高度稀释的葡萄糖溶液提高含亚砷酸盐培养基中大肠埃希氏杆菌的葡萄糖摄取

目的：高度稀释的顺势疗法药物对活体系统的作用一直被质疑。因此,本研究检测依据顺势医学理论而高度稀释的葡萄糖溶液对暴露于亚砷酸盐的大肠埃希氏杆菌的作用。方法：大肠埃希氏杆菌在Luria-Bertani培养基中培养至对数期后分组。分别加入1%或3%的葡萄糖溶液、葡萄糖30C（在70%乙醇中稀释1060倍）、1mmol/L或2mmol/L的亚砷酸钠、1mmol/L或2mmol/L的亚砷酸钠加葡萄糖30C、1mmol/L或2mmol/L的亚砷酸钠加乙醇30C（安慰剂）。分析用药后45min及90min大肠埃希氏杆菌的葡萄糖摄取、己糖激酶及葡糖激酶活性、细胞膜电位、细胞内三磷酸腺苷含量以及葡萄糖通透酶基因的表达情况,并测定细胞内及细胞外（培养基内）亚砷酸盐的浓度。结果：暴露于亚砷酸盐的大肠埃希氏杆菌的葡萄糖摄取量增加,己糖激酶及葡糖激酶活性、细胞内三磷酸腺苷含量及细胞膜电位降低,葡萄糖通透酶基因的表达增加。在加入1%或3%葡萄糖或高度稀释的葡萄糖30C的培养基内,大肠埃希氏杆菌的葡萄糖摄取量进一步增加,而在加入乙醇30C（安慰剂）的培养基内,大肠埃希氏杆菌的葡萄糖摄取量没有明显增加。结论：本研究的结果证实了高度稀释的葡萄糖溶液对于真正的葡萄糖溶液的模仿作用。这种顺势疗法理论下高度稀释的葡萄糖溶液能够调节大肠埃希氏杆菌己糖激酶和葡糖激酶的表达以及葡萄糖通透酶基因的表达,证实了顺势疗法中高度稀释的药物的有效性。     

Closed Abdomen Hyperthermic Intraperitoneal Chemotherapy with Irinotecan and Mitomycin C: a Phase I Study

Purpose  

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now a recognized treatment for peritoneal carcinomatosis (PC). The objective of this phase I study is to determine the maximum tolerated dose of irinotecan (CPT-11) when used with mitomycin C (MMC) for closed abdomen HIPEC.     

北美香柏叶的乙醇提取物阻断A549细胞增殖并引起细胞凋亡的体外研究

目的：研究北美香柏叶的乙醇提取物对非小细胞肺癌A549细胞的抗肿瘤及抗增殖作用。方法：噻唑蓝法检验不同剂量北美香柏叶的乙醇提取物对细胞活性的影响。确定半数最大抑制浓度为282μg／mL,另外选择两个浓度188μg／mL和376μg／mL进行剂量依赖性检测。进行溴脱氧尿苷结合实验和细胞迁移实验检测药物的抗肿瘤细胞增殖活性。膜联蛋白V-异硫氰酸荧光黄-碘化丙啶双染色后采用荧光激活细胞分类分析仪对细胞早期凋亡进行检测。Hoechst33258及吖啶橙-溴化乙啶荧光染色法进行DNA片段分析。间接酶联免疫吸附法分析Bax-Bcl2的调节和表达情况。逆转录聚合酶链反应检测caspase3基因表达情况,其活性和蛋白水平的表达则使用间接酶联免疫吸附法和蛋白印迹法进行检测。结果：A549的细胞活性在暴露于北美香柏叶的乙醇提取物24h后呈剂量依赖性下降。脱氧尿苷结合实验和细胞迁移实验表明细胞的增殖活性与暴露于药物的时间有时间依赖性关系。11．72％的细胞在双染色后呈阳性反应,表明药物引起了细胞的早期凋亡。药物作用24h后DNA片段彗星尾的出现以及Hoechst33258荧光染色的增加提示显著的DNA缺口出现以及染色质凝聚。Bax的上调及Bcl2的下调表明了细胞凋亡的出现。逆转录聚合酶链反应、间接酶联免疫吸附法以及蛋白印迹法的检测结果表明caspase3的活性随着抗聚（腺苷二磷酸-核糖）聚合酶的表达的增加而增加。结论：北美香柏叶的乙醇提取物能够促进A549细胞凋亡并抑制其增殖活性。     

Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD₅₀) of scorpion and snake venoms appears to be an important step to assess (and compare) venom toxic activity. Such LD₅₀ values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD₅₀ values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP) versus intravenous (IV)). The analysis of experimental LD₅₀ values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am) is intrinsically more toxic than Androctonus australis hector (Aah) species, whereas the latter is more toxic than Buthus occitanus (Bo). Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc) is more toxic than either Bitis arietans (Ba) or Macrovipera lebetina (Ml) species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh) is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of toxins, might be attributed to the rich composition of high molecular weight enzymes in the case of viper venoms.     

Lycopodine triggers apoptosis by modulating 5-lipoxygenase,and depolarizing mitochondrial membrane potential in androgen sensitive and refractory prostate cancer cells without modulating p53 activity: Signaling cascade and drug–DNA interaction

When the prostate cancer cells become unresponsive to androgen therapy, resistance to chemotherapy becomes imminent, resulting in high mortality. To combat this situation, lycopodine, a pharmacologically important bioactive component derived from Lycopodium clavatum spores, was tested against hormone sensitive (LnCaP) and refractory (PC3) prostate cancer cells in vitro. This study aims to check if lycopodine has demonstrable anti-cancer effects and if it has, to find out the possible mechanism of its action. The MTT assay was performed to evaluate the cytotoxic effect. Depolarization of mitochondrial membrane potential, cell cycle, EGF receptor activity and apoptosis were recorded by FACS; profiles of different anti- and pro-apoptotic genes and their products were studied by semi-quantitative RT-PCR, indirect-ELISA, western blotting. Drug–DNA interaction was determined by CD spectroscopy. Administration of lycopodine down-regulated the expression of 5-lipoxygenase and the 5-oxo-ETE receptor (OXE receptor1) and EGF receptor, and caused up-regulation of cytochrome c with depolarization of mitochondrial inner membrane potential, without palpable change in p53 activity, resulting in apoptosis, cell arrest at G0/G1 stage and ultimately reduced proliferation of cancer cells; concomitantly, there was externalization of phosphotidyl serine residues. CD spectroscopic analysis revealed intercalating property of lycopodine with DNA molecule, implicating its ability to block cellular DNA synthesis. The overall results suggest that lycopodine is a promising candidate suitable for therapeutic use as an anti-cancer drug.     

Childbearing After Hyperthermic Intraperitoneal Chemotherapy: Results From an International Survey

Background  

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) can improve survival in selected patients with primary or secondary peritoneal malignancies. With the opportunity for long-term survival, questions about the impact of those procedures in fertility in women of childbearing age can be raised.