ABSTRACT
The present study sought to characterize the rheological and thickening properties of Konjac glucomannan (KGM) and prepare thickening components for special medical purposes using KGM and maltodextrin as the primary raw materials and guar gum (GG), xanthan gum (XG), locust bean gum (LBG), and carrageenan (KC) as the supplemented materials. The formulation and preparation processes were optimized through single factor experiments taking sensory evaluation as an indicator. The results confirm that KGM had excellent thickening performance, reaching about 90 times its own mass. The optimal formulation process of the thickening components based on KGM was as follows: the mass concentration of the compound thickener (KGM/GG/XG/LBG/KC = 13:2:2:2:1) was 5.0-7.0 mg/mL; the maltodextrin concentration was 10.0 mg/mL; the brewing temperature of the thickening component was 60 °C with no restriction on consumption time. The rheology test results revealed that the thickening components had shear thinning characteristics, which could provide three different thickening effects of nectar-thick level (350 mPa·s), honey-thick level (1250 mPa·s), and pudding-thick level (1810 mPa·s) suitable for people with different degrees of chewing disorders. Overall, this study provides a theoretical basis and technical reference for KGM as a dietary nutrition support for patients with dysphagia.
Subject(s)
Deglutition Disorders , Carrageenan , Humans , Mannans , Rheology/methods , ViscosityABSTRACT
Neurodegenerative diseases and postoperative cognitive dysfunction involve the accumulation of ß-amyloid peptide (Aß). High glucose can inhibit autophagy, which facilitates intracellular Aß clearance. The α2-adrenoreceptor agonist dexmedetomidine (DEX) can provide neuroprotection against several neurological diseases; however, the mechanism remains unclear. This study investigated whether DEX regulated autophagy via the AMPK/mTOR pathway to improve high glucose-induced neurotoxicity in SH-SY5Y/APP695 cells. SH-SY5Y/APP695 cells were cultured with high glucose with/without DEX. To examine the role of autophagy, the autophagy activator rapamycin (RAPA) and autophagy inhibitor 3-methyladenine (3-MA) were used. The selective AMPK inhibitor compound C was used to investigate the involvement of the AMPK pathway. Cell viability and apoptosis were examined by CCK-8 and annexin V-FITC/PI flow cytometric assays, respectively. Autophagy was analyzed by monodansylcadaverine staining of autophagic vacuoles. Autophagy- and apoptosis-related protein expression and the phosphorylation levels of AMPK/mTOR pathway molecules were quantified by western blotting. DEX pretreatment significantly suppressed high glucose-induced neurotoxicity in SH-SY5Y/APP695 cells, as evidenced by the enhanced viability, restoration of cellular morphology, and reduction in apoptotic cells. Furthermore, RAPA had a protective effect similar to that of DEX, but 3-MA eliminated the protective effect of DEX by promoting mTOR activation. Moreover, the AMPK/mTOR pathway was involved in DEX-mediated autophagy. Compound C significantly suppressed autophagy and reversed the protective effect of DEX against high glucose in SH-SY5Y/APP695 cells. Our findings demonstrated that DEX protected SH-SY5Y/APP695 cells against high glucose-induced neurotoxicity by upregulating autophagy through the AMPK/mTOR pathway, suggesting a role of DEX in treating POCD in diabetic patients.
Subject(s)
Dexmedetomidine , Neuroblastoma , Humans , AMP-Activated Protein Kinases/metabolism , Dexmedetomidine/pharmacology , Neuroblastoma/metabolism , TOR Serine-Threonine Kinases , Cell Line, Tumor , Autophagy , Apoptosis , Glucose/toxicityABSTRACT
Hypoxic-ischemic brain damage (HIBD) can result in significant global rates of neonatal death or permanent neurological disability. N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism, and m6A dysregulation is implicated in various neurological diseases. However, the biological roles and clinical significance of m6A in HIBD remain unclear. We currently evaluated the effect of HIBD on cerebral m6A methylation in RNAs in neonatal rats. The m6A dot blot assay showed a global augmentation in RNA m6A methylation post-HI. Herein, we also report on demethylase FTO, which is markedly downregulated in the hippocampus and is the main factor involved with aberrant m6A modification following HI. By conducting a comprehensive analysis of RNA-seq data and m6A microarray results, we found that transcripts with m6A modifications were more highly expressed overall than transcripts without m6A modifications. The overexpression of FTO resulted in the promotion of Akt/mTOR pathway hyperactivation, while simultaneously inhibiting autophagic function. This is carried out by the demethylation activity of FTO, which selectively demethylates transcripts of phosphatase and tensin homolog (PTEN), thus promoting its degradation and reduced protein expression after HI. Moreover, the synaptic and neurocognitive disorders induced by HI were effectively reversed through the overexpression of FTO in the hippocampus. Cumulatively, these findings demonstrate the functional importance of FTO-dependent hippocampal m6A methylome in cognitive function and provides novel mechanistic insights into the therapeutic potentials of FTO in neonatal HIBD.
