Comparison of action of the anti-neoplastic drug lonidamine on drug-sensitive and drug-resistant human breast cancer cells:31 P and 13C nuclear magnetic resonance studies

Lonidamine (LND) is a relatively new anti-cancer drug,and several clinical trials have indicated that it may be effectivein combinations with other therapeutic modalities. LND isclassified within the metabolic inhibitor agents. Multidrugresistance (MDR) phenomenon is often associated with increasedenergy requirements, and enhanced glycolysis rate. These studieswere performed to delineate the mechanism of action of LNDon MDR human breast cancer cells, and to investigate whetherLND as a single agent, or in combination with anotheranti-metabolism drug, 2-deoxyglucose (2-DG), may be usefulagainst MDR tumors. The effects of LND on intact perfuseddrug-sensitive (WT) and 33-fold resistant to Adriamycin(Adr) MCF-7 cells, embedded in alginate micro capsules, were continuouslymonitored by ³¹P and ¹³C nuclearmagnetic resonance (NMR) spectroscopy. ³¹PNMR studies showed that LND induced intracellular acidificationand depletion of NTP in both WT and Adr cells. However, pH and NTPlevels decreased less in the Adr cells than in the WT cells(p < 0.05 for both parameters). ¹³CNMR demonstrated that LND inhibited lactate transport,and lactate signals were elevated in both cell lines. However, theintracellular lactate levels increased to a greater extentin the WT than in the Adr cells (p < 0.05).There were major differences in the effects of LND onmetabolism between sensitive and resistant cells.While LND enhanced glucose uptake in the WT cells, and itsadministration was followed by continuous increase oflactate signal, both processes were not affected by LNDin the Adr cells. 2-DG is a glucose analogue that inhibitsboth cellular uptake and utilization of glucose, leading to cell starvation. Combined treatment with LND and2-DG yielded at best additive, but not synergistic,cellular toxicity, and the metabolic effects of LNDwere attenuated by 2-DG. These results showed that the principalmechanism of action of LND is inhibition of lactate transportleading to intracellular lactate accumulation and acidificationin both WT and Adr cells. The Adr cells were only 2-fold resistantto LND (compared to the WT cells), and since cellular uptakeof alkaloid chemotherapy is improved in acidic environment,LND may have a role in the treatment protocols of MDR tumors,especially when given as the initial means for inductionof intracellular acidification.     

Intracranial leiomyosarcoma: A neuro-oncological consequence of acquired immunodeficiency syndrome

We describe a case of glioblastoma treated with chemoradiotherapy that spread to the dura mater with direct invasion of the skull base, protrusion into the homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall and the ethmoidal sinuses. Only eight cases of glioblastoma showing this development have been described in the literature; one of these, however, had a sarcomatous component which was absent in our case.     

论阿是穴与穴位特异性

中医理论认为,阿是穴是体表具有按之快然或疼痛等特点的位点。从理论上来说,阿是穴包含有具有特异性的经穴和其它常用穴;从功能上来讲,阿是穴实际上与现代医学的牵涉痛的体表部位类似。因此,阿是穴乃是在反映病邪和治疗疾病等两大穴位功能方面具有明显特异性的穴位,本文就此进行了论述。     

2型糖尿病患者心理防御机制与血糖变化关系的研究

[目的]探讨心理防御机制、2型糖尿病患者的焦虑以及血糖变化的关系.[方法]对符合1999年世界卫生组织（WHO）糖尿病诊断标准的2型糖尿病患者随机取样192名,对他们进行糖化血红蛋白测查和心理测查,通过SPSS11.0进行统计分析.[结果]焦虑与心理防御机制共同对2型糖尿病患者血糖的变化起着重要作用.[结论]证实研究假设——心理防御机制与2型糖尿病患者的焦虑情绪、血糖变化存在内在结构关系,并提示出2型糖尿病患者进行心理治疗时应考虑到患者心理防御机制与焦虑情绪的问题.     

