Bile duct ligation of C57BL/6 mice as a model of hepatic encephalopathy

Background: Bile duct ligation (BDL) has been used for experimental research on hepatic encephalopathy (HE) caused by chronic liver disease. However, little research has been done on a BDL model in C57BL/6 mouse. Therefore, we evaluated the suitability of a BDL model in C57BL/6 mouse for the study of HE and determined which behavioral tests are appropriate for the identification of HE in this model. Methods: Twelve to fourteen-week-old male C57BL/6 mice were randomly assigned to either sham group or BDL group. Histological changes in liver were confirmed by hematoxylin/ eosin and Masson’s trichrome staining. Liver function alterations were detected by alanine aminotransferase (ALT) and ammonia levels. To identify behavioral changes, open field, elevated plus maze, novel object recognition, and passive avoidance tests were performed. Results: Inflammatory liver injury and fibrosis were observed 14 days after BDL. ALT and ammonia levels were significantly higher in BDL group than in sham group. There were no differences in general locomotor activity or anxiety between the groups. No difference was observed between these two groups in the novel object recognition test, but BDL group showed significant learning/memory impairment in the passive avoidance test compared to sham group. Conclusions: Fourteen days of BDL in 12–14-week-old male C57BL/6 mice is a clinically relevant model for HE, as these mice have liver fibrosis with impaired liver function, hyperammonemia, and learning/memory impairment. Passive avoidance can be used as the major behavioral test in this model of HE.ope

The Incidence of Low Saturation by Pulse Oximetry in the Postanesthesia Care Unit

BACKGROUND: Patients are most likely to develop severe arterial desaturation during the early postoperative period. Respiratory complications in postanesthesia care unit (PACU) increase the risk of major adverse cardiac outcomes, unanticipated ICU admission or delay in PACU discharges. The increased use of inhalation agents with low blood : gas partition coefficient, intermediate-acting muscle relaxants and continuous pulse oximeter monitoring over the past 10 years may have altered the incidence of immediate postoperative hypoxemia. This study was undertaken to determine the overall incidence of immediate postoperative hypoxemia in PACU. METHODS: Hypoxemia was definsed as a pulse oxygen saturation (SpO2) of less than 90% lasting for at least 20 sec. The occurrence of hypoxemia was documented and notified to the anesthesiologist by PACU nurses. The anesthesiologist recorded contributory factors and the management modalities used in patients with hypoxemia. RESULTS: The incidence of hypoxia was 3.5 per 1,000 patients after general anesthesia. Most hypoxemic events (88%) occurred during the first 5 minutes after arrival in PACU. Upper airway obstruction was the major contributory factor for hypoxemia (75.5%) and most of these patients recovered simply after a jaw thrust or the insertion of an oral or nasal airway. CONCLUSIONS: Postoperative hypoxemia does not occur often in PACU, but when it does, it is associated with major morbidity and increased medical costs. Therefore, oxygen supply is recommended in patients with risk factors of hypoxemia during transfer from operating rooms to PACU. Close monitoring of hypoxemia in PACU is needed in all patients after general anesthesia.ope

Anandamide inhibition of 5-HT3A receptors varies with receptor density and desensitization

Converging evidence has suggested that anandamide (AEA), an endogenous agonist of cannabinoid (CB) receptors, can directly interact with certain types of ligand-gated ion channels (LGICs). However, little is known about the molecular and cellular mechanisms of AEA-induced direct effects on LGICs. Here, we report that AEA inhibited the function of serotoningated ion channels (5-HT(3A)) expressed in Xenopus laevis oocytes and human embryonic kidney 293 cells in a manner that was dependent on the steady-state receptor density at the cell surface. The magnitude of AEA inhibition was inversely correlated with the expression levels of receptor protein and function. With increasing surface receptor expression, the magnitude of AEA inhibition decreased. Consistent with this idea, pretreatment with actinomycin D, which inhibits transcription, decreased the amplitude of current activated by maximal concentrations of 5-hydroxytryptamine (5-HT) and increased the magnitude of AEA inhibition. AEA did not significantly alter 5-HT(3A) receptor trafficking. However, AEA accelerated 5-HT(3A) receptor desensitization time in a concentration-dependent manner without significantly changing receptor activation and deactivation time. The desensitization time was correlated with the AEA-induced inhibiting effect and mean 5-HT current density. Applications of 5-hydroxyindole and nocodazole, a microtubule disruptor, significantly slowed 5-HT(3A) receptor desensitization and reduced the magnitude of AEA inhibition. These observations suggest that 5-HT(3) receptor density at the steady state regulates receptor desensitization kinetics and the potency of AEA-induced inhibiting effect on the receptors. The inhibition of 5-HT(3) receptors by AEA may contribute to its physiological roles in control of pain and emesis.ope

