心肾同治方对心力衰竭大鼠心功能的影响

目的：观察心肾同治方对心力衰竭大鼠心功能的影响。方法：60只大鼠制备为心力衰竭模型,随机平均分为心肾同治方低剂量组、中剂量、高剂量组,曲美他嗪组,模型组,假手术组。造模2周后对除假手术对照组之外的大鼠进行药物灌胃8周。分析两种ATP酶活性及浓度、琥珀酸脱氢酶（succinodehydrogenase,SDH）值以及血流动力学参数。结果：与模型组比较,假手术组心肌左室内压上升最大速率及左室收缩压值均有所上升,同时心肌左室内压下降最大速率及左室舒张压表现为显著下降。心肾同治方中剂量组、高剂量组的左室收缩压、左室舒张压、心肌左室内压上升最大速率、心肌左室内压下降最大速率相关指标均接近于曲美他嗪组和假手术组,其中以高剂量组的改善尤为明显。对大鼠中药干预治疗后,实验数据显示其心肌Na＋-K＋ATP酶及Ca2＋-Mg2＋ATP酶和SDH的活力指标低于假手术组相关指标,但较模型组大鼠的指标有明显的提升。随着中药心肾同治方剂量的增加,心肌Na＋-K＋ATP酶、Ca2＋-Mg2＋ATP酶、SDH活力也逐渐增强;心肾同治方高剂量与曲美他嗪干预大鼠后的指标数据基本趋同。结论：心肾同治方在改善大鼠心力衰竭及提高其心功能的过程中,主要机制为：增加心肌Na＋-K＋ATP酶及Ca2＋-Mg2＋ATP酶分泌,提升SDH活力,改善心力衰竭大鼠血流动力学参数。     

重症真菌性角膜炎患者的临床特征分析

目的:探讨重症真菌性角膜炎病因、人群特征及临床特点。方法:搜集2008-01/2013-11就诊于我院眼科的233例233眼重症真菌性角膜炎患者的临床资料,回顾性分析其病因、人群特征、临床特点等情况。结果:重症真菌性角膜炎233例患者中,男153例(65.7%),男女比例约为1.9∶1;年龄分布中,中老年龄段人数居多,平均年龄52.7±11.3岁;居住地多为农村(78.1%);并且其职业以农民为主(66.1%),发病患者文化程度普遍较低(59.7%);重症患者中,188例(80.7%)患者具有明确的眼部外伤史,以植物性外伤为主(60.9%)。主要致病菌属为镰刀菌属,为90例(57.3%),其次为曲霉菌属47例(29.9%);治疗中手术率为87.9%。其中多数行穿透性角膜移植术,为83例(52.9%),在镰刀菌及曲霉菌感染的重症角膜炎患者中,行穿透性角膜移植术者比例较高,为58.4%(80/137);行眼内容剜除术或眼球摘除术的重症患者中,68.4%(13/19)的患者为镰刀菌属感染。结论:我院重症真菌性角膜炎患者多为农村居住的中老年男性农民,可能与其经济条件及诊疗意识差有关。其主要致病菌为镰刀菌及曲霉菌属,穿透性角膜移植手术为主要治疗手段,且预后差的重症患者多为镰刀菌感染。     

小切口非超声乳化白内障摘除术与超声乳化白内障吸除术的对比

目的：对比分析小切口非超声乳化白内障摘除术与超声乳化白内障吸除术的临床应用效果。

方法：选取2010-03/2013-02收治的老年性白内障患者93例124眼随机分为两组,42例59眼行小切口非超声乳化白内障摘除术(SICS组),51例65眼行超声乳化白内障吸除术(Phaco组),比较两组患者术后视力、角膜散光、手术源性散光及术中、术后并发症。

结果：术后1d; 1wk两组患者视力≥0.5分别为SICS组38眼(64.4%),41眼(69.5%),Phaco组29眼(44.6%),32眼(49.2%),SICS组的视力优于Phaco组(χ²=4.877,5.243,P<0.05)。术后1,3mo两组视力≥0.5眼数比较差异无统计学意义(χ²=0.005,0.085,P>0.05)。平均角膜散光采用重复测量设计方差分析：组内比较不同时间有统计学意义(F=25.624,P<0.05),且有随时间降低的趋势; 组间比较无统计学意义(F=0.986,P>0.05),两组患眼术后1wk平均角膜散光较术前增大,差异有统计学意义(t=2.906,2.427,P<0.05)。术后1wk; 1mo Phaco组手术源性散光SIA均低于SICS组(t=-4.628,2.770,P<0.05),术后3mo两组SIA对比差异无统计学意义(t=0.754,P>0.05), 组内比较和组间比较不同时间的SIA均有统计学意义(F=26.37,P<0.05,F=14.29,P<0.05)。两组患者术中后囊膜破裂、术后角膜水肿、前房色素膜反应对比差异无统计学意义。

结论：小切口非超声乳化白内障摘除术与超声乳化白内障吸除术对比,两种手术术后效果相近,对于白内障的治疗方案选择,白内障超声乳化手术并非唯一最佳手术方案,在缺少超乳设备的边远地区,选择小切口非超声乳化手术同样可以达到与超乳手术接近的术后视觉效果。     

Protective role of caffeic acid in an Aβ25-35-induced Alzheimer's disease model

BACKGROUND/OBJECTIVES

Alzheimer''s disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide (Aβ) and oxidative stress in the brain are the most common causes of AD.

