Fabrication of Alginate-Based O/W Nanoemulsions for Transdermal Drug Delivery of Lidocaine: Influence of the Oil Phase and Surfactant

Transdermal drug delivery of lidocaine is a good choice for local anesthetic delivery. Microemulsions have shown great effectiveness for the transdermal transport of lidocaine. Oil-in-water nanoemulsions are particularly suitable for encapsulation of lipophilic molecules because of their ability to form stable and transparent delivery systems with good skin permeation. However, fabrication of nanoemulsions containing lidocaine to provide an extended local anesthetic effect is challenging. Hence, the aim of this study was to address this issue by employing alginate-based o/w nanocarriers using nanoemulsion template that is prepared by combined approaches of ultrasound and phase inversion temperature (PIT). In this study, the influence of system composition such as oil type, oil and surfactant concentration on the particle size, in vitro release and skin permeation of lidocaine nanoemulsions was investigated. Structural characterization of lidocaine nanoemulsions as a function of water dilution was done using DSC. Nanoemulsions with small droplet diameters (d < 150 nm) were obtained as demonstrated by dynamic light scattering (DLS) and cryo-TEM. These nanoemulsions were also able to release 90% of their content within 24-h through PDMS and pig skin and able to the drug release over a 48-h. This extended-release profile is highly favorable in transdermal drug delivery and shows the great potential of this nanoemulsion as delivery system.     

二氯苯染毒对小鼠组织中Zn、Cu、Fe含量的影响

采用亚急性试验,探讨对二氯苯（P—DCB）对小鼠组织中Zn、Cu、Fe的影响。选用36只小鼠,雌雄各半,随机分成3组,每组12只,分别给予P—DCBO（对照组）、450、900mg·kg^-1,每天灌胃染毒1次,连续7d,染毒结束后24h处死动物并称体质量、肝、肾质量,计算脏器系数。用火焰原子吸收法测定肝脏、血液和肾脏中Zn、Cu、Fe含量。与对照组相比,各染毒组体质量无明显变化。各组肝体系数无差异,但染毒组肾体系数明显高于对照组（P〈O．05）。900mg·kg^-1组肝脏中Zn含量及w（Zn）／w（Cu）值较450mg·kg^-1组有明显升高。与对照组相比,各染毒组血液中Zn含量呈现下降趋势,900nag·kg^-1组较对照组明显下降（P〈0．05）。900mg·kg^-1组肾脏中Cu质量分数明显低于450mg·kg^-1组,Fe质量分数则较对照组及450mg·kg^-1组均有降低,P—DCB可影响小鼠组织中元素Zn、Cu、Fe的含量及不同器官的再分布,提示微量元素失衡可能是P—DCB毒作用的重要机制。     

基于液相色谱-质谱技术的肾脏代谢组学分析方法研究

建立了一种基于高效液相色谱-超高分辨质谱技术的肾脏代谢组学分析方法。肾脏组织于液氮中研磨成粉后,采用甲基叔丁基醚/甲醇/水溶剂体系进行提取,分别得到强极性部分(下层)和弱极性部分(上层)提取物,依次采用HILIC亲水色谱柱和反相C18色谱柱进行梯度洗脱分离后,进行高分辨质谱分析。采用电喷雾离子源(ESI),正、负离子模式检测,扫描方式为全扫描,扫描范围为100~1000 Da,质量分辨率为120000。结果表明,该方法灵敏度高,专属性强,稳定性良好,可同时获取肾脏组织中的强极性和弱极性代谢物信息,可为肾脏疾病和药物肾毒性生物标志物的发现提供一种新的方法。     

