Analysis of Sphingosine and Sphinganine from the Aqueous Humor for Signaling Studies Using Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry.

Sphingolipids, including sphingosine and sphinganine, are one of the major classes of lipids. They serve as constituents of cell membranes and lipid rafts and aid in the performance of cell-cell communication and adhesion. Abnormal levels of sphingolipids in the aqueous humor can indicate impaired sphingolipid metabolism and associated ocular pathologies. Sphingolipids can be extracted from the aqueous humor by the methyl-tert-butyl ether (MTBE) lipid extraction method and subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). This chapter describes a modified protocol for an MTBE lipid extraction from the aqueous humor, followed by analysis with ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS).

Comparison of the Influence of Intraoperative Use of Sevoflurane and Isoflurane on Postoperative Nausea, Vomiting, and Cough.

INTRODUCTION: Postoperative nausea, vomiting, and cough are the most common adverse effects of general anesthesia resulting in high discomfort to the patient resulting in uneasiness during the recovery period. This study aimed to compare the influence of intraoperative use of sevoflurane and isoflurane on postoperative nausea, vomiting, and cough. MATERIALS AND METHODS: After approval from the institutional ethical committee, this quantitative observational institutional study was conducted on all patients aged between 18 and 65 years undergoing surgery under general anesthesia at KMC Hospital, Mangalore. Patients were allocated into the sevoflurane group or isoflurane group. RESULTS: All demographic parameters such as age, sex, American Society of Anesthesiologists physical status, and duration were comparable (P > 0.05). The sevoflurane group had higher number of patients (11 [14.86%]) with postoperative nausea at 0 h as compared isoflurane group (7 [9.45%]). Two patients in the isoflurane group reported postoperative vomiting at 0 h, whereas no patient in the sevoflurane group reported vomiting. For cough, a statistically significant correlation was seen between the two groups (P = 0.000) with majority of patients in the isoflurane group, i.e., 50 (67.6%) patients reporting cough at 0 h while only 15 (20.3%) reported cough in the sevoflurane group. CONCLUSION: Sevoflurane was found to be better than isoflurane in terms of postoperative nausea vomiting and cough immediately after emergence in our study. Isoflurane cause the emergence of cough whereas no significant difference in nausea and vomiting was observed in both groups.

Résumé Introduction:Les nausées, vomissements et toux postopératoires sont les effets indésirables les plus courants de l'anesthésie générale, entraînant un inconfort élevé pour le patient, entraînant un malaise pendant la période de récupération. Cette étude visait à comparer l'influence del'utilisation peropératoire du sévoflurane et de l'isoflurane sur les nausées, vomissements et toux postopératoires.Méthode:Après approbation du comité d'éthique institutionnel, cette étude institutionnelle observationnelle quantitative a été menée sur tous les patients âgés de 18 à 65 ans subissant une intervention chirurgicale sous anesthésie générale à l'hôpital KMC de Mangalore. Les patients ont été répartis dans le groupe sévoflurane ou le groupe isoflurane.Résultats:Tous les paramètres démographiques comme l'âge, le sexe, l'ASA PS et la durée étaient comparables. ( P > 0,05) Le groupe sévoflurane avait un nombre plus élevé de patients [11 (14,86 %)] présentant des nausées postopératoires à 0 heure par rapport au groupe isoflurane [7 (9,45 %)]. 2 patients du groupe Isoflurane ont signalé des vomissements postopératoires à 0 heure alors qu'aucun patient du groupe Sévoflurane n'a signalé de vomissements. Pour la toux, une corrélation statistiquement significative a été observée entre les deux groupes ( P = 0,000) avec une majorité de patients dansle groupe isoflurane, c'est-à-dire 50 (67,6 %) patients signalant une toux à 0 heure, alors que seulement 15 (20,3 %) ont signalé une toux dans le groupe sévoflurane.Conclusion:Le sévoflurane s'est révélé meilleur que l'isoflurane en termes de nausées, vomissements et toux postopératoires immédiatement après l'émergence dans notre étude. L'isoflurane provoque une toux d'émergence alors qu'aucune différence significative en termes de nausées et de vomissements n'a été observée dans les deux groupes.

Possible role of high calcium concentrations in rat neocortical neurons in inducing hyper excitatory behavior during emergence from sevoflurane: a proposed pathophysiology.

