新型酰胺类局部麻醉药阿替卡因

阿替卡因是一种新的酰胺类药物，最初于1969年由Rusching等制成成药．1976年在德国用于临床，1983年进入加拿大及美国北部，1998年进入英联邦国家，1999年进人中国市场。日前美国的大多数牙科，4％阿替卡因加1：200000肾上腺素替代了常用的2％利多卡因加1：100000肾上腺素。在德国．阿替卡因占牙科局麻药物的80％。     

Long-term application of diethylstilbestrol upregulates expressions of μ- and m-calpains in pituitary intermediate lobe of female Wistar rats

BACKGROUND: During formation of prolactin neoplasia, how cells and its structure in adenohypophysis affect prolactin cells should be further studied. Intermediate lobe can be regarded as a driving region to release prolactin (PRL) and may promote formation of prolactin neoplasia in pituitary anterior lobe. OBJECTIVE: To observe the effect of diethylstilbestrol (DES) on the expressions of μ and m-calpains in pituitary intermediate lobe of female Wistar rats. DESIGN: Observational contrast animal study. SETTING: Beijing Neurosurgical Institute. MATERIALS: A total of 21 female Wistar rats, 3 weeks old weighing 70–80 g were housed with free access to tap water and standard pellet food. They were kept in a CL-grade condition, at (24±1)℃ and a humidity of (55±5)%, and with a 12 hours day-night cycle. Caprine anti-μ- and m-calpains antibodies were provided by Santa Cruz Biotechnology, CA, USA; rabbit-anti-PRL antibodies by Dako, Denmark; rabbit-anti-ACTH antibody by Boster Company, Wuhan. METHODS: The experiment was carried out in Pathophysiological Department and Animal Laboratory, Beijing Neurosurgical Institute from August 2006 to January 2007. ① Rats were randomly divided into groups with 7 in each group, including vehicle control group, in which rats were injected intraperitoneally with sun-flower seed oil (1 mL/kg, twice a week) for 16 weeks; DES group, where animals were administered with DES (5 mg/kg, twice a week) for 16 weeks; DES + vehicle control group, in which DES was administered for 12 weeks at the same dose with those in DES group, and then was discontinued and replaced by sun-flower seed oil (1 mL/kg, twice a week) for the following 4 weeks. ② At 16 weeks later, pituitary tissue was dealt with HE staining and PRL immunohistochemical examination to observe evoke of tumor; meanwhile, immunohistochemical examination was used to observe expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. MAIN OUTCOME MEASURES: ① Expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. ② Morphological observation of pituitary tissue. RESULTS: All 21 rats were involved in the final analysis. ① Results of immunohistochemical examination: Morphological changes of neoplasia in DES group were strongly positive to PRL, and this suggested that formation of prolactin adenoma was observed in pituitary tissue. As compared with vehicle control group, expression of adrenoeorticotropic hormone (ACTH) was increased in both DES group and DES + vehicle control group. In addition, expressions of μ- and m-calpains in pituitary intermediate lobe were higher in DES group than that in vehicle control group. Otherwise, expressions of m-calpains in pituitary intermediate lobe was decreased in DES + vehicle control group, but expression of μ-calpains was still increased. ② Morphological observation of pituitary tissue: Gland tubes were orderly arranged in rats in vehicle control group. Anterior pituitary gland in rats of DES group demonstrated an apparent disappearance of gland tubes and a relatively large-scaled vasculature formation, namely the vascular lake lined by tightly arranged endothelial cells. Local integrated tumor cell arrangements were also detected. In addition, the border between the IL and the anterior lobe was locally blurred. The definite tumor-like changes in pituitary tissues were confirmed in 6 of 7 female Wistar rats in DES group, and one spontaneous occurrence of tumor formation was found in vehicle control group. In DES + vehicle control group, DES withdrawal led to the subtile emergence of gland tube cavity, although tumor-like cells still existed in 4 of 7 rats, suggesting occurrence of the tumor regression due to the withdrawal of DES. CONCLUSION: A long-term application of DES can enhance the expressions of ubiquitours neutral cysteine protease in pituitary intermediate lobe and this suggests that both of them play a key role in release of hormone and formation of prolactin neoplasia through directly promoting PRL expression and release of neighboring pituitary intermediate lobe.     

大鼠肾γ-GT的分离提纯及其免疫化学的初步研究

本文报告正常大鼠肾γ—GT的分离提纯,主要的程序为:超速离心,脱氧胆酸钠和Triton X—100增溶,丙酮沉淀,硫酸铵分级分离,ConA—Sepharose亲和层析。最终产物提纯倍数为83倍,聚丙烯酰胺凝胶电泳呈现一条带。由纯化的γ—GT制备的抗血清可以完全抑制大鼠肝、肾及肝癌肝的γ—GT活性。     

