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991.
992.
10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H), a novel active derivative of ginkgolide B, is a platelet-activating factor antagonist which is being under clinical trial. Two unknown related impurities were observed in analysis of XQ-1H bulk drug. A scaling up preparative liquid chromatography (Prep LC) was used for isolation of the two impurities. Based on LC–MS/MS and nuclear magnetic resonance (NMR) spectra, they were characterized as 10-O-(N,N-dimethylaminoethyl)-11,12-seco-ginkgolide B (imp-1) and 10-O-(N,N-dimethylaminoethyl)-11,12,2,15-diseco-3,14-dehydroginkgolide B (imp-2), respectively. A reversed-phase liquid chromatography (RP-LC) was developed for simultaneous determination of XQ-1H as well as imp-1 and imp-2. Main variables that significantly influence the chromatographic procedure were optimized and efficient chromatographic separation was achieved on a CN column with mobile phase consisting of 5 mM dipotassium hydrogen phosphate (pH 7.5) and methanol delivered in a gradient mode at the flow rate of 1.0 mL min−1. The method was validated and found to be suitable to check the quality of bulk samples of XQ-1H at test concentration of 5.0 mg mL−1 for a 20 μL injection volume. 相似文献
993.
Synthesis,molecular docking and biological evaluation of 1‐phenylsulphonyl‐2‐(1‐methylindol‐3‐yl)‐benzimidazole derivatives as novel potential tubulin assembling inhibitors 下载免费PDF全文
Yan‐Ting Wang Xun‐Chao Cai Tian‐Qi Shi Ya‐Liang Zhang Zhong‐Chang Wang Chang‐Hong Liu Hai‐Liang Zhu 《Chemical biology & drug design》2017,90(1):112-118
A series of new 1‐phenylsulphonyl‐2‐(1‐methylindol‐3‐yl)‐benzimidazole derivatives were designed, synthesized and evaluated as potential inhibitors of tubulin polymerization and anthropic cancer cell lines. Among them, compound 33 displayed the most potent tubulin polymerization inhibitory activity in vitro (IC50 = 1.41 μM) and strong antiproliferative activities against A549, Hela, HepG2 and MCF‐7 cell lines in vitro with GI50 value of 1.6, 2.7, 2.9 and 4.3 μM, respectively, comparable with the positive control colchicine (GI50 value of 4.1, 7.2, 9.5 and 14.5 μM, respectively) and CA‐4 (GI50 value of 2.2, 4.3, 6.4 and 11.4 μM, respectively). Simultaneously, we evaluated that compound 33 could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Immunofluorescence microscopy also clearly indicated compound 33 a potent antimicrotubule agent. Docking simulation showed that compound 33 could bind tightly with the colchicine‐binding site and act as a tubulin inhibitor. Three‐dimensional‐QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin assembling inhibitory activity in the future. 相似文献
994.
Case studies covering carbonaceous nanomaterials, metal oxide and metal sulphate nanomaterials, amorphous silica and organic pigments were performed to assess the Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). The usefulness of the DF4nanoGrouping for nanomaterial hazard assessment was confirmed. In two tiers that rely exclusively on non-animal test methods followed by a third tier, if necessary, in which data from rat short-term inhalation studies are evaluated, nanomaterials are assigned to one of four main groups (MGs). The DF4nanoGrouping proved efficient in sorting out nanomaterials that could undergo hazard assessment without further testing. These are soluble nanomaterials (MG1) whose further hazard assessment should rely on read-across to the dissolved materials, high aspect-ratio nanomaterials (MG2) which could be assessed according to their potential fibre toxicity and passive nanomaterials (MG3) that only elicit effects under pulmonary overload conditions. Thereby, the DF4nanoGrouping allows identifying active nanomaterials (MG4) that merit in-depth investigations, and it provides a solid rationale for their sub-grouping to specify the further information needs. Finally, the evaluated case study materials may be used as source nanomaterials in future read-across applications. Overall, the DF4nanoGrouping is a hazard assessment strategy that strictly uses animals as a last resort. 相似文献
995.
