ABSTRACT
Objective To determine the median effective plasma concentration (Cp50) of remifentanil inhibiting cardiovascular response to CO2 pneumoperitoneum stimulus when combined with propofol in patients undergoing laparoscopic gynaecological surgery.Methods Twenty-two female patients scheduled for elective laparoscopic gynaecological surgery under general anesthesia, aged20-60 years, with a BMI 18-30 kg/m2, falling into ASA physical statusⅠ orⅡ, were enrolled in this study.Anesthesia was induced with propofol and remifentanil target-controlled infusion and iv injection of rocuronium 0.6 mg/kg.The target plasma concentration (Cp) of remifentanil and propofol were set at 5 ng/ml and 4μg/ml respectively.3 minutes after endotracheal intubation, the Cp of remifentanil was adjusted.The target Cp was set at 6 ng/ml in the first patient.CO2 pneumoperitoneum was performed after the target effect-site concentration and Cp were balanced.Each time Cp increased/decreased by 20％in the next patient depending on whether or not the cardiovascular response to CO2 pneumoperitoneum occurred.The positive cardiovascular response was defined as HR and/or MAP increasing by 20％ within 3 minutes after CO2 pneumoperitoneum.The Cp50 and 95％ confidence interval (CI) of remifentanil required to inhibit cardiovascular response to CO2 pneumoperitoneum stimulus when combined with propofol in patients undergoing laparoscopic gynaecological surgery were calculated.Results The Cp50 (95％ CI) of remifentanil required to inhibit cardiovascular response to CO2 pneumoperitoneum stimulus was 4.58 (4.14-5.08) ng/ml when combined with propofol in patients undergoing laparoscopic gynaecological surgery.Conclusion The Cp50 of remifentanil required to inhibit cardiovascular response to CO2 pneumoperitoneum stimulus was 4.58 ng/ml when combined with propofol in patients undergoing laparoscopic gynaecological surgery.
ABSTRACT
UNLABELLED: Pathways controling cell proliferation and cell survival require flexible adaptation to environmental stress. Our previous studies showed that latent membrane protein1 (LMP1) encoded by Epstein-Barr virus (EBV) could trigger the expression of Survivin, an apoptosis inhibitor and essential regulator of mitosis. The aim of the work was to analyze the role of Survivin signal pathway in mediating effects triggered by LMP1. METHODS: Tet-on LMP1 HNE2, a tetracycline-regulated LMP1-expression nasopharyngeal carcinoma cell line, was used as cell model. The subcellular location of Survivin was detected by indirect immunofluorescence and Western-blotting assay. Using Ab-knock-out and gene transfection, we introduced anti-sense PS-ODN-Survivin and anti-body to Survivin into the Tet-on LMP1 HNE2, and then the apoptosis and the proliferation of cells were analyzed by flow cytometry, cell colony formation and detection of caspase-3. The results show that upon induction of LMP1 expression, the expression of Survivin in nucleus, level of phosphorylated retinoblastoma gene (Rb), the number of cells in S stage of cell cycle, and the cell colony formation rate were higher than those without LMP1 induction; if the expression of Survivin and the nucleus translocation of Survivin were knocked by introduction of anti-sense PS-ODN-Survivin and anti-Survivin-antibodies respectively, apoptosis rates and the activity of caspase-3 increased. CONCLUSION: LMP1 could trigger the nucleus translocation of Survivin, which led to the shift of S stage and cell proliferation. LMP1 may promote cell proliferation and inhibits apoptosis via Survivin signal pathway.
Subject(s)
Apoptosis , Cell Proliferation , Gene Expression Regulation, Neoplastic , Microtubule-Associated Proteins/metabolism , Nasopharyngeal Neoplasms/metabolism , Neoplasm Proteins/metabolism , Viral Matrix Proteins/metabolism , Caspase 3 , Caspases/metabolism , Colony-Forming Units Assay , Humans , Inhibitor of Apoptosis Proteins , Microtubule-Associated Proteins/antagonists & inhibitors , Microtubule-Associated Proteins/genetics , Nasopharyngeal Neoplasms/genetics , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/genetics , Oligonucleotides, Antisense/pharmacology , Phosphorylation , Retinoblastoma Protein/metabolism , S Phase , Signal Transduction/physiology , Subcellular Fractions , Survivin , Tumor Cells, Cultured , Viral Matrix Proteins/antagonists & inhibitors , Viral Matrix Proteins/geneticsABSTRACT
AIM: To investigate the mechanism of the AP-1 signal transduction pathway inhibited by JIP in nasopharyngeal carcinoma cells. METHODS: AP-1 activity was triggered by Dox-induced LMP1 expression in Tet-on-LMP1-HNE 2 cells (L7). The retention of phospho-JNK in the cytoplasm caused by JIP was examined with immunofluroscence assay. RESULTS: 24 h after transfection of L7 cells with the JIP expression plasmid, the translocation of activated JNK was inhibited, which resulted in the retention of phospho-JNK in the cytoplasm and down-regulation of the AP-1 activity. CONCLUSION: JIP down-regulates the activity of AP-1 through the inhibition of the translocation of JNK.
