol)为基质制得凝胶。并建立了一阶导数紫外分光光度法进行测定。结果 :测得样品低、中、高 3个浓度的平均回收率分别为 (10 1 1± 0 86 ) % ,(99 90± 1 0 4 ) %和 (10 0 5± 0 91) %。脂质体经凝胶柱分离后测得平均包封率为 4 3 6 % ,经库尔特计数器测得平均粒径为 1 37μm。凝胶分别于冰箱 (4℃ )和室温下密封保存 0 5、1、3、6mo ,6mo后的包封率下降分别为 4 4 %、6 8%。结论 :经初步评价 ,将双氯芬酸钠制成脂质体凝胶剂是可行的     

RP-HPLC测定乳香伤筋搽剂中士的宁的含量

目的　测定乳香伤筋搽剂中士的宁的含量。方法　将样品制成甲醇溶液 ,用C18柱为固定相 ,以乙腈 -水 (37∶6 3) (pH 4 .2 ,含十二烷基硫酸钠 0 .0 0 1mol·L-1)为流动相 ,检测波长 2 5 4nm。结果　士的宁在 0 .0 4～ 0 .2 0 μg范围内 ,线性关系良好 (r=0 .9999) ,平均加样回收率为 97.14 % ;方法精密度RSD =1.76 % (n =5 )。结论　该方法可用于乳香伤筋搽剂的质量控制     

急性上呼吸道感染患儿未使用退热剂临床结局分析

目的 :探讨未使用退热剂对上呼吸道感染患儿能否缩短病程及减少并发症的发生率。方法 :对 1 1 6例上呼吸道感染患儿随机分为未使用退热剂组 (观察组 )和使用退热剂组(对照组 )各 5 8例进行比较。两组的发病年龄、性别、季节相仿 ,具有可比性 (P>0 .0 5 )。结果 :观察组病程明显少于对照组 (t=7.1 0 4,P<0 .0 1 )。观察组并发症发生 3例 ,并发症发生率为 5 .1 7% ,对照组并发症发生 1 8例 ,并发症发生率为 3 1 % ,两组相比有极显著差异 (X2 =1 3 .0 8,P<0 .0 1 )。结论 :对上呼吸道感染患儿未使用退热剂可有效缩短病程和减少并发症的发生率 ,并能维护正常的机体免疫功能     

不同包装材料与大输液剂的相容性

目的 :研究不同包装材料与大输液剂相容性。方法 :配制 10 %葡萄糖注射液、0 .9%氯化钠注射液及灭菌注射用水分装于 6种包装材料中 ,在 1年的不同时间观察检测各项指标 ,并与玻璃瓶为对照进行比较。结果 :在不同包装材料中注射液的含量、细菌内毒素、无菌检查、微粒检查项目 ,与玻璃瓶相比 ,差异均无显著性 (P >0 .0 5 )。PVC1、PVC2这两种包装材料 ,引起 0 .9%氯化钠注射液、灭菌注射用水 pH值下降 ,引起灭菌注射用水电导率升高、易氧化物含量增加以及吸收度出现明显的升高 (P <0 .0 5 ,P <0 .0 1) ,而其他几种材料与玻璃瓶相比 ,无明显差异 (P >0 .0 5 )。结论 :PVC输液袋用于大输液剂应引起注意 ,非PVC多层共挤膜输液袋与大输液剂相容性良好 ,具有较好的应用开发前景。     

高效液相色谱法测定盐酸地匹福林眼用凝胶剂的含量

目的 :测定盐酸地匹福林 (DPE)眼用凝胶剂的含量。方法 :在ODS -C1 8色谱柱上采用流动相甲醇 - 0 0 2mol·L- 1 磷酸二氢钾溶液 (80∶2 0 ) ,波长 2 2 0nm进行检测。结果 :在 10 0～ 10 0 0 μg·mL- 1 范围内 ,DPE对照品的峰面积 (Y)与其浓度 (X)呈现良好的线性关系 ,r=0 9999,最低检测限 40ng·mL- 1 ,高、中、低 3种浓度平均回收率为 98 40 %～ 10 0 5 %(n =5 ) ,RSD分别为 1 17% ,1 15 % ,0 6 6 % ,平均日内、日间RSD分别为 0 70 % (n =6 )和 0 89% (n =5 )。结论 :本法快速、灵敏、准确、专属性高。     

