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Guo J.-Y.,Sun Yat Sen University | Fang J.-Y.,Sun Yat Sen University | Xu S.-R.,Zhangzhou Municipal Hospital of Fujian Province | Wei M.,Sun Yat Sen University | Huang W.-Q.,Sun Yat Sen University
Therapeutics and Clinical Risk Management | Year: 2016

Background: Postoperative neurocognitive dysfunction induced by anesthetics, particularly in elderly patients with impaired oxygenation, is a common complication of surgery and is eliciting increased interest in clinical practice. To investigate the effects of anesthetics on neurocognition, we compared the effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation undergoing general anesthesia.Methods: Sixty-three patients with impaired cerebral oxygenation (jugular venous bulb oxygen saturation [SjvO2]<50%) or cerebral blood flow/cerebral metabolic rate of oxygen ([CBF/CMRO2]≤15%) undergoing elective abdominal surgery were randomly allocated into propofol group (group P) or sevoflurane group (group S). The clinical parameters and jugular venous bulb blood gas analysis were monitored throughout the surgical procedure. Cognitive function was assessed with the mini-mental state examination and Montreal Cognitive Assessment at day 1 and day 7 following surgery. S100β protein in plasma was measured using enzyme-linked immunosorbent assay.Results: The SjvO2 increased during anesthesia induction and surgery when compared to base-line but had no significant difference between group P and group S. When compared to baseline, the CBF/CMRO2 was increased only at the end of surgery and extubation in group P; however, the CBF/CMRO2 in group S was increased during anesthesia induction at 1hour, 2hours, end of surgery, and extubation. Furthermore, the CBF/CMRO2 in group S was significantly higher than that in group P during anesthesia induction at 1hour, 2hours, and end of surgery. S100β protein did not significantly change at extubation and 1day after surgery in both groups when compared to baseline. There was no significant difference in mini-mental state examination and Montreal Cognitive Assessment scores between group P and group S at all time points.Conclusion: Sevoflurane showed similar effects in postoperative neurocognitive function as propofol but could improve cerebral oxygenation in patients with impaired cerebral oxygenation. © 2016 Guo et al. Source


Cao H.-L.,Harbin Medical University | Zhou T.-Y.,Harbin Medical University | Luo F.-R.,Zhangzhou Municipal Hospital of Fujian Province | Bai B.,Harbin Medical University | And 4 more authors.
Chinese Journal of Interventional Imaging and Therapy | Year: 2012

Objective: To explore the protective effects of grape seed proanthocyanidins extracts (GSPE) on liver injury caused by transcatheter hepatic arterial embolization with lipiodol. Methods: Twelve healthy dogs were randomly divided into 3 groups, and transcatheter hepatic arterial embolization was performed. In group A, 10 ml lipiodol was infused into hepatic artery, while in group B, 10 ml lipiodol and 5 ml GSPE saturated solution were infused. Dogs in group C received 10 ml saline. The blood serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) were analyzed and compared statistically. Pathological changes of the liver were also observed. Results: After embolization, the serum levels of ALT, AST, MDA and TNF-α in group A and group B were significantly highter than those in group C (all P<0.05), as well as the injury of liver tissue; while the serum indicators in group B were obviously lower than those in group A (all P<0.05), and also the damage of liver tissue. Conclusion: Dogs' liver injury was successfully induced by transcatheter hepatic arterial embolization with lipiodol. GSPE can effectively prevent liver injury induced by transcatheter hepatic arterial embolization with lipiodol. The mechanism probably relate to the antioxidant and anti-inflammatory activities of GSPE. Source


Zong R.,Xiamen University | Zhou T.,Zhangzhou Municipal Hospital of Fujian Province | Lin Z.,Xiamen University | Bao X.,Xiamen University | And 7 more authors.
Investigative Ophthalmology and Visual Science | Year: 2016