Subject(s)
Cognitive Dysfunction , RNA , Animals , Rats , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism , Animals, Newborn , Cognitive Dysfunction/genetics , RNA/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
Background: A variety of regional analgesia methods are used during video-assisted thoracic surgery (VATS). Our network meta-analysis (NMA) sought to evaluate the advantages of various methods of localized postoperative pain management in VATS patients. Methods: PubMed, the Cochrane Library, and EMBASE were searched from their date of inception to May 2021 for randomized controlled trials (RCTs) comparing two or more types of locoregional analgesia in adults using any standardized clinical criteria. This was done using Bayesian NMA. Results: A total of 3,563 studies were initially identified, and 16 RCTs with a total of 1,144 participants were ultimately included. These studies, which spanned the years 2014 to 2021 and included data from eight different countries, presented new information. There were a variety of regional analgesia techniques used, and in terms of analgesic effect, thoracic epidural anesthesia (TEA) [SMD (standard mean difference) = 1.12, CrI (Credible interval): (-0.08 to -2.33)], thoracic paravertebral block (TPVB) (SMD = 0.67, CrI: (-0.25 to 1.60) and erector spinae plane block (ESPB) (SMD = 0.34, CrI: (-0.5 to 1.17) were better than other regional analgesia methods. Conclusion: Overall, these findings show that TEA, TPVB and ESPB may be effective forms of regional analgesia in VATS. This research could be a valuable resource for future efforts regarding the use of thoracic regional analgesia and enhanced recovery after surgery. Systematic Review Registration: Identifier [PROSPERO CRD42021253218].
ABSTRACT
INTRODUCTION: Pain management for older patients with hip fractures is challenging. This study aimed to investigate the effect of ultrasound-guided fascia iliac compartment block (UGFICB) using different doses of nalbuphine in combination with ropivacaine on preoperative analgesia in older patients with hip fractures. METHODS: In this multicenter randomized controlled trial, 280 elderly patients with hip fracture were randomly allocated into four UGFICB groups (n = 70 in each group): a ropivacaine group (30 mL 0.1% ropivacaine + 0.9% normal saline) and three ropivacaine plus nalbuphine groups (5, 10, and 20 mg nalbuphine, respectively). The primary outcomes were the duration of analgesia at rest and on passive movement. Secondary outcomes included sensory block area, side effects, and vital signs. The doses of rescue analgesia with parecoxib sodium were also analyzed. RESULTS: The addition of nalbuphine dose-dependently increased the duration of analgesia at rest and on passive movement (P < 0.05) and expanded the area of sensory block (P < 0.05). Compared with the ropivacaine group, the pain scores at rest and on movement at 6 and 8 h after the block were lower in three ropivacaine plus nalbuphine groups (P < 0.05), without between-group differences at 2, 4, and 12 h. The four groups had comparable side effects (nausea and vomiting) and vital signs (P > 0.05). CONCLUSIONS: UGFICB with 5, 10, and 20 mg nalbuphine added to ropivacaine prolonged the analgesia duration, increased sensory block area, reduced pain, and decreased the doses of rescue parecoxib sodium for older patients after hip fracture, without obvious side effects. Among these three doses, nalbuphine 20 mg in combination with ropivacaine provided the longest duration of analgesia and the largest sensory block area. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000029934).
