Effects of regional anesthesia aided sedation on patients’ psychological stress and postoperative recovery
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2665415 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Background: Propofol is a short-acting anesthetic, which is often used for induction and maintenance of general anesthesia, sedation for mechanically ventilated adults and procedural sedation. Several side effects of propofol are known and a substantial number of patients suffer from post-operative delirium after propofol application. In this study, we analyzed the effect of propofol on the function and protein expression profile on a proteome-wide scale. Methods: We cultured human brain microvascular endothelial cells in the absence and presence of propofol and analyzed the permeability of the blood-brain barrier (BBB) by fluorescein passage and protein expression on a proteome-wide scale by mass spectrometry. Results: Propofol interfered with the function of the blood-brain barrier. This was not due to de-creased adhesion of propofol-treated human brain microvascular endothelial cells. The proteomic analysis revealed that some key pathways in these cells were disturbed, such as oxygen metabolism, DNA damage recognition and response to stress. Conclusions: Propofol has strong effects on protein expression which could explain several side effects of propofol.
2022-10-13 | PXD033856 | Pride
Project description:Ciprofol is a new anesthetic, which combines with γ- Aminobutyric acid-a (GABAA) receptor. Ciprofol has shown equivalent anesthetic efficacy of propofol at 1/4 to 1/5 of the dosage. Ciprofol has the pharmacodynamic characteristics of rapid onset, stable and rapid recovery. Phase III clinical results showed that the incidence of injection pain and respiratory and circulatory depression of ciprofol was lower than that of propofol. Therefore, ciprofol has a good application prospect in sedation for gastrointestinal endoscopy, especially for obese patients. In the current study, we would explore the proper dose of Ciprofol in sedated gastrointestinal endoscopy in obese patients.
| 2746487 | ecrin-mdr-crc
Project description:1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the metabolic consequences of general anesthesia in the plasma of two groups of patients with diagnosis for non-metastatic colorectal cancer and metastatic colorectal cancer with liver-metastasis, respectively. Patients were treated with Etomidate or Propofol, two frequently used sedation agents. Plasma samples were obtained via Ficoll separation. Here, we demonstrated that this procedure introduces a number of limitations for NMR-based metabolomics studies, due to the appearance of spurious signals. Nevertheless, the comparison of the 1H NMR metabolomic profiles of patients treated with Etomidate or Propofol at equipotent dose ranges was still feasible and proved that both agents significantly decrease the plasma levels of several NMR-detectable metabolites. Consequently, samples collected during anesthesia are not suitable for metabolic profiling studies aimed at patient stratification, because interpersonal variability are reduced by the overall depression of metabolites levels. On the other hand, this study showed that plasma metabolomics could represent a valuable tool to monitor the effect of different sedation agents and/or the individual metabolic response to anesthesia, providing hints for an appropriate tuning of personalized sedation procedures. In our reference groups, the metabolomic signatures were slightly different in patients anesthetized with Etomidate versus Propofol. The importance of standardized collection procedures and availability of exhaustive metadata of the experimental design for the accurate evaluation of the significance of the observed changes in metabolites levels are critically discussed.
2015-11-17 | MTBLS172 | MetaboLights
Project description:Chloride intracellular channels (CLICs) are a unique family of evolutionarily conserved metamorphic proteins, switching between stable conformations based on redox conditions. CLICs have been implicated in a wide variety biological processes including ion channel activity, apoptosis, membrane trafficking, and enzymatic oxidoreductase activity. Understanding the molecular mechanisms by which CLICs engage in these activities is an area of active research. Here, the sole Drosophila melanogaster ortholog, Clic, was targeted for RNAi knockdown to identify genes and biological processes associated with Clic expression. Clic knockdown had a substantial impact on global transcription, altering expression of over 9% of transcribed Drosophila genes. Overrepresentation analysis of differentially expressed genes identified enrichment of 23 Gene Ontology terms including Cytoplasmic Translation, Oxidation-Reduction Process, Heme Binding, Membrane, Cell Junction, and Nucleolus. The top term, Cytoplasmic Translation, was enriched almost exclusively with downregulated genes. Drosophila Clic and vertebrate ortholog Clic4 have previously been tied to ethanol sensitivity and ethanol-regulated expression. Clic knockdown-responsive genes from the present study were found to overlap significantly with gene sets from 4 independently published studies related to ethanol exposure and sensitivity in Drosophila. Bioinformatic analysis of genes shared between these studies revealed an enrichment of genes related to amino acid metabolism, protein processing, oxidation-reduction processes, and lipid particles among others. To determine whether the modulation of ethanol sensitivity by Clic may be related to co-regulated oxidation-reduction processes, we evaluated the effect of hyperoxia on ethanol sedation in Clic knockdown flies. Consistent with previous findings, Clic knockdown reduced acute ethanol sedation sensitivity in flies housed under nomoxia. However, this effect was reversed by exposure to hyperoxia, suggesting a common set of molecular-genetic mechanism may modulate each of these processes. This study suggests that Drosophila Clic has a major influence on regulation of oxidative stress signaling and that this function overlaps with the molecular mechanisms of acute ethanol sensitivity in the fly.
2021-07-01 | GSE164090 | GEO
Project description:We sequenced microRNA from heads of two D. melanogaster populations: an ethanol treated group (30 minutes after sedation with ethanol saturated vapor), and an age-matched untreated control group; and calculated differential microRNA expression between the two groups.
