4,5-Diaryl-3-aminopyrazole derivatives as analogs of Combretastatin A-4: synthesis and biological evaluation

A series of cis-restricted 4,5-diaryl-3-aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA-109, A549, SMMC-7721, and PC-3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G(2)/M phase. The docking research showed the conformation of 5a overlaps well with CA-4 in the crystallized protein complex, suggesting the 4,5-diaryl-3-aminopyrazoles were good mimics of CA-4.     

黄芩属植物中二萜类成分研究进展

黄芩属植物遍布世界各地,资源丰富。化学成分除黄酮外,目前从该属中还发现了一百余个二萜类化合物。本文综述了国内外对黄芩属植物萜类成分分布、化学结构和生物活性的研究进展,为该属植物二萜类化合物的药用价值开发利用提供参考。     

Effects of metoprolol,methyldopa, and nifedipine on endothelial progenitor cells in patients with gestational hypertension and preeclampsia

Endothelial progenitor cells (EPCs) are critical for vascular regeneration and function, but are reduced in hypertensive disorders of pregnancy. We aimed to determine the possible effects of antihypertensive drugs, such as metoprolol, methyldopa, and nifedipine, on EPC number and functions in patients with gestational hypertension and preeclampsia. We collected blood samples from 30 normal pregnant women, 67 patients with gestational hypertension and 48 patients with preeclampsia. The patients received no drug or an antihypertensive drug, such as metoprolol, methyldopa, or nifedipine, between 20 and 24 weeks of gestation. The number of EPCs and circulating endothelial cells (CECs) in the blood was measured by flow cytometry. Moreover, colony formation and migration assays were performed on the isolated EPCs. Both the systolic and diastolic blood pressure (BP) increased, while the percentage of flow‐mediated vasodilatation (FMD) decreased in patients with gestational hypertension and preeclampsia, compared to the healthy controls at 20 weeks of gestation. CEC number increased in the patients, whereas EPC counts decreased. Furthermore, EPC colony formation and migration abilities were also impaired in the patients. However, administration of metoprolol, methyldopa, or nifedipine effectively restored the systolic and diastolic BP, FMD%, EPCs, and CEC numbers, as well as EPC migration capacity. Endothelial progenitor cells colony formation ability selectively improved with methyldopa and nifedipine. In patients receiving no drugs, most of these indexes worsened within 4 weeks (study duration). This study revealed a new pharmacological action of these antihypertensive drugs against gestational hypertension and preeclampsia, thus supporting their clinical use.     

降压类保健食品中非法添加的氢氯噻嗪与氨苯蝶啶的检查

目的 建立HPLC法检查降压类保健食品中非法添加的氢氯噻嗪与氨苯蝶啶.方法 用Diamonsil C18(4.6mm×200 mm,5μm)色谱柱,流动相:乙腈-0.1％磷酸溶液(14∶86),流速:1.0 mL·min-1,检测波长:203 nm.结果 检查2种保健品中均含非法添加的化学药品成分.结论 本法测定简便,结果准确,专属性强,适用于检查降压类保健食品中非法添加的氢氯噻嗪与氨苯蝶啶.     

住院患者抗菌药物临床应用情况分析

目的调查分析本院住院患者抗菌药物应用情况,以加强抗菌药物的管理以及为规范本院合理使用抗菌药物提供依据。方法抽取医院2011年6月第2周患者出院病历301份,从抗菌药物使用率、品种选择、联合使用、用药频度及分级管理等情况进行调查、统计,用Excel分类汇总。结果抗菌药物使用率为44.19%,联合用药占26.32%,抗菌用药金额占总用药金额的20.69%;头孢菌素类药物金额居第一;在DDDs排序中注射类药物的DDDs高于口服类。结论本院抗菌药物使用基本合理,但仍需要进一步加强《抗菌药物临床用药指导原则》的学习,同时加大管理、干预力度和严格控制用药指证。     

注重科学的抗菌给药方案

本文从制定科学的抗菌给药方案的5个要点着手即准确的给药剂量、合适的给药途径、规范的给药次数、足够适当的疗程,以及必要时的联合用药,阐述社区临床医师与药师如何理解与应用抗菌药物。     

