溶剂纯度及吸收池品质对紫外测定的影响

目的：考察溶剂纯度及吸收池对紫外测定的影响。方法：选择不同品质的吸收池有不同纯度的溶剂在三台紫外仪器上作对照实验。结果：不同品质吸收池自身的紫外光吸收存在着差异性,这种差异性将直接影响溶剂是否符合紫外测定的要求,当溶剂含“醛与酮”超标时将使供试液测定波长发生位移,吸收度发生改变。结论：溶剂纯度及吸收池品质都会影响紫外测定的结果。     

相对分子质量及取代度对寡聚精氨酸壳聚糖体外透皮吸收促进作用的影响

摘 要 目的： 考察相对分子质量（Mr）及取代度对寡聚精氨酸壳聚糖（CS-R9）体外透皮吸收作用的影响。方法: 分别以低、中、高Mr的壳聚糖（LCS、MCS、HCS）为原料,合成具有相近取代度的LCS-R9、MCS-R9、HCS-R9;以LCS为原料,通过改变CS与R9的摩尔比,合成具有不同取代度的LCS-R9-1、LCS-R9-2、LCS-R9-3;以替硝唑（TNZ）为模型药物,采用Franz扩散池法,考察各种CS-R9的体外透皮促进作用。结果:经过FTIR、¹H-NMR的图谱分析,可以确定本实验所合成的LCS-R9-1、MCS-R9、HCS-R9、LCS-R9-2、LCS-R9-3的取代度分别为2.30,2.17,2.20,8.05,15.87;与空白组、氮酮组、LCS组、R9组、LCS+R9组等对照组相比,LCS-R9-1对TNZ有明显的透皮促进作用（P<0.05）;当取代度相似,CS的Mr不同时,12 h之内,LCS-R9-1与HCS-R9的促进作用相似,均明显大于MCS-R₉（P<0.05）;12-24 h,HCS-R9的作用有下降趋势,但与LCS-R9-1比较,差异无统计学意义（P>0.05）;当CS的Mr相同,而取代度不同时,21 h内,促进作用随着取代度的增加而增加,之后,则呈相反趋势。结论: Mr及取代度对CS-R9的透皮吸收促进作用有较大影响,值得进一步研究其体内作用规律及相关机制。     

GC法测定羟乙基淀粉摩尔取代度的研究

目的对气相色谱法(GC)测定羟乙基淀粉摩尔取代度进行研究。方法色谱柱为DB-624石英毛细管柱(L=60 m,=0.53 mm),FID检测器;进样口温度为200℃,检测器温度为280℃;柱温采用程序升温,载气为氮气,流速为8 mL.min-1,分流比为1∶20。以甲苯为内标物。结果对照品碘乙烷在0.30～2.1 mg.mL-1(r=0.999 9)范围内呈良好线性关系。反应温度、时间对测定结果影响显著,最佳反应条件为135℃反应15 h;样品水分、氯化钠含量对测定结果无影响。结论该方法测定结果准确,简便快捷,适合羟乙基淀粉摩尔取代度的测定。     

不同取代度的寡聚精氨酸壳聚糖的合成与鉴定

目的合成不同分子量、不同取代度的寡聚精氨酸壳聚糖（CS-PR）,并对其化学结构及取代度进行鉴定。方法用高分子量壳聚糖（HCS）、低分子量壳聚糖（LCS）和寡聚精氨酸（R9）为主要原料,通过改变反应物的摩尔比,合成不同取代度CSPR,应用FTIR及1H-NMR对其结构及取代度进行分析。结果通过改变反应物的摩尔比,获得了取代度为0.96和1.87的HCS-R9,以及取代度为2.61和10.10的LCS-R9。结论不同分子量不同取代度的CS-PR合成成功,为进一步实验奠定了基础。     

HPLC法对天麻素纯度标准物质的定值与不确定度研究

目的：对研制的天麻素纯度标准物质建立化学纯度定值分析方法,并进行不确定度评估.方法：根据我国标准物质研制技术规范和国家计量相关法规要求,进行基于HPLC法的天麻素纯度标准物质的化学纯度标准值分析与不确定度评估.结果：研制的天麻素纯度标准物质化学纯度标准值及不确定度值为99.79％±0.15％（k=2,P=0.95）.结论：采用HPLC法可实现对天麻素的化学纯度进行定值分析与不确定度评估,研究结果可为其他药物或天然产物的标准物质定值及不确定度研究提供科学参考依据.     

