Chongqing, China
Chongqing, China

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Mu Y.,Chongqing Medical University | Li G.,Chongqing Medical University | Wang Z.-H.,Chongqing Medical University | Zhang C.-J.,Chongqing Xijiao Hospital
Acta Cardiologica Sinica | Year: 2011

Purpose: To investigate the changes of phosphorylated ataxia- telangiectasia-mutated (ATM)/ATM and Rad3-related (ATR) substrate and Akt proteins (p-ATM/ATR substrate and p-Akt) and their regulations by phenylephrine (PE) in the peri-infarct myocardium in rats. Methods: Myocardial infarction (MI) and Sham-operation were established by Litwin's method. Three days after operation, surviving Sprague-Dawley male rats were divided into four groups: MI, Sham, MI+PE, and Sham+PE group. Physiological buffered saline (1 ml/kg) or PE (0.65 mg/kg) were injected into the peritoneal cavity every day for 8 weeks, respectively. Twelve weeks after treatment, p-ATM/ATR substrate and p-Akt expression in myocardium around the infarcted regions were detected by Western blot. Results: Twelve weeks after treatment, p-ATM/ATR substrate and p-Akt expression were detected through Western blot in myocardium around the infarcted regions. The intensity (represented as normalized integrated optical density, IOD) for p-ATM/ATR substrate and p-Akt were (0.59 ± 0.07 and 0.68 ± 0.03) in theMI group, (0.63 ± 0.05 and 0.72 ± 0.04) in the Sham group, (0.99 ± 0.07 and 1.03 ± 0.05) in the MI+PE group and (0.65 ± 0.04 and 0.75 ± 0.04) in the Sham+PE group, respectively. Both presented with significantly increased expression in the MI+PE group as compared with the Sham+PE group (p < 0.05); and in theMI+PE group as compared with theMI group (p < 0.05). No difference was observed between theMI and Sham groups, or between the Sham+PE and Sham groups (p > 0.05). Conclusion: PE can significantly up-regulate p-ATM/ATR substrate and p-Akt expression and thus might activate ATM/ATR substrate/Akt pathway in myocardium around the infarcted regions. The activated ATM/ATR substrate/Akt pathway might be associated with the attenuation of post-infarction cardiac remodeling, fibrosis, ischemic cardiomyopathy and heart failure induced by PE.


Liu J.,Chongqing Medical University | Zhang L.,Chongqing Medical University | Hu W.,Chongqing Xijiao Hospital | Tian R.,Chongqing Medical University | And 2 more authors.
Carbohydrate Polymers | Year: 2012

The current study aims to develop and evaluate a colon-specific, pulsatile drug delivery system based on an impermeable capsule. A pulsatile capsule was prepared by sealing a 5-aminosalicylic acid rapid-disintegrating tablet inside an impermeable capsule body with a konjac glucomannan (KGM)-hydroxypropyl methylcellulose (HPMC)-lactose plug. The drug delivery system showed a typical pulsatile release profile with a lag time followed by a rapid release phase. The lag time was determined by the KGM/HPMC/lactose ratio, the type of HPMC, and the plug weight. The addition of β-glucanase and rat cecal contents into the release medium shortened the lag time significantly, which predicted the probable enzyme sensitivity of the KGM plug. The in vivo studies show that the plasma drug concentration can only be detected 5 h after oral administration of the capsule, which indirectly proves the colon-specific characteristics. These results indicate that the pulsatile capsule may have therapeutic potential for colon-specific drug delivery. © 2011 Elsevier Ltd. All Rights Reserved.


Lou J.,Chongqing Medical University | Hu W.,Chongqing Xijiao Hospital | Tian R.,Chongqing Medical University | Zhang H.,Chongqing Medical University | And 3 more authors.
International Journal of Nanomedicine | Year: 2014

This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic® F127 and Pluronic® F68 concentrations on the sol-gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application. © 2014 Lou et al.


Huang Y.,Chongqing Medical University | Tian R.,Chongqing Medical University | Hu W.,Chongqing Xijiao Hospital | Jia Y.,Chongqing Medical University | And 3 more authors.
Carbohydrate Polymers | Year: 2013

This study developed and evaluated a colon-specific pulsatile capsule with tablet of self-microemulsifying drug delivery system (SMEDDS). This system is based on an impermeable capsule containing a rapid-disintegrating curcumin-loaded SMEDDS tablet inside it, and a highly methoxylated pectin (H-pectin)/lactose tablet plugged in the capsule mouth. The SMEDDS tablet enhanced the solubility of curcumin, a water-insoluble drug. An in vitro release study of the pulsatile capsule showed a typical pulsatile release profile with a specific lag time. The lag time, which determines the efficiency of colon-specific delivery, could be regulated by varying the H-pectin/lactose ratio. Pectinase and rat cecal contents added to the release medium significantly shortened the erosion time, which proved that the H-pectin plug is sensitive to enzyme degradation. These results show that the pulsatile capsule with SMEDDS tablet has potential for the colon-specific delivery of water-insoluble drugs. © 2013 Elsevier Ltd.