3种微生态制剂对抗菌药物的敏感性检测

目的 检测常用微生态制荆双歧杆菌四联活菌片、地衣芽孢杆菌活菌胶囊、酪酸梭菌活菌片对16种抗菌药物的敏感性.方法 从3种微生态制剂中培养并分离供试菌,用微生物鉴定分析仪和药敏纸片进行药物敏感性检测.结果 双歧杆菌四联活菌片对抗菌药物均敏感;地衣芽孢杆菌活菌胶囊对青霉素类、头孢菌素类、红霉素、克林霉素有不同程度的耐药,对氨基苷类、喹诺酮类等抗菌药物敏感;酪酸梭菌活菌片对头孢菌素类、氨基苷类、复方新诺明耐药,对青霉素类、红霉素、克林霉素、喹诺酮类等抗菌药物敏感.结论 根据药物敏感性试验,地衣芽孢杆菌活菌胶囊、酪酸梭菌活菌片可以与耐药的抗菌药物联用,双歧杆菌四联活菌片与抗菌药物有配伍禁忌,避免联用,必须联用时应错开服用时间.     

不稳定性心绞痛患者调脂干预对C反应蛋白的影响

目的 探讨阿托伐他汀对不稳定性心绞痛(UA)患者血浆高敏C-反应蛋白(hs-CRP)的影响.方法 测定60例不稳定性心绞痛患者在常规治疗基础上口服阿托伐他汀(商品名立普妥)20mg,治疗12个月前后血浆hs-CRP.结果 60例不稳定性心绞痛患者经阿托伐他汀治疗12个月后血浆hs-CRP显著下降(P＜0.01).结论 阿托伐他汀对不稳定性心绞痛患者减少炎症反应起着重要的作用.     

Chronic Treatment with Naltrexone Prevents Memory Retention Deficits in Rats Poisoned with the Sarin Analog Diisopropylfluorophosphate (DFP) and Treated with Atropine and Pralidoxime

Humans and rats poisoned with sarin develop chronic neurological disabilities that are not prevented with standardized antidotal therapy. We hypothesized that rats poisoned with the sarin analogue diisopropylfluorophosphate (DFP) and resuscitated with atropine and pralidoxime would have long-term memory deficits that were preventable with naltrexone treatment. Long Evans rats (250–275 g) were randomized to: DFP (N = 8): single subcutaneous (SC) injection of DFP (5 mg/kg). Treatment (N = 9): DFP (5 mg/kg) followed by chronic naltrexone (5 mg/kg/day × 12 weeks). Control (N = 12): single SC injection of isopropyl alcohol, (DFP vehicle) followed by chronic naltrexone (5 mg/kg/day). If toxicity developed after injection, antidotal therapy was initiated with atropine (2 mg/kg) and pralidoxime (25 mg/kg) and repeated as needed. After 12 weeks, rats underwent testing for place learning (acquisition) across 5 days of training using the Morris Water Maze. On day 6 a memory retention test was performed. Statistical analysis was performed using IBM SPSS Statistics. Rats receiving DFP rapidly developed toxicity requiring antidotal rescue. No differences in acquisition were seen between the DFP vs. DFP + naltrexone rats. During memory testing, DFP-poisoned rats spent significantly less time (29.4 ± 2.11 versus 38.5 ± 2.5 s, p < 0.05) and traveled less distance (267 ± 24.6 versus 370 ± 27.5 cm, p < 0.05) in the target quadrant compared to the treatment group. Treatment rats performed as well as control rats (p > 0.05) on the test for memory retention. Poisoning with DFP induced impaired memory retention. Deficits were not prevented by acute rescue with atropine and pralidoxime. Chronic naltrexone treatment led to preserved memory after DFP poisoning.     

某院尿路感染病原菌分布及耐药性分析

目的研究尿路感染病原菌的分布及其耐药性,为临床使用抗菌药物提供依据。方法收集2011年1月至2014年6月尿培养阳性菌株,应用M icro Scan Walk Aw ay40细菌鉴定及药敏分析系统对分离菌进行鉴定及药敏测定,根据CLSI 2014版标准判断药敏结果,用WHONET 5.6软件进行数据分析。结果共分离出2 028株病原菌,革兰阴性杆菌占65.3%,革兰阳性球菌占22.1%,真菌占12.6%。革兰阴性杆菌对亚胺培南、美洛培南、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦较敏感。屎肠球菌对所测试抗菌药物耐药率显著高于其他肠球菌,未发现耐万古霉素、利奈唑胺的革兰阳性球菌。结论尿路感染病原菌分布广泛,仍以革兰阴性杆菌为主,细菌耐药谱有较大差异,建议临床医生根据病原学监测资料有针对性地选择抗菌药物。