Sevoflurane has been shown to increase the incidence of emergence delirium in children; however, the mechanism remains unclear. Sevoflurane increases cytoplasmic calcium concentration which in turn may play a role in emergence delirium. This study aimed to investigate the level of intracellular calcium in rats experiencing hyperexcitatory behavior after exposure to sevoflurane, as well as the role of magnesium in preventing this phenomenon. After ethical approval, 2-5-week-old Sprague-Dawley rats (n = 34) were insufflated with sevoflurane in a modified anesthesia chamber. One group received magnesium sulphate intraperitoneally. After termination of sevoflurane exposure, the occurrence of hyperexcitation was observed. Brain tissue samples from the rats were studied for intracellular calcium levels under a two-channel laser scanning confocal microscope and were quantitatively calculated using ratiometric calculation. The presence of inflammation or oxidative stress reaction was assessed using nuclear factor κB and malondialdehyde. The incidence of hyperexcitatory behavior post sevoflurane exposure was 9 in 16 rats in the observation group and none in the magnesium group. Tests for inflammation and oxidative stress were within normal limits in both groups. The rats showing hyperexcitation had a higher level of cytosol calcium concentration compared to the other groups. To conclude, the calcium concentration of neocortical neurons in Sprague-Dawley rats with hyperexcitatory behavior is increased after exposure to sevoflurane. Administration of magnesium sulphate can prevent the occurrence of hyperexcitation in experimental animals.

Comparison of the effects of axillary brachial plexus block, inhalation anesthesia, and total intravenous anesthesia on tourniquet-induced ischemia-reperfusion injury in upper extremity surgery.

BACKGROUND: Post-ischemia reperfusion can lead to oxidative stress and an increase in oxidative markers. Employing preventive strategies and antioxidant agents may help mitigate ischemia-reperfusion injury (IRI). The use of a tourniquet in extremity surgery has been associated with IRI. This study aims to investigate the impact of three different approaches- brachial plexus block, total intravenous anesthesia (TIVA), and inhalation anesthesia-on IRI during upper extremity surgery using a tourniquet. METHODS: Patients aged 18 to 45 with American Society of Anesthesiologists (ASA) I-II scores were randomly assigned to one of three groups: Group A received an axillary block with bupivacaine; Group I underwent inhalation anesthesia with sevoflurane; and Group T received TIVA with propofol and remifentanil infusion. Blood samples were collected to measure glucose, lactate, total anti-oxidant status (TAS), total oxidant status (TOS), and ischemia-modified albumin (IMA) levels at various time points: before anesthesia (t1), 1 minute before tourniquet release (t2), 20 minutes after tourniquet release (t3), and 4 hours after tourniquet release (t4). RESULTS: In Group I, lactate levels at t3, and glucose levels at t2 and t3, were higher compared to the other groups. Group A exhibited lower IMA levels at t2, t3, and t4 than the other groups. Additionally, Group I had lower IMA levels at t2, t3, and t4 compared to Group T. TAS levels were higher in Group I at t2, t3, and t4 compared to the other groups. TOS levels at t2 and t3 were lower in Group A than in Group I. CONCLUSION: Axillary anesthesia results in a sympathetic block, promoting better perfusion of the upper extremity. This study demonstrated lower levels of oxidative stress markers with axillary plexus block. Therefore, these results suggest that the axillary block has the potential to mitigate IRI.

Measurement of cellular MDA content through MTBE-extraction based TBA assay by eliminating cellular interferences.

Malondialdehyde (MDA) has long been served as a crucial indicator for assessing cellular oxidative stress levels. In this study, we introduce a new approach to determine cellular MDA levels based on a methyl tert-butyl ether (MTBE) extraction, aimed at eliminating interferences from cellular components during thiobarbituric acid (TBA) derivatization of MDA. By leveraging the effective MTBE extraction, we identified that the determination of the MDA-TBA adduct formed from the MTBE extraction layer can effectively eliminate the interferences from cellular proteins and metabolites. This method demonstrated acceptable linearity and precision in cellular samples and showed significant differences in H2O2 treated cellular oxidative stress models. The MTBE extraction-based MDA-TBA approach provides a reliable, cost-effective, and feasible method to determine cellular MDA levels using batch microplate reader approach for the assessment of cellular oxidative stress.

