Résistance au vécuronium chez le brûlé. Influence de la surface brûlée sur la dose efficace 95

ObjectiveTo assess the neuromuscular blocking effect of vecuronium in adult bum patients, to draw dose-response curves, to determine the ED 95 according to burn surface area, to analyze the time course of this pattern in order to recognize the development of a resistance according to the length of postinjury period.Study designProspective open study, extending over a 12 month period.PatientsSixty-three consecutive adult burn patients in an acute phase and 13 control patients who had been thermally injured at least 500 days before their inclusion in the study.MethodsAnaesthesia was achieved with thiopentone, fentanyl and vecuronium in patients undergoing excision and autograft surgery. Neuromuscular blockade was assessed by thumb adduction, measured by electromyography using evoked train of four responses to ulnar nerve stimulation. Dose-response curves were determined using the single dose method from only one predetermined dose of vecuronium per patient on each day of the study. Dose-response curves were compared using linear regression and ED 95 were calculated from log-probit data.ResultsIn the control group, ED 95 was 53 mg·kg⁻¹. Before the 7th postinjury day, patients did not differ from controls. Between the 7th and the 70th postinjury day the ED 95 increased significantly. Patients with a burn surface area (BSA) of less than 20% had a ED 95 of 69 mg·kg⁻¹, between 20% and 40% of BSA the ED 95 was 103 mg·kg⁻¹, between 40% and 60% BSA the ED 95 was 134 mg·kg⁻¹ and patients with a BSA over 60% had a ED 95 at 154 mg·kg⁻¹. The onset of action increased in all groups and was significantly different from control group.ConclusionAcutely burn patients become resistant to the neuromuscular blocking effect of vecuronium. This resistance is related to the magnitude of burn injury. The mechanism of resistance is related to an increase in nicotonic acetylcholine receptors.In these patients, the dose of vecuronium must be titrated to achieve effective muscular paralysis: The correcting factor is 1.3 for a BSA under 20%, 1.9 for a BSA between 20 and 40%, 2.5 for a BSA between 40 and 60%, and 2.9 for a BSA between 60%.     

Protein tyrosine phosphatase non-receptor type 12 suppresses tumor progression in osteosarcoma cells

BackgroundProtein tyrosine phosphatase non-receptor 12 (PTPN12) plays a prominent role in various cancers as a tumor suppressor. However, the expression of PTPN12 and its biological functions in osteosarcoma (OS) remains to be determined.MethodsPTPN12 expression in OS was explored in public databases and detected by immunohistochemistry and Western blot. The cell viability was determined by Cell Counting Kit-8 (CCK-8) assay and colony formation. The cell migration and invasion were assessed by the Transwell assay. Flow cytometry analysis was applied to detect cell apoptosis and cell cycle distribution. To investigate the related mechanism, the levels of EGFR and downstream proteins were detected by Western blot.ResultsPTPN12 expression was significantly decreased in OS samples in GEO database and our hospital. OS cell lines in Cancer Cell Line Encyclopedia (CCLE) database and our cultured OS cells also demonstrated low PTPN12 expression. Lentivirus-induced overexpression of PTPN12 significantly inhibited the cell viability, migration and invasion of 143B and U2OS cells. The results of flow cytometry found that PTPN12 overexpression promoted cell apoptosis and induced cell cycle arrest at G1 phase in 143B and U2OS cells. The phosphorylation levels of EGFR and subsequent proteins of the PI3K/AKT and ERK pathways were inactivated as a result of PTPN12 overexpression in OS.ConclusionPTPN12 plays a tumor suppressive role in OS cells. Restoring of PTPN12 activity may provide new insights for the treatment of this disease.