目的观察金柴抗病毒胶囊对甲型H1N1流感病毒PR8株感染小鼠肺炎的防治作用,为进一步临床应用提供依据。方法采用滴鼻感染正常小鼠和免疫低下小鼠建立流感病毒感染肺炎模型,分别采用治疗和预防性给药,观察给药后各组对小鼠肺指数、死亡率、生存时间的影响。结果①金柴抗病毒胶囊所试3个剂量组均可明显降低正常小鼠感染后和免疫低下小鼠感染后肺指数、减少死亡率并延长生存时间。②金柴抗病毒胶囊所试3个剂量组在降低以上两种动物模型肺指数、降低免疫低下小鼠感染后死亡率的作用方面与达菲比较,差异无统计学意义。结论金柴抗病毒胶囊对流感病毒感染有较好的治疗和预防作用。 相似文献
996.
Pabst D Kuehn J Schuler-Luettmann S Wiebe K Lebiedz P 《European Journal of Internal Medicine》2011,22(6):e119-e124
Introduction
The new strain of influenza A (H1N1) 2009, often referred to colloquially as “swine flu”, which was first detected in April 2009, raised to a pandemic of which the impact was not completely predictable. As reported, numerous cases with severe respiratory failure were also seen among young previously healthy people.Patients
In the present study, we report eight cases of influenza A (H1N1) 2009 admitted to our medical intensive care with severe respiratory failure between November and December 2009 and in January 2011. All patients were older than 30 but younger than 50 years, had clinical and radiological evidence of an Acute Respiratory Distress Syndrome (ARDS) and needed invasive ventilatory support.Results
Six of the eight patients had no relevant underlying disease; one had a pre-existing idiopathic lung fibrosis and another had a chronic obstructive pulmonary disease (COPD), an abuse of alcohol and an adiposities grade 3. Four patients needed an extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure with global respiratory insufficiency that could not be treated by conservative ventilatory support. The one patient with a pre-existing lung fibrosis died shortly after lung transplantation despite use of an extracorporeal membrane oxygenation. One other patient died due to a subarachnoidal bleeding under the anticoagulatory regime during ECMO therapy. The adipose COPD-patient died due to septic shock with multiple organ failure without possibility for ECMO support.Conclusions
The clinical course of severe cases of influenza A (H1N1) 2009-infection is markedly different from the disease pattern seen during epidemics of seasonal influenza. Most of the patients admitted to our intensive care unit due to influenza A (H1N1) 2009 associated ARDS were previously healthy young people. 相似文献997.
肾上腺髓质素前体N端20肽在血压调节中的作用 总被引:5,自引:0,他引:5
目的 探讨肾上腺髓质素前体N端 2 0肽 (PAMP)的心血管效应以及原发性高血压(EH)患者血浆PAMP的浓度变化。方法 静注PAMP ,观察其对大鼠的血压、心率、左室收缩峰压及舒张血管平滑肌的作用。用放免法测定EH患者的血浆PAMP浓度。结果 PAMP可以降低大鼠血压和舒张大鼠主动脉环张力 ,并呈剂量依赖性 ;EH患者血浆PAMP含量〔(30 .6 0± 2 .2 6 )ng/L〕明显高于对照组〔(18.41± 2 .33)ng/L ,P <0 .0 1〕 ,随病期的加重升高更明显 (P均 <0 .0 1) ,与平均动脉压呈正相关 (r=0 .431,P <0 .0 5 )。结论 PAMP是一种舒血管肽 ;EH患者血浆PAMP浓度升高可能是机体维持自稳态的一种保护性代偿机制 相似文献
998.
