The role of astrocytic γ-aminobutyric acid in the action of inhalational anesthetics.

BACKGROUND: Inhalational anesthetics target the inhibitory extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. Both neuronal and glial GABA mediate tonic inhibition of the extrasynaptic GABAA receptors. However, the role of glial GABA during inhalational anesthesia remains unclear. This study aimed to evaluate whether astrocytic GABA contributes to the action of different inhalational anesthetics. METHODS: Gene knockout of monoamine oxidase B (MAOB) was used to reduce astrocytic GABA levels in mice. The hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane were assessed by evaluating the loss of righting reflex (LORR) and tail-pinch withdrawal response (LTWR) in MAOB knockout and wild-type mice. Minimum alveolar concentration (MAC) for LORR, time to LORR, MAC for LTWR and time to LTWR of isoflurane, sevoflurane, and desflurane were assessed. RESULTS: Time to LORR and time to LTWR with isoflurane were significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001 and P = 0.032, respectively). Time to LORR with 0.8 MAC of sevoflurane was significantly longer in MAOB knockout mice than in wild-type mice (P < 0.001), but not with 1.0 MAC of sevoflurane (P=0.217). MAC for LTWR was significantly higher in MAOB knockout mice exposed to sevoflurane (P < 0.001). With desflurane, MAOB knockout mice had a significantly higher MAC for LORR (P = 0.003) and higher MAC for LTWR (P < 0.001) than wild-type mice. CONCLUSIONS: MAOB knockout mice showed reduced sensitivity to the hypnotic and immobilizing effects of isoflurane, sevoflurane, and desflurane. Behavioral tests revealed that the hypnotic and immobilizing effects of inhalational anesthetics would be mediated by astrocytic GABA.

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.

Similarity and dissimilarity in alterations of the gene expression profile associated with inhalational anesthesia between sevoflurane and desflurane.

Although sevoflurane is one of the most commonly used inhalational anesthetic agents, the popularity of desflurane is increasing to a level similar to that of sevoflurane. Inhalational anesthesia generally activates and represses the expression of genes related to xenobiotic metabolism and immune response, respectively. However, there has been no comprehensive comparison of the effects of sevoflurane and desflurane on the expression of these genes. Thus, we used a next-generation sequencing method to compare alterations in the global gene expression profiles in the livers of rats subjected to inhalational anesthesia by sevoflurane or desflurane. Our bioinformatics analyses revealed that sevoflurane and, to a greater extent, desflurane significantly activated genes related to xenobiotic metabolism. Our analyses also revealed that both anesthetic agents, especially sevoflurane, downregulated many genes related to immune response.

Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats.

OBJECTIVE: Anesthetics have been linked to cognitive alterations, particularly in the elderly. The current research delineates how Fibroblast Growth Factor 2 (Fgf2) modulates tau protein phosphorylation, contributing to cognitive impairments in aged rats upon sevoflurane administration. METHODS: Rats aged 3, 12, and 18 months were subjected to a 2.5% sevoflurane exposure to form a neurotoxicity model. Cognitive performance was gauged, and the GEO database was employed to identify differentially expressed genes (DEGs) in the 18-month-old cohort post sevoflurane exposure. Bioinformatics tools, inclusive of STRING and GeneCards, facilitated detailed analysis. Experimental validations, both in vivo and in vitro, examined Fgf2's effect on tau phosphorylation. RESULTS: Sevoflurane notably altered cognitive behavior in older rats. Out of 128 DEGs discerned, Fgf2 stood out as instrumental in regulating tau protein phosphorylation. Sevoflurane exposure spiked Fgf2 expression in cortical neurons, intensifying tau phosphorylation via the PI3K/AKT/Gsk3b trajectory. Diminishing Fgf2 expression correspondingly curtailed tau phosphorylation, neurofibrillary tangles, and enhanced cognitive capacities in aged rats. CONCLUSION: Sevoflurane elicits a surge in Fgf2 expression in aging rats, directing tau protein phosphorylation through the PI3K/AKT/Gsk3b route, instigating cognitive aberrations.

Consistency analysis of consciousness index and bispectral index in monitoring the depth of sevoflurane anesthesia in laparoscopic surgery.