2016-10-26 | GSE89137 | GEO
Project description:Propofol is an intravenous anesthetic that has been widely used in the clinical setting. Besides its anesthetic effects, propofol has been reported to influence the regulation of autonomic system. Controversies exist with regards to whether propofol exposure is safe for pregnant women and young children. The recent emergence of human induced pluripotent stem cells (hiPSCs) has provided a promising and theoretically inexhaustible source of neural progenitor cells (NPCs) for drug testing, which could be extended to in vitro experiments for anesthetics such as propofol. NPCs derived from three hiPSC lines, NES-GFP (a NESTIN-GFP reporter), USCK7 (iPSCs derived from urine derived cells), and ND2-0 (NIH), were treated with propofol at different concentrations (20, 50, 100 and 300 µM) for 6 h or 24 h. Early and late cell injury, cell proliferation and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for propofol-treated and untreated control iPSC-NPCs. Propofol treatment of NPCs for 6 h at the clinically relevant concentration (20 or 50 µM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 µM) decreased NPC viability and induced apoptosis. Prolonged treatment of propofol for 24 h significantly decreased cell viability. In addition, 20 µM propofol treatment for 6 h did not alter global gene expression. Higher concentration of propofol exerted potential cytotoxicity via multiple cellular mechanisms. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration of propofol treatment could decrease NPC viability and induce apoptosis.
2017-07-21 | GSE101724 | GEO
Project description:Blood plasma was collected from 9 naval aviation students 24 hours prior to and no more than 20 minutes after Modular Egress Training (psychological stressor).
2009-12-01 | PRD000158 | Pride
Project description:Interventions: Endoscopic submucosal dissection is performed using sedation of dexmedetomidine.
Primary outcome(s): Two hours after the treatmentwas finished, patient’s quaestionaire about pain, nausea and satisfaction of the sedation is evaluated.
Study Design: Single arm Non-randomized
| 2635391 | ecrin-mdr-crc
Project description:Individual differences in basal leukocyte gene expression profiles as a function of child's and parent's perception of family stress, and as a function of parent's psychological well-being. Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 273 individuals (129 parent:child pairs + 15 parent-or-child) who were also assessed on their perceptions of family stress (both parent's and child's perception). Each dyad is labeled by a case ID, with p suffix indicating parent's gene expression profile and c suffix indicating child's gene expression profile. Variations in gene expression are analyzed as a function of both parent's perception of family stress and child's perception of family stress (using UCLA Life Stress Interview, as previously described: Hammen C (1991) Generation of stress in the course of unipolar depression. J Abnorm Psychol 100:555-561; Adrian C, Hammen C (1993) Stress Exposure and Stress Generation in Children of Depressed Mothers. Journal of Consulting and Clinical Psychology 61:354-359; Rudolph KD, Hammen C (1999) Age and gender as determinants of stress exposure, generation, and reactions in youngsters: A transactional perspective. Child Development 70:660-677). Higher values indicate greater levels of subjectively perceived family stress. Additional data are available for 107 parents who completed all 6 subscales of the Psychological Well-Being (PWB) Scale (Ryff CD (1989) Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J. Pers Soc. Psychol 57: 1069-1081), resulting in scores for PWB_Total (average score across all 6 subscales) as well as scores for subscales measuring Purpose in Life (PWB_Purpose), Environmental Mastery (PWB_Environmental_Mastery), Self-Acceptance (PWB_Self_Accept), Autonomy (PWB_Autonomy), Personal Growth (PWB_Growth), Positive Relations with Others (PWB_Relationship). Higher scores indicate greater psychological well being. Also available for those individuals are measures of age (years), male gender (0/1), ethnic group (1=White, 2=Chinese, 3=Indian, 4=Other Asian, 5=Other Ethnicity), Body Mass Index (kg/m^2), heavy alcohol consumption history (0/1), smoking history (0/1), and abundance of 8 mRNA transcripts indicating the relative prevalence of major leukocyte subsets (CD3E, CD3D, CD19, CD4, CD8A, FCGR3A, NCAM1, CD14). key word: Risk prediction
2015-03-28 | E-GEOD-45329 | biostudies-arrayexpress
Project description:Anesthetic management of heart failure patients undergoing noncardiac surgery remains challenging due to cardiac suppressive properties of anesthetics. Due to varying electrophysiological properties, small and large animals are not good models for studying human myocardial anesthetic responses. Here we use hypertrophic (HCM), dilated (DCM) and healthy human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) to evaluate the cardiac suppression of propofol and etomidate. We demonstrate that propofol and etomidate act through GABAA receptors and contractile inhibition can occur without cell-cell junction. At supraphysiological dosage (100mM), we discovered that cardiac suppression induced by etomidate is reversible while propofol is not. Using transcriptome profiling, we uncover that etomidate was capable of inducing autophagy, likely through induction of cytosolic calcium. Lack of autophagy induction in propofol treated cardiomyocytes were associated with increased apoptosis. Together, we provide the robustness of using hiPSC-CMs as an in vitro cardiotoxicity platform for anesthetics. To delineate how etomidate confers cardioprotection during contraction inhibition, we performed transcriptome profiling on DCM hiPSC-CMs treated with either 10 μM propofol, 10 μM etomidate or DMSO control.
2022-08-30 | GSE212044 | GEO