赤芍提取物的抗疱疹病毒Ⅱ型作用

为探讨赤芍提取物对Ⅱ型单纯疱疹病毒（ＨＳＶ－ Ⅱ） 的抑制作用, 用兔肾细胞作体外治疗、预防及中和实验, 对赤芍抗ＨＳＶ＿Ⅱ作用进行评价。结果： 赤芍无毒浓度为１２．５ｇ／Ｌ, 有效抑制浓度为１ ．５６ｇ／Ｌ,对ＨＳＶ＿Ⅱ的感染有抑制病毒生长和对病毒颗粒有直接杀伤作用。提示赤芍提取物确有明显的抗ＨＳＶ＿Ⅱ复制的作用     

Bicyclic tripeptide mimetics with reverse turn inducing properties

Analogues of the hypertensive octapeptide angiotensin II, comprising novel constrained 5,8-bicyclic and 5,9-bicyclic tripeptide units adopting nonclassical beta-turn geometries, as deduced from theoretical conformational analysis, have been synthesized. Spontanous bicyclization upon acid-catalyzed deprotection of a model peptide, encompassing a protected omega-formyl alpha-amino acid in position 5 and cysteine residues in positions 3 and 7, revealed a strong preference for bicyclization toward the C-terminus. The bicyclic thiazolidine related angiotensin II analogues synthesized exhibited no affinity for the angiotensin II AT1 receptor.     

Angiotensin II analogues encompassing 5,9- and 5,10-fused thiazabicycloalkane tripeptide mimetics

A simple experimental procedure on solid phase for the construction of new tripeptidic 5,9- and 5,10-fused thiazabicycloalkane scaffolds that adopt beta-turns has been developed. This N-terminal-directed bicyclization, relying on masked aldehyde precursors derived from glutamic acid as key building blocks, provides a complement to the related bicyclization previously reported, where an aspartic acid-derived precursor was employed to induce cyclization toward the C-terminal end of the peptide. Thus, the regioselectivity of the bicyclization can be altered simply by varying the chain length of the incorporated aldehyde precursor. Four analogues of the hypertensive octapeptide angiotensin II, comprising the new scaffolds in the 3-5- and 5-7-positions, were synthesized. One of these conformationally constrained angiotensin II analogues exhibited AT(1) receptor affinity (K(i) = 750 nM). Results from theoretical conformational analysis of model compounds of the bicyclic tripeptide mimetics are presented, and they demonstrate that subtle differences in geometry have a strong impact on the affinity to the AT(1) receptor.     

药流与负压吸宫法的效果和可接受性研究

研究的目的:比较RU486/Cytotec药物和负压吸宫术两种流产方法的效果,以及医学的和个人的可接受性.对象为通过咨询,介绍两种流产方法后,让对象自愿选择而组成.年龄在20～34岁.药物组100例,闭经35～42天,第1天口服RU486 600mg,第3天服Cytotec(PGE1)0.4mg,第17、43天回医院随访.手术组100例,闭经≤56天,负压吸宫术后第14、43天回医院随访.结果:完全流产率药物组为89%,手术组为100%.对象选择这两种流产方法的主要原因:药物组94%的人认为痛苦少,手术组的55%认为手术快、节省时间,而且手术同时可取出或放置宫内节育器(占45%).结论:RU486/Cytotec药物流产和负压吸宫术在各自适合的人群中都具有高度的可接受性.两种方法各具优缺点,不能相互取代,二者相辅相成,取长补短,将使终止妊娠的措施更为安全     

Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide.

Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule.     

Cervene (Nalmefene) in acute ischemic stroke : final results of a phase III efficacy study. The Cervene Stroke Study Investigators

BACKGROUND AND PURPOSE: The goals of the present study were to assess the efficacy and safety of nalmefene (Cervene) in patients with acute (< or =6 hours) ischemic stroke and to investigate the safety of combined recombinant tissue plasminogen activator and nalmefene in a separate subset of patients. Nalmefene, an opioid antagonist with relative kappa receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. Results from an earlier phase II study in patients with acute ischemic stroke suggested that nalmefene was safe and tolerable and may be effective for patients <70 years old. METHODS: This investigation was a phase III, placebo-controlled, double-blind, randomized study of a 24-hour infusion of nalmefene. Patients with acute ischemic stroke who had an onset of symptoms within 6 hours and a baseline score of > or =4 on the NIH Stroke Scale were randomized to receive either 60 mg nalmefene administered as a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75 hours or placebo. The primary efficacy outcome was the proportion of patients achieving a score of > or =60 on the Barthel Index and a rating of "moderate disability" or better on the Glasgow Outcome Scale at 12 weeks. Assessments were performed at baseline (predose), hours 12 and 24, days 2 and 7, and week 12. RESULTS: A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old. CONCLUSIONS: Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours.