明胶-阿霉素抗癌缓释剂对膀胱肿瘤细胞株BIU-87的生长抑制研究

应用含２０ｍｌ／Ｌ小牛血清的完全培养基浸泡明胶－阿霉素抗癌缓释剂，每隔２４ｈ重复更换培养基，而后将每ｄ浸泡所得的培养基与ＢＩＵ－８７细胞混合培养。结果发现，直至第１９ｄ经抗癌缓释剂浸泡过的培养基仍对ＢＩＵ－８７细胞具有生长抑制作用，其中第１ｄＢＩＵ－８７细胞生长率仅为１０％，第５ｄＢＩＵ－８７细胞生长率为６０％，第１９ｄＢＩＵ－８７细胞生长率仍低于８０％。这为明胶－阿霉素抗癌缓释剂应用于临床治疗膀胱肿瘤提供了实验依据。     

生脉注射液对损伤心肌细胞乳酸脱氢酶及心肌细胞超微结构的影响

本实验运用体外培养心肌细胞,观察了中药生脉注射液对阿霉素引起心肌细胞损伤时,心肌细胞内乳酸脱氢酶释放及超微结构的影响。结果表明,生脉注射液30、100、300mg/L 对阿霉素1 mg/L 作用4 h 引起的培养心肌细胞乳酸脱氢酶释放没有影响;对其引起的心肌细胞超微结构损伤也无改善作用。结果提示:生脉注射液对阿霉素引起的心肌损害的保护作用,可能是在整体情况下产生的。     

REGIONAL DISTRIBUTION OF THE CARDIAC OUTPUT AND RENAL RESPONSES TO ATRIAL ATRIURETIC PEPTIDE INFUSION IN RABBITS WITH CONGESTIVE HEART FAILURE

1. A biventricular, low-output congestive cardiomyopathy was induced in 19 rabbits by administering adriamycin (16 mg/kg). The effects of alpha-rat atrial natriuretic peptide (ANP) infused at 0.1, 0.2 and 0.4 micrograms/kg per min, were then examined in terms of (i) central haemodynamics (ii) regional blood flow (iii) renal function and (iv) plasma norepinephrine and plasma renin. 2. In this dose range, ANP produced progressive and significant falls in stroke volume, cardiac output and mean arterial pressure, owing to a fall in venous return. The heart rate response to this was blunted. 3. Using radiolabelled microspheres, significant falls in the perfusion of cutaneous, gastrointestinal and musculoskeletal tissues were observed, due to reduced vascular conductances in these beds. These changes were accompanied by activation of the sympathetic nervous system as evidenced by a progressive rise in plasma norepinephrine. A significant increase in plasma renin was only observed with the highest infusion of ANP. 4. Renal blood flow was maintained in the face of a falling mean arterial pressure and cardiac output, but diuretic and natriuretic effects were absent. 5. It was concluded that the dominant influence of ANP infusion in this model of heart failure appeared to be a reduction in cardiac preload with detrimental overall haemodynamic consequences.     

Absence of correlation between cytotoxicity and drug transport by P-glycoprotein in clinical leukemic cells.

Development of resistance to cytotoxic agents is a common problem in the treatment of acute leukemia. In cell lines having multidrug resistance (MDR) phenotype, a decrease in the intracellular accumulation of drugs has been closely related to the overexpression of P-glycoprotein/mdr1 genes. We analyzed the relationship between the cytotoxicity of adriamycin (ADR) in vitro, intracellular accumulation of ADR, and the expression of P-glycoprotein on fresh leukemic cells from 19 patients at their initial presentation and from 9 relapsed patients. Pretreatment patients showed significantly higher ratio of complete remission than relapsed patients, and mean value of IC50 for adriamycin in initial presentation was higher than at relapse. But we found no significant relationship between in vitro cytotoxicity and drug transport. In addition, only 2 of the 5 relapsed patients examined by monoclonal antibody C219 expressed the P-glycoprotein. These results suggest that the acquisition of clinical drug resistance may involve various mechanisms other than the reduction of drug accumulation with P-glycoprotein expression.     