促渗剂促进氨氯地平凝胶剂透皮作用的研究

目的 :研究促渗剂对氨氯地平凝胶剂透皮作用的影响。方法 :采取简单小室法 ,用离体小鼠皮肤进行体外透皮扩散试验 ,计算含不同促渗剂的 2 %氨氯地平凝胶的累积渗透量Q及渗透速率k。结果 :1%～ 5 %薄荷脑、1%～ 5 %氮酮对 2 %氨氯地平凝胶的累积渗透量Q及渗透速率k均显著地提高 (P <0 0 1) ;10 %～ 30 %丙二醇显著地降低 2 %氨氯地平凝胶的Q与k值 (P <0 0 1) ,并明显抑制薄荷脑、氮酮的促渗作用 ;薄荷脑与氮酮的联用则无联合增效作用。结论 :提示薄荷脑、氮酮可作为促渗剂在氨氯地平凝胶剂中单独使用     

Structure Activity Relationship of Antiproliferative Agents using Multiple Linear Regression

With cancer‐related fatalities being the second leading cause of death in the USA, understanding the activity of effective chemotherapeutic agents is critical to addressing prostate and other cancers. Celecoxib, an FDA‐approved drug for the treatment of colon tumors, has been used successfully as a lead compound in the development of antiproliferative agents. The ability of celecoxib to inhibit the development and progression of tumors has been connected to a number of mechanisms of actions that are both dependent on and independent of its cyclooxygenase‐2 activity. A structure‐based approach has been employed to develop a model that underscores the structural significance of celecoxib as an antiproliferative agent. By evaluating the structure activity of this library of molecules, we were able to create a QSAR model for predicting the antiproliferative activity of structurally similar molecules. The development of the model will be presented in this paper.     

Predicting the Effects of Anti-angiogenic Agents Targeting Specific VEGF Isoforms

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis, whose effect on cancer growth and development is well characterized. Alternative splicing of VEGF leads to several different isoforms, which are differentially expressed in various tumor types and have distinct functions in tumor blood vessel formation. Many cancer therapies aim to inhibit angiogenesis by targeting VEGF and preventing intracellular signaling leading to tumor vascularization; however, the effects of targeting specific VEGF isoforms have received little attention in the clinical setting. In this work, we investigate the effects of selectively targeting a single VEGF isoform, as compared with inhibiting all isoforms. We utilize a molecular-detailed whole-body compartment model of VEGF transport and kinetics in the presence of breast tumor. The model includes two major VEGF isoforms, VEGF(121) and VEGF(165), receptors VEGFR1 and VEGFR2, and co-receptors Neuropilin-1 and Neuropilin-2. We utilize the model to predict the concentrations of free VEGF, the number of VEGF/VEGFR2 complexes (considered to be pro-angiogenic), and the receptor occupancy profiles following inhibition of VEGF using isoform-specific anti-VEGF agents. We predict that targeting VEGF(121) leads to a 54% and 84% reduction in free VEGF in tumors that secrete both VEGF isoforms or tumors that overexpress VEGF(121), respectively. Additionally, 21% of the VEGFR2 molecules in the blood are ligated following inhibition of VEGF(121), compared with 88% when both isoforms are targeted. Targeting VEGF(121) reduces tumor free VEGF and is an effective treatment strategy. Our results provide a basis for clinical investigation of isoform-specific anti-VEGF agents.     