不同方法对氨基比林纯度联合定值及不确定度评定

摘 要 目的：采用两种不同原理方法对氨基比林纯度联合定值,并建立其不确定度评定方法。方法: 采用高效液相色谱法（HPLC）与酸碱滴定法对氨基比林纯度进行测定,并依据标准物质技术规范及相关计量技术规范要求,对两种不同原理方法测定过程的不确定度进行系统分析。结果:采用HPLC与酸碱滴定法联合测定氨基比林纯度的标准值及其不确定度为99.66%±0.08%（k=2,P=0.95）。结论:采用HPLC与酸碱滴定法联合测定氨基比林纯度及不确定度评定结果准确可靠,避免了采用一种技术带来的分析方法缺陷,有利于提高氨基比林的质量评价与控制水平,同时对氨基比林纯度标准物质的研制提供科学依据。     

羧甲基-β-环糊精取代度对毛细管电泳手性拆分的影响

目的:研究羧甲基-β-环糊精取代度对毛细管电泳手性拆分影响。方法:以氯醋酸为羧甲基化试剂,通过调整物料比例合成了3种不同取代度的羧甲基-β-环糊精,并通过核磁共振直接对它们的平均取代度和取代位置进行表征;以萘哌地尔和吲哒帕胺为模型化合物,考察了不同取代度的羧甲基-β-环糊精对毛细管电泳手性拆分的影响。结果:随着羧甲基-β-环糊精取代度的增大,萘哌地尔分离随之改善;相反,吲哒帕胺对映体在较低取代度的羧甲基-β-环糊精条件下获得良好分离。结论:羧甲基-β-环糊精的取代度对毛细管电泳手性拆分和运行缓冲液的离子强度有重要影响,因此在手性分离中使用表征清晰的环糊精衍生物是至关重要的。     

瑰及乳膏中白及多糖的体外释放度考察

目的考察瑰及乳膏的体外释放度,为合理用药提供依据。方法以无水葡萄糖为对照品、白及多糖为指标、生理盐水为释放介质、0.2%蒽酮-硫酸试液为染色剂,采用透析袋法研究瑰及乳膏的体外释药特性。结果 10 h内白及多糖累积释放度为84.2%,为速释期;在12 h以后其释放度为15.8%,为缓释期;48 h内累积释放度为97.9%。结论瑰及乳膏具有缓释特性,每10 h使用一次可保持疗效。透析袋法用于瑰及乳膏的体外释放度考察,操作便利、方法稳定、结果可靠。     

取代度对灯盏花素羧甲基壳聚糖鼻黏膜微球体外释药的影响

摘要：目的:探讨羧甲基壳聚糖（CMCS）的取代度对灯盏花素（BRE）鼻黏膜微球体外释药速度的影响。方法:合成取代度分别为40%,60%,80%的CMCS,并进行取代度检测及红外分析。分别以取代度为40%,60%,80%,95%的CMCS为载体,制备BRE微球,并对其体外释药、空白CMCS微球溶蚀及两者之间的关系进行研究。结果:合成得到3种CMCS的取代度分别为（41.60±1.44）%,（59.39±2.15）%,（80.72±2.38）%。当CMCS的取代度分别为40%,60%,80%,95%时,BRE微球体外释药均呈现缓释特性,分别符合Higuchi方程:累积释放度（Q,%）=41.49t1/2-11.66（R2=0.984 3）,Q=39.74t1/2-12.82（R2=0.991 6）,Q=35.35t1/2-10.89（R2=0.992 8）,Q=31.12t1/2-8.80（R2=0.990 2）;空白CMCS微球溶蚀分别符合Higuchi方程:累积溶蚀量（A,%）=39.25t1/2-10.97（R2=0.984 0）,A=37.59t1/2-12.04（R2=0.990 4）,A=33.61t1/2-10.61（R2=0.992 5）,A=29.41t1/2-8.32（R2=0.989 6）。释药与CMCS溶蚀之间均呈现高度一致的线性相关性,且随着CMCS取代度的增加,BRE微球体外释药速度逐渐减慢。结论:CMCS取代度对BRE鼻黏膜微球的体外释药有明显的影响,取代度越高,释药越慢,缓释效果越明显。     