Background: The Index of Consciousness (IoC) is a new monitoring index of anesthesia depth reflecting the state of consciousness of the brain independently developed by China. The research on monitoring the depth of anesthesia mainly focuses on propofol, and bispectral index (BIS) is a sensitive and accurate objective index to evaluate the state of consciousness at home and abroad. This study mainly analyzed the effect of IoC on monitoring the depth of sevoflurane anesthesia and the consistency and accuracy with BIS when monitoring sevoflurane maintenance anesthesia. Objective: To investigate the monitoring value of the Index of Consciousness (IoC) for the depth of sevoflurane anesthesia in laparoscopic surgery. Methods: The study population consisted of 108 patients who experienced elective whole-body anesthesia procedures within the timeframe of April 2020 to June 2023 at our hospital. Throughout the anesthesia process, which encompassed induction and maintenance using inhaled sevoflurane, all patients were diligently monitored for both the Bispectral Index (BIS) and the Index of Consciousness (IoC). We conducted an analysis to assess the correlation between IoC and BIS throughout the anesthesia induction process and from the maintenance phase to the regaining of consciousness. To evaluate the predictive accuracy of IoC and BIS for the onset of unconsciousness during induction and the return of consciousness during emergence, we employed receiver operating characteristic (ROC) curve analysis. Results: The mean difference between BIS and IoC, spanning from the pre-anesthesia induction phase to the completion of propofol induction, was 1.3 (95% Limits of Agreement [-53.4 to 56.0]). Similarly, during the interval from the initiation of sevoflurane inhalation to the point of consciousness restoration, the average difference between BIS and IoC was 0.3 (95% LOA [-10.8 to 11.4]). No statistically significant disparities were observed in the data acquired from the two measurement methodologies during both the anesthesia induction process and the journey from maintenance to the regaining of consciousness (P > 0.05). The outcomes of the ROC curve analysis disclosed that the areas under the curve (AUC) for prognosticating the occurrence of loss of consciousness were 0.967 (95% CI [0.935-0.999]) for BIS and 0.959 (95% CI [0.924-0.993]) for IoC, with optimal threshold values set at 81 (sensitivity: 88.10%, specificity: 92.16%) and 77 (sensitivity: 79.55%, specificity: 95.45%) correspondingly. For the prediction of recovery of consciousness, the AUCs were 0.995 (95% CI [0.987-1.000]) for BIS and 0.963 (95% CI [0.916-1.000]) for IoC, each associated with optimal cutoff values of 76 (sensitivity: 92.86%, specificity: 100.00%) and 72 (sensitivity: 86.36%, specificity: 100.00%) respectively. Conclusion: The monitoring of sevoflurane anesthesia maintenance using IoC demonstrates a level of comparability to BIS, and its alignment with BIS during the maintenance phase of sevoflurane anesthesia is robust. IoC displays promising potential for effectively monitoring the depth of anesthesia.

Effects of propofol versus sevoflurane on surgical field visibility during arthroscopic rotator cuff repair: a randomized trial.

BACKGROUND: During arthroscopic rotator cuff repair (ARCR), clear surgical field visibility (SFV) is the basis of successful surgery, but the choice of anesthesia maintenance drugs may have different effects on SFV. In this study, we aimed to compare the effects of propofol- and sevoflurane-based general anesthesia on SFV in patients undergoing ARCR. METHODS: Patients (n = 130) undergoing elective ARCR in the lateral decubitus position were randomized into either the propofol group or sevoflurane group (65 per group). The duration of surgery and increased pressure irrigation (IPI), Boezaart score, rocuronium consumption and usage of remifentanil were recorded. The time of both spontaneous respiration recovery and extubation and the incidences of postoperative nausea and vomiting and agitation were also recorded. RESULTS: The Boezaart score, duration of IPI and ratio of the duration of IPI to the duration of surgery (IPI/S ratio) were similar between the groups (P > 0.05). Rocuronium consumption, number of patients requiring remifentanil infusion and total remifentanil consumption were significantly lower in the sevoflurane group (P < 0.05). The spontaneous respiration recovery time was significantly longer in the propofol group (P < 0.05), but there were no differences in the extubation time between the groups(P > 0.05). CONCLUSIONS: Compared with propofol, sevoflurane provides equally clear SFV while improving the convenience of anesthesia maintenance in ARCR patients with interscalene plexus (ISB) combined with general anesthesia. TRIAL REGISTRATION: This single-center, prospective, RCT was retrospective registered at Chinese Clinical Trial Registry with the registration number ChiCTR2300072110 (02/06/2023).