Immunoconjugates of Soybean Bowman-Birk Protease Inhibitor as Targeted Antitumor Polymeric Agents

To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (slgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the K_i, values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.     

Nanoparticles Containing Anti-inflammatory Agents as Chemotherapy Adjuvants: Optimization and In Vitro Characterization

The pre-administration of dexamethasone (DEX) has previously been shown to enhance the anti-tumor efficacy of chemotherapeutic agents. The delivery of anti-inflammatory agents specifically to tumors via nanoparticle carriers is expected to promote the effectiveness of chemotherapeutic agents while avoiding systemic toxicities. The process for preparing solid lipid nanoparticles containing anti-inflammatory agents using the nanotemplate engineering method was optimized. Due to the solubilization of DEX in the bulk aqueous phase, its more lipophilic palmitate ester was synthesized and incorporated in nanoparticles that included a pegylating agent, PEG6000 mono-stearate, as part of the formulation. The stealth properties of these nanoparticles were demonstrated to be enhanced compared to latex particles by measuring the adsorption of radioiodinated IgG (185 microg vs. 6.7 microg IgG/mg NP). In addition, the uptake of (14)C-labeled nanoparticles by murine macrophages was shown to decrease from 36.6% to 14.7% of the nanoparticles/mg cell protein as the amount of pegylating agent in the formulation increased from 0 to 4 mg/mL. The high loading values and low burst effect observed for these DEX palmitate-containing nanoparticles in addition to their stealth properties are expected to allow for the delivery of sufficient amounts of DEX to tumors to enhance the uptake of chemotherapeutic agents.     

黏着斑激酶及其小分子抑制剂作为抗肿瘤药物的研究进展

抗黏着斑激酶是一种非受体型酪氨酸蛋白激酶,在许多肿瘤的发生和发展过程中均有过表达。研究表明,作为细胞内重要的骨架蛋白和调节多种细胞信号通路的关键分子,黏着斑激酶在肿瘤发生、发展、迁移和侵袭的各个阶段都起着重要作用。因此,以黏着斑激酶作为抗肿瘤靶点开发其抑制剂的研究受到广泛关注。综述黏着斑激酶的结构与功能、它与肿瘤的关联及其小分子抑制剂的研究与开发。     

Effects of diflubenzuron on growth of malignant melanoma and skin carcinoma tumors in mice

Summary The insect growth regulator diflubenzuron (DFB), which may also inhibit growth of imaginal epidermal cells in insects, was studied for antitumor activity in two mouse tumor models of epidermal origin. DFB inhibits chitin deposition, but the mechanisms by which DFB controls chitin deposition or regulates growth of insect epidermal cells are unknown. A single injection of 20 mg (800 mg/kg) of DFB into C57BL/6 mice with B16 malignant melanomas or AKR mice with skin tumors (CA 1025) induced a rapid (24 h) decrease in tumor volume in 78% and 66% of the tumors, respectively. In contrast, 85% of the melanomas and 91% of skin tumors in control mice increased in volume during the same 24-h period. Tumor volume decreased by as much as 55% for about 1% of the tumors, but the median decrease was 20% for both types of tumors. Since control tumors concommitantly increased, DFB-treated tumors decreased, relatively, to 60% of the volume of matched control tumors. After the initial volume decrease, both types of tumors resumed exponential growth resulting in an average growth curve delay, calculated for 12–14 days, of about 2.0 days. Subsequent treatment of melanomas with DFB 24 h after the initial treatment resulted in a further decrease in relative tumor volume to 40–50% of control tumor volume and a growth curve delay of 2.6 days. The most effective regimen used was 5 daily, 20-mg doses of DFB. Melanomas decreased to 40% of control tumor volume after the third injection and the mean growth curve delay was extended to 4.3 days. These data suggest that DFB, one of many benzoylphenyl ureas, has antitumor activity and further that the effects are dose-schedule dependent.     

