缺血性脑血管病与颈动脉粥样硬化及其危险因素的关系

目的探讨缺血性脑血管病(ICVD)与颈动脉粥样硬化及其危险因素的关系。方法对186例ICVD患者与194例非脑血管病患者和正常体检者(对照组)行颈部血管超声检查和血液生化检查;比较两组间的颈动脉硬化程度及脑卒中危险因素的差异。结果ICVD组年龄[(69±7)岁]和患有高血压(66.1%)、糖尿病(53.4%)、代谢综合征患者(44.6%)的比率非常明显高于对照组[(61±5)岁、48.8%、15.2%、12.9%](均P<0.001)。ICVD组颈动脉粥样硬化分级计分≥2分(斑块发生率)、≥3分(血管狭窄发生率)分别为69.3%、20.4%,明显高于对照组的33.5%和5.1%(均P<0.05)。结论颈动脉粥样硬化是ICVD的危险因素之一;各种危险因素的聚集对ICVD的发生起重要作用。     

重组人血小板因子4的表达、纯化及活性鉴定

目的: 用基因工程手段去获取有活性的重组人血小板因子4(rhPF4),为下一步的基础理论研究和临床应用奠定基础.方法: 用PCR手段获得人PF4的编码序列,克隆入质粒pRSET,构建融合表达载体pRSET-PF4,转化大肠杆菌,以IPTG诱导表达融合的人PF4蛋白,经镍柱亲和层析纯化,用SDS-PAGE分析所表达的目的蛋白及纯化后蛋白,用鸡胚绒毛膜尿囊膜实验(CAM)验证rhPF4的活性.结果: 成功构建了表达载体pRSET-PF4,DNA序列测定结果与预期结果一致.IPTG诱导表达的rhPF4融合蛋白部分以可溶形式存在,占菌体总蛋白量的11%.亲和层析纯化后目的蛋白纯度为84%.CAM实验表明,经纯化获得的rhPF4对鸡胚血管形成具有抑制作用.结论: 成功地获得了具有高度生物学活性的rhPF4蛋白.     

荆芥连翘汤对促进皮肤溃疡愈合的影响

目的 观察荆芥连翘汤对小鼠皮肤溃疡的治疗作用。方法 建立小鼠皮肤创伤和烫伤两种皮肤溃疡模型．比较荆芥连翘汤以及rhEGF的用药组和自身对照组小鼠皮肤溃疡面积，用昆微镜观察溃疡面炎症细胞浸润情况。结果 和自身对照组相比，荆芥连翘汤可明显缩小小鼠皮肤溃疡面积（P〈0．001），同时炎症细胞浸润显著减少（P〈0．001）；荆芥连翘汤用药组疗效显著优于rhEGF用药组。结论 荆芥连翘汤可明显促进小鼠皮肤溃疡的愈合。     

NGD及NRF对大鼠坐骨神经缺损修复的电生理学检测

目的 :观察神经生长液 ( NGD)及神经再生素 ( NRF)修复大鼠坐骨神经缺损的效果。方法 :用生理盐水( NS)、NRF桥接以及 NRF桥接 +口服 NGD修复大鼠坐骨神经缺损 ,术后 12周检测大鼠坐骨神经干动作电位传导速度及肌电图。结果 :行为方面 NGD+ NRF组比 NS组恢复早 ,NS组、NRF组、NRF+ NGD组神经干动作电位传导速度的平均值分别为 5 .72 0 m/ s、16 .5 14 m/ s、2 1.310 m/ s。NS组与 NGD+ NRF组的神经干动作电位传导速度经统计学分析有显著性差异 ( P<0 .0 1)。NGD+ NRF组与 NS组的肌电图比较 ,前者的潜伏期短、峰谷值大、运动神经传导速度快。结论 :NGD+ NRF具有良好促进神经再生作用     

H—TdR前体掺入技术在复方中药抗癌制剂研究中的应用

将一种快速、灵敏、可靠、简便的抗癌活性微量测定技术——~3H—TdR前体掺入技术用于复方中药抗癌制剂制备工艺筛选,短期内即拟定出较合理的工艺,经临床及14项生物学指标综合评定,该制剂疗效好,无明显的毒副作用。表明把一些快速、灵敏的医学检测技术引入药物制备工艺、质量标准及稳定性研究,可克服由于活性成分不清楚带来的一些困难,拓宽了研究途径,提高了研究水平。     

Expression of TGF-α, EGF and their common receptor in human fetal kidney

Summary: Transforming growth factor-α (TGF-α) and epidermal growth factor (EGF) are structurally related mitogenic polypeptides. They share the same receptor; EGF receptor. the EGF receptor is widely expressed in human fetal tissues including the kidney, but little is known about the role of TGF-α/EGF/EGF receptor system in human fetal kidney. the expression of TGF-α, EGF and their common receptor was investigated immunohistochemically in the human fetal kidneys. In the cortex, immunoreactivity for TGF-α was found in the differentiating proximal tubules. In contrast, immunoreactivity for EGF was present in the thick ascending limbs of the Henle's loop (TAL) and medullary collecting duct cells (CD). Immunoreactivity for their common receptor was present mainly in the TAL and medullary CD. These data support the assumption that the system of TGF-α, EGF and its receptor has an important role in the proliferation and differentiation of the TAL and medullary CD. the different localization of TGF-α and its receptor may indicate that TGF-α acts through a paracrine mechanism. the co-localization of EGF and its receptor in the TAL and medullary CD suggests that EGF may act as an autocrine growth factor.     