Necroptosis involved in sevoflurane-induced cognitive dysfunction in aged mice by activating NMDA receptors increasing intracellular calcium.

Perioperative neurocognitive disorders are a common surgical and postanesthesia complication. Necroptosis contributes to the emergence of various neurological disorders. We conjecture that cognitive impairment is associated with necroptosis of hippocampal neurons, which is mediated by NMDA receptors leading to cytoplasmic calcium imbalance. C57BL/6 J male mice ( 18 months) were randomly divided into the C ( control group), S ( sevoflurane group), S+M ( sevoflurane plus the NMDA receptor antagonist memantine group) and S+N ( sevoflurane plus necrostatin-1) group. We exposed the mice to 3% sevoflurane for 2 h a day for three consecutive days in the S, S+M and S+N groups. Memantine ( 20 mg/kg) or Nec-1 ( 10 mg/kg) was injected intraperitoneally 1 h before sevoflurane anesthesia in the S+M or S+N group. We used the animal behavior tests to evaluate the cognitive function. Pathological damage, the rate of necroptosis, [Ca2+]i, and the expression of necroptosis-related proteins were evaluated. The cognitive function tests, pathological damage, the rate of necroptosis, the expression of necroptosis-related proteins, NMDAR2A and NMDAR2B were significantly different in the S group ( P < 0.05). Alleviated pathological damage, decreased the rate of necroptosis and down-regulated the expression of necroptosis-related proteins occurred in the S+M and S+N group ( P < 0.05). The lower elevated [Ca2+]i, expression of NMDAR2A and NMDAR2B were found in the S+M group. Our findings highlighted sevoflurane-induced cognitive dysfunction is associated with an imbalance in cytoplasmic calcium homeostasis by activating NMDA receptors, which causes hippocampus neurons to undergo necroptosis and ultimately affects cognitive performance in aged mice.

Electroencephalographic density spectral array monitoring during propofol/sevoflurane coadministration in children, an exploratory observational study.

INTRODUCTION: Propofol and sevoflurane have a long history in pediatric anesthesia. Combining both drugs at low dose levels offers new opportunities. However, monitoring the hypnotic effects of this drug combination in children is challenging, because the currently available processed EEG-based systems are insufficiently validated in young children and the co-administration of anesthetics. This study investigated electroencephalographic density spectral array monitoring during propofol/sevoflurane coadministration with fixed sevoflurane- and variable propofol dosages. PATIENTS AND METHODS: We analyzed the density spectral array pattern recorded during propofol/sevoflurane anesthesia in pediatric patients from birth to 11 years of age. Data from 78 patients were suitable for analysis. The primary outcome parameter of this study was the correlation between variable propofol dosages and the expression of the four electroencephalogram frequency bands ß, α, θ, and δ. The main secondary outcome parameters were the intra-operative total EEG power and the prevalence of burst suppression. RESULTS: In patients above the age of 1 year, a dose-dependent correlation between the propofol dosage and the relative percentage of ß (-12.2%, p < 0.001) and δ (5.1%, p < 0.001) was found. There was an age-dependent trend toward increasing mean EEG power, with the most significant increase in the first year of life. In 14.1% of our patients, at least one episode of burst suppression occurred. CONCLUSION: DSA-guided augmentation of propofol anesthesia with sevoflurane provides sufficient depth of anesthesia at doses usually considered sub-anesthetic in children, leading to less anesthetic drug exposure for the individual child.

Stress Pathways Induced by Volatile Anesthetics and Failure of Preconditioning in a Mitochondrial Complex I Mutant.