Newer Neuromuscular Blocking Agents

Four neuromuscular blocking drugs, doxacurium, mivacurium, pipecuronium, and rocuronium have been or are about to be introduced into clinical practice. The purpose of this MiniReview is to describe their pharmacology, to consider their place in clinical anaesthetic practice, and to examine whether the needs of the clinican have been met. Two of the agents (doxacurium, mivacurium) are benzylisoquinolines resembling atracurium and two (pipecuronium, rocuronium) are aminosteroids related to pancuronium and vecuronium. Two (doxacurium, pipecuronium) are long-acting compounds, similar in duration of action to pancuronium, although the need for such a profile is questionable. Rocuronium has an intermediate duration of action and produces its maximum effect within two minutes which is much more rapid than any other non-depolarizing relaxant and this is probably a result of its poor potency. However, the onset of paralysis is not as quick as after succinylcholine. Mivacurium is unique because it is metabolized by plasma cholineslerase which produces a rapid recovery although slower than succinylcholine. All of the new drugs are devoid of serious cardiovascular or other side effects. The anaesthetist is now presented with an armamentarium of safe, non-depolarizing muscle relaxants with varying durations of action. However, the rapid onset and recovery associated with succinylcholine are unique and important in the urgent control of a patient's airway and respiration. The indications for succinylcholine will not disappear and the search for a non-polarizing replacement will continue.     

椎管内肿瘤83例分析

目的 :总结治疗椎管内肿瘤的经验。方法 :回顾分析过去 12a来我科对 83例椎管内肿瘤的手术疗效结果。结果 :本组椎管内肿瘤神经鞘瘤 36例 ,其中 1例恶变 ,占 4 3.4 % ;脊膜瘤 16例 ,占 19.3% ;先天性肿瘤 (皮样囊肿、上皮样囊肿、畸胎瘤 ) 13例 ,占 15 .7% ;脂肪瘤 10例 ,其中 6例合并脊柱裂和脊膜膨出 ,占 12 .0 % ;胶质瘤 5例 ,占 6 .0% ;其他有 :硬脊膜外滑膜囊肿 1例 ,肠源性囊肿 1例 ,囊虫病 1例。肿瘤位于髓外硬脊膜下 6 1例 ,占 73.3% ;硬脊膜外肿瘤 15例 ,占 18.4 % ;脊髓内肿瘤 7例 ,占 8.3%。肿瘤位于胸段者 4 1例 ,占 4 9.4 % ;腰骶段者 2 3例 ,占 2 7.8% ;颈段者 19例 ,占 2 2 .9%。 83例患者均行手术治疗 ,其中显微外科手术 2 9例 ,肿瘤全切 4 8例 ,次全切 16例 ,大部分切除 19例 ,术后症状和体征明显好转 6 9例 ,轻度好转 12例 ,2例术后肢体瘫痪加重。结论 :椎管内肿瘤以良性居多 ,手术效果好 ,显微外科手术的应用尤其是提高疗效的关键     

皮肤科用药中几则药物相互作用的处方分析

目的：探讨皮肤科系统用药中有关药物的相互作用。方法：对我院2008年7～12月药剂师审核中发现的具有潜在药物相互作用的处方进行回顾性分析。结果：共收集有关药物相互作用的处方156张,占不合理用药处方的16．12％,药物相互作用的方式涉及到药剂学、药动学、药效学等多方面因素。结论：药物相互作用是药物不良反应或毒性反应发生的重要原因,研究药物的相互作用对评价临床合理用药具有现实的指导意义。     

常用抗病毒药物的临床应用

抗病毒药物是病毒性感染治疗的主要药物，近年来，随着抗逆转录病毒药物开发，治疗其他病毒感染的药物也得到了发展。本文对临床常用的抗病毒药物(不包括艾滋病和病毒性肝炎)的药理、临床、毒副反应等进行了综述，并对临床常见病毒性感染的治疗方案以及抗病毒药物发展情况做简略介绍。