Development of a Global Metabo-Lipid-Prote-omics Workflow to Compare Healthy Proximal and Distal Colonic Epithelium in Mice.

A multimetabo-lipid-prote-omics workflow was developed to characterize the molecular interplay within proximal (PC) and distal (DC) colonic epithelium of healthy mice. This multiomics data set lays the foundation to better understand the two tissue types and can be used to study, for example, colon-related diseases like colorectal cancer or inflammatory bowel disease. First, the methyl tert-butyl ether extraction method was optimized, so that from a single tissue biopsy >350 reference-matched metabolites, >1850 reference-matched lipids, and >4500 proteins were detected by using targeted and untargeted metabolomics, untargeted lipidomics, and proteomics. Next, each omics-data set was analyzed individually and then merged with the additional omics disciplines to generate a deep understanding of the underlying complex regulatory network within the colon. Our data demonstrates, for example, differences in mucin formation, detected on substrate level as well as on enzyme level, and altered lipid metabolism by the detection of phospholipases hydrolyzing sphingomyelins to ceramides. In conclusion, the combination of the three mass spectrometry-based omics techniques can better entangle the functional and regional differences between PC and DC tissue compared to each single omics technique.

The duration-dependent and sex-specific effects of neonatal sevoflurane exposure on cognitive function in rats.

Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.

Environmental-friendly extraction of di(2-ethylhexyl) phthalate from poly(vinyl chloride) using liquefied dimethyl ether.

Poly(vinyl chloride) (PVC) is one of the most widely used plastics. However, a major challenge in recycling PVC is that there is no economical method to separate and remove its toxic phthalate plasticizers. This research made a breakthrough by extracting PVC with liquefied dimethyl ether (DME) and successfully separating the plasticizer components. Nearly all (97.1 %) of the di(2-ethylhexyl) phthalate plasticizer was extracted within 30 min by passing liquefied DME (285 g) through PVC at 25 °C. The compatibility of PVC with organic solvents, including liquefied DME, was derived theoretically from their Hansen solubility parameters (HSP), and actual dissolution experiments were conducted to determine the optimal PVC solvents. A liquefied DME mixture was used to dissolve PVC, and the extract was diluted with ethanol to precipitate the dissolved PVC. We demonstrated that liquefied DME is a promising method for producing high quality recycled products and that the process retains the fundamental properties of plasticizers and PVC without inducing degradation or depolymerization. Because of its low boiling point, DME can be easily separated from the solute after extraction, allowing for efficient reuse of the solvent, extracted plasticizer, and PVC. DME does not require heat and produces little harmful wastewater, which significantly reduces the energy consumption of the plasticizer additive separation process.

Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflurane Anesthesia for Pediatric Liver Surgery.

BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for pediatric liver surgery. MATERIAL AND METHODS Sixty children who underwent liver surgery in our hospital were prospectively selected and randomly allocated into group A (placebo+remifentanil+sevoflurane) or group B (Dex+remifentanil+sevoflurane). Mean arterial pressure (MAP) and heart rate (HR) at different time points, agitation score during awakening, behavioral status, pain level, and the incidence of postoperative adverse effects were compared in both groups. RESULTS Children in group B had lower HR and MAP levels immediately after tracheal extubation and 5 min after tracheal extubation than those in group A. The Aono's scores, PAED agitation scores, and CHIPP scores at 15 min and 30 min of admission to the PACU were lower in group B than in group A. The incidence of agitation during postoperative anesthesia awakening was lower in group B in contrast to group A. There was no significant difference in postoperative adverse reactions between group A and group B. CONCLUSIONS In pediatric liver surgery, the use of Dex+remifentanil+sevoflurane anesthesia can reduce the incidence of EA during the awakening period, stabilize hemodynamic levels, and relieve postoperative pain, and has fewer postoperative adverse effects, which warrants clinical application.

Sevoflurane acts as an antidepressant by suppression of GluN2D-containing NMDA receptors on interneurons.