PURPOSE. Although microRNA-184 (miR-184) is abundantly expressed in the corneas, the role of miR-184 in corneal neovascularization remains unknown. Here we investigated the association between miR-184 expression and corneal neovascularization. METHODS. Quantitative real-time PCR assay was conducted to detect the expression of miR-184 and its potential target genes in the corneal epithelium of rats with corneal suture-induced neovascularization. MicroRNA-184 was also applied topically to the suture rats. Mimic and inhibitor of miR-184 were transfected into the cultured human umbilical vein endothelial cells (HUVECs), human corneal epithelial (HCE) cells, and simian choroidal endothelial cells (RF/ 6A). The following experiments were performed to evaluate the effects of miR-184 in these transfected cells: cell proliferation by cell viability assay, cell migration by a scratch wound test, VEGF-induced tube formation, and VEGF and β-catenin levels by Western blot analysis. RESULTS. The expression of miR-184 was significantly reduced, whereas the gene expression of frizzled-4, a receptor of the Wnt pathway, was up-regulated in the corneal epithelium of corneal suture rats. The corneal neovascularization induced by suture was ameliorated by topical administration of miR-184. In the cells transfected with mimic and inhibitor of miR-184, miR-184 significantly suppressed the cell proliferation and cell migration of HUVECs, miR-184 down-regulated VEGF, and β-catenin expression in HUVECs and HCE cells. Furthermore, miR-184 inhibited the tube formation of RF/6A cells. CONCLUSIONS. Down-regulation of miR-184 is associated with up-regulation of VEGF and Wnt/ β-catenin expression as well as corneal neovascularization, indicating that miR-184 negatively regulates corneal neovascularization. © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved. Source


Cai N.-F.,Zhangzhou Municipal Hospital of Fujian Province | Cai N.-F.,Central South University | Cheng Z.-N.,Central South University | Zi Y.,Central South University | And 4 more authors.
Acta Pharmacologica Sinica | Year: 2014

Aim: Pharmacodynamic analysis of intravenous recombinant urate oxidase produced by Escherichia coli was performed in healthy subjects using a pharmacokinetic/pharmacodynamic (PK/PD) model.Methods: A randomized, single-blind, placebo-controlled study was performed in 40 healthy Chinese subjects (4 groups of 10 subjects each, placebo 4:1 ratio) who received infusions of uricase (single doses of 0.1, 0.2, and 0.3 mg/kg; multiple doses of 0.2 mg·kg-1·d-1 for 7 d). PK profiles were determined through plasma uricase activity, and PD profiles were established using uric acid levels in plasma and urine. The plasma PD parameter was estimated as changes in plasma uric acid levels as the effect in the indirect response model. Adverse events were also monitored.Results: A two-compartment PK model with constant iv input and first-order output was used to describe the kinetic process of plasma uricase. The low value (2.8 U/L) of drug concentration that achieved 50% of maximum effect (EC50) indicated that low plasma uricase concentrations were sufficient to produce pharmacological effects. A strong relationship (r2 =0.9991) between the mean uric acid concentration in blood and the mean uric acid excretion rate in urine in the range of 11 to 30 h after single dosing was found. Infusions of uricase were well tolerated in all subjects.Conclusion: The PK/PD model predicted the effective dose to be 0.1 mg/kg in healthy subjects. The excretion rate of uric acid in urine may be used as a new index for pharmacological effects in further clinical trials. © 2014 CPS and SIMM. Source


Luo X.,Central South University | Zhu L.-J.,Central South University | Cai N.-F.,Zhangzhou Municipal Hospital of Fujian Province | Zheng L.-Y.,Central South University | Cheng Z.-N.,Central South University
Acta Pharmacologica Sinica | Year: 2016

To examine how the endogenous CYP3A4 phenotype and CYP3A5∗3 genotype of Chinese renal transplant recipients influenced the dose-corrected trough concentration (C0/D) and weight-corrected daily dose (D/W) of tacrolimus.Methods:A total of 101 medically stable kidney transplant recipients were enrolled, and their blood and urine samples were gathered. The endogenous CYP3A4 phenotype was assessed by the ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone in urine. CYP3A5∗3 genotype was determined using PCR-RELP.Results:In overall renal transplant recipients, a multiple regression analysis including the endogenous CYP3A4 phenotype, CYP3A5∗3 genotype and post-operative period accounted for 60.1% of the variability in C0/D ratio; a regression equation consisting of the endogenous CYP3A4 phenotype, post-operative period, body mass index, CYP3A5∗3 genotype, gender, total bilirubin and age explained 61.0% of the variability in D/W ratio. In CYP3A5∗3/∗3 subjects, a combination of the endogenous CYP3A4 phenotype, post-operative period and age was responsible for 65.3% of the variability in C0/D ratio; a predictive equation including the endogenous CYP3A4 phenotype, post-operative period, body mass index, gender and age explained 61.2% of the variability in the D/W ratio. Base on desired target range of tacrolimus trough concentrations, individual daily dosage regimen was calculated, and all the observed daily doses were within the predicted range.Conclusion:This study provides the equations to predict tacrolimus metabolism and dosage requirements based on the endogenous CYP3A4 phenotype, CYP3A5∗3 genotype and other non-genetic variables. © 2016 CPS and SIMM. Source

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