益气养阴化痰活血法治疗糖尿病周围神经病变机制探讨

认为糖尿病周围神经病变为本虚标实、虚实夹杂之证,其病机特点为:气阴两虚为本,痰浊瘀血阻络为标。因此,治疗本病应益气养阴治其本,化痰活血治其标。以此为组方原则,组成糖周宁方。经临床研究证实,益气养阴、化痰活血法治疗糖尿病周围神经病变具有较好的疗效。     

落叶松阿拉伯半乳聚糖滴丸制备工艺及其速释机制研究

目的:研究落叶松阿拉伯半乳聚糖滴丸的制备工艺并初步探讨其速释机制。方法:采用正交设计对滴丸制备工艺进行优化,并通过相图分析和DSC分析研究滴丸的速释机制。结果与结论:滴丸制备最佳的工艺条件为药液温度75℃,二甲基硅油冷凝液上部温度30℃,滴头与冷凝液的距离6cm,滴速为30滴/min;相图分析和DSC分析结果显示在AG-PEG4000固体分散体中形成了某种形式的复合物,使熔点降低,药物在基质中的溶解度增加而达到速释。     

所有权与经营权分离是城市公立医院改革和发展的途径

传统卫生管理体制承袭了计划经济的所有特征,价格扭曲的宏观政策环境、资源的集中计划配置体制与公立医院在微观上的缺乏经营自主权三者并存.这种制度安排越来越不适应市场经济条件下卫生改革和发展的需要,而卫生经济体制改革始自微观经营机制,核心是两权分离和放权让利,这是自然的,同时也是正确的改革方向.     

建立农村突发公共卫生事件应急机制的对策

SARS提醒我们，建立农村突发公共卫生事件应急机制是当前迫切需要解决的问题。尽快出台一部完善的《公共卫生法》，把农村突发公共卫生事件处理的相关环节纳入法制轨道；建立健全农村三级医疗卫生服务体系，形成县、乡、村三级应急机制；加大农村公共卫生投入，完善农村公共卫生体系；建立农村公共卫生资源储备制度，为突发事件的应急处理迅速提供必要的支持；加强健康教育宣传力度，探索适合农村社会、农民心理的救助机制。     

德国小蠊抗性及敏感品系羧酸酯酶生化特征比较研究

目的 研究德国小蠊敏感品系和抗性品系羧酸酯酶(CarE)生化性质上的差异，旨在从生化水平上确定CarE在德国小蠊抗性中的作用，初步揭示德国小蠊抗性机制。方法 参照Asperen(1962)和高希武(1991)方法测定CarE活性。结果 德国小蠊抗性品系中的CarE活性要高于敏感品系中的CarE活性。抗性品系与敏感品系对α-乙酸萘酯(α-NA)的亲和力要大于对β-乙酸萘酯(β—NA)的亲和力，而敏感品系CarE对α—NA的亲和力要大于抗性品系CarE。时间进程曲线显示，在以α-NA为底物时，抗性品系与敏感品系CarE时间进程曲线趋势不一致。对9种德国小蠊野外品系CarE活性的测定结果表明，除1种品系外，其余品系均使CarE活性提高，幅度在1．23～2．83倍之间。结论 德国小蠊抗性品系和敏感品系在CarE生化特征上的差异，显示出德国小蠊抗性品系对几种拟除虫菊酯类杀虫剂产生的高度抗性，与其体内CarE活性的提高有密切关系，表明CarE活性的提高是北京地区野外德国小蠊品系普遍存在的一种抗性机制。     

鲍曼不动杆菌对喹诺酮类耐药机制

目的 探讨鲍曼不动杆菌对氟喹诺酮类药物的耐药机制。方法 采用K-B法检测35株鲍曼不动杆菌对氟喹诺酮类药物的药敏情况。十二烷基磺酸钠一聚丙酰胺凝胶电泳(SDS-PAGE)法检测鲍曼不动杆菌的外膜蛋白(OMP)，直接荧光法检测鲍曼不动杆菌对环丙沙星的吸收和积累，PCR法扩增gyrA基因并对其进行测序。结果 35株鲍曼不动杆菌中有20株对氟喹诺酮类药物耐药，耐药菌株与敏感菌株相比，外膜蛋白在约29Ku条带处消失，在26Ku条带处明显增强。耐药菌株药物积累量不及敏感菌株，经叠氮钠处理后，积累量上升并接近敏感菌株，对PCR扩增产物gyrA测序未发现有突变。结论 鲍曼不动杆菌对氟喹诺酮类药物的耐药与外膜蛋白的低通透性和主动外运有关。