硬膜外混合不同浓度舒芬太尼分娩镇痛时罗哌卡因的半数有效浓度

目的测定产妇硬膜外分娩镇痛时不同浓度舒芬太尼混合罗哌卡因的半数有效浓度(EC50),寻找舒芬太尼混合罗哌卡因的适宜浓度。方法100例ASAⅠ或Ⅱ级的足月初产妇,妊娠37～42周,随机分为2组:0.4μg/ml舒芬太尼混合罗哌卡因组(A组)(n=45)和0.6μg/ml舒芬太尼混合罗哌卡因组(B组)(n=55)。2组均在宫口扩张至2～3 cm时行硬膜外穿刺,置管。2组第1例产妇罗哌卡因浓度均为0.12%,随后的罗哌卡因浓度按序贯法确定:即前1例若镇痛有效(注药后30 min时VAS评分≤3分)。则下1例接受的药物降低一个浓度梯度,若镇痛无效,则上升一个浓度梯度,浓度梯度0.01%。若镇痛效果可疑,则下1例接受的药物维持原浓度,计算罗哌卡因的EC50及其95%可信区间。观察镇痛期间发生的不良反应。结果A组、B组皮肤瘙痒发生率分别为11.9%、29.4%(P< 0.05),A组、B组各有1例发生恶心呕吐(P>0.05)。A组罗哌卡因的EC50为0.059%(95%可信区间为0.056%～0.062%),B组罗哌卡因的EC50为0.054%(95%可信区间为0.053%～0.055%)。结论硬膜外混合0.4、0.6μg/ml舒芬太尼分娩镇痛时,罗哌卡因的EC50分别为0.059%、0.054%;舒芬太尼的推荐浓度为0.4μg/ml。     

番荔枝酰胺的全合成研究

番荔枝(Annona squamosa)是番荔枝科番荔枝属植物,有抗菌和抗肿瘤作用。番荔枝酰胺(squamosamide)是从该植物中提取得到的一个新化合物。为进一步探明该化合物的药理活性,进行了全合成研究工作。经七步反应首次制得天然目标物,总收率14%。     

黄皮酰胺促钾通道开放

一种新发现的具有促智作用的药物——黄皮酰胺能抑制去甲肾上腺素(NE)或KCl引起的血管平滑肌收缩。本研究旨在应用膜片钳(patch clamp)技术探讨黄皮酰胺对Wistar大鼠尾动脉平滑肌细胞膜钾离子通道的作用。单个平滑肌细胞用酶法分离,以细胞封接方式记录离子通道活动。在细胞池内注入2μM黄皮酰胺后,钾离子通道活动明显增强。用本实验室开发的计算机软件(patch clamp analysis system,Version 1.0)计算分析通道活动的特征参数。     

HIV-1整合酶抑制剂的研究进展

HIV 1中病毒编码的酶有三种 ,即逆转录酶、蛋白酶和整合酶。目前 ,FDA已批准上市了 9个逆转录酶抑制剂和 6个蛋白酶抑制剂 ,虽然对整合酶有抑制作用的化合物很多 ,但到目前为止还没有一个上市。　　抗逆转录病毒组合疗法 (有效的逆转录酶抑制剂和蛋白酶抑制剂的联合用药 )可以抑制HIV 1的复制 ,在被感染者血浆中两年多都检测不出病毒来。但病毒仍存在于某些细胞中 ,例如周边血液的单核细胞和休眠的T 淋巴细胞 ,处于早期复制阶段后的潜伏状态。从组合疗法 1 995年应用于临床以来 ,事实证明用这种疗法能控制HIV 1感染但不能根除。此外 ,…     

三甲氧桂皮酰胺类化合物的抗惊和镇静作用

观察了三个三甲氧桂皮酰胺类化合物:3,4,5-三甲氧桂皮酰异丙胺(8701)、3,4,5-三甲氧桂皮酰环戊胺(8702)和3,4,5-三甲氧桂皮酰另丁胺(8703)的抗惊和镇静作用,发现8701具有明显的影响。它能有效的对抗最大电休克发作、戊四唑和印防己毒素所引起的惊厥,但对士的宁惊厥无效。8702和8703对上述实验性癫痫均无明显影响。8701抗戊四唑惊厥作用的机制可能与其对中枢神经递质NE和5-HT的影啊有关。     

乙二胺羟丙基壳聚糖固定化天门冬酰胺酶的研究

研制了新型壳聚糖胺基衍生物-乙二胺羟丙基壳聚糖（EDA-HPCS）,并将其用于固定天门冬酰胺酶,分别考察了甲醛活化载体和戊二醛活化载体对固定化酶活力的影响,结果表明,在适当的固定化条件下,甲醛活化EDA-HPCS的固定化酶活力约为30U/g载体,而戊二醛活化EDA-HPCS固定化酶活力约为16U/g载体。     

蒺藜果实化学成分及其抗氧化活性研究

目的 研究蒺藜Tribulus terrester果实的化学成分及其抗氧化活性。方法 综合利用硅胶柱色谱、Sephadex LH-20凝胶柱色谱等分离手段进行分离纯化;结合NMR、MS、IR、UV等波谱学技术来鉴定化合物的结构;通过DPPH法、ABTS法以及羟基自由基清除方法测定化合物的抗氧化活性。结果 从蒺藜果实75%甲醇提取物中分离鉴定了10个化合物,分别为(E)-4-hydroxy-N-(3-(4-hydroxy-3-methoxyphenyl)acryloyl)benzamide(1)、蒺藜酰胺（2）、海柯皂苷元（3）、25R-螺甾-4-烯-3,12-二酮（4）、槲皮素（5）、3,4’-二羟基-3’-甲氧基苯丙酮（6）、对羟基苯甲酸（7）、(9Z,11E)-13-hydroxy-9,11-octadecadienoic acid(8)、(8E,12Z)-10-hydroxy-8,12-octadecadienoic acid(9)、肉豆蔻酸（10）,其中化合物1～6对DPPH、ABTS自由基以及羟基自由基均有较显著的活性,并且化合物5清除ABTS自由基和羟基自由基半数抑制浓度（...