Pharmacokinetics,biodistribution and bioavailability of isoliquiritigenin after intravenous and oral administration

Context: Isoliquiritigenin (ISL) has been shown to exhibit a variety of biological activities. However, there is little research on the pharmacokinetic behavior and tissues distribution of ISL.

Objective: Pharmacokinetics, biodistribution and bioavailability of ISL after intravenous and oral administration were determined by systematic investigation in Sprague–Dawley rats.

Materials and methods: ISL was dissolved in medicinal ethanol-Tween 80–0.9% sodium chloride saline in a volume ratio of 10:15:75. The ISL solution was injected in rats via a tail vein at a single dose of 10, 20 and 50?mg/kg and administered orally in rats at a single dose of 20, 50 and 100?mg/kg, respectively. Blood samples were collected at time intervals of 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8 and 12?h after intravenous injection. Tissues of interests in mice were collected immediately at each determined time point (0.5, 1, 2, 3 and 6?h) after cervical dislocation.

Results: The dose-normalized AUC values were 7.3, 7.6 and 8.7?μg?×?h/ml (calculated based on the dose of 10?mg/kg) for intravenous doses of 10, 20 and 50?mg/kg, respectively. The elimination half-lifes (t_1/2λ) were 4.9, 4.6 and 4.8?h at 10, 20 and 50?mg/kg intravenous doses, respectively. The F values were 29.86, 22.70, 33.62% for oral doses of 20, 50 and 100?mg/kg, respectively. Liver, heart and kidney were major distribution tissues of ISL in mice. The plasma protein binding of ISL in rats was 43.72%.

Conclusion: The work may useful for further study of the bioactive mechanism of ISL.     

经伤椎椎弓根置钉内固定手术与跨伤椎短节段内固定手术治疗青年胸腰椎骨折的疗效比较

目的 经伤椎椎弓根置钉内固定手术与跨伤椎短节段内固定手术治疗青年胸腰椎骨折疗效比较.方法 将80例青年胸腰椎骨折患者按手术固定方法不同分为对照组和观察组,每组40例.对照组患者行跨伤椎短节段内固定手术,观察组患者行经伤椎椎弓根置钉内固定手术.两组矢状面Cobb角、伤椎前缘高度手术矫正情况以及术后随访期间丢失情况比较;于术后12个月采用视觉模拟评分法(VAS)评价患者疼痛情况,采用日本骨科协会(JOA)评价患者腰椎功能障碍情况.结果 术后,观察组Cobb角为(7.1±2.2)°,对照组Cobb角为(7.7±2.5)°,差异无统计学意义(P＞0.05);至随访末期,观察组Cobb角丢失(4.1±1.6)°,明显小于对照组(6.5±2.1)°,差异有统计学意义(P＜0.05).术后,观察组伤椎椎体前缘高度为(97.1±6.6)％,对照组伤椎椎体前缘高度(95.2±7.3)％,差异无统计学意义(P＞0.05);至随访末期,观察组伤椎椎体前缘高度丢失(4.4±1.1)％,明显小于对照组(8.3±2.3)％,差异有统计学意义(P＜0.05).术后12个月,两组VAS评分、JOA评分分别为(2.4±0.6)分、(25.8±7.2)分与(2.6±0.8)分、(26.1±8.4)分,组间比较差异无统计学意义(P＞0.05).结论 根据适应证应用经伤椎椎弓根置钉内固定手术,既可减少术后后凸畸形矫正的丢失,又可更好维持伤椎高度,为临床治疗青年胸腰椎骨折有效手段.     

剖宫产3584例指征分析

目的分析本院3年来3 584例剖宫产指征的构成及合理性,剖宫产指征动态变化及原因,寻找控制剖宫产率的办法,旨在进一步降低剖宫产率.方法本文对3 584例剖宫产的手术原因进行回顾性总结及分析.结果 3年来总剖宫产率49.06%,前8位指征依次为头盆不称、臀位、羊水过少、胎儿窘迫、巨大儿、脐带绕颈、社会因素、疤痕子宫.结论应加强产前检查,防治并发症,加强产科工作人员责任感,正确掌握剖宫产指征,利用社会舆论,宣传正确的分娩观.     

