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Inhibition versus potentiation of ligand-gated ion channels can be altered by a single mutation that moves ligands between intra- and intersubunit sites.

Pentameric ligand-gated ion channels (pLGICs) are similar in structure but either inhibited or potentiated by alcohols and anesthetics. This dual modulation has previously not been understood, but the determination of X-ray structures of prokaryotic GLIC provides an ideal model system. Here, we show that a single-site mutation at the F14' site in the GLIC transmembrane domain turns desflurane and chloroform from inhibitors to potentiators, and that this is explained by competing allosteric sites. The F14'A mutation opens an intersubunit site lined by N239 (15'), I240 (16'), and Y263. Free ener

Effect of inhalational anesthesia on cerebral circulation in Moyamoya disease.

To clarify the effects of inhalational anesthesia on cerebral circulation in patients with Moyamoya disease, the authors measured regional cortical blood flow (CoBF), jugular bulb oxygen saturation (SjO2), and frontal regional oxygen saturation (rSO2) by near infra-red spectroscopy under total intravenous and inhalational anesthesia in 13 patients undergoing revascularization procedures. Cortical blood flow decreased in some regions under inhaled anesthesia in all cases, and the mean value decreased significantly (p<0.01). Patients' SjO2 levels rose during inhalational anesthesia in 10 of 11 c

Desflurane versus propofol maintenance for outpatient laparoscopic cholecystectomy.

BACKGROUND: The aims of the study were to evaluate costs and clinical characteristics of desflurane-based anaesthetic maintenance versus propofol for outpatient cholecystectomy. METHODS: All 60 patients received ketamine 0.2 mg kg(-1), fentanyl 2 microg kg(-1) and propofol 2 mg kg(-1) for induction. Ketorolac 0.4 mg kg(-1) and ondansetron 0.05 mg kg(-1) +droperidol 20 microg kg(-1) was given as prophylaxis for postoperative pain and emesis, respectively. The patients were randomly assigned into Group P with propofol maintenance and opioid supplements, or Group D with desflurane in a low-flow

Mouse model of severe recessive RYR1-related myopathy.

Ryanodine receptor type I (RYR1)-related myopathies (RYR1 RM) are a clinically and histopathologically heterogeneous group of conditions that represent the most common subtype of childhood onset non-dystrophic muscle disorders. There are no treatments for this severe group of diseases. A major barrier to therapy development is the lack of an animal model that mirrors the clinical severity of pediatric cases of the disease. To address this, we used CRISPR/Cas9 gene editing to generate a novel recessive mouse model of RYR1 RM. This mouse (Ryr1TM/Indel) possesses a patient-relevant point mutation

[-The effect of desflurane on cerebral blood flow velocity and cerebrovascular reactivity to CO2 in children-].

OBJECTIVE: To assess in children with a transcranial Doppler the effect on cerebral blood flow velocities of desflurane, whose cerebral vasodilator effects have been studied in animals and in adults with intracranial lesions. STUDY DESIGN: Prospective clinical study. PATIENTS: Ten healthy children, mean age: 3.4 yr, ASA physical class 1, undergoing minor urologic surgery, were included in this study. METHOD: Induction was obtained with atropine 10 micrograms.kg-1, fentanyl 3 micrograms.kg-1 and propofol 3 mg.kg-1. Endotracheal intubation was facilitated by atracurium 0.3 mg.kg-1. Mechanical

Perioperative anesthetic management of children with congenital central hypoventilation syndrome and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation undergoing thoracoscopic phrenic nerve-diaphragm pacemaker implantation.

BACKGROUND: Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomi … ung isolation. Anesthesia was maintained using a balanced technique of volatile agents (sevoflurane/isoflurane) and opioids (fentanyl). Bradyarrhythmias developed in six patients (43%) during surgery, 5 (36%) responded to anticholinergics and one patient (7%) required backup cardiac pacing using a previously implanted bipolar cardiac pacemaker. Intraoperativ …

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine.

AIM: To study the effect of H2 gas on liver injury in massive hepatectomy using the intermittent Pringle maneuver in swine. METHODS: Male Bama pigs (n = 14) treated with ketamine hydrochloride and Sumianxin II as induction drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups: Hydrogen-group (n = 7), the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; contrast-group (n = 7), underwent 70% hepatotectomy w…

Knock-Down of Glucocorticoid Receptor Beta (GRβ) Enhances the Ocular Hypertensive Response to Dexamethasone in C57BL/6J Mice.