Comparison of Sufentanil- and Fentanyl-based Intravenous Patient-controlled Analgesia on Postoperative Nausea and Vomiting after Laparoscopic Nephrectomy: A Prospective, Double-blind, Randomized-controlled Trial

Background: The incidence of postoperative nausea and vomiting (PONV) remains high. The effects of sufentanil for PONV is not firmly confirmed. The aim of this study was to compare the effect of sufentanil- and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) on the incidence of PONV after laparoscopic nephrectomy. Methods: Eighty-six patients were randomly allocated to receive either the sufentanil (n =43) or fentanyl (n =43). IV-PCA was prepared using either sufentanil 3 µg/kg or fentanyl 20 µg/kg, ramosetron 0.3 mg, and ketorolac 120 mg. The primary outcome of was the incidence of PONV during 24 h after post anesthesia care unit (PACU) discharge. The secondary outcomes were the modified Rhodes index and patient satisfaction scores at 24 h after PACU discharge, need for rescue antiemetics, pain score, need for additional analgesics, and cumulative consumption of IV-PCA Results: The incidence of PONV was comparable between the sufentanil and fentanyl groups (64.3% vs. 65%, p = 0.946; respectively). The number of patients who required antiemetics (p = 0.946) and the modified Rhodes index at 24 h after post-anesthesia care unit discharge (p = 0.668) were also comparable in both groups. No significant differences were found in the secondary outcomes, including the analgesic profiles and adverse events between the groups. Conclusions: In conclusion, sufentanil- and fentanyl-based IV-PCA showed similar incidence of PONV with comparable analgesic effects after laparoscopic nephrectomy. Based on these results, we suggest that sufentanil and fentanyl may provide comparable effects for IV-PCA after laparoscopic nephrectomy.ope

Repeated neonatal propofol administration induces sex-dependent long-term impairments on spatial and recognition memory in rats

Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner.ope

A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS

Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31+F4/80+ hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain. These cells expressed additional macrophage markers such as CD206 and CD11b. Moreover, the CD31+F4/80+ cells phagocytosed apoptotic cells as functionally matured macrophages, adhered to the newly formed subventricular vascular plexus, and then divided into daughter cells. Eventually, these CD31+F4/80+ cells transdifferentiated into NG2/PDGFRβ/desmin-expressing cerebrovascular pericytes, enwrapping and associating with vascular endothelial cells. These data indicate that a subset of cerebrovascular pericytes derive from mature macrophages in the very early phase of CNS vascular development, which in turn are recruited from sites of embryonic hematopoiesis such as the yolk sac by way of blood flow.ope

Anesthetic induced neurotoxicity in children

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Psychotropic and nonpsychotropic cannabis derivatives inhibit human 5-HT(3A) receptors through a receptor desensitization-dependent mechanism.

Δ⁹ tetrahydrocannabinol (THC) and cannabidiol (CBD) are the principal psychoactive and nonpsychoactive components of cannabis. While most THC-induced behavioral effects are thought to depend on endogenous cannabinoid 1 (CB1) receptors, the molecular targets for CBD remain unclear. Here, we report that CBD and THC inhibited the function of human 5-HT(3A) receptors (h5-HT(3A)Rs) expressed in HEK 293 cells. The magnitude of THC and CBD inhibition was maximal 5 min after a continuous incubation with cannabinoids. The EC₅₀ values for CBD and THC-induced inhibition were 110 nM and 322 nM, respectively in HEK 293 cells expressing h5-HT(3A)Rs. In these cells, CBD and THC did not stimulate specific [³⁵S]-GTP-γs binding in membranes, suggesting that the inhibition by cannabinoids is unlikely mediated by a G-protein dependent mechanism. On the other hand, both CBD and THC accelerated receptor desensitization kinetics without significantly changing activation time. The extent of cannabinoid inhibition appeared to depend on receptor desensitization. Reducing receptor desensitization by nocodazole, 5-hydroxyindole and a point-mutation in the large cytoplasmic domain of the receptor significantly decreased CBD-induced inhibition. Similarly, the magnitude of THC and CBD-induced inhibition varied with the apparent desensitization rate of h5-HT(3A)Rs expressed in Xenopus oocytes. For instance, with increasing amount of h5-HT(3A)R cRNA injected into the oocytes, the receptor desensitization rate at steady state decreased. THC and CBD-induced inhibition was correlated with the change in the receptor desensitization rate. Thus, CBD and THC inhibit h5-HT(3A) receptors through a mechanism that is dependent on receptor desensitization.ope

Guidelines help us to keep calm when facing a difficult airway

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Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm-elevated levels of hyperactivated immune cells-and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.ope