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。     

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.     

高频彩色多普勒超声在乳腺硬化性腺病中的应用

目的探讨乳腺高频彩色多普勒超声检查超声乳腺影像报告和数据系统（BI—RADS）分级诊断标准在硬化性腺病中的诊断和治疗中的应用。方法回顾性分析经手术病理证实为良性病变的且有完整资料的BI-RADS3级和4级患者共68例,其中包括病理证实为硬化性腺病的33例患者与病理证实为其他良性病变的35例患者,并将BI—RADS3级和4级良性病变的超声表现进行比较。结果33例硬化性腺病患者（37个病灶）中,BI—RADS分级3级31个,4级6个。35例其他良性病变患者（42个病灶）中,BI—RADS分级3级41个,4级1个。结论在乳腺高频彩色多普勒超声检查中,应用BI—RADS分级诊断标准对硬化性腺病进行临床诊断具有重要意义。     

Differences in neuroplasticity after spinal cord injury in varying animal models and humans

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.