Topical ocular treatment with glucocorticoids (GCs) yields an increase in intraocular pressure (IOP) in a subset (~35-40%) of the human popu … scope) assessments were made. Animals were divided into 4 cohorts (n = 5/cohort), and anesthetized (isoflurane (2.5%) and O2(g) (0.8 L/min)). Cohorts 1 and 2 (n = 10 animals) were given an intravitreal (IVT) injection in both eyes (OU) of Lenti.shRNA.Scramble (2.2 × 109 TU/mL; 1 μL bolus injection (total 2.2 × 106 TU/eye)). Cohorts 3 and 4 (n = 10 animals) w …

Positron Emission Tomography (PET) and Pharmacokinetics: Classical Blood Sampling Versus Image-Derived Analysis of [18F]FAZA and [18F]FDG in a Murine Tumor Bearing Model.

PURPOSE: Pharmacokinetic (PK) data are generally derived from blood samples withdrawn serially over a defined period after dosing. In small … aring mouse model, is reported here. METHODS: Two study groups were used: normal BALB/c mice under isoflurane anesthesia were intravenously injected with either [18F]FDG or [18F]FAZA. For the first group, blood-sampling by tail artery puncture was used to collect blood samples which were then analyzed with Radio-microTLC. Dynamic PET experiments were perfor …

Factors Governing P-Glycoprotein-Mediated Drug-Drug Interactions at the Blood-Brain Barrier Measured with Positron Emission Tomography.

The adenosine triphosphate-binding cassette transporter P-glycoprotein (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distr … ar (15 mg/kg) treated animals by 14.1- and 18.3-fold, respectively, as compared with vehicle group. Isoflurane anesthesia altered [(11)C]-N-desmethyl-loperamide but not (R)-[(11)C]verapamil metabolism, and this had a direct effect on the magnitude of the increase in brain distribution following ABCB1 inhibition. Our data furthermore suggest that in the absen …

[Ondansetron versus droperidol. Postoperative treatment against nausea and vomiting. Comparison of action, adverse effects and acceptance by gynecologic inpatients].

INTRODUCTION: Ondansetron is more effective than a placebo in treating postoperative nausea and vomiting (PONV), but it has not been proved … nce after intubation. Anaesthesia was maintained with nitrous oxide/oxygen, enflurane, halothane or isoflurane and fentanyl up to 0.3 mg. Statistical evaluation was performed by the unpaired Student's t-test and the Mann-Whitney U test. Categoric variables were examined by the chi 2 test. Significance was defined as P < 0.05. RESULTS: Of 271 patients, 100 ( …

Anaesthetic management and outcome in right-lobe living liver-donor surgery.

BACKGROUND AND OBJECTIVE: We reviewed retrospectively the anaesthetic management and perioperative course of eight right hepatectomies for l … ion. Anaesthesia was maintained during normocapnic ventilation of the lungs with oxygen 40% in air, isoflurane 1-1.5 MAC and sufentanil. Routine anaesthetic monitoring included electrocardiography, pulse oximetry, invasive blood pressure, central venous pressure, urine output, state of neuromuscular blockade and core temperature. Periods of hypotension (<80% …

[Mechanistic study of cGAS-STING signaling pathway-mediated blood-brain barrier injury in the prefrontal cortex of 15-month-old mice with postoperative cognitive dysfunction].

Objective: To investigate the role and mechanism of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in med … es by quantitative real-time polymerase chain reaction (RT-qPCR). The POCD model was established by isoflurane anesthesia combined with laparotomy. The cGAS-STING pathway was inhibited or activated by intraperitoneal injection of the cGAS inhibitor RU.521 (5 mg/kg), the STING agonist diABZI (2.5 mg/kg), or diABZI combined with RU.521 at 2 h before surgery, r …

Economic and Environmental Considerations During Low Fresh Gas Flow Volatile Agent Administration After Change to a Nonreactive Carbon Dioxide Absorbent.