BACKGROUND AND PURPOSE: Sevoflurane, a commonly used inhaled anaesthetic known for its favourable safety profile and rapid onset and offset, has not been thoroughly investigated as a potential treatment for depression. In this study, we reveal the mechanism through which sevoflurane delivers enduring antidepressant effects. EXPERIMENTAL APPROACH: To assess the antidepressant effects of sevoflurane, behavioural tests were conducted, along with in vitro and ex vivo whole-cell patch-clamp recordings, to examine the effects on GluN1-GluN2 incorporated N-methyl-d-aspartate (NMDA) receptors (NMDARs) and neuronal circuitry in the medial prefrontal cortex (mPFC). Multiple-channel electrophysiology in freely moving mice was performed to evaluate sevoflurane's effects on neuronal activity, and GluN2D knockout (grin2d-/-) mice were used to confirm the requirement of GluN2D for the antidepressant effects. KEY RESULTS: Repeated exposure to subanaesthetic doses of sevoflurane produced sustained antidepressant effects lasting up to 2 weeks. Sevoflurane preferentially inhibited GluN2C- and GluN2D-containing NMDARs, causing a reduction in interneuron activity. In contrast, sevoflurane increased action potentials (AP) firing and decreased spontaneous inhibitory postsynaptic current (sIPSC) in mPFC pyramidal neurons, demonstrating a disinhibitory effect. These effects were absent in grin2d-/- mice, and both pharmacological blockade and genetic knockout of GluN2D abolished sevoflurane's antidepressant actions, suggesting that GluN2D is essential for its antidepressant effect. CONCLUSION AND IMPLICATIONS: Sevoflurane directly targets GluN2D, leading to a specific decrease in interneuron activity and subsequent disinhibition of pyramidal neurons, which may underpin its antidepressant effects. Targeting the GluN2D subunit could hold promise as a potential therapeutic strategy for treating depression.

Using the nociception level index to compare the intraoperative antinociceptive effect of propofol and sevoflurane during clinical and experimental noxious stimulus in patients under general anesthesia.

STUDY: Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. OBJECTIVE: To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. DESIGN: A prospective randomized monocentric trial. SETTING: Perioperative care. PATIENTS: 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. INTERVENTIONS: We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. MEASUREMENTS: We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. MAIN RESULTS: We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. CONCLUSIONS: Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties.

Encapsulation of propolis extracted with methylal in the chitosan nanoparticles and its antibacterial and cell cytotoxicity studies.

In this study we develop novel type of antibacterial chitosan-propolis NPs to improve theantimicrobial activity against various pathogens. To this aim, we primarily extracted propolis with methylal and ethanol as green solvents and its encapsulation with chitosan NPs. The developed propolis loaded chitosan NPs indicated antimicrobial and anti-biofilm properties against various gram positive and negative. FTIR revealed the successful encapsulation of the propolis extract with Ethanol (PE) and Methylal (PM) into the chitosan nano career matrix. HPLC and GC-MASS also confirmed the presence of flavonoids and phenols compounds of propolis extracted with both solvents. In addition, we confirmed the total phenolic and flavonoid compounds in propolis by calorimetric method of Folin-Ciocalteu and aluminum trichloride complex formation assays, respectively. PE-CH and PM-CH were optimized regarding physicochemical properties such as particle size, zeta potential, and poly dispersity index (PDI) index. DLS and SEM micrographs confirmed a spherical morphology in a range of 360-420 nm with Z potential values of 30-48 mV and PDI of 0.105-0.166 for PE-CH and PM-CH, respectively. The encapsulation efficiency was evaluated using colorimetric analysis, with median values ranging from 90 to 92%. The MIC values within the range of 2 to 230 µg/ml and MBC values between 3 to 346 µg/ml against both gram-positive and negative bacteria. While both PE and PM showed a significant reduction in the number of E. coli, S. aureus, and S. epidermidis, the use of PE-CH and PM-CH led to a statistically significant and greater reduction in number of E. coli, S. aureus, and S. epidermidis strains on the biofilm, pre-formed biofilm and planktonic phases. Besides, the DPPH assay showed significant antioxidant activity for these NPs within the range of 36 to 92%. MTT assay for MHFB-1, HFF, L929, MDF, and MCF-7 cells exhibited statistically significant differences in each other that show the IC50 between 60-160 µg/ml for normal cells and 20 for cancer cells. Finally the present study indicated that both PM and PM-CH greater than PE and PE-CH in which contain high flavonoid and phenolic contents with a high antioxidation potential antioxidant properties, which could be beneficial for cell proliferation and antibiotic and anticancer applications.

Comparison between inhalational anesthetics in terms of DNA damage and immunological markers.

