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。     

取代四氢异喹啉衍生物的合成及其生物活性

粉防己碱有钙拮抗作用,临床试用于治疗高血压,其裂解产物钙拮抗作用降低,但有α-肾上腺素能受体拮抗作用,本文以裂解物为先导化合物设计合成了两类取代的四氢异喹啉衍生物Ⅲ及Ⅳ。初步药理试验表明:大部分化合物有α-肾上腺素能受体拮抗作用,少数化合物钙拮抗活性有所增强,其中Ⅲ_15,19对正常麻醉大鼠有一定的降压作用、Ⅳ_17,19对实验性动物心律失常有明显的保护作用。部分化合物量化计算表明:化合物与α₁-受体作用方式可能是形成电荷转移复合物。     

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.      

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．     

乐脉颗粒促进鸡胚绒毛尿囊膜血管的生成

目的:乐脉颗粒在缺血性心脑血管病的治疗中具有较好的效果,其是否通过促进血管生成而发挥作用还不清楚。观察乐脉颗粒对鸡胚绒毛尿囊膜血管生成的影响。方法:实验于2005-03/08在江西省重点实验室南昌大学第二附属医院分子中心完成。①实验材料:新西兰大白兔8只,体质量2～2.5kg;新鲜白皮种蛋70只,质量50～60g。②实验方法:种蛋在(37.5±0.5)℃条件下孵育,种蛋受精率90%以上。第7天开窗暴露鸡胚绒毛尿囊膜建立鸡胚绒毛尿囊膜模型。将60枚存活鸡胚随机分为生理盐水组、正常血清组、乐脉血清组、内膜损伤血清组、内膜损伤乐脉治疗组以及血管内皮生长因子(20mg/L)组,每组10枚鸡胚。新西兰大白兔腹主动脉用球囊导管损伤建立血管内膜损伤模型,乐脉血清组及内膜损伤乐脉治疗组给予乐脉颗粒25mg/(kg·d)喂饲,各组7d后取血清。第8天,在鸡胚绒毛尿囊膜上放一直径为5mm的滤膜作为载体,分别加样5μL,1次/d,连续3d,③实验评估:第11天取鸡胚绒毛尿囊膜,数码相机拍照后平铺于载玻片上,计数载体周围血管数目及滤膜周围0.5cm范围内的血管分支点数并进行比较。结果:纳入大白兔8只,存活鸡胚60枚,均进入结果分析,无脱落。与正常血清组相比较,乐脉血清组鸡胚绒毛尿囊膜周围血管总数明显增多,血管以载体为中心呈辐辏状生长,差异具有显著性意义(P<0.05);与正常血清组相比较,内膜损伤血清组血清载体周围血管数量明显增多,差异具有极显著性意义(P<0.01);与内膜损伤乐脉治疗组相比较,血管总数差异无显著性。结论:①兔乐脉颗粒血清能够明显促进鸡胚绒毛尿囊膜上血管生成。②血管内膜损伤7d后的血清能够促进鸡胚绒毛尿囊膜上血管生成。