BACKGROUND: Reducing fresh gas flow (FGF) during general anesthesia reduces costs by decreasing the consumption of volatile anesthetics and … RESULTS: A total of N = 20,235 cases were analyzed (80.2% sevoflurane, 15.1% desflurane, and 4.7% isoflurane). Intraoperative FGF was reduced for cases in which sevoflurane was administered by 435 mL/min (95% confidence interval [CI], 391 to 479 mL/min; P < 10). Hypothesis 1 was accepted. Sevoflurane consumption per minute of administration decreased by 0. …

Erratum: Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock.

An erratum was issued for: Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock. The Protocol section w … mpact oxygen transmitter Invasive tissue oxygen sensor Presens PM-PSt7 Profiling oxygen microsensor Isoflurane Vetone 501017 To maintain sedation throughout the experiment Isotonic crystalloid solution HenrySchein 1537930 or 1534612 Used during resuscitation in the critical care period Liquid flow sensor Sensirion LD20-2600B Part of noninvasive PuO2 monitor …

Postoperative cognitive dysfunction: spotlight on light, circadian rhythms, and sleep.

Postoperative cognitive dysfunction (POCD) is a neurological disorder characterized by the emergence of cognitive impairment after surgery. A growing body of literature suggests that the onset of POCD is closely tied to circadian rhythm disruption (CRD). Circadian rhythms are patterns of behavioral and physiological change that repeat themselves at approximately, but not exactly, every 24 h. They are entrained to the 24 h day by the daily light-dark cycle. Postoperative CRD affects cognitive function likely by disrupting sleep architecture, which in turn provokes a host of pathological process

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… Anesthetic agents such as isoflurane have been shown to exert a phase-shifting effect on the clock by activating SCN GABA receptors ( Chong et al., 2021 ). Furthermore, anesthesia alters the expression of several core clock genes, notably PER2 . … Indeed, isoflurane anesthesia was shown to inhibit CSF circulation and glymphatic activity, particularly at high doses (3%) ( Gakuba et al., 2018 ). …

A Standardized Method for Vertical Sleeve Gastrectomy Bariatric Surgery Investigations in Cancer.

Obesity is a global epidemic that has affected the lives of over 14% of adults worldwide and over a third of Americans. Obesity is associated with the increased risk of thirteen obesity-associated cancers and poor cancer outcomes. Bariatric surgery is the most effective method of sustained weight loss and has been steadily increasing in clinical use over the past 4 decades. Importantly, bariatric surgery is established to decrease cancer risk. Vertical sleeve gastrectomy (VSG) is currently the most common bariatric surgery procedure. To evaluate underlying mechanisms of bariatric associated ca

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… Prepare your anesthetic machine as necessary for your specific system (fill isoflurane, check supply gas levels, etc.). We recommend using a SomnoSuite Low-Flow Anesthesia System (Kent Scientific, Torrington, CT, Figure 1C ) set up with 5mL of isoflurane. 4. … Euthanize mouse with isoflurane and perform a secondary method of euthanasia in accordance with IACUC protocol. 3. …

Videolaparoscopic prostatectomy in porcine model for training residents.

INTRODUCTION:: Surgical training models prepare the resident for a more ethical surgical practice as well as providing a less steep learning … zine (1.5mg/kg), Cetamine (22mg/kg) and Atropine (0.04mg/kg) for orotracheal intubation followed by Isoflurane (2%). Animals were euthanized at the end of the procedure with a lethal dose of KCl (2mEq/kg). The trocar insertion points were marked using the epigastric vessels and umbilical region as reference points. Initially, urethral catheterization was per …

[Renal protection during surgical procedures on the infrarenal aorta].

INTRODUCTION: Despite the progress in surgical and anaesthetic management, decreased renal function is still observed after abdominal infrar … ilation was controlled using 50% of nitrous oxyde and oxygen. Supplemental anaesthesia consisted of isoflurane and fentanyl, in order to maintain the mean arterial pressure and heart rate +/- 20% regarding preoperative values. In all patients two peripheral vein and radial artery catheters were cannulated before anaesthesia. Central venous catheter and Foley …

Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra.

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinr

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… At completion of the study, rats were anaesthetised with 5% isoflurane in an induction chamber, followed by cardiac puncture and cervical dislocation (isoflurane provided by a facemask). … N = 4 rats per group were terminated at the exploratory time points (day 4, and 7) and N = 8 on day 10 (recovery phase) by isoflurane inhalation (3%) and cervical dislocation. …