霸王花药材HPLC指纹图谱研究

目的:建立霸王花药材的HPLC指纹图谱分析方法。方法:采用高效液相色谱法对10批霸王花药材进行分析。色谱条件:Phonemenex Luna PFP色谱柱(250 mm×4.6 mm,5μm),乙腈-甲醇-0.2%甲酸水溶液梯度洗脱,流速1.0 mL.min-1,检测波长为360 nm,柱温35℃。结果:10批药材的相似度均在0.92以上,建立了霸王花药材的HPLC指纹图谱,确定了18个共有峰,并利用对照品对照法和LC-MS法对其中的10个共有峰进行了成分指认。结论:本法准确、简便,重现性好,可用于霸王花药材的定性鉴别。     

小儿心血管临床专业学位研究生培养模式探索

临床专业学位研究生培养模式在实现复合型、应用型、高层次临床医学专业人才方面发挥着重要作用。小儿心血管临床医学较其他专业而言,有其多学科交叉的特殊性,怎样达到其临床专业学位研究生的培养目标,需要一个全面规范的培养体系,首都医科大学附属北京安贞医院在小儿心血管临床专业研究生培养方面结合国内外经验并经过长期探索实践,在系统培训和督导评估方面形成合理规范的培养模式,值得推广,对未来学科发展具有重要现实意义。     

下瘀血汤中大黄生熟互换对热结血瘀模型大鼠血管内皮功能及微循环的影响

目的 研究下瘀血汤中大黄生熟互换对热结血瘀模型大鼠血管内皮功能及微循环的影响。方法 采用ig 热性中药结合sc 盐酸肾上腺素的方法,复制热结血瘀大鼠模型。大鼠ig 热性中药28 d,第22 天起sc 盐酸肾上腺素,并ig 相应的药物。第29 天,眼眶取血检测检测血管内皮素（ET）、一氧化氮（NO）、前列环素（PGI₂）、血管性血友病因子（vWF）;股动脉取血,检测血液流变学各项指标。结果 含生大黄（复方A）和熟大黄（复方B）下瘀血汤均具有改善热结血瘀模型大鼠血液流变学、血管内皮细胞损伤和微循环的作用;与复方A 相比,复方B 各剂量组对血液流变学各指标、ET、NO、PGI₂、vWF 因子水平具有显著的改善作用（P<0.05、0.01）。结论 含熟大黄下瘀血汤的活血化瘀作用更强,可能是通过调节ET、NO、PGI₂、vWF 因子水平而实现的。     

熊去氧胆酸联用思美泰对妊娠期肝内胆汁淤积症患者生化指标及瘙痒程度的影响

目的 分析熊去氧胆酸联用思美泰对妊娠期肝内胆汁淤积症（ICP）患者生化指标及瘙痒程度的影响.方法 选择医院ICP患者129例,随机均分为3组,分别给予熊去氧胆酸、思美泰单用及联合使用,比较其肝脏相关生化指标、瘙痒评分及缓解时间、妊娠结局等情况.结果 联合用药组患者治疗后丙氨酸氨基转移酶（46.12±14.25）U/L,天门冬酸氨基转移酶（43.18±11.25）U/L,总胆汁酸（12.04±4.92）μmol/L,总胆红素（13.29±3.84）μmol/L,平均瘙痒评分（2.01±0.54）分,平均瘙痒缓解时间（3.13±0.74）d,妊娠不良结局发生率2.33％,均明显低于对照组;联合用药组的平均结束妊娠孕周（37.04±1.23）周,明显长于单独用药组（P＜0.05）.结论 熊去氧胆酸联用思美泰可有效改善ICP患者的肝功能指标,缓解瘙痒程度,改善妊娠结局,具有积极的临床意义.     

Separation and partial characterization of smooth muscle contractile material in the venom of the scorpion Heterometrus bengalensis

P. K. Kar, B. Sarangi, A. Datta, A. Gomes and S. C. Lahiri. Separation and partial characterization of smooth muscle contractile material in the venom of the scorpion Heterometrus bengalensis. Toxicon21, 353 – 361, 1983. — A smooth muscle contractile material was separated from crude venom of the scorpion Heterometrus bengalensis (found in Eastern India) by solvent extraction, gel filtration and thin layer chromatography. Smooth muscle contractile material could be extracted, in descending order of efficiency, with methanol, butanol, ethanol and acetone. The contractile material separated by gel filtration (Sephadex G-25) when further extracted, using the Folch procedure, showed a single spot in thin layer chromatography with one solvent system. Rechromatography of an eluate from this spot with another solvent system resolved it into three spots (SL1, SL2 and SL3, the mixture being designated as Substance L) which could be visualized either with iodine vapour, ninhydrin or molybdenum reagent. Eluates from the three spots contracted guinea-pig ileum which had been pretreated with antagonists of ACh, histamine, 5-HT and prostaglandins. Substance L and its fractions (SL1, SL2 and SL3) contain inorganic phosphorus, amino nitrogen and amino sugar, which point to the likelihood of their being glycophosphatides.     