This study compared genetic damage and immunological markers between surgical patients who underwent inhalational anesthesia with isoflurane or sevoflurane. Blood samples were collected from surgical patients (n = 18 in the isoflurane group and n = 17 in the sevoflurane group) at baseline (before the anesthesia procedure) and the day after anesthesia. DNA damage was detected using an alkaline comet assay; proinflammatory interleukin (IL)-6 was detected by flow cytometry, and white blood cells were detected via an automatic hematology analyzer. The characteristics of both groups were similar, and neither of the two anesthetics induced DNA damage. Similarly, mild neutrophilia was observed after anesthesia in both groups. Increased IL-6 levels were observed 1 day after anesthesia regardless of the type of anesthetic, but this increase was greater in the isoflurane group. Our study suggested that isoflurane and sevoflurane administration may contribute to changes in the immune parameters measured, though no genotoxic hazard was identified, in healthy adult patients who undergo low-stress surgery.

Improved lipid analysis using a 2D-LC-MS system with a novel injection procedure.

The aim of this study was to improve analysis of nonpolar lipidomics sample extracts using reversed phase (RP) chromatography. A 4/3/3 (v/v/v) mixture of methanol/methyl tert-butyl ether/chloroform (MeOH/MTBE/CHCl3, MMC) was chosen for sample extraction solvent based on its proven extraction capability for several lipid classes. To avoid carry over, loss of analytes and peak distortion the loops and all capillaries of the presented LC system were flushed and filled up with methanol until the analytical column. The choice of methanol was due to its weak elution strength and being infinitely miscible with MMC and several other nonpolar solvents. This allowed injection of a 100 µl sample that was 20 µl nonpolar extraction solvent diluted fivefold with methanol. All lipids of 25 lipid classes were transferred quantitatively to the column head where the online dilution of methanol was carried out with aqueous eluent for focusing the lipid analytes. The weak elution strength of methanol prevented peak distortions. The consecutive reversed phase elution resulted in remarkably narrow peaks (full width at half maximum was 0.07-0.08 min typically) and enhanced sensitivity (limit of detection usually in sub nM region) because of increased sample injection volume and narrow peaks. Calibration and quality control samples made by diluting commercial lipid standards 200-50000 times confirmed the applicability of this approach both for targeted lipid quantification and for untargeted quantitative comparison of lipids from different sources.

Urinary biomonitoring of fuel ether oxygenates using a needle trap device packed with a novel molecularly imprinted polymer surface modified Zeolite Y.

This study introduces an innovative needle trap device (NTD) featuring a molecularly imprinted polymer (MIP) surface-modified Zeolite Y. The developed NTD was integrated with gas chromatography-flame ionization detector (GC-FID) and employed for analysis of fuel ether oxygenates (methyl tert­butyl ether, MTBE, ethyl tert­butyl ether, ETBE, and tert­butyl formate, TBF) in urine samples. To optimize the key experimental variables including extraction temperature, extraction time, salt concentration, and stirring speed, a central composite design-response surface methodology (CCD-RSM) was employed. The optimal values for extraction in the study were found to be 51.2 °C extraction temperature, 46.2 min extraction time, 27 % salt concentration, and 620 rpm stirring speed. Under the optimized conditions, the calibration curves demonstrated excellent linearity within the range of 0.1-100 µg L-1, with correlation coefficients (R2) exceeding 0.99. The limits of detection (LODs) for MTBE, ETBE, and TBF were obtained 0.06, 0.08, and 0.09 µg L-1, respectively. Moreover, the limits of quantification (LOQs) for MTBE, ETBE, and TBF were obtained 0.18, 0.24, and 0.27 µg L-1, respectively. The enrichment factor was also found to be in the range of 98-129.The NTD-GC-FID procedure demonstrated a high extraction efficiency, making it a promising tool for urinary biomonitoring of fuel ether oxygenates with improved sensitivity and selectivity compared to current methods.

Damage-associated molecular patterns as a mechanism of sevoflurane-induced neuroinflammation in neonatal rodents.

BACKGROUND: General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. METHODS: A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. RESULTS: In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. CONCLUSIONS: In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

In silico and in vivo study of anti-inflammatory activity of Morinda longissima (Rubiaceae) extract and phytochemicals for treatment of inflammation-mediated diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-ß-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

Minimal alveolar concentration of sevoflurane in combination with remimazolam in adults during laryngeal mask insertion: an up-down sequential allocation study.

