Molecular interactions, internal structure and drug release kinetics of rationally developed polymer–lipid hybrid nanoparticles

This paper presents the first study of molecular interactions of ingredients and internal nanostructure in relation to drug loading and release mechanisms/kinetics of rationally designed solid polymer–lipid hybrid nanoparticles (PLN). The PLN were prepared by using a rationally selected composition that was found in our previous work to provide optimized interactions of verapamil hydrochloride (VRP) with dextran sulfate sodium (DS) and then the VRP–DS complex with dodecanoic acid (DA). The solid-state properties of the components, their molecular interactions and the morphology, particle size and internal structure of PLN were determined by use of differential scanning calorimetry, powder X-ray diffraction, ¹³C nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering. The distribution of VRP in PLN was examined by TEM imaging using a cationic gold tracer. Drug release studies were conducted in various media. Drug loading as high as 36% and loading efficiencies up to 99% were achieved in the rationally formulated PLN. Hydrogen bonding between drug, polymer and lipid and a uniform distribution of amorphous VRP within the solid lipid matrix were evident. Sustained drug release from the PLN was mainly controlled by ion exchange and diffusion processes. The results demonstrated that strong molecular interactions among the drug, the polymer and the lipid in the optimized formulation were responsible for the improved drug loading and release performance of the PLN.     

阵发性心房颤动触发因素的分析

目的了解阵发性心房颤动的触发因素。方法回顾性分析28例阵发性心房颤动患者动态心电图检查资料。结果阵发性心房颤动发生前出现房性早搏218次，占88．98％；短阵房性心动过速18次，占7．35％；窦性心动过缓5次，占2．04％；长R—R间歇1次，占0．4t％；其余3次占1．22％。结论阵发性心房颤动的触发因素中房性早搏最常见，动态心电图记录时间长，为临床诊断提供了充足的依据，进一步为临床治疗打下基础。     

淫羊藿炮制机制研究进展

综述淫羊藿炮制前后化学成分、药理作用及临床药效的变化.通过总结淫羊藿炮制研究现状,找出存在的问题,提出了淫羊藿炮制机制研究应从规范炮制工艺,结合中药指纹图谱研究炮制前后物质基础的变化,采用血药浓度法和药理效应法研究淫羊藿炮制机制的研究思路.     

炉甘石炮制机制研究

目的:探讨炉甘石炮制机制。方法:采用XRD,IR,TEM等方法对炮制前后的样品进行成分分析和结构表征,测定炮制前后炉甘石的抑菌活性。结果:700℃煅制1 h能使炉甘石分解较完全,ZnO含量高,水飞后颗粒变得小而均匀。ZnO,ZnCO3,Zn5(CO3)2(OH)6均有抑菌效果。结论:经高温煅烧水飞,炉甘石部分分解为ZnO,颗粒变小,可溶性杂质减少,ZnO含量增加,抑菌活性增强;炉甘石的有效成分是锌元素。     

硒和维生素E对前列环素和血栓素合成的调控机制

前列环素（ＰＧＩ２）和血栓素（ＴＸＡ２）是一对生物功能相反的强烈的细胞生理调节剂，其生物合成是由花生四烯酸经前列腺素合酶催化生成ＰＧＨ２，再在前列环素合酶和血栓素合酶的作用下分别异构为ＰＧＩ２和ＴＸＡ２。由于过氧化物对前列腺素合酶、前列环素合酶和血栓素合酶的催化活性有不同影响，所以能控制体内过氧化物水平的抗氧化剂硒和维生素Ｅ对ＰＧＩ２和ＴＸＡ２的合成具有调控作用。硒和维生素Ｅ缺乏促进ＰＧＩ２／ＴＸＡ２比值下降，补硒和维生素Ｅ可以纠正这种作用     

Effect of chromatic mechanisms on the detection of mesopic incremental targets at different eccentricities

Spectral sensitivity functions for the threshold detection of mesopic incremental targets were compared for different target eccentricities (10, 20, and 30°) and for different mesopic backgrounds (0.1, 0.5 and 1.0 cd m⁻²). Relative responsivities of achromatic mechanisms (L + M and rods) and chromatic mechanisms (S and |L–M|) were estimated for each eccentricity and background. Chromatic mechanisms contribute significantly to detection but their effect is lower at 30°. A new contrast metric ( C _CHC2) is introduced to account for the selective adaptation of the photoreceptors and the effects of the chromatic mechanisms i.e. broadening of the range of spectral sensitivity with multiple local maxima and yellow sub-additivity of detection performance. The C _CHC2 metric is compared with the achromatic contrast metric of the MOVE model ( C _MOVE). For the same target, C _CHC2 generally predicts a higher visibility level than C _MOVE. However, in accordance with visual observations, for grey or yellowish incremental targets appearing at the eccentricities of 20 and 30°, the visibility predicted by C _CHC2 is less than the visibility predicted by C _MOVE.     

Expression of PADI4 in hepatocellular carcinoma

Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.     

新型免疫抑制剂FTY720作用机制浅析

2-氨基-[2-（4-辛基苯基）乙基]-1，3-丙二醇盐酸盐（简称为FTY720）是一种来源于冬虫夏草的新型免疫抑制剂。从结构上不同于环孢素A（CsA）、他克莫司（FK506）以及雷帕霉素（Rapa）等，与其他免疫抑制剂相比，该药具有免疫抑制效果明显，毒副作用低等特点，有望成为新一代的免疫抑制剂。     

神经病理性疼痛机制研究进展

神经病理性疼痛程度重、治疗效果差,严重影响患者生活质量.神经病理性疼痛的病因有创伤、压迫、神经毒性药物、感染、自身免疫性疾病、肿瘤、维生素缺乏等,模拟这些病因的神经病理疼痛动物模型已大部分建立起来,极大地促进了对神经病理性疼痛的研究.神经病理性疼痛的发病机制复杂,目前认为既有外周神经敏化又有中枢神经系统敏化,除受损神经敏化,未受损神经以及胶质细胞也参与发病过程.现对近10年来的神经病理性疼痛机制研究的进展作一综述.     

手舟骨骨折损伤机制分析

目的探讨手舟骨骨折的原因、机制，为减少手舟骨骨折的发生提供预防措施。方法2006年11月-2007年11月，临床收集手舟骨骨折病例16例，详细询问并记录病史，结合X片、CT表现，从物理力学的角度分析受伤机制。结果16例均为腕过伸位着地受伤；5例为军事训练（单双杠、倒功）中受伤，其中1例受伤时上臂呈后伸位，4例呈前屈位；8例为打球时受伤，其中2例受伤时上臂呈后伸位，6例呈前屈位；3例为高处坠落（2-6m）时受伤，均为上臂前屈位手掌着地所致。结节部骨折0例，远端（粉碎性骨折）3例，腰部横形骨折10例，斜形骨折3例，纵形骨折0例，近端骨折0例。结论手舟骨骨折主要发病原因为高强度训练、运动及高处坠落时腕关节过伸位手掌着地受伤。受伤时手掌的不同位置及人体的不同运动倾向综合作用，通过不同的损伤机制造成手舟骨不同类型的损伤。