青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。     

Localization of plasminogen activator and inhibitor, LH and androgen receptors and inhibin subunits in monkey epididymis

Epididymis is a site of sperm maturation and storage. Limited and directed-proteolysis regulated by plasminogen activator (PA), plasminogen activator inhibitor type-1 (PAI-1) and other related factors may play an essential role in these processes. Our previous studies have demonstrated that rat epididymis expressed luteinizing hormone receptor (LHR), tissue type (t) and urokinase type (u)PA, mRNAs, and tPA activity was stimulated in vitro by human chorionic gonoadotrophin (HCG). In the present study we further examined localization of mRNAs for tPA, uPA, LHR, androgen receptor (AR), as well as inhibin subunits alpha, betaA and betaB in rhesus monkey epididymis. Using in-situ hybridization with digoxygenin-labelled cRNA probes, we have demonstrated that tPA and PAI-1 mRNAs were localized in epithelial cells of adult monkey epididymis. uPA mRNA was localized in the same areas, but to a much smaller extent. tPA, uPA and PAI-1 mRNAs were greatly expressed in the caput and corpus of adult epididymis than in other regions. In-vitro experiments showed that both tPA and uPA activities in epididymal cells were dramatically stimulated by HCG, but not by follicle stimulating hormone (FSH). LHR (but not FSH receptor) and AR mRNAs were localized in the epithelial cells of the epididymis. However, LHR mRNA was detected in both adult and immature infant monkeys, whereas AR was found only in the adult. Inhibin alpha, betaA and betaB mRNAs were also detected in this organ, betaA mRNA being more strongly expressed in the caput than in other regions of the epididymis. We suggest that LH and androgen may be the key hormones in coordination with the PA-PAI-1 system in regulating epididymal differentiation and sperm maturation.      

柱前手性衍生化反相高效液相色谱法拆分地佐西平对映异构体的研究

用乙酰葡萄糖异硫氰酸酯(GITC)作柱前手性衍生化试剂,以反相高效液相色谱法成功地拆分了地佐西平对映异构体。在此基础上建立了地佐西平对映异构体纯度和血药浓度测定方法。已用于测定右旋地佐西平的光学纯度和小鼠血药浓度。     

Interleukin-10 is a growth factor for human myeloma cells by induction of an oncostatin M autocrine loop

We have a previously reported that interleukin-10 (IL-10) is a potent but IL-6-unrelated growth factor for freshly explanted myeloma cells (Lu et al, Blood 85:2521, 1995). We have also shown that exogenous IL- 10 supported the growth of XG-1 and XG-2 human myeloma cell lines (HMCL) through an IL-6-independent mechanism. (Lu et al, Blood 85:2521, 1995). Because the IL-10 receptor does not involve the gp 130 IL-6 transducer, we have attempted to elucidate the mechanisms of IL-10 action on myeloma cells. Our results indicate that the myeloma cell growth factor activity of IL-10 was abrogated by an antibody to the gp 130 IL-6 transducer, indicating that it was mediated through one of the gp 130-activating cytokines. We found that myeloma cells from XG-1 and XG-2 HMCL and from 5 of 6 patients' tumoral samples produced oncostatin M (OM) constitutively but failed to produce IL-6, IL-11 and leukemia- inhibitory factor (LIF). The autocrine OM was inactive in the absence of IL-10 due to lack of a functional OM receptor on myeloma cells. IL- 10, by inducing the receptor for LIF (LIFR), produced a functional autocrine OM loop in XG-1 and XG-2 cells and in primary myeloma cells from 2 patients. We also found that some myeloma cell lines (XG-4, XG- 6, and XG-7) an fresh myeloma cells from 3 of 6 patients produced an autocrine IL-10 and that these cells constitutively expressed LIFR. One HMCL (XG-7) produced IL-10, OM, and IL-6 an expressed LIFR. The XG-7 cells used OM and IL-6 as autocrine growth factors. We have previously shown that IL-10 could induce IL-11 receptor in myeloma cells and confer on them sensitivity to IL-11 (Lu et al, FEBS Lett 377:515, 1995). Taken together, these results show that IL-10 is a key cytokine for inducing the expression of LIFR and IL-11R and possibly another uncharacterized OM coreceptor on myeloma cells and that OM and IL-10 might be produced by myeloma cells. They also emphasize that all myeloma cell growth factors reported to data involve an activation of the gp130 IL-6 transducer.     

利福平外用致原位肝移植术后患者过敏反应1例

肝炎后肝硬化患者,原发性肝癌行原位肝移植术,于术后7 d皮肤破溃处涂利福平胶囊粉后出现过敏反应．利福平为临床常用的广谱抗菌素,外用后快速导致过敏反应未见报道, 该病例既往无过敏史,特殊之处在于为原位肝移植术后患者,移植术后用药有很多特殊之处,可供参考的资料不多．抗过敏治疗上以尽快纠正低氧血症对移植肝功能的恢复至关重要．     

大鼠颈动脉球囊损伤后管壁血管内皮生长因子和血管内皮细胞黏附分子1表达及雷公藤多甙的干预

目的:观察不同剂量雷公藤多甙对颈动脉球囊损伤后大鼠血管内皮生长因子、血管内皮细胞黏附分子1的影响,探讨雷公藤多甙在再狭窄防治方面的作用。方法:实验于2006-01/05在上海复旦大学医学院动物实验中心及上海瑞金医院烧伤研究所完成。①实验材料:SPF级SD雄性大鼠32只;雷公藤多甙(复旦复华药业)。②实验分组:随机分为正常对照组、模型组、雷公藤多甙小剂量组、大剂量组各8只。③实验干预:采用右颈动脉内膜剥脱法制备大鼠颈动脉狭窄模型。模型组术后予蒸馏水3mL/(kg·d)灌胃,雷公藤多甙小剂量和大剂量组分别给予雷公藤多甙30,60mg/(kg·d)灌胃。④实验评估:于术后2周麻醉后处死各实验组动物,取材,采用免疫组织化学方法检测大鼠颈总动脉血管内皮生长因子和血管内皮细胞黏附分子1含量。结果:32只大鼠全部进入结果分析。①正常大鼠颈动脉血管壁少量表达血管内皮生长因子,球囊损伤后表达量增加,雷公藤多甙大、小剂量组血管内皮生长因子表达的趋势与模型组基本相同,但表达量较模型组明显增加,雷公藤多甙小剂量组与模型组比较,P<0.05;大剂量组与模型组相比,P<0.01。②正常大鼠颈动脉管壁少量表达血管内皮细胞黏附分子1。球囊损伤后,模型组管壁血管内皮细胞黏附分子1表达增加;雷公藤多甙小剂量组和大剂量组管壁血管内皮细胞黏附分子1表达的趋势与模型组基本相同,但数量明显下降,雷公藤多甙小剂量组与模型组比较,P<0.05,大剂量组与模型组比较P<0.01。结论:雷公藤多甙能有效促进内皮细胞生成,减少内皮细胞间的黏附,对大鼠血管球囊损伤后的狭窄有一定的防治作用。