BACKGROUND: Remimazolam is a novel ultrashort-acting intravenous benzodiazepine sedative-hypnotic. The combination of remimazolam and sevoflurane does not increase respiratory sensitivity, produce bronchospasm, or cause other adverse conditions. We aimed to observe the effects of different remimazolam doses on the minimum alveolar concentration (MAC) of sevoflurane at end-expiration during laryngeal mask insertion and evaluate the effect of sex on the efficacy of the combination of remimazolam on the suppression of laryngeal mask insertion in adult patients. METHODS: We included 240 patients undergoing laparoscopic surgery under general anesthesia with elective placement of a laryngeal mask (120 males and 120 females). The patients were randomly divided into four groups according to sex: a control group (randomization for female patients, RF0; randomization for male patients, RM0) and three remimazolam groups (RF1, RM1 / RM2, RF2 / RM3, RF3), with 30 patients in each group. Induction was established by vital capacity rapid inhalation induction (VCRII), using 8% sevoflurane and 100% oxygen (6 L/min) in all patients. The (RF1, RM1), (RM2, RF2), and (RM3, RF3) groups were continuously injected with remimazolam at doses of 1, 1.5, and 2.0 mg/kg/h, respectively, while the (RM0, RF0) group was injected with an equal volume of normal saline. The end-expiratory concentration of sevoflurane was adjusted to a preset value after the patient's eyelash reflex disappeared. After the end-expiratory concentration of sevoflurane was kept stable for at least 15 min, the laryngeal mask was placed, and the patient's physical response to the mask placement was observed immediately and within 30 s of placement. The MAC of sevoflurane was measured using the up-and-down sequential method of Dixon. RESULTS: The calculated MAC of end-expiratory sevoflurane during laryngeal mask insertion in adult females was (2.94 ± 0.18)%, (2.69 ± 0.16)%, (2.32 ± 0.16)% and (1.83 ± 0.15)% in groups RF0, RF1, RF2 and RF3; (2.98 ± 0.18)%, (2.80 ± 0.19)%, (2.54 ± 0.15)% and (2.15 ± 0.15)% in male groups RM0, RM1, RM2 and RM3, respectively. The MAC values were significantly lower in the (RF1-RF3, RM1-RM3) group when compared to the (RF0, RM0) group. There was no significant difference between (RF0, RF1) and (RM0, RM1), but the MAC value of the RF2-RF3 group was significantly lower than that of the RM2-RM3 group. CONCLUSIONS: Remimazolam can effectively reduce end-expiratory sevoflurane MAC values during laryngeal mask placement in adults. When remimazolam was measured above 1.5 mg/kg/h, the effect of inhibiting laryngeal mask implantation in female patients was stronger than that in male patients. Remimazolam at a dose of 1-2 mg/kg/h combined with sevoflurane induction can be safely and effectively used in these patients.

Echinatin mitigates sevoflurane-induced neurotoxicity through regulation of ferroptosis and iron homeostasis.

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity. Our investigation began with cellular models, where Echinatin demonstrated a significant reduction in sevoflurane-induced apoptosis. Mechanistically, we identified ferroptosis, a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, as a key player in sevoflurane-induced neuronal injury. Echinatin notably suppressed ferroptosis in sevoflurane-exposed cells, suggesting a pivotal role in neuroprotection. Expanding our research to a murine model, we observed perturbations in iron homeostasis, inflammatory cytokines, and antioxidants due to sevoflurane exposure. Echinatin treatment effectively restored iron balance, mitigated inflammation, and preserved antioxidant levels in vivo. Behavioral assessments using the Morris water maze further confirmed Echinatin's neuroprotective potential, as it ameliorated sevoflurane-induced spatial learning and memory impairments. In conclusion, our study unveils Echinatin as a promising candidate for mitigating sevoflurane-induced neurotoxicity. Through the regulation of ferroptosis, iron homeostasis, and inflammation, Echinatin demonstrates significant neuroprotection both in vitro and in vivo. These findings illuminate the potential for Echinatin to enhance the safety of surgical procedures involving sevoflurane anesthesia, minimizing the risk of cognitive deficits and neurotoxicity.