赵玉庸教授治疗原发性肾小球疾病经验介绍

赵玉庸教授认为，原发性肾小球疾病的病机是湿热蕴结、肾络瘀阻、脾肾亏虚，结合临床分析各病机因素在疾病过程中的作用与影响，拟定清热利湿、化瘀通络、补脾益肾的治疗大法。     

Ε-cadherin和β-catenin在大肠癌组织中的表达及与预后的关系

目的 探讨E-cd及β-cat的表达与大肠癌临床病理因素和预后的关系。方法 采用免疫组化S-P法,检测139例大肠癌组织标本中E-cd及β-cat的表达。结果 研究显示E-cd异常表达率与大肠癌分化程度呈负相关,与淋巴结转移及Dukes分期呈正相关。而β-cat异常表达率只与大肠癌分化程度呈负相关。且E-cd及β-cat异常表达均与不良预后相关。结论 E-cd及β-cat的异常表达与刁肠癌的侵袭、转移及预后相关。     

Differential expression of the enzyme that esterifies retinol, lecithin:retinol acyltransferase, in subtypes of human renal cancer and normal kidney.

PURPOSE: Retinoids, a group of compounds, including vitamin A (retinol), and related metabolites, have been shown to regulate the growth and differentiation of many types of cells. IFN-alpha and either 13-cis-retinoic acid or liposomal all-trans retinoic acid have been used in the treatment of patients with metastatic renal cell carcinoma. We knew that samples from renal cell carcinomas contained greatly reduced levels of retinol and retinyl esters relative to samples from normal human kidney. This prompted us to examine the levels of LRAT (lecithin:retinol acyltransferase) protein in various subtypes of human kidney cancers relative to normal human kidney by immunohistochemistry. EXPERIMENTAL DESIGN: We examined 31 partial or radical nephrectomy specimens diagnosed with kidney tumors between 1997 and 1998. Representative paraffin-embedded tissue blocks from each tumor, with each containing adjacent nonneoplastic renal parenchyma, were used for immunohistochemical analysis with affinity purified antibodies to human LRAT protein. RESULTS: LRAT protein was detected at high levels in the epithelial cells in the tubules and the lining of Bowman's capsule in the glomeruli of normal, nonneoplastic kidney sections. Among the 31 tumors, there were 13 cases of conventional (clear cell) renal cell carcinoma (RCC; including 2 multilocular cystic RCCs), 7 papillary RCC, 6 chromophobe RCC, 1 RCC, unclassified, and 4 renal oncocytoma. All tumors showed diffuse immunoreactivity for LRAT. In each case, the staining was uniform throughout the tumor, with only minimal variation in the staining intensity between different areas. All 4 renal oncocytomas, 2 of 6 chromophobe RCCs, 1 conventional (clear cell) carcinoma, 1 RCC, unclassified, and 2 conventional RCCs, which were of the multilocular cystic-type stained strongly (3+) for LRAT. In contrast, the remaining conventional RCCs and the papillary RCC samples stained much less intensely for LRAT. Of the 10 tumors that stained 3+ for LRAT in the study, 9 were either benign tumors or tumors with low malignant potential. CONCLUSIONS: These data show that LRAT expression is higher in renal tumors with an indolent biological behavior. Additional studies will ascertain if LRAT possesses any prognostic or therapeutic role in renal cancer.     

A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy.

PURPOSE: To perform a Phase I study of SR-4554, a fluorinated 2-nitroimidazole noninvasive probe of tumor hypoxia detected by (19)F magnetic resonance spectroscopy (MRS). EXPERIMENTAL DESIGN: SR-4554 administration, on days 1 and 8, was followed by plasma sampling for pharmacokinetic studies and by three MRS studies performed over 24 h on days 8 and 9. Unlocalized MR spectra were acquired from tumor (10- or 16-cm dual resonant 1H/19F surface coil; 1.5 T Siemens Vision MR system; 2048 transients acquired over 34 min; 1.28-ms adiabatic pulse; repetition time, 1 s). Plasma drug concentrations were measured with a validated high-performance liquid chromatography method. Noncompartmental pharmacokinetic analysis was performed. RESULTS: Eight patients underwent pharmacokinetic studies, receiving doses of SR-4554 of 400-1600 mg/m(2). Peak plasma concentrations increased linearly with the SR-4554 dose (r(2) = 0.80; P = 0.0002). The plasma elimination half-life was relatively short (mean +/- SD, 3.28 +/- 0.59 h), and plasma clearance was quite rapid (mean +/- SD, 12.8 +/- 3.3 liters/h). Urinary recovery was generally high. SR-4554 was well tolerated. A single patient experienced dose-limiting toxicity (nausea and vomiting) at 1600 mg/m(2). The maximum tolerated dose was 1400 mg/m(2). SR-4554 was detected spectroscopically in tumors immediately after infusion at doses of 400-1600 mg/m(2). At the highest dose (1600 mg/m(2)), SR-4554 was detectable in tumor at 8 h, but not at 27 h. CONCLUSIONS: SR-4554 has plasma pharmacokinetic and toxicity profiles suitable for use as a hypoxia probe. It can be detected in tumors by unlocalized MRS. Additional clinical studies are warranted.     

苯唑西林钠细菌内毒素检查法的建立

目的: 建立苯唑西林钠细菌内毒素检查法.方法: 参照中国药典2000年版二部附录XIE 细菌内毒素检查法和附录XIXF 细菌内毒素检查法应用指导原则,采用凝胶法进行干扰试验.结果: 本品的最大不干扰浓度为2.5mg*ml-1.结论: 本品适用于细菌内毒素检查法.     

复方苦参洗剂中小檗碱的含量测定

目的: 建立三元络合物比色法测定复方苦参洗剂中小檗碱的含量,为制剂质量控制提供依据.方法: 小檗碱在pH6.7的溶液中, 与溴酚蓝、奎宁形成三元络合物比色, 经氯仿提取, 在610 nm波长处测定吸收度.结果: 回归方程为A=0.182C-0.004(r=0.999 9),小檗碱在0.8～4 mg·L-1浓度范围内线性关系良好(r=0.999 9),平均回收率为98.65%,RSD为1.12%.结论: 本方法准确,灵敏度好,可用于复方苦参洗剂中小檗碱的含量测定.     

3种基因工程药物对大鼠动脉阻塞性脑损伤治疗作用的比较研究

目的 :探讨基因工程药物NIF、NHH、TNHH对大鼠动脉阻塞性脑损伤的治疗作用。方法 :用线栓法将24只大鼠制成动脉阻塞性脑缺血损伤模型后分为治疗组 (3组 )和模型对照组 ,每组6只。治疗组静脉给予NIF、NHH、TNHH ,模型组给予生理盐水。分别于术后4、8、24、48、72h进行神经行为学评分 ;术后72h取血测定血清APTT ,判断凝血功能 ;取脑组织行TTC染色 ,计算梗塞灶体积 ;HE染色观察脑组织病理变化。结果 :治疗组各时间点行为学评分均优于模型组 (P<0 05) ,血清APTT比模型组均有明显延长 (P<0 05) ,脑组织梗塞灶体积比模型组小 (P<0 05) ,HE染色脑组织病理变化均较模型组轻。结论 :NIF、NHH、TNHH对大鼠动脉阻塞性脑缺血损伤有明显的保护作用 ,其中以TNHH最优。     

细胞凋亡及增殖细胞核抗原在肝癌组织中的表达及意义

目的探讨经肝动脉化疗栓塞(TACE)后肝癌细胞中增殖细胞核抗原(PCNA)广凋亡细胞比值与肝细胞肝癌分化程度的关系。方法应用原位末端标记法(TUNEL)及免疫组化双染色技术，对60例肝细胞肝癌石蜡包埋组织进行检测。结果不同分化程度癌组织中细胞凋亡和PCNA的阳性率不同。分化程度高，细胞凋亡阳性率高、PCNA阳性率偏低；分化程度低，细胞凋亡阳性率偏低、PCNA阳性率高。随分化程度的降低，PCNA广凋亡细胞的比值显著增加，两者有相关性。结论PCNA/凋亡细胞的比值可作为评估肝细胞肝癌分化程度的指标。     

液相色谱-电喷雾质谱联用法测定人血浆中托吡酯

目的:建立测定人血浆中托吡酯的液相色谱-电喷雾质谱联用(LC/ESI-MS)法。方法:待测血浆0.2 mL经甲醇沉淀除去蛋白,离心,取上清液10μL在Diamonsil C18柱上分离,流动相为甲醇-2.5 mmol·L-1醋酸铵(80:20),流速0.4 mL·min-1,LC/ESI-MS选择离子检测,负离子模式,用于定量分析的离子分别为m/z338(托吡酯)和m/z 356(吲哚美辛,内标)。结果:血浆中无干扰测定的内源性物质,每个样品分析时间小于7 min;本法线性范围为40-2560 ng·mL-1,最低定量浓度为40 ng·mL-1;日内、日间RSD分别小于3.8％和13.4％,相对偏差小于5.9％。结论:该法操作简便、快速、准确、灵敏度高,适用于临床药物动力学研究。     

艾拉莫德片溶出度测定方法研究

目的:建立紫外分光光度法测定艾拉莫德片溶出度的方法。方法:以磷酸盐缓冲液(pH 8.0)1000 mL为溶出介质,转速75 r·min-1,紫外分光光度法测定溶出量,检测波长257 nm。结果:在1.04-16.7μg·mL-1范围内呈良好的线性关系,r=0.9999,精密度RSD为0.3％(n=6)。结论:本方法简便、准确,可用于艾拉莫德片剂的溶出度测定。