UPLC法测定一捻金中人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1的含量

目的:建立超高效液相色谱法测定一捻金中人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1含量的方法。方法:色谱柱:ZORBAX Eclipse Plus C18柱(2.1 mm×50 mm,1.8μm);流速:0.21 ml·min-1;柱温:30℃;流动相:乙腈-水梯度洗脱;检测波长:203 nm;进样量:1μl。结果:人参皂苷Rg1在浓度为0.020 3~0.303 9 mg·ml-1时线性关系良好(r=0.999 6),平均回收率为99.05%,RSD为1.3%(n=6);人参皂苷Re在浓度为0.020 2~0.302 7 mg·ml-1时线性关系良好(r=0.999 8),平均回收率为101.31%,RSD为1.1%(n=6);人参皂苷Rb1在浓度为0.020 3~0.305 1 mg·ml-1时线性关系良好,r=0.999 8,平均回收率为100.71%,RSD为0.9%(n=6)。结论:该方法简单、准确,可同时测定3种人参皂苷的含量,可作为一捻金的质量控制。     

药师在全胃肠外营养支持中的技术作用

目的：介绍和探讨药师在临床全胃肠外营养支持过程中的技术作用,以保证其临床使用的安全、有效,经济。方法：以有代表性的文献及工作实际为基础进行总结、归纳。结果：阐述了药师在全胃肠外营养支持过程中工作的必要性、基本方法和注意事项。结论：药师在全胃肠外营养支持中起到不可替代的作用。     

60例老年乳腺癌的临床病理特点及分子分型

目的 探讨老年女性乳腺癌临床病理特点及分子分型.方法 回顾性分析郑州人民医院2011年1月至2016年8月收治的60例60岁以上(包括60岁)老年女性乳腺癌及同期随机选取的60例青年乳腺癌(年龄≤35岁)的临床及病理资料.结果 60例老年女性乳腺癌中临床分期Ⅰ期12例,Ⅱ期44例,Ⅲ期4例;浸润性导管癌49例,有腋窝淋巴结转移32例;雌激素受体阳性48例,孕激素受体阳性43例,CerbB-2受体阳性表达18例;与青年组比较,在临床分期、肿块大小及ER、PR受体阳性表达差异均有统计学意义(P值分别为0.028、0.040、0.044、0.038);而在淋巴结有无转移、病理类型及CerbB-2受体阳性表达上差异均无统计学意义(P值分别为0.199、0.178、0.404);老年组LuminalA 29例、Luminal B 19例、TNBC(三阴性乳腺癌)5例、CerbB-2过表达7例,与青年组乳腺癌分子分型比较,P值为0.035.结论 老年乳腺癌具有独特的生物学特点,临床分期以Ⅰ、Ⅱ期为主,ER、PR受体阳性较多,病理类型以浸润性导管癌为主,分子分型以Luminal A、Luminal B较多.     

A natural lipopeptide of surfactin for oral delivery of insulin

Abstract

Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid α-helix and β-turn, but with increased flexible β-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.     

获取高质量生物样品图象的电镜技术浅析

获取高分辨率和高反差的生物样品电镜图象受许多因素的影响,它包括切片厚度的选择,电镜的校直合轴、加速电压的选择、以及聚焦方法和曝光时间等。除生物样品制备技术这一重要因素外,必须考虑到上述各因素间的相互关系及其综合选择、然后才有可能获得高质量的生物样品的超微结构图象。     

张琪以加味甘露饮治疗慢性肾功能衰竭的经验分析

张琪教授是全国著名中医临床学家,精于仲景学说,对金元四大家、明清各家学派及温病学术理论有高深造诣。临证善治多种疑难病症,如肾病、心病、神志病、肝病、风湿病、糖尿病等,但尤对慢性肾脏病有较深造诣,治疗方法独具特色。