控释缓释微球制剂的研究进展

讨论了国内外用白蛋白，明胶，聚丙交酯，聚乙烯，萄聚糖与乙基纤维素等所制微球的研究进展情况。     

雅胆子乳治疗原发性肝癌38例临床效果观察

为了探讨中药鸦胆子乳在原发性肝癌导向治疗中的多功能载体作用，我院从1993年1月～1996年10月采用鸦胆子乳乳化碘油（A组）和单纯碘油（B组）为载体，对38例患者进行80多次的临床对照研究．三年生存期A组为12％，B组为0，结果表明A组的疗效明显高于B组。分析鸦胆子乳载体作用、栓塞及化疗作用，证明鸦胆子乳是一种有发展前途的多功能载体，且使用方便、经济、副作用少，可以在临床上广泛使用。     

扩张型心肌病家兔血浆脑钠肽水平的改变及其意义

目的　观察实验性阿霉素扩张型心肌病 (DCM)模型家兔血浆脑钠肽 (BNP)的改变 ,并探讨其意义。方法　 2 2只健康家兔随机分为正常对照组 (n=10 )和 DCM模型组 (n=12 ) ,经兔耳缘静脉注射盐酸阿霉素 8周建立 DCM模型。分别于给药前及给药后第 8周和第 11周进行超声心动图、血浆 BNP水平检测 ,第11周测定血流动力学指标并观察心肌病理学改变。结果　模型组动物的超声心动图、血流动力学指标及病理学变化符合 DCM的病理改变。模型组给药前的血浆 BNP水平与正常对照组比较差异无显著性 (P>0 .0 5 ) ;用药后血浆 BNP水平显著增高 (P均 <0 .0 1) ,第 11周的血浆 BNP水平显著高于第 8周 (P<0 .0 5 )。血浆BNP水平与左室舒张末期容积 (L VEDV)、左室收缩末期容积 (L VESV)、左室舒张末期压 (L VEDP)均呈显著正相关关系 ,与左室内压峰值 (L VSP)和左室射血分数 (L VEF)均呈负相关关系。结论　阿霉素 DCM模型适合于研究衰竭心脏神经内分泌异常 ;心室负荷和室壁张力的增加是调节 BNP分泌的关键因素 ;血浆 BNP水平是评价 DCM心功能损伤严重程度的良好指标。     

脂质体载药降低阿霉素抗SRS淋巴瘤毒性的实验研究

本文将阿霉素包封在多层脂质体中,观察治疗SRS淋巴瘤小鼠的毒性反应。与游离阿霉素比较,脂质体阿霉素能明显降低小鼠的早期死亡率,骨髓抑制作用减轻。通过血液生化检测与心、肝组织的病理观察,结果表明脂质体载药后能明显降低阿霉素治疗SRS淋巴瘤小鼠的毒副作用。     

卵巢癌术后血浆CA125的半衰期与预后的关系

对18例经手术和病理证实为卵巢上皮癌患者，术后施以顺铂、阿霉素、环磷酰胺（PAC方案）联合化疗。在术前、化疗及随访过程中采取静脉血用放射免疫法测定CA125浓度。由化疗第一、第三疗程前CA125水平，根据Buller等提供的公式计算半衰期。结果发现18例患者中半衰期＞20天者10例（56％），有8例出现复发或死亡；而半衰期＜20天的8例则存活良好。提示化疗早期CA125水平及血浆半衰期对卵巢癌患者的预后评定有一定的价值，检测该指标可及时发现耐药或复发，从而及早采取相应的治疗措施。     

奥美沙坦酯对阿霉素肾病大鼠klotho蛋白表达及氧化应激的影响

目的探讨奥美沙坦酯对阿霉素肾病大鼠klotho蛋白(KL)表达和氧化应激的影响。方法阿霉素肾病大鼠随机分为阿霉素肾病组(ADR组)、奥美沙坦酯干预组(OLM组),每组11只,另设10只正常大鼠作为对照组(NC组)。OLM组大鼠给予奥美沙坦酯10mg/(Kg·d)灌胃,ADR组及NC组大鼠给予等量生理盐水灌胃。于第8周时检测大鼠24h尿蛋白、血清白蛋白、总胆固醇、甘油三酯、尿素氮、肌酐、氧化应激指标(SOD、MDA)、KL mRNA及klotho蛋白表达水平。结果与NC组比较,第8周时ADR组与OLM组24h尿蛋白、总胆固醇、甘油三酯、MDA水平明显增加,KL mRNA、klotho蛋白表达、SOD活性降低,差异具有统计学意义(P<0.05);ADR组与OLM组相比,上述改变更加明显,差异具有统计学意义(P<0.05)。结论阿霉素肾病大鼠klotho蛋白的表达降低,奥美沙坦酯可提高阿霉素肾病大鼠肾脏klotho蛋白的表达,抑制氧化应激,延缓肾病进展。