Effects of the Environmental Oestrogens Bisphenol A,Tetrachlorobisphenol A,Tetrabromobisphenol A, 4‐Hydroxybiphenyl and 4,4′‐Dihydroxybiphenyl on Oestrogen Receptor Binding,Cell Proliferation and Regulation of Oestrogen Sensitive Proteins in the Human Breast Cancer Cell Line MCF‐7

Abstract: Bisphenol A is extensively used in the manufacturing of epoxy resins and polycarbonate plastics, whereas several brominated and chlorinated analogues are used as flame retardants and intermediates in the plastic industry. Due to the structural relationship between these chemicals and the high production volumes, we wanted to characterize and compare their potential oestrogen‐like potency using several end‐points in MCF‐7 cells: induction of pS2 protein and progesterone receptor, reduction of oestrogen receptor level, and stimulation of cell growth. Bisphenol A, tetrachloro‐ and tetrabromo‐bisphenol A, 4‐hydroxybiphenyl and 4,4′‐dihydroxybiphenyl all showed oestrogen‐like properties in MCF‐7 cells. The chemicals tested had affinity to the oestrogen receptor isolated from MCF‐7 cells, although their EC₅₀s were 1,000 to 80,000 times higher than the EC₅₀ of 17β‐oestradiol. Bisphenol A and 4‐hydroxybiphenyl induced cell growth in MCF‐7 cells, and the highest test concentrations induced responses, apparently exceeding the cell growth induced by 17β‐oestradiol. The other chemicals tested induced less than 50% of the maximum 17β‐oestradiol‐stimulated cell growth. Bisphenol A, 4‐hydroxybiphenyl, tetrabromobisphenol A and tetrachlorobisphenol A all increased the level of the oestrogen‐regulated proteins, progesterone receptor and pS2, whereas 4,4′‐dihydroxybiphenyl showed no such effect. Bisphenol A was the only chemical tested that clearly mimicked 17β‐oestradiol in its ability to reduce the level of cytosolic oestrogen receptors in MCF‐7 cells. By measuring several oestrogen‐dependent endpoints it seems that some xeno‐oestrogens cause an imbalanced oestrogen‐response. Their ability and potency in mimicking 17β‐oestrogen in one parameter is not necessarily accompanied by a similar effect in another oestrogen‐linked parameter.     

白术对抗体形成细胞的作用研究

目的：观察白术对小鼠抗体形成细胞的作用。方法：用100％浓度白术浸出液定期给小鼠灌胃，然后检测小鼠抗体产生能力．特异玫瑰花环结形成细胞检测(SRFC)、血清IgG检测。结果：用药组以上三项免疫学指标均增高，结论：白术有明显促进抗体形成细胞的作用。     

Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.     

Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors.

PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics. EXPERIMENTAL DESIGN: An initial i.v. bolus was administered to assess the bioavailability of diflomotecan. Fourteen days later, diflomotecan was administered p.o. once daily for 5 days to adult patients with solid malignant tumors and repeated every 3 weeks. BN80915 and its open lactone form BN80942 were measured. RESULTS: Twenty-two patients entered the study and received a total of 57 cycles of oral diflomotecan at flat dose levels of 0.10, 0.20, 0.27, and 0.35 mg. The main toxicity was hematological, but some patients experienced alopecia, mild gastrointestinal toxicity, and fatigue. At the 0.35-mg dose level, 2 of 4 patients experienced dose-limiting toxicity comprising grade 3 thrombocytopenia with epistaxis and febrile neutropenia in 1 patient and uncomplicated grade 4 neutropenia lasting for >7 days in another. Toxicity was acceptable at the 0.27-mg dose level at which dose-limiting toxicities were observed in 3 of 12 patients (grade 4 neutropenia > 7 days, complicated by fever in 1 patient but without other signs of infection). After two cycles of diflomotecan, 6 patients had disease stabilization, which was maintained in 2 patients for 9 months and >1 year, respectively. Diflomotecan pharmacokinetics were linear over the dose range studied. Systemic exposure correlated with the fall in WBC counts. The mean oral bioavailability (+/-SD) was 72.24 +/- 59.2% across all dose levels. Urinary excretion of BN80915 was very low. CONCLUSIONS: The recommended oral diflomotecan dose for Phase II studies is 0.27 mg/day x 5 every 3 weeks. This regimen is convenient and generally well tolerated with a favorable pharmacokinetic profile and high but variable bioavailability.     