The ameliorating effect of the extract of the flower of Prunella vulgaris var.lilacina on drug-induced memory impairments in mice

Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and its flowers are used to treat inflammation in traditional Chinese medicine. In the present study, we studied the effects of the ethanolic extract of the flower of P. vulgaris var. lilacina (EEPV) on drug-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. EEPV (25 or 50 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (P < 0.05). In the Morris water maze task, EEPV (25 mg/kg, p.o.) significantly shortened escape latencies in training-trials. Furthermore, swimming times within the target zone during the probe-trial were significantly increased as compared with scopolamine-treated mice (P < 0.05). In addition, the reduced latency induced by MK-801 treatment in the passive avoidance task was ameliorated by EEPV (25 mg/kg, p.o.) (P < 0.05). Additionally, the ameliorating effect of EEPV on scopolamine-induced memory dysfunction was antagonized by a sub-effective dose of MK-801. These results suggest that EEPV would be useful for treating cognitive impairments induced by cholinergic dysfunction, and that it exerts its effects via NMDA receptor signaling.     

Effect of Asparagus polysaccharide on the number and activity of erythrocyte complement receptor 1 (CD35) of S_(180) mice

Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat anti-mouse CD35 monoclonal antibody and FITC-conjugated goat anti-mouse antibody.Using flow cytometry,we determined the number of ECR1.Using microscope,we studied the adherence between erythrocyte immunity and C3b receptor or tumor-cell by RBC-C3bRR and DTER.Results Comparing the mean value of the number of CR1 on each RBC of high and middle groups with control groups,the mean value of the number of CR1,RBC-C3bRR and DTER of Asparagus officinalis polysaccharide groups are increased significantly.Conclusions Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice,which may be one of its most important antitumor mechanisms.     

Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro

Tea drinking is widely practiced in the world and has recently increased among cancer patients. However, the effects of concurrent consumption of tea on the bioavailability and the net therapeutic potential of co-administered chemical drugs are not clear. In this study, the effects of green tea on the pharmacokinetics of 5-fluorouracil (5-FU) in rats and the pharmacodynamics in human cell lines in vitro were studied. The pharmacokinetic experiment indicated that there was an approximately 151% increase in the maximum plasma concentration (C_max) and an approximately 425% increase in the area under the plasma concentration curve (AUC) of 5-FU in the green tea-treated group compared with the control group. Green tea consumption increased the plasma concentration of 5-FU. In addition, the pharmacodynamics experiment showed that at the moderate dose level (equivalent to <6 cups daily in human), neither fresh green tea extract nor (−)-epigallocatechin-3-gallate (EGCG) showed significant additive effects on the cytotoxicity of 5-FU in human cell lines. The results showed that it is crucial to perform therapeutic drug monitoring (TDM) when the cancer patients have a habit of drinking green tea.     

The neuroprotective effects of the seeds of Cassia obtusifolia on transient cerebral global ischemia in mice

The aim of this study was to determine the mechanism underlying the neuroprotective effects of the ethanolic extract of the seeds of Cassia obtusifolia (COE) (10 or 50 mg/kg/day, p.o) on transient cerebral global ischemia induced by bilateral common carotid artery occlusion (2VO) in mice. Immunohistochemical and western blot studies showed that levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the hippocampal CA1 region at 1 day post-2VO were attenuated by COE (50 mg/kg/day, p.o), which was administered immediately after 2VO. Furthermore, OX-42 – and glial fibrillary acidic protein (GFAP)-positive cell numbers at 4 days post-2VO were markedly attenuated by COE (50 mg/kg/day, p.o) treatment for 4 days in CA1. Viable neurons detected by Nissl at 7 days post-2VO were increased by administering COE (50 mg/kg/day, p.o) for 7 days. In addition, COE increased the expressions of phosphorylated cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in CA1 in naïve-control within 1 and 6 h, respectively, and these expressions were also profoundly increased in 2VO-treated mice by COE at immediately post-2VO. These results suggest that the neuroprotective effects of COE are due to its anti-inflammatory effects and to its upregulation of BDNF expression and CREB phosphorylation.     

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.