曲安奈德玻璃体内注射对视网膜的影响

目的研究曲安奈德（TA）玻璃体内注射的不同剂量和有无赋形剂对视网膜的影响。方法纯种新西兰白兔32只，随机分成4组行TA玻璃体内注射。第1组为去赋形剂的4 mg TA组，第2组为去赋形剂的25 mg TA组，第3组为含赋形剂的4 mg TA组，第4组为含赋形剂的25 mg TA组。每只动物注药前及注药后1周、1、2个月时行视网膜电图（ERG）检查，注药2个月后处死动物，摘除眼球行光学和电子显微镜检查。结果各组兔眼注药前后各时间点ERG潜伏期无明显变化，但含赋形剂组注药后ERG振幅较注药前降低，差异有统计学意义(P<0.01)；光学和电子显微镜检查显示含赋形剂组视网膜有不同程度的组织结构损害。结论TA玻璃体内注射时，≤25 mg的无赋形剂TA对视网膜形态和功能无影响；赋形剂的存在可导致视网膜功能和形态改变。(中华眼底病杂志,2005,21:229-232)     

脱氢表雄酮对大鼠的发育毒性

背景与目的:探讨脱氢表雄酮(dehydroe piandrosterone,DHEA)的发育毒性。材料与方法:将SD孕鼠随机分为5组,每组16只,分别为阳性对照组(阿司匹林300mg/kg),阴性对照组(蒸馏水)和DHEA10.4、20.8、41.7mg/kg3个剂量组,在受孕第7~16d连续10d给大鼠灌胃DHEA,第20d解剖取出胎鼠,观察DHEA对母体及胎鼠的影响。结果:DHEA剂量在10.4mg/kg时导致孕鼠流产;20.8、41.7mg/kg时孕鼠、胎鼠体重增加减缓,胸骨发育迟缓;41.7mg/kg时,胎鼠内脏畸形增加。3个剂量组胎鼠活胎率均降低。结论:DHEA对孕鼠及胎鼠均有毒性表现。     

The bottom line: Outcomes after conservation treatment in anal cancer

At the Department of Radiation Oncology, Westmead Hospital, between 1980 and 2000, 60 patients with squamous cell carcinoma of anal canal or margin (including 15 with Stage IIIA or IIIB) were treated radically; 55 received chemoradiation (89% were prescribed mitomycin C and 5‐fluorouracil). Five‐year overall survival was 64% (95% confidence interval (CI): 48–79%), with a median survival of 9.75 years (median follow up 5.6 years, range 5 months to 22.5 years). Ten patients have died of disease. At 2 years the local control rate was 86%, and colostomy‐free survival was 83%. Relapse after 2 years was uncommon. Tumour size was the main factor driving outcomes, especially survival. Patients with larger tumours (T > 4 cm) had a hazard ratio for survival of 5.7 (95% CI: 1.8–17). Fourteen (24%) patients experienced treatment interruptions as a result of acute toxicity, including one death from neutropoenic sepsis. Seven (12%) patients, in total, experienced one or more late toxicities, grade 3 or above, including four women (all postmenopausal) who developed a radiation‐induced bone injury. Most patients with anal cancer can expect to retain a functional sphincter after chemoradiation/radiation. Further studies are in progress to determine the optimal chemoradiation protocol.     

A phase I dose-finding clinical pharmacokinetic study of an oral formulation of irinotecan (CPT-11) administered for 5 days every 3 weeks in patients with advanced solid tumours.

BACKGROUND: Oral administration of irinotecan (CPT-11) should allow sustained exposure to the drug without the inconvenience of intravenous delivery and with fewer side-effects. PATIENTS AND METHODS: The present phase I trial of CPT-11, administered orally as a powder-filled capsule for 5 consecutive days every 3 weeks at doses ranging from 30 to 90 mg/m(2)/day, was conducted in 47 patients for whom a satisfactory standard treatment option was no longer available (24 males/23 females; median age 51 years, range 26-85). Tumour types included melanoma (11), colorectal (4), urinary tract (3), lung/pleura (4), thyroid (3), liver (3), gallbladder (2), cervix/uterus (3), breast (2), pancreas (2), carcinoma and other cancer types (10). RESULTS: A total of 171 cycles were administered (median 3, range 1-11). Dose limiting toxicities (DLTs) occurred during the first cycle in five of 31 patients in the dose-escalation part of the study: one patient at the 50 mg/m(2)/day dose level (diarrhoea grade 4); one patient at the 80 mg/m(2)/day dose level (prolonged neutropenia grade 4 and diarrhoea grade 3); and three patients at the 90 mg/m(2)/day dose level (diarrhoea, vomiting and neutropenia). The 80 mg/m(2)/day dose level was expanded, as a feasibility study, to include 16 additional patients, five of whom had received extensive prior pelvic irradiation. A further three patients in this cohort experienced DLTs, two of whom had received extensive prior pelvic irradiation. One patient died on study day 15 during the first cycle of oral CPT-11 following grade 3 diarrhoea, febrile neutropenia and a necrotic enterocolitis. Overall the grade 3/4 toxicities in 47 patients were asthenia (19%), anorexia (17%), neutropenia (14.9 %), diarrhoea (13%), nausea (12.7%), vomiting (8.5%) and thrombocytopenia (8.5%). Partial responses were observed in two melanoma patients and disease stabilisation was noted in 17 (36.1%) patients. Pharmacokinetic parameters were recorded for 46 patients. CONCLUSIONS: At the maximum tolerated dose, defined as 80 mg/m(2)/day for 5 days every 3 weeks, oral CPT-11 was shown to be well tolerated and safe with few of the haematological toxicities associated with the intravenous formulation.     

