金翼黄芪甙A的化学结构和绵毛黄芪甙ⅩⅤ及7,2′-二羟基-3′,4′二甲氧基异黄烷-7-O-β-D-葡萄糖甙二维核磁共振谱的研究

从金翼黄芪中分离出金翼黄芪甙A(Ⅰ),绵毛黄芪甙XV (Ⅱ),7,2′-二羟基-3′,4′-二甲氧基异黄烷-7-O-β-D-葡萄糖甙(Ⅲ),大豆皂甙Ⅰ,胡萝卜甙及β-谷甾醇。Ⅰ为新化合物,确定其结构为3-O-[α[-L-鼠李吡喃糖基(1→2)-D-木吡喃糖基]-环黄芪醇。并应用二维核磁共振相关谱对Ⅱ和Ⅲ的~1H和~(13)C化学位移信号进行了全面归属。     

3'-Deoxythymidin-2'-ene permeation of human lymphocyte H9 cells by nonfacilitated diffusion.

3'-Deoxythymidin-2'-ene (d4T) is a potent and selective inhibitor of human immunodeficiency virus replication in a variety of human cell types and is currently undergoing phase I clinical trials for the treatment of acquired immunodeficiency syndrome. As part of our ongoing studies of the cellular pharmacology of d4T, and in light of recent reports in which such nucleoside analogs as 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyadenosine were shown to permeate cells by the unusual mechanism of nonfacilitated diffusion, we have investigated the uptake of d4T in the human lymphocyte cell line H9. Several lines of evidence suggest that d4T permeation of H9 cells occurs by nonfacilitated diffusion; 1) [3H]d4T influx was linear for the first 10 sec and was nonconcentrative, reaching equilibrium with the extracellular drug concentration in 2-3 min, 2) the initial rates of influx were a linear function of concentration over the range from 1 microM to 5 mM, with no sign of uptake by a saturable mechanism, and 3) the uptake of [3H]d4T was insensitive to the nucleoside transport inhibitors nitrobenzylthioinosine and dipyridamole, as well as a large molar excess of AZT, thymidine, or adenosine. The octanol/water partition coefficient of d4T was 0.179, intermediate between those of thymidine and AZT. Thus, d4T does not appear to be a substrate for the nucleoside transport system responsible for the uptake of physiological nucleosides as well as most nucleoside analogs, and it enters the cell by nonfacilitated diffusion.     

核苷酸还原酶抑制剂抗癌活性与电子结构的关系

用CNDO/2量化方法计算了32个异羟肟酸化合物、6个酰胺化合物和9个羧甲酯类化合物的电子结构,对其中的44个化合物的量化指数与其抑制核苷酸还原酶的活性参数PC进行逐步回归计算,得到关于异羟肟酸化合物、酰胺类化合物和羧甲酯类化合物的二个QSAR,由QSAR表明化合物抑制核苷酸还原酶的机制是络合机制。同时,用模式识别方法研究了其中35个化合物的结构对治疗患L₁₂₁₀肿瘤小鼠药效的影响,得到满意的分类图,结果表明化合物的抗癌活性是通过抑制核苷酸还原酶所致,但化合物在体内到达受体的过程和难易程度对药效的影响较大。     

氯胺酮和硝苯吡啶对培养神经元谷氨酸兴奋毒性的保护作用

以体外培养的大鼠胚胎皮层神经元为对象,以培养上清液中乳酸脱氢酶活性为指标,研究了谷氨酸兴奋毒性及药物的保护作用。结果表明,培养10d的皮层神经元置于含10或50μmol·L^-1谷氨酸和低糖(1g·L^-1)的DMEM培养液中后,随着作用时间的延长,LDH漏出逐渐增加。在谷氨酸处理前,于培养液中加入氯胺酮或硝苯吡啶,则LDH漏出量明显低于对照组。氯胺酮和硝苯吡啶并用,LDH漏出量比单独使用氯胺酮或硝苯吡啶下降更加明显。结果表明,谷氨酸对培养的神经元可产生严重损伤。氯胺酮和硝苯吡啶单用或并用均有明显的保护作用。     

Pericardial haemangiosarcoma in a horse

A primary pericardial haemangiosarcoma with metastasis to the parietal pleura and left adrenal gland is described in a 22-year-old Clydesdale x Percheron gelding. Although haemangiosarcomas have been reported in horses, the pericardium has not hitherto been described as the primary site of origin.     

Administration of dexamethasone induces proteinuria of glomerular origin in mice

The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration. One fourth of mice also intermittently presented with slight hematuria beginning on day 12. Renal lesions in the dexamethasone-treated mice, which were killed on day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme inhibitor. Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice.