复方决明子口服液的制备工艺研究

目的 :用正交法优选复方决明子口服液的最佳工艺条件。方法 :以决明子中蒽醌的含量及浸出物的含量为指标 ,应用L9(3′)正交试验法优选复方决明子口服液的最佳工艺条件。结果 :最佳提取条件为 :加 1 0倍量水 ,煎煮 3次 ,每次 1 .5h。结论 :优越工艺验证表明 ,最佳提取工艺为A1 B2 C1 。说明优选工艺稳定可靠。     

人白细胞干扰素诱导慢性乙型肝炎病人DNA损伤修复的探讨

应用不同浓度人白细胞干扰素处理10例慢性乙型肝炎病人外周血淋巴细胞,观察病人姐妹染色单体互换(SCE)频率的动力学变化.结果表明,人白细胞干扰素处理组SCE平均频率明显低于对照组,差异高度显著(P<0.01);慢性迁延性肝炎和慢性活动性肝炎处理组之间SCE平均频率无显著性差异;但人白细胞干扰素处理低浓度组SCE平均频率低于高浓度组,差异不显著(P>0.05).提示人白细胞干扰素具有诱导HBV损伤人体DNA的修复作用;大剂量人白细胞干扰素对HBV损伤人体DNA的修复未必有益.     

131I对甲状腺细胞凋亡的影响

由于每个患者特异性基因决定的个体辐射敏感性不同,使得每个接受131I治疗的患者对治疗的反应不一,因而疗效差异较大.针对不同的个体,采用不同的剂量治疗才可以提高131I治疗的效率,降低甲状腺功能减退症的发病率.通过目前的分子生物学技术,我们已经了解到一些基因的蛋白表达产物(Fas/FasL、Bcl-2等)与细胞凋亡和射线诱导凋亡的联系,使对凋亡基因表达产物的体外监测成为可能.也许通过对这些指标的监测,可以使我们在131I治疗过程中实现对不同的个体给予恰当的个体剂量.     

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.     

The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: report of a synergistic effect between topotecan and radiation

Summary Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (1354) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed.     

Binding of cardiolipin to polystyrene beads: evidence for a lamellar phase orientation

Summary. The association of cardiolipin with polystyrene beads was studied using ³¹P-NMR and electron microscopy. In the presence and absence of fetal calf serum, cardiolipin appeared to bind to the polystyrene beads in lamellar phase as assessed by ³¹P-NMR imaging. Electron microscopic analysis revealed an even coating of phospholipid about the beads with extensive micelle binding. Cardiolipin-coated beads challenged with ACA-positive sera followed by immunogold indicated antibody bound to micelles associated with the bead. Studies conducted with ACA IgG purified from patient sera indicated that some ACA bound to CL beads in the absence of a source of ACA cofactor (i.e. gelatin-blocked beads), some ACA required β₂-GPI for binding (i.e. no binding in the presence of β₂-GPI-depleted plasma), whereas other ACA which showed negliglible binding with gelatin-blocked beads, showed enhanced binding in the presence of /?₂-GPI-depleted plasma. The data indicate that: (1) cardiolipin binds to polystyrene beads in lamellar phase, (2) ACA bind to phospholipid micelles bound directly to the polystyrene beads, and (3) ACA differ between individuals displaying varying phospholipid and phospholipid/cofactor substrate specificities.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

血清Tg、TgAb对甲状腺癌根治术联合131I治疗后随访期间复发/转移的评估价值

目的 研究血清甲状腺球蛋白（Tg）、甲状腺球蛋白抗体（TgAb）对甲状腺癌根治术联合¹³¹I治疗后随访期间复发/转移的评估价值。方法 回顾性分析2018年6月—2020年6月中国贵航集团三〇二医院收治的106例分化型甲状腺癌患者的临床资料,患者均接受甲状腺癌根治术治疗,术后均采用¹³¹I进行清除残留的甲状腺组织（清甲）治疗。随访24个月,将患者分为复发转移组（21例）和未复发转移组（85例）。比较两组临床资料、¹³¹I治疗情况及血清促甲状腺激素（TSH）、Tg、TgAb。绘制受试者工作特征（ROC）曲线分析血清Tg、TgAb检测对甲状腺癌根治术联合¹³¹I治疗后复发/转移的预测价值。采取非条件一般Logistic回归模型进行多因素分析。结果 与未复发转移组比较,复发转移组原位肿瘤T₄分期、手术方式为腺叶切除或近全切、残余甲状腺质量≥1 g、手术至¹³¹I治疗时间> 3个月、24 h摄¹³¹I率≤ 20%患者的占比均较高（P <0.05）;复发转移组血清Tg和TgAb水平均较高（P <0.05）;ROC曲线分析结果显示：血清Tg预测甲状腺癌根治术联合¹³¹I治疗后复发或转移的最佳截断值为1.674 μg/L,AUC为0.803（95% CI：0.721,0.884）,敏感性为81.1%（95% CI：0.724,0.898）,特异性为63.8%（95% CI：0.585,0.691）;血清TgAb预测的最佳截断值为44.19 3 IU/mL,AUC为0.911（95% CI：0.859,0.963）,敏感性为89.2%（95% CI：0.813,0.971）,特异性为72.5%（95% CI：0.674,0.774）。非条件Logistic一般回归分析结果显示：原位肿瘤T₄分期［O^R=2.916（95% CI：1.325,6.417）］、腺叶切除或近全切［O^R=3.243（95% CI：2.174,4.838）］、残余甲状腺质量≥ 10 g［O^R=1.835（95% CI：1.514,2.224）］、手术至¹³¹I治疗时间> 3个月［O^R=1.962（95% CI：1.371,2.808）］、24 h摄¹³¹I率≤ 20%［O^R=2.638（95% CI：1.219,5.709）］、血清Tg ≥ 1.674 μg/L［O^R=2.503（95% CI：1.430,4.360）］、血清TgAb≥ 44.193 IU/mL［O^R=2.944（95% CI：2.016,4.299）］可能是甲状腺癌根治术联合¹³¹I治疗后复发或转移的危险因素（P <0.05）;风险因素预测模型预测甲状腺癌根治术联合¹³¹I治疗后复发/转移的ROC曲线下面积为0.961（95% CI：0.935,0.987）,标准误为0.010,临界值为73.162,敏感性为91.9%（95% CI：0.863,0.957）,特异性为88.2%（95% CI：0.845,0.922）。结论 甲状腺癌根治术联合¹³¹I治疗后出现复发/转移的患者血清Tg、TgAb水平明显升高,Tg、TgAb对预测复发/转移具有较好的价值,联合其他危险因素建立风险因素预测模型可进一步提高预测价值。     

Cardiovascular effects of endothelin 1 in pithed spontaneously hypertensive rats: evaluation of its mechanism(s) of action

Summary The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1 – 3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals died following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC₅₀ 2.1 ±0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 g/kg i.v.), phenylephrine (8 g/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca²⁺ channels.Send offprint requests to A. K. Mir at the above address