MATERIALS/METHODS

Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an Aβ_25-35-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress.

RESULTS

In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the Aβ_25-35-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the Aβ_25-35-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day.

CONCLUSIONS

The present results suggest that CA improves Aβ_25-35-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.     

Determination of uric acid in biological samples by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry and study on pathogenesis of pulmonary arterial hypertension in pulmonary artery endothelium cells

Pulmonary arterial hypertension (PAH) is a severe cardiovascular disease that can lead to vascular remodelling and hypertension. Clinical diagnosis of PAH is very difficult. Uric acid (UA) can act as a biological marker for screening of PAH in patients. Multiple studies have indicated that reactive oxygen species (ROS) play an important role in the development of PAH. Thus, it is important to study the relationship between UA and ROS based on the pathogenesis of PAH. For monitoring PAH, a high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed to measure the concentration of UA from rat models and pulmonary arterial endothelial cells (PAECs) models, which were induced by monocrotaline (MCT) and hypoxia, respectively. In addition, the treatment groups were treated by N-acetyl-l-cysteine (NAC), a ROS scavenger. With the confirmation from hematoxylin-eosin (H&E) staining, the HPLC-ESI-MS/MS method was adopted to successfully analyze the concentration of UA. In this study, for the first time, thymine was used as an internal standard (I.S.) of uric acid. The results showed that the UA concentration in the PAH groups was higher than that in the normal groups, while the UA concentration in the treatment groups decreased compared to that in the PAH group (p < 0.05). It was experimentally proven that the HPLC-ESI-MS/MS method is a rapid, efficient and reliable quantitative method to detect PAH. Furthermore, our results indicated that UA and ROS have a double-regulator role.

Thymine firstly was used as an internal standard for uric acid.     

Physiologically based pharmacokinetics model predicts the lack of inhibition by repaglinide on the metabolism of pioglitazone

Purpose: Repaglinide and pioglitazone are both CYP2C8 and CYP3A4 substrates. This study was to determine whether repaglinide has an inhibitory effect on the metabolism of pioglitazone in vitro, in silico and in vivo. Method: In vitro, the effect of repaglinide on the metabolism of pioglitazone was assessed in pooled human liver microsomes. In silico, an IVIVE‐PBPK linked model was built with Simcyp®. Then, a randomized, 2‐phase cross‐over clinical study was conducted in 12 healthy volunteers. Results: Repaglinide showed a strong inhibitory effect on the metabolism of pioglitazone in vitro (K_i = 0.0757 µm ), [I]/K_i > 0.1. The Simcyp® prediction ratios of AUC and C_max between the two treatment groups were both about 1.01. The pharmacokinetics of pioglitazone in clinical trials showed no significant difference between these two treatment groups (p > 0.05). Conclusion: Repaglinide has no significant inhibitory effect on the metabolism of pioglitazone in vivo, which is inconsistent with the in vitro results. The lack of an inhibitory effect was partly due to extensive plasma protein binding and to the high in vivo clearance of repaglinide, for the concentration of repaglinide in vivo was far smaller than in vitro. Copyright © 2015 John Wiley & Sons, Ltd.     

Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX ? SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX ? SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and ?22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX ? SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX+ empty SLN) and VLX solution with Verapamil (VLX + Ver), respectively. Furthermore, the protein mass of P-gp in VLX ? SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.     

肌肽对局灶性脑缺血大鼠bcl-2、bax表达的影响

目的研究肌肽对局灶性脑缺血大鼠缺血皮质区B淋巴细胞瘤/白血病-2(bcl-2)、bcl-2相关蛋白X(bax)表达的影响。方法 30只SPF级雄性SD大鼠随机分为假手术组、模型组和肌肽组,每组10只。模型组和肌肽组以线栓法制作大鼠永久性脑缺血模型,肌肽组于造模后予肌肽水溶液灌胃[1 000 mg/(kg·d)],其余2组予等量生理盐水灌胃。分别于造模后清醒时、24 h、72 h通过神经功能缺损评分观察神经功能,于72 h采用2,3,5-三苯基氯化四氮唑(TTC)染色观察脑梗死体积、HE染色观察病理形态学改变,并用免疫组化法检测bcl-2和bax表达。结果肌肽组神经功能评分72 h较模型组降低(P<0.05);脑组织缺血损伤病理学改变轻于模型组;脑梗死体积72 h较模型组减小(P<0.01);脑缺血后72 h与假手术组相比,模型组bcl-2表达下降、bax表达上升、bcl-2/bax比值下降(均P<0.05);经肌肽处理后bcl-2表达上升、bax表达下降,bcl-2/bax比值上升(P<0.01或P<0.05)。结论肌肽处理能提高bcl-2表达、降低bax表达及提高bcl-2/bax比值,这可能是肌肽发挥神经保护作用的分子机制之一。