In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (¹H) to a J-coupled phosphorus (³¹P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (～1.2) is lower than the theoretical maximum of γ¹H/γ³¹P≈ 2.4 resulting from ¹H-¹H homonuclear J couplings of similar magnitude competing with the ¹H →³¹P transfer. Nevertheless, compared with direct ³¹P Ernst-angle excitation, signal gains of up to × 1.8 were obtained mainly as a result of T¹ differences between ³¹P and the ¹H. Spectral interpretation is simplified by editing out all non-proton-coupled ³¹P signals. The duration, ～50 min, and power deposition, ～1 W · kg^?1, make the application suitable for human studies.     

大肠癌高发区嘉善县大肠癌危险因子的调查研究

在大肠癌高发区嘉善县进行了病例对照调查,以探索大肠癌的致癌危险因子。病例160名(结肠癌61名,直肠癌99名),对照320名。调查询问项目分食物项目和非食物项目。计算结果表明,在非食物方面,RR数值达到显著水平的有:肠息肉、腹泻、粘液血便、精神刺激、阑尾炎、阑尾切除和家族肿瘤史等;在食物方法,对照组比病例组摄入的粗纤维和维生素C的量多,且达到显著水平。     

Patch clamp studies on the kinetics and selectivity of N-methyl-d-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan)

Memantine (1-amino-3,5-dimethyladamantan) was tested as an antagonist of N-methyl-d-aspartate (NMDA) receptors on cultured superior collicular and hippocampal neurones using the patch clamp technique and its actions were compared to those of Mg²⁺ ions, ketamine, dextrorphan, dextromethorphan, phencyclidine and dizocilpine (MK-801). Memantine (2–33 μM) concentration-dependently antagonized responses to NMDA 100 μM with an IC₅₀ of 2.92 ± 0.05 μM. In contrast, current responses to (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (l-AMPA 50–100 μM) and γ-amino butyric acid (GABA 10 μM) were unaffected by Memantine 8 μM. Memantine 8 μM caused a non-parallel shift of the NMDA concentration-response curve to the right in a manner indicative of uncompetitive open channel block. The effects of memantine were similar to ketamine in that both antagonists were weakly use- and strongly voltage-dependent. In contrast, MK-801, phencyclidine and dextrorphan showed much slower kinetics that was reflected in their marked use- and weaker voltage-dependency. The antagonistic effects of memantine were not reversed by increasing concentrations of glycine (0.1–100 μM) ruling out the possibility of an interaction of memantine with the strychnine-insensitive glycine modulatory site associated with the NMDA receptor-channel complex. Memantine (1–100 μM) also selectively antagonized responses to NMDA (40 μM) in the cortical wedge preparation with IC₅₀ of 12.9 ± 1.5 μM.     

Concentration-dependent metabolism of diazepam in mouse liver

Previous mouse liver studies with diazepam (DZ),N-desmethyldiazepam (NZ), and temazepam (TZ) confirmed that under first-order conditions, DZ formed NZ and TZ in parallel. Oxazepam (OZ) was generatedvia NZ and not TZ despite that preformed NZ and TZ were both capable of forming OZ. In the present studies, the concentration-dependent sequential metabolism of DZ was studied in perfused mouse livers and microsomes, with the aim of distinguishing the relative importance of NZ and TZ as precusors of OZ. In microsomal studies, theK _ms andV _maxs, corrected for binding to microsomal proteins, were 34 μM and 3.6 nmole/min per mg and 239 μM and 18 nmole/min per mg, respectively, forN-demthylation andC ₃-hydroxylation of DZ. TheK _ms andV _maxs forN-demethylation andC ₃-hydroxylation of TZ and NZ, respectively, to form OZ, were 58 μM and 2.5 nmole/min per mg and 311 μM and 2 nmole/min per mg, respectively. The constants suggest that at low DZ concentrations, NZ formation predominates and is a major source of OZ, whereas at higher DZ concentrations, TZ is the important source of OZ. In livers perfused with DZ at input concentrations of 13 to 35 μM, the extraction ratio of DZ (E{DZ}) decreased from 0.83 to 0.60. NZ was the major metabolite formed although its appearance was less than proportionate with increasing DZ input concentration. By contrast, the formation of TZ increased disporportionately with increasing DZ concentration, whereas that for OZ decreased and paralleled the behavior of NZ. Computer simulations based on a tubular flow model and thein vitro enzymatic parameters provided a poorin vitro-organ correlation. TheE{DZ}, appearance rates of the metabolites, and the extraction ratio of formed NZ (E{NZ, DZ}) were poorly predicted; TZ was incorrectly identified as the major precursor of OZ. Simulations with optimized parameters imporved the correlations and identified NZ as the major contributor of OZ. Saturation of DZN-demethylation at higher DZ concentrations increased the role of TZ in the formation of OZ. The poor aqueous solubility (limiting the concentration range of substrates usedin vitro), avid tissue binding and the coupling of enzymatic reactions in liver, favoring sequential metabolism, are possible explanations for the poorin vitro-organ correlation. This work emphasizes the complexity of the hepatic intracellular milieu for drug metabolism and the need for additional modeling efforts to adequately describe metabolite kinetics. This work was supported by the Medical Research Council of Canada (MA-9104).