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941.
942.
Low‐Dose Aspirin Ameliorated Hyperlipidemia,Adhesion Molecule,and Chemokine Production Induced by High‐Fat Diet in Sprague‐Dawley Rats
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Hui‐Li Lin Hsueh‐Wei Yen Su‐Ling Hsieh Li‐Mei An Kuo‐Ping Shen 《Drug development research》2014,75(2):97-106
Preclinical Research |
943.
Richard J Shannon Ivan Timofeev Jürgens Nortje Peter J Hutchinson Keri L H Carpenter 《British journal of clinical pharmacology》2014,78(5):981-995
AimsThe aims were to determine blood–brain barrier penetration and brain extracellular pharmacokinetics for the anticonvulsant vigabatrin (VGB; γ-vinyl-γ-aminobutyric acid) in brain extracellular fluid and plasma from severe traumatic brain injury (TBI) patients, and to measure the response of γ-aminobutyric acid (GABA) concentration in brain extracellular fluid.MethodsSevere TBI patients (n = 10) received VGB (0.5 g enterally, every 12 h). Each patient had a cerebral microdialysis catheter; two patients had a second catheter in a different region of the brain. Plasma samples were collected 0.5 h before and 2, 4 and 11.5 h after the first VGB dose. Cerebral microdialysis commenced before the first VGB dose and continued through at least three doses of VGB. Controls were seven severe TBI patients with microdialysis, without VGB.ResultsAfter the first VGB dose, the maximum concentration of VGB (Cmax) was 31.7 (26.9–42.6) μmol l−1 (median and interquartile range for eight patients) in plasma and 2.41 (2.03–5.94) μmol l−1 in brain microdialysates (nine patients, 11 catheters), without significant plasma–brain correlation. After three doses, median Cmax in microdialysates increased to 5.22 (4.24–7.14) μmol l−1 (eight patients, 10 catheters). Microdialysate VGB concentrations were higher close to focal lesions than in distant sites. Microdialysate GABA concentrations increased modestly in some of the patients after VGB administration.ConclusionsVigabatrin, given enterally to severe TBI patients, crosses the blood–brain barrier into the brain extracellular fluid, where it accumulates with multiple dosing. Pharmacokinetics suggest delayed uptake from the blood. 相似文献
944.
Min-Hyo Ki Ji-Eon Kim Young-Nam Lee Sang Myoung Noh Sung-Won An Hyun-Jong Cho Dae-Duk Kim 《Pharmaceutical research》2014,31(12):3323-3334
Purpose
Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.Methods
Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.Results
Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.Conclusions
A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum. 相似文献945.
Irena Loryan Vikash Sinha Claire Mackie Achiel Van Peer Wilhelmus Drinkenburg An Vermeulen Denise Morrison Mario Monshouwer Donald Heald Margareta Hammarlund-Udenaes 《Pharmaceutical research》2014,31(8):2203-2219
Purpose
The current project was undertaken with the aim to propose and test an in-depth integrative analysis of neuropharmacokinetic (neuroPK) properties of new chemical entities (NCEs), thereby optimizing the routine of evaluation and selection of novel neurotherapeutics.Methods
Forty compounds covering a wide range of physicochemical properties and various CNS targets were investigated. The combinatory mapping approach was used for the assessment of the extent of blood-brain and cellular barriers transport via estimation of unbound-compound brain (Kp,uu,brain) and cell (Kp,uu,cell) partitioning coefficients. Intra-brain distribution was evaluated using the brain slice method. Intra- and sub-cellular distribution was estimated via calculation of unbound-drug cytosolic and lysosomal partitioning coefficients.Results
Assessment of Kp,uu,brain revealed extensive variability in the brain penetration properties across compounds, with a prevalence of compounds actively effluxed at the blood-brain barrier. Kp,uu,cell was valuable for identification of compounds with a tendency to accumulate intracellularly. Prediction of cytosolic and lysosomal partitioning provided insight into the subcellular accumulation. Integration of the neuroPK parameters with pharmacodynamic readouts demonstrated the value of the proposed approach in the evaluation of target engagement and NCE selection.Conclusions
With the rather easily-performed combinatory mapping approach, it was possible to provide quantitative information supporting the decision making in the drug discovery setting. 相似文献946.
