Purpose Remimazolam is a new type of ultrashort benzodiazepine drug with an unclear optimal dose for general anesthesia induction in elderly patients aged >60 years. Therefore, this study aimed to determine the effective dose of remimazolam tosilate induction and explore its correlation with the bispectral index (BIS). Patients and Methods A total of 42 elderly patients were divided into two age groups: 60–69 (group A) and 70–85 (group B) years. An initial dose of 0.1mg/kg(Group A) and 0.05 mg/kg(Group B) remimazolam tosilate was administered, and the Modified Observer’s Assessment of Alertness/Sedation scale was used to assess adequate responses. The dose was calculated using the up-and-down allocation technique based on the previous response. The sequential formula and probit regression model were used to calculate ED50 and BIS50. ED95 was determined using the probit regression model. Results The ED50 of remimazolam tosilate for anesthesia induction were 0.088 mg/kg (95% confidence interval [CI] 0.071–0.108) and 0.061 mg/kg (95% CI 0.053–0.069) in groups A and B, respectively. ED95 was 0.118 mg/kg (95% CI 0.103–0.649) and 0.090 mg/kg (95% CI 0.075–0.199) in groups A and B, respectively. The remimazolam tosilate administration could decrease BIS. BIS50 was 86.0 (95% CI 83.7–88.6) and 85.4 (95% CI 84.1–86.8) in groups A and B, respectively. Conclusion During the induction process, patients’ consciousness should be observed. The dose of remimazolam tosilate could be chosen after careful consideration of individual variations.
Neuroinflammation is a common pathogenic mechanism in several neurodegenerative diseases, and glial cells are the primary inflammatory mediators of the central nervous system (CNS). Acute neuronal injury, infection, and chronic neurodegeneration may induce astrocyte activation, which is a response characterized by hyperproliferation and release of multiple inflammatory signaling factors. The opioid analgesic oxycodone has demonstrated anti-inflammatory efficacy in peripheral tissue, but its effects on the CNS have not been studied. We evaluated the inhibitory effects of oxycodone on astrocyte activation and proinflammatory mediator production in response to lipopolysaccharide (LPS). Our results showed that oxycodone (5–20 μg/ml) dose-dependently inhibited the LPS-induced astrocytosis, as measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide and bromodeoxyuridine assays, as well as the overexpression of glial fibrillary acidic protein, which are two hallmarks of reactive astrogliosis in neurodegenerative diseases. Oxycodone also decreased both the mRNA and protein expression levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β. Besides, oxycodone increased the expression of the nuclear factor kappa-B (NF-κB) endogenous inhibitor IκB-α, and blocked NF-κB translocation to the nucleus. The anti-inflammatory efficacy of oxycodone on rat astrocytes increased with pretreatment duration. These results suggest that oxycodone can suppress neuroinflammation by inhibiting NF-κB signaling in astrocytes. Targeting the astrocytic NF-κB-mediated inflammatory response may be an effective therapeutic strategy against diseases involving neuroinflammatory damage.
: Transmembrane protein 166 (TMEM166) is a lysosomal/endoplasmic reticulum (ER)-associated protein found in different species where it functions as a regulator of programmed cell death through autophagy and apoptosis. It is expressed in a variety of normal tissues and organs, and it is involved in a wide variety of physiological and pathological processes, including cancers, infection, autoimmune diseases, and neurodegenerative diseases. Previous studies indicated that TMEM166 is associated with autophagosomal membrane development. TMEM166 can cause lysosomal membrane permeabilization (LMP) leading to the release of proteolytic enzymes, e.g., cathepsins, that may cause potential mitochondrial membrane damage, which triggers several autophagic and apoptotic events. A low level of TMEM166 expression is also found in tumors, while high level of TMEM166 is found in brain ischemia. In addition, loss of TMEM166 leads to impaired NSC selfrenewal and differentiation along with a decrease in autophagy. These findings offer a comprehensive understanding of the pathways involved in the role of TMEM166 in programmed cell death and treatment of various diseases.
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