高效液相色谱法测定淡豆豉药材中异黄酮的含量

目的:建立高效液相色谱法测定淡豆豉中异黄酮含量。方法:采用HPLC法,色谱柱为YWG C18柱(250 mm×4.5 mm,10μm),以甲醇-水-乙酸(10:10:1)为流动相,流速为0.8 mL·min-1,检测波长260 nm,测定淡豆豉中染料木素(genistein)、大豆黄素(daidzein)含量。结果:染料木素及大豆黄素的线性范围分别为2.00-40.00μg·mL-1和2.64-52.70μg·mL-1,相关系数分别为0.9994和0.9993,不同产地的淡豆豉中异黄酮含量差异较大。结论:本法准确、简便、快速,对于控制和评价淡豆豉的品质有重要意义。     

循环式扩张治疗食管化学灼伤后狭窄20例

目的　探讨食管化学灼伤后狭窄的简单、有效治疗方法 .方法　胃造瘘术后 ,食管内置入丝线 ,从鼻腔和胃造瘘口拉出连结 .用自制的食管扩张器 ,在丝线引导下进行扩张 .结果　食管上段狭窄 4例 ,中段 4例 ,下段 2例 ,全程不规则线状狭窄 1 0例 .经 3～ 8m o间断扩张治疗 ,全部顺利通过 1 8mm扩张器 ,进普食顺利 .经 2～ 5 a随访 ,效果良好 .结论　食管化学灼伤后狭窄行循环式扩张治疗是一种简单、有效、安全、经济的好方法 ,值得推广应用     

醒神胶囊对抗小鼠中枢及躯体疲劳的作用初探

目的:研究中药制剂醒神胶囊(茶叶、人参等)抗小鼠中枢及躯体疲劳的作用.方法:连续给药6d,分别观察第1、第6天小鼠的体重、自主活动、转棒耐力以及戊巴比妥钠对其的催眠效应.结果:醒神胶囊可以明显增加小鼠自主活动次数,延长小鼠转棒耐力时间,延长戊巴比妥钠催眠的潜伏时间、缩短其睡眠时间;其作用呈剂量依赖和时间依赖性.结论:醒神胶囊有良好的提神醒脑健体功效.     

子宫内膜异位症中单核-巨噬细胞分泌VEGF水平的研究

目的 :探讨单核 -巨噬细胞分泌血管内皮生长因子(VEGF)的水平在子宫内膜异位症(内异症)发病机制中的作用。方法 :采用酶联免疫吸附试验 ,检测20例内异症患者 (内异症组Ⅱ期2例 ,Ⅲ期8例 ,Ⅳ期10例 )、30例非内异症患者 (对照组 )外周血单核细胞及腹腔液巨噬细胞培养上清液中VEGF的含量。结果 :内异症组腹腔液巨噬细胞培养上清液中VEGF的含量高于对照组 (P<0.05),而外周血单核细胞培养上清液中VEGF的含量与对照组差别无统计学意义。各期内异症组外周血单核细胞及腹腔液巨噬细胞分泌VEGF的水平差别无统计学意义 ,与AFS -r评分无关。结论 :内异症患者主要通过腹腔液巨噬细胞分泌高水平的VEGF ,促进异位内膜的黏附、种植 ,VEGF的分泌水平与临床分期无关。     

阴沟肠杆菌质粒型AmpC酶基因的研究

目的调查阴沟肠杆菌质粒型AmpC酶基因的流行状况及基因型。方法采用ATB药敏试验板微量肉汤法,对44株临床分离的阴沟肠杆菌进行抗菌药物敏感试验,PCR方法检测DHA和ACT型AmpC酶基因。结果44株阴沟肠杆菌呈多重耐药;36株质粒AmpC酶基因阳性(81.8%),DHA和ACT-1基因阳性率分别为11.4%、79.5%,而且3株阴沟肠杆菌同时携带DHA和ACT-1基因。结论临床分离的阴沟肠杆菌多重耐药严重、质粒AmpC酶基因携带率高;阴沟肠杆菌中检出ACT-1基因为国内首次报道。     

医院人员咽部机会致病菌与岗位相关性的研究

目的 了解医院各类人员咽部带菌及药敏状况，以加强医院感染的预防和控制。方法 采用常规方法进行302份咽拭子标本培养和菌种鉴定，选择15种抗菌药物，用纸片扩散法对所分离的菌种进行药敏试验。结果 医院人员咽部机会致病菌的分离率为30．13％，护理人员咽部带菌率为41.32％，明显高于医技（20％，P〈0．05）和管理人员（9．52％，P〈0．01），临床医师（29．29％）高于管理人员（9．52％，P〈0．05）；副流感嗜血菌占分离菌株的56．57％，金黄色葡萄球菌占20．2％，肺炎克雷伯菌占10．1％，表皮葡萄球菌占7．07％；金黄色葡萄球菌对青霉素和苯唑西林的耐药率分别为75％和60％，表皮葡萄球菌对青霉素和苯唑西林的耐药率分别为57．1％和85．7％；副流感嗜血菌对哌拉西林、头孢唑林、头孢哌酮和庆大霉素耐药率为100．0％，对阿米卡星耐药率达98．2％。结论 医院各类人员咽部机会致病菌携带率存在差异；临床医护人员带菌率最高，管理人员最低；G^＋菌对青霉素和苯唑西林耐药率高，副流感嗜血菌对多种常用抗菌药物耐药；医院工作人员中临床医护人员是预防和控制医院感染的重点。