Sun-A. Cho Yun Hyeok Jeong Ji Hoon Kim Seoyoung Kim Jun-Cheol Cho Young Heo Kyung-Do Suh Susun An Kyeho Shin 《Toxicology letters》2014
Cosmetics are normally composed of various ingredients. Some cosmetic ingredients can act as chemical haptens reacting toward proteins or peptides of human skin and they can provoke an immunologic reaction, called as skin sensitization. This haptenation process is very important step of inducing skin sensitization and evaluating the sensitizing potentials of cosmetic ingredients is very important for consumer safety. Therefore, animal alternative methods focusing on monitoring haptenation potential are undergoing vigorous research. To examine the further usefulness of spectrophotometric methods to monitor reactivity of chemicals toward peptides for cosmetic ingredients. Forty chemicals (25 sensitizers and 15 non-sensitizers) were reacted with 2 synthetic peptides, e.g., the cysteine peptides (Ac-RFAACAA-COOH) with free thiol group and the lysine peptides (Ac-RFAAKAA-COOH) with free amine group. Unreacted peptides can be detected after incubating with 5,5′-dithiobis-2-nitrobenzoic acid or fluorescamine™ as detection reagents for free thiol and amine group, respectively. Chemicals were categorized as sensitizers when they induced more than 10% depletion of cysteine peptides or more than 30% depletion of lysine peptides. The sensitivity, specificity, and accuracy were 80.0%, 86.7% and 82.5%, respectively. These results demonstrate that spectrophotometric methods can be an easy, fast, and high-throughput screening tools predicting the skin sensitization potential of chemical including cosmetic ingredient. 相似文献
947.
目的观察当归多糖对AD模型小鼠学习记忆功能,测定脑组织中NO含量、p16蛋白含量、NOS及AchE活性,探讨当归多糖治疗衰老的作用机制。方法 KM小鼠72只,采用Y型迷宫实验测定小鼠的学习记忆能力,应用生化法测定脑组织NO含量、NOS及AchE活性,ELISA法测定p16蛋白含量。结果当归多糖各剂量组小鼠学习记忆能力明显得到改善,脑组织中NO浓度、NOS活性、AchE活性和p16蛋白含量与对照组比较显著降低。结论当归多糖具有延缓衰老的作用,可能机制是通过抗氧化作用和调控细胞周期实现的。 相似文献
948.
目的分析急诊科危重症患者的疾病种类、患病性别、年龄、时间分布等特点,用以合理安排医疗资源,提高急诊应急能力和诊疗质量。方法回顾整理我院2006年1月1日~2010年-12月30日急诊科575名资料完整APACHE-II评分大于15分(含15),年龄大于16岁(含16)患者病例,分析危重症构成及规律。用EXCEL软件进行计算。结果急诊危重症患者人数呈逐年上升趋势,急诊危重症位居前五位的是:神经科系统疾病、循环系统疾病、呼吸系统疾病、中毒、颅脑损伤。急诊危重症患者男多于女,发病年龄段前5位的是:76岁以上,66~75岁,46~55岁,56~65岁,36—45岁。就诊量位居前五位月份是:1月、2月、3月、1off、4月。结论本研究揭示了我院16岁以上危重症疾病谱及性别、年龄、时间分布规律,为应对疾病高峰期,合理安排医疗资源,提高抢救成功率提供资料。 相似文献
949.
目的分析护理督导在社区产后访视中的应用效果。方法收集2010年5月至2013年5月本社区600例自愿接受产后访视的产妇,进行产后访视及护理督导,最后分析产妇在督导前后的知识和技能掌握程度。结果护理督导后,产妇恶露观察(83.67%)、母乳喂养(86.17%)、身体部位护理(88.17%)、体能训练(90.83%)、产后营养(77.17%)、沐浴(88.00%)、抚触(79.83%)等知识和技能掌握程度明届优于督导前,差异具有统计学意义(P〈0.05)。结论在社区产后访视中应用护理督导,可以及时解决产妇出院后护理方面产生的问题,为产妇提供延续护理,提高产妇生活质量。 相似文献
950.
医院药物不良反应127例分析 总被引:2,自引:0,他引:2
目的 总结医院药物不良反应(ADR)发生情况,为临床合理用药提供依据.方法 应用Excel软件对解放军第二六四医院2012年上报的127例ADR报告,分别从患者性别、年龄、引起ADR的药品种类、涉及器官或系统以及临床表现等进行分类统计、分析.结果 ADR报告涉及的127例患者中,男61例(48.0%),女66例(52.0%),男女比例为1∶1.08;60岁以上患者占比最高(49例,38.6%).ADR的临床表现以皮疹、瘙痒等皮肤及其附件损害为主(61例,48.0%),其次为消化系统(24例,18.9%)和免疫系统(20例,15.7%).损害涉及的药品有56种,抗感染药占首位(19种,52例,40.9%),其次为中成药(17种,31例,24.4%);头孢菌素类是引发ADR的主要抗感染药(25例,48.1%),以头孢西丁为首.结论 本院ADR主要累及皮肤及附件,抗感染药引发ADR最多,以头孢菌素类多见. 相似文献