RESUMEN
In the clinical settings, patients often develop opioid-induced hyperalgesia (OIH) after utilization of high dose intra-operative remifentanil. Systemic α2 agonists, including dexmedetomidine, are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of hyperalgesia. The present study aimed to investigate the effect of dexmedetomidine on remifentanil-induced hyperalgesia and explored the sex differences. A total of 48 patients (24 male, 24 female) with an American Society of Anesthesiologists physical status of I-II that were undergoing thyroidectomy were randomly assigned to one of the following six groups: Male controlled group (MC) and female controlled group (FC) (group MC, n=8 and group FC, n=8), which received a preoperative placebo of 0.2 µg.kg-1 normal saline and intraoperative remifentanil 0.2 µg.kg-1.min-1; male and female group with low-dose dexmedetomidine (group MD1, n=8 and group FD1, n=8), which received preoperative dexmedetomidine 0.2 µg.kg-1 and intraoperative remifentanil 0.2 µg.kg-1.min-1; and male and female groups with high-dose dexmedetomidine (group MD2, n=8 and group FD2, n=8), which received dexmedetomidine 0.6 µg.kg-1 and intraoperative remifentanil 0.2 µg.kg-1.min-1. Result indicated that the visual analog scale (VAS) scores and morphine dosing frequency were significantly higher in MC and FC groups compared with the other same sex groups. Furthermore, the mechanical hyperalgesia threshold and patients' analgesia satisfaction score after surgery were significantly lower in MC and FC groups. Notably, the frequency of post-operative chills, nausea and vomiting were significantly lower in groups MD1, MD2, FD1 and FD2. The present findings indicated that low- and high-dose dexmedetomidine injection significantly decreased the patient's risk of enhanced pain intensity and increased postoperative morphine dosing caused by remifentanil-induced hyperalgesia. These findings suggest that the influence of dexmedetomidine displayed minimal significant differences between sex. Trial registration no., IRB2018-YX-001 (Name of registry: Institutional Medical Ethics Committee of Tianjin Medical University General Hospital; date of registration: February 1, 2016).
RESUMEN
BACKGROUND: O-GlcNAcylation is a highly dynamic post-translational modification that plays a key role in regulating phosphorylation of protein and cell survival. The proteins O-GlcNAcylation level is regulated dynamically by O-GlcNAc transferase (OGT) and ß-N-acetylglucosaminidase (O-GlcNAcase, OGA). Although previous studies have suggested the role of O-GlcNAcylation in neurodegenerative diseases, the mechanism of O-GlcNAcylation in Alzheimer's disease (AD) remains unclear. METHODS: The decrease of O-GlcNAcylation by alloxan, an OGT inhibitor, and increase by NAG-thiazolines (NAG-Ae), an O-GlcNAcase inhibitor were tested to investigate the effects of O-GlcNAc alteration on AD like neurodegeneration in SK-N-SH cells. RESULTS: The level of O-GlcNAcylation was decreased in alloxan treated cells and increased in NAG-Ae treated cells. Meanwhile, it was observed that both abnormal phosphorylation of NFs in cell bodies and apoptosis induced by alloxan treatment can be resisted by pretreatment or simultaneous treatment with appropriate NAG-Ae. CONCLUSION: These results demonstrated that increasing O-GlcNAc with NAG-Ae protected AD like neurodegeneration from NFs hyperphosphorylation and the cell loss, suggesting the role of O-GlcNAc in the pathogenesis and therapy of AD.