ABSTRACT
OBJECTIVE: To observe the clinical effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients who underwent abdominal external hernia surgery at the time of consciousness and pain disappearing by target-controlled infusion (TCI) and bispectral index (BIS). METHODS: Fifty patients who underwent elective abdominal hernia surgery were randomly assigned into an observation group and a control group, 25 cases in each one. In the observation group, 30 minutes before anesthesia induction, Fugugou (Extra), Gan (CO12), Pizhixia (AT4), and Shenmen (TF4) were embedded by auricular needles until the end of surgery, 10 times of counter press each point. In the control group, the same amount of auricular tape was applied until the end of surgery at the same points without stimulation 30 minutes before anesthesia induction. Patients in the two groups were given total intravenous anesthesia, and BIS was monitored by BIS anesthesia depth monitor. Propofol was infused by TCI at a beginning concentration of 1.5µg/L and increased by 0.3µg/L every 30s until the patients lost their consciousness. After that, remifentanil was infused by TCI at a beginning concentration of 2.0µg/L and increased by 0.3µg/L every 30s until the patients had no body reaction to pain stimulation (orbital reflex). Indices were recorded, including mean arterial pressure (MAP), heart rate (HR) and the BIS values, at the time of T0 (entering into the operation room), T1 (losing consciousness) and T2 (pain relief), the plasma and effect site concentrations of propofol at T1, the plasma and effect site concentrations of remifentanil at T2. After surgery we recorded the total amounts of propofol and remifentanil, surgery time and anesthesia time. RESULTS: At T1 and T2, MAP and HR of the observation group were higher than those of the control group (P<0.05, P<0.01). At T1, the plasma and effect site concentrations of propofol in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). At T2, the plasma and effect site concentrations of remifentanil in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). There was no significant difference in BIS values at T1 and T2 between the two groups (bothP>0.05). There was no significant difference in operation time and anesthesia time between the two groups (bothP>0.05). The total amount of remifentanil in the observation group was significantly lower than that in the control group (P<0.01). There was no significant difference in the total amount of propofol between the two groups (P>0.05). CONCLUSIONS: Ear points embedding combined with propofol-remifentanil TCI could reduce the plasma and effect site concentrations of propofol and remifentanil and the total amount of remifentanil in elderly patients with extra-abdominal hernia surgery, and had the effect of assisting sedation and analgesia.
Subject(s)
Acupuncture Analgesia/methods , Acupuncture, Ear/methods , Anesthesia, Intravenous/methods , Anesthetics, Intravenous/administration & dosage , Hernia, Abdominal/surgery , Piperidines/administration & dosage , Propofol/administration & dosage , Acupuncture Points , Aged , Anesthesia, General , Elective Surgical Procedures , Electroencephalography , Humans , RemifentanilABSTRACT
Tricyclic antidepressant amitriptyline (AM) has been shown to exert neurotrophic activity on neurons. We thus explored whether AM may aid the neuronal development and protect anesthesia-induced neuro-injury in young spinal cord dorsal root ganglion (DRG) neurons.The DRG explants were prepared from 1-day-old rats. The effect of AM on aiding DRG neural development was examined by immunohistochemistry at dose-dependent manner. AM-induced changes in gene and protein expressions, and also phosphorylation states of tyrosine kinases receptor A (TrkA) and B (TrkB) in DRG, were examined by quantitative real-time polymerase chain reaction and western blot. The effect of AM on attenuating lidocaine-induced DRG neurodegeneration was examined by immunohistochemistry, and small interfering RNA (siRNA)-mediated TrkA/B down-regulation.Amitriptyline stimulated DRG neuronal development in dose-dependent manner, but exerted toxic effect at concentrations higher than 10âM. AM activated TrkA in DRG through phosphorylation, whereas it had little effect on TrkB-signaling pathway. AM reduced lidocaine-induced DRG neurodegeneration by regenerating neurites and growth cones. Moreover, the neuroprotection of AM on lidocaine-injured neurodegeneration was blocked by siRNA-mediated TrkA down-regulation, but not by TrkB down-regulation.Amitriptyline facilitated neuronal development and had protective effect on lidocaine-induced neurodegeneration, very likely through the activation of TrkA-signaling pathway in DRG.