RESUMO
INTRODUCTION: Midazolam, a benzodiazepine, has a hypnotic effect and is widely used as an intravenous sedative. Past studies have clearly established that midazolam has beneficial effects in attenuating ischemia-reperfusion injury more than other currently used sedative drugs. However, the role of midazolam on chondroprotection via inhibition of matrix metalloproteinases (MMPs) is warrant investigation. The aim of this study was to examine the mechanisms of action of midazolam on MMP expression via nuclear factor κB (NF-κB) signaling in activated chondrosarcoma cells maintained in vitro. MATERIAL AND METHODS: Chondrocytes, SW1353 cells, were stimulated with phorbol 12-myristate 13-acetate (PMA) in the absence or presence of various concentrations of midazolam (5-20 µM). Release of MMP-9 into the culture media was determined by gelatin zymography. The expressions of MMP-1, MMP-9 and MMP-13, phosphorylation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases and degradation of IκB-α were determined by western blotting assay. RESULTS: Midazolam significantly down-regulated PMA-induced MMP-9 protein expression at concentrations of 5, 10 and 20 µM, the values were 1.95 ±0.09 (p < 0.01), 1.71 ±0.12 (p < 0.01) and 1.35 ±0.20 (p < 0.001), respectively. At concentrations of 5, 10 and 20 µM, it was significantly inhibited the PMA-induced expressions of MMP-1 (2.27 ±0.10, 1.98 ±0.11 and 1.56 ±0.15; p < 0.001) and MMP-13 (0.89 ±0.04, 0.81 ±0.07, and 0.74 ±0.09; p < 0.001), respectively. Midazolam at concentrations of 10 and 20 µM for 15 min significantly reversed the rate of degradation (0.895 ±0.051; p < 0.05 and 0.926 ±0.060; p < 0.01, respectively) of IκB-α in PMA-chondrocyte cells. In addition, this sedative drug inhibited PMA-induced levels of phos-ERK (1.243 ±0.12, 1.108 ±0.16 and 0.903 ±0.19, respectively) and phos-p38 (1.146 ±0.10, 1.063 ±0.13 and 0.946 ±0.18, at concentrations of (5, 10 and 20 µM), respectively. CONCLUSIONS: These results are important for understanding the mechanism of midazolam in inhibiting PMA-induced MMP expression through the signaling pathways of either NF-κB or ERK/p38 MAPKs down-regulation.
RESUMO
BACKGROUND: The bispectral index (BIS) and A-line autoregressive index (AAI) are electroencephalogram-derived monitoring indices of anesthesia. This study evaluated the efficacy of BIS- and AAI-guided sevoflurane anesthesia in children receiving ambulatory urologic surgeries. METHODS: One hundred sixty children (aged 3-12 years) undergoing ambulatory urologic surgery were randomized to receive sevoflurane anesthesia controlled either solely by clinical parameters (standard practice group), BIS-guided group within the BIS range of 40-60 (BIS group), or AAI-guided group within the AAI range of 15-30 (AAI group). The primary outcome was the recovery time, and the secondary outcome was the quality of recovery, including the incidence of emergency delirium measured by Pediatric Anesthesia Emergence Delirium score, incidence of postoperative nausea and vomiting, and parental satisfaction. RESULTS: Compared with the standard practice group, patients with BIS or AAI monitoring had shortened recovery time and consumed less sevoflurane. There were no significant differences in the incidences of emergence delirium, postoperative nausea and vomiting, or parental satisfaction among the three groups. CONCLUSION: BIS- and AAI- guided titration sevoflurane anesthesia could result in shortened recovery and reduced sevoflurane concentration and consumption without affecting the quality of recovery in children receiving ambulatory urologic surgery. The beneficial effects of AAI- and BIS-guided anesthesia in pediatric ambulatory surgeries are similar.