SOFA评分联合超声对脓毒症合并AKI患者的预后价值分析

本文主要探究SOFA评分联合超声对脓毒症合并急性肾损伤(AKI)患者的预后价值。选取2017年1月~2019年1月本院脓毒症合并AKI患者50例作为观察组,并分为AKI 1、2、3期,将同期入院的50例脓毒症患者作为对照组,两组患者均采用SOFA评分联合超声进行预后评估。结果发现,观察组PDU评分低于对照组(P<0.05),RI值、SOFA评分高于对照组(P<0.05);不同分期的3组间的PDU评分、SOFA评分不同,随着AKI分期的增加,PDU评分降低、SOFA评分增加(P<0.05),但3组间的RI值并无不同(P>0.05);50例脓毒症合并AKI患者发生院内死亡率为44.00%。经单因素分析发现,年龄、机械通气时间、ICU住院时间、AKI分期、脓毒症休克、SOFA评分、PDU评分为影响患者预后不佳的因素(P<0.05);AKI3期、发生脓毒性休克、SOFA评分、PDU评分是脓毒症合并AKI患者预后不佳的独立因素(P<0.05),ROC曲线下面积(AUC)越大,对预后的预测效能越好,当AUC>70.00%时具有临床价值。两者联合显著高于单独应用SOFA评分(AUC=74.28%)或PDU评分(P<0.001)。上述结果说明,脓毒症合并AKI患者采用SOFA评分联合超声用于评估患者的预后,优于单独采用SOFA评分或超声,两者联合的预测价值更大。     

Determination of Immunosuppressive Pharmaceuticals in Whole Blood Following Kidney Transplantation by High-performance Liquid Chromatography–Tandem Mass Spectrometry

Cyclosporine, tacrolimus, sirolimus, and everolimus are commonly used immunosuppressants following organ transplantation. Their monitoring is used to determine the optimal dose for therapeutic effectiveness and minimize toxicity. High-performance liquid chromatographic–tandem mass spectrometry with positive electrospray ionization and multiple reaction monitoring mode was validated for the determination of cyclosporine A, tacrolimus, sirolimus, and everolimus in whole blood. A C18 analytical column was employed with a gradient elution of pH 4.0 aqueous 10?mmol/L ammonium acetate and acetonitrile. For the pretreatment of whole blood, simple protein precipitation was used with methanol:zinc sulfate. The calibration curves were linear from 20.0 to 1000?ng/mL for cyclosporine A, 1.0 to 50?ng/mL for tacrolimus and sirolimus, and 1.0 to 30?ng/mL for everolimus. The intra-assay precision and inter-assay precision were less than 15%. The method provides reliable and reproducible results according to the linearity, precision, accuracy, recovery, and matrix effects. The method has been introduced to routine clinical practice in Slovakia for the determination of immunosuppressants in patients after kidney transplantation.     

肾脏热物性测量及低温下细胞形态分析

肾脏热物性参数获取和微观结构的观察,对研究冰温延时保存器官的机理非常重要。采用差示扫描量热仪测量了离体肾脏导热系数、冰点和器官保存液冰点;利用低温显微系统对肾脏组织不同保存温度及不同降温速率等状态条件,做了细胞形态的观察与分析。研究结果认为,鲜活肾脏导热系数值对肾脏冷却速率影响较大,同时发现在实验条件范围内较小的降温速率对细胞的损伤较轻。     

Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca(2+)-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death.     

微量进样-火焰原子吸收光谱法测定豚鼠内耳外淋巴液中钙、镁、钾、钠等元素含量

采用直接定量取样稀释、微量进样-火焰原子吸收光谱法测定了豚鼠内耳外淋巴液中Ca、Mg、K、Na等元素含量。方法简便、可靠，满足了生物样品测定的要求。     

High‐contrast Noninvasive Imaging of Kidney Clearance Kinetics Enabled by Renal Clearable Nanofluorophores

Noninvasive imaging of kidney clearance kinetics (KCK) of renal clearable probes is key to studying unilateral kidney function diseases, but such imaging is highly challenging to achieve with in vivo fluorescence. While this long‐standing challenge is often attributed to the limited light penetration depth, we found that rapid and persistent accumulation of conventional dyes in the skin “shadowed” real fluorescence signals from the kidneys and prevented noninvasive imaging of KCK, which, however, can be addressed with renal clearable nanofluorophores. By integrating near infrared emission with efficient renal clearance and ultralow background interference, the nanofluorophores can increase kidney‐contrast enhancement and imaging‐time window by approximately 50‐ and 1000‐fold over conventional dyes, and significantly minimize deviation between noninvasive and invasive KCK, laying down a foundation for translating in vivo fluorescence imaging in preclinical noninvasive kidney function assessments.