Tamer Ahmed Simon D. French Emmanuelle Belanger Ricardo Oliveira Guerra Maria Victoria Zunzunegui Mohammad Auais 《Journal of the American Medical Directors Association》2019,20(10):1199-1205.e4
ObjectivesWe examined the lower extremity function trajectories of older men and women over 4 years and baseline predictors of these trajectories.DesignLongitudinal analysis of an international cohort study.Settings and participantsOlder adults from the International Mobility in Aging Study (IMIAS) aged between 65 and 74 years at baseline.MeasuresPhysical performance of the lower extremities was measured in 2012, with follow-ups in 2014 and in 2016, using the Short Physical Performance Battery (SPPB). Group-based trajectory analysis of physical performance by gender was performed. Multinomial logistic regression was used to derive relative risk ratios with 95% confidence intervals between the physical performance trajectories and the potential baseline predictors in men and women separately.ResultsThree physical performance trajectories were identified in men and women: high-stable (30.0% vs 35.5%), gradual functional decline (63.1% vs 54.3%), and rapid functional decline (6.9% vs 10.2%). Common baseline characteristics associated with memberships in the gradual functional decline and rapid functional decline trajectory groups in men and women were age, single marital status, and multiple chronic conditions (>3). Among men, depression was a strong predictor of the membership in the rapid functional decline trajectory group. Women in the rapid functional decline trajectory group were more likely to be obese, with feminine and undifferentiated gender roles, and have poor self-rated health at baseline.Conclusions/ImplicationsThere are gender differences in the physical performance trajectories and related factors among older adults. Programs aiming at preventing or slowing functional decline in old age should be sensitive to gender. 相似文献
999.
Attention to Color: An Analysis of Selection, Controlled Search, and Motor Activation, Using Event-Related Potentials 总被引:3,自引:0,他引:3
Albertus A. Wijers Gijsbertus Mulder Tsunetaka Okita Lambertus J.M. Mulder Marten K. Scheffers 《Psychophysiology》1989,26(1):89-109
In this study the organization of information processing in a selective search task was examined by analyzing event-related potentials. This task consisted of searching for target letters in a relevant (attended) color. The ERPs revealed two different effects of attention: an early occipital negativity (+/- 150 ms) reflecting feature-specific attention, and a later, central N2b component (+/- 240 ms) reflecting covert orienting of attention. A later, prolonged negativity (search-related negativity) (+/- 300 ms), maximal at Cz, was related to controlled search to letters in the attended color. Detection of relevant targets resulted in a parietal P3b component. Depending on stimulus presentation conditions an earlier response to both attended and unattended targets was found: an N2 component (+/- 250 ms). In these same conditions, C'3-C'4 asymmetries (Corrected Motor Asymmetries--CMA) suggested motor activation at +/- 300 ms, in the same time range as search-related negativity. It was argued that N2 and CMA suggest the existence of a preattentive target detection system, operating in parallel with a slower serial attentive system, as reflected by N2b and search negativity. 相似文献
1000.
Objective The patient started from St. Louis (U. S.), and reached Chengdu (China) after 3 days of flight(St. Louis- Tokyo- Beijing - Chengdu). The patient felt unwell, so he and the two relatives took a taxi to the Emergency Center of Sichuan Provincial People' s Hospital for treatment. The epidemiological survey showed that, the patient had been living in the University of Missouri in the United States, no pigs died locally, there were no markets for the living pigs, farmers markets, farms, and slaughterhouses, and he hadn't contact with pigs. But 4 days before the onset, he closely contacted with a schoolmate, who had cold symptoms. The pa-tient had never been to virus laboratory 7 days before the onset. Clinical examinations showed that, the patient had a fever (37.8 ~ 38.8℃), WBC 7.9×10-9 L-1, N 5.475 × 10-9 L-1, L 19.5% ;the chest X-ray shewed that texture increased and the heart shadow augmented on both lungs; the result of throat swab culture was negative. The result of virus nucleic aeid detected by Sichnan Provincial Center for Disease Control showed H1N1 influenza virus, suspected. Sichuan Province Health organization organized experts on the prevention and control of H1N1 influenza for consultation, and the patient was diagnosed as the first suspected H1N1 influenza case in mainland China based on the epidemiological investigation, symptoms and signs of the patient, the results of laboratory ex-amination, and the result of virus test. Confirmed by the experts from Chinese center for disease control and pre-vention and The Ministry of Health of the People's Republic of China, the patient was diagnosed as the first H1N1 influenza case in mainland China. 相似文献