Zhu X.-F.,Chongqing Medical University | Li G.,Chongqing Medical University | Zhang C.-J.,Chongqing Xijiao Hospital | Wang L.-P.,Chongqing Medical University | And 2 more authors.
Experimental and Clinical Cardiology | Year: 2014

BACKGROUND: The expression of integrin subunits and its downstream molecules was reported to be up-regulated in the peri-infarct myocardium. As a component of the integrin pathway, the phosphorylated v-crk avian sarcoma virus CT-10 oncogene homolog-like (p-CrkL) protein expression remains unclear in the peri-infarct myocardium. OBJECTIVES: To investigate the change of p-CrkL protein expression in the non-infarcted myocardium around the infarct lesions in rats treated with isoproterenol (ISO) or not. METHODS: Experimental myocardial infarction (MI) and sham-operation models were established. Seven days after operation, surviving rats were divided into MI, sham, MI+ISO and sham+ISO groups, and were treated with physiological buffered saline 5mL/kg or ISO 5mg/kg intraperitoneally once every 3 d for 12 weeks respectively. p-CrkL expression in the non-infarcted myocardium around the infarc lesions was detected by Western blot. RESULTS: Twelve weeks after treatment, the p-CrkL expression was (0.88 ± 0.19) in the MI group, (0.50 ± 0.16) in the sham group, (1.20 ± 0.21) in the MI+ISO group and (0.72 ± 0.18) in the sham+ISO group respectively. p-CrkL expression in the non-infarcted myocardium around the infarct lesions was significantly increased in the MI and MI+ISO groups compared with the sham group, and in the MI+ISO group compared with the sham+ISO group, and in the MI+ISO group compared with the MI group respectively (All p < 0.05). CONCLUSION: p-CrkL was significantly up-regulated in the non-infarcted myocardium around the infarct lesions. Moreover, ISO treatment could further significantly up-regulate its expression in the non-infarcted myocardium.


Li G.,Chongqing Medical University | Wang Z.-H.,Chongqing Medical University | Zhu B.-B.,Chongqing Medical University | Zhang C.-J.,Chongqing Medical University | Zhang C.-J.,Chongqing Xijiao Hospital
International Journal of Gerontology | Year: 2012

Background: The increased plasma uric acid has been documented in ischemic cardiomyopathy (ICM) and heart failure in other age ranges in human and in animal models. However, it remains incompletely clear whether plasma uric acid is associated with cardiac remodeling, ischemic cardiomyopathy and heart failure in elderly. So, the objective of the study was to investigate whether plasma uric acid was associated with postinfarction cardiac remodeling in elderly with a previous myocardial infarction. Methods: Data of 246 elderly aged 60 years and older with angiography-confirmed coronary heart disease and myocardial infarction were analyzed. Among the patients, 89 had ICM defined as left ventricular end-diastolic diameter [men > 55 mm, women > 50 mm (60.74 ± 5.79 mm)] measured by echocardiography. Difference in plasma uric acid was analyzed between patients with and without ICM. Results: There was significant increase in plasma uric acid in ICM compared with non-ICM (444.66 ± 160.97 umol/L vs. 372.59 ± 131.31 umol/L, p = 0.000), and plasma uric acid was significantly positively related to left ventricular end-diastolic diameter (r = 0.312, p = 0.000). Conclusions: Plasma uric acid is significantly increased in elderly with ICM complicated with previous myocardial infarction as well as with those elderly patients who have postinfarction cardiac remodeling and previous myocardial infarction. Copyright © 2012, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier.


Liu J.,Chongqing Medical University | Zhang L.,Chongqing Medical University | Jia Y.,Chongqing Medical University | Hu W.,Chongqing Xijiao Hospital | And 2 more authors.
Archives of Pharmacal Research | Year: 2012

The purpose of this study was to develop and evaluate a colon-specific, pulsatile drug delivery system, which consists of an impermeable capsule body filled with a 5-aminosalicylic acid rapid-disintegrating tablet and a pectin-based erodible plug placed in the opening of the capsule body. To obtain an appropriate gel-forming ability and suitable lag time for the colon-specific drug delivery, high-methoxy pectin (HM-pectin) was formulated with lactose and lowmethoxy pectin (LM-pectin) with HPMC to prepare the plug tablet. In order to evaluate the lag time, prior to the rapid drug release, both the formulation of the plug tablet and in vitro release medium were studied. The lag time prior to the rapid drug release was mainly determined by the HM-pectin/lactose or LM-pectin/HPMC ratio. The addition of pectinase or rat cecal content into the release medium shortened the lag time significantly, which predicted the probable enzyme sensitivity of pectin plug tablet. In vivo studies showed that the plasma concentration of drug can only be detected 6h after oral administration of the pulsatile capsule, which indirectly proved the colon-specific characteristics. These results show that the pulsatile capsule may have the therapeutic action for colon-specific drug delivery. © 2012 The Pharmaceutical Society of Korea and Springer Science+Business Media Dordrecht.


Yuan P.,Chongqing Medical University | Jia Y.,Chongqing Medical University | Zhang L.,Chongqing Medical University | Zhang J.,Chongqing Medical University | And 2 more authors.
Journal Wuhan University of Technology, Materials Science Edition | Year: 2012

The aim of the present work was to investigate the swelling behavior and the in vitro release of acemetacin and bovine serum albumin from alginate gel beads crosslinked with Ca 2+ or Ba 2+. The release profiles suggested that the extent of swelling of the alginate beads played an important role in the release of drug. Small drugs are mainly released via diffusion through the alginate gel matrix. Compared with small drugs, large molecule drugs are difficult to diffuse through the pores of the matrix bead until the beads swell to a certain extent to provide enough large pores. The Ba 2+ crosslinked alginate beads showed slower release rate compared with the Ca 2+ crosslinked alginate beads, whether loaded the large molecules or small drugs. In conclusion, the Ba 2+ crosslinked alginate beads are considered more suitable than Ca 2+ crosslinked alginate beads for using as a sustained release vehicle especially for large molecule drugs. © 2012 Wuhan University of Technology and Springer-Verlag Berlin Heidelberg.

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