奥沙利铂周围神经系统毒性的预防与治疗

周围神经毒性是奥沙利铂的临床剂量限制性毒性,随着对其机制的认识,临床上已有一些预防和治疗其毒性的药物,目前报道有预防和治疗作用的药物有镁盐、钙盐、卡马西平、阿米硫定、谷胱甘肽和加巴喷丁等。现就奥沙利铂神经毒性临床预防和治疗药物的进展做一综述。     

Insulin receptors and insulin action in the brain: review and clinical implications

Insulin receptors are known to be located on nerve cells in mammalian brain. The binding of insulin to dimerized receptors stimulates specialized transporter proteins that mediate the facilitated influx of glucose. However, neurons possess other mechanisms by which they obtain glucose, including transporters that are not insulin-dependent. Further, insulin receptors are unevenly distributed throughout the brain (with particularly high density in choroid plexus, olfactory bulb and regions of the striatum and cerebral cortex). Such factors imply that insulin, and insulin receptors, might have functions within the central nervous system in addition to those related to the supply of glucose. Indeed, invertebrate insulin-related peptides are synthesized in brain and serve as neurotransmitters or neuromodulators. The present review summarizes the structure, distribution and function of mammalian brain insulin receptors and the possible implications for central nervous system disorders. It is proposed that this is an under-studied subject of investigation.     

天麻对中枢神经系统影响的基础研究进展

概述了天麻对中枢神经系统的影响,探讨了其部分作用机理,为更深入地研究天麻及其在临床上的应用提供理论依据。天麻是我国民间用于治疗癫痫、中风等疾病的一种常用药。     

论中药不良反应的客观真实性

中药不良反应是当今人们关注的热点问题之一,国外应对方法是颁布与之相关的中药的禁令,国内对如何正确应对中药不良反应没有制定一种切实可行的措施。因此,本研究在回顾性研究的基础上,选取国家在中药安全性评价中作为示范研究的千里光、青木香、大黄、益母草、附子、柴胡等具有代表性的中药,审视中药不良反应的客观真实性,进而维护中药的良好声誉,释除人们对中药安全性的担忧。     

痔瘘熏洗颗粒毒理学研究

目的:观察痔瘘熏洗颗粒的毒性反应和评价其毒性大小。方法:采用家兔肛门粘膜,家兔完整或破损皮肤、豚鼠皮肤涂抹不同浓度的痔瘘熏洗颗粒混悬液,观察该药对肛门粘膜、皮肤有无刺激性和过敏性。采用大鼠直肠给予痔瘘熏洗粉混悬液,观察其对大鼠的急性毒性作用。结果:肉眼观察和病理检查均表明该药外用对家兔肛门粘膜、肛周皮肤和背部完整和破损皮肤均未显示局部刺激性,对豚鼠皮肤未显示过敏性反应,大鼠直肠给予3.84g干膏粉/kg亦未见明显毒性。结论:该制剂毒性小,安全性高。     

壮尔颗粒的毒理学实验研究

目的:考查动物灌胃给予壮尔颗粒的急性毒性和长期毒性。方法:以最大浓度、最大容积的壮尔颗粒给予小鼠,求出最大给药量;大鼠分壮尔颗粒高、中、低剂量组,对照组,连续灌胃13周,停药恢复期2周。观察实验期间大鼠的行为活动、外观体征、体重、摄食量的变化,给药末和恢复期末两次解剖,检测血液常规、血液生化、脏器系数,观察组织器官病理学变化。结果:24h最大给药剂量为72g/kg壮尔颗粒(相当于生药264g/kg,为临床有效剂量31倍);长期毒性实验,壮尔颗粒对大鼠经口给药的高剂量为24.0g/(kg·d)壮尔颗粒(相当于生药88g/(kg·d),为临床有效剂量的15.3倍),无明显毒性反应。结论:壮尔颗粒安全可靠。