BACKGROUND: Carriers of mutations in the mitochondrial electron transport chain are at increased risk of anesthetic-induced neurotoxicity. To investigate the neurotoxicity mechanism and to test preconditioning as a protective strategy, this study used a Drosophila melanogaster model of Leigh syndrome. Model flies carried a mutation in ND23 (ND2360114) that encodes a mitochondrial electron transport chain complex I subunit. This study investigated why ND2360114 mutants become susceptible to lethal, oxygen-modulated neurotoxicity within 24 h of exposure to isoflurane but not sevoflurane. METHODS: This study used transcriptomics and quantitative real-time reverse transcription polymerase chain reaction to identify genes that are differentially expressed in ND2360114 but not wild-type fly heads at 30 min after exposure to high- versus low-toxicity conditions. This study also subjected ND2360114 flies to diverse stressors before isoflurane exposure to test whether isoflurane toxicity could be diminished by preconditioning. RESULTS: The ND2360114 mutation had a greater effect on isoflurane- than sevoflurane-mediated changes in gene expression. Isoflurane and sevoflurane did not affect expression of heat shock protein (Hsp) genes (Hsp22, Hsp27, and Hsp68) in wild-type flies, but isoflurane substantially increased expression of these genes in ND2360114 mutant flies. Furthermore, isoflurane and sevoflurane induced expression of oxidative (GstD1 and GstD2) and xenobiotic (Cyp6a8 and Cyp6a14) stress genes to a similar extent in wild-type flies, but the effect of isoflurane was largely reduced in ND2360114 flies. In addition, activating stress response pathways by pre-exposure to anesthetics, heat shock, hyperoxia, hypoxia, or oxidative stress did not suppress isoflurane-induced toxicity in ND2360114 mutant flies. CONCLUSIONS: Mutation of a mitochondrial electron transport chain complex I subunit generates differential effects of isoflurane and sevoflurane on gene expression that may underlie their differential effects on neurotoxicity. Additionally, the mutation produces resistance to preconditioning by stresses that protect the brain in other contexts. Therefore, complex I activity modifies molecular and physiologic effects of anesthetics in an anesthetic-specific manner.

Melatonin attenuates sevoflurane-induced hippocampal damage and cognitive deficits in neonatal mice by suppressing CypD in parvalbumin neurons.

BACKGROUND: Sevoflurane, a commonly administered inhaled anesthetic, is found to induce synaptic and mitochondrial damage in neonatal mice. Mitochondrial membrane potential (MMP) changes, mediated by Cyclophilin D (CypD), are implicated in mitochondrial function. Melatonin, known for its significant neuroprotective properties, was investigated in this study to elucidate its mechanisms in mitigating the cognitive impairment caused by sevoflurane. METHODS: The mice were categorized into several groups, including the control, vehicle, sevoflurane, vehicle plus sevoflurane, and melatonin plus sevoflurane groups. From postnatal day 6 to day 8, the mice were administered inhaled sevoflurane or intraperitoneal melatonin. MMP and reactive oxygen species (ROS) were measured using appropriate detection kits. The protein expression levels of PSD95, Synapsin Ⅰ, and CypD in the hippocampus were analyzed through western blotting in acute and prolonged terms. Immunofluorescence staining was used to assess the co-localizations of PSD95 or CypD in parvalbumin (PV) neurons. Cognitive ability was evaluated through novel object recognition, social interaction experiment, and the Morris water maze. RESULTS: The findings revealed that repeated exposure to sevoflurane in neonatal mice resulted in cognitive and synaptic impairment. Furthermore, melatonin administration suppressed the ROS and CypD protein expression, enhanced the MMP in mitochondria and synaptic protein expression in PV neurons, and ameliorated cognitive deficits. CONCLUSION: Melatonin alleviated sevoflurane-induced cognitive deficits by suppressing CypD and promoting synaptic development in hippocampal PV neurons. These results provide valuable insights into a promising therapeutic approach for preventing neurotoxic injuries caused by general anesthetics.

Prediction of blood pressure changes during surgical incision using the minimum evoked current of vascular stiffness value under sevoflurane anesthesia.

Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = - 0.735 (P < 0.01), similar to that in a previous study with propofol (R = - 0.723). Thus, a high correlation was observed. The slope of the linear regression equation was - 0.27, similar to that obtained in the study on propofol (- 0.28). These results suggest that, as with propofol anesthesia, MECK can be used as a predictive index for ROCBP under 0.7 MAC sevoflurane anesthesia.Clinical trial registration: Registry, University hospital Medical Information Network; registration number, UMIN000047425; principal investigator's name, Noboru Saeki; date of registration, April 8, 2022.

Effects of anesthetics on nociceptive sensory evoked potentials by intraepidermal noxious electrical stimulation of A-δ fibers.

PURPOSE: Generation of nociceptive sensory evoked potentials (NEPs) by selective stimulation of nociceptive intraepidermal nerve fibers is a simple technique which could be used as intraoperative nociception monitor. We evaluated the effects of remifentanil, propofol and sevoflurane on NEPs by this technique. METHODS: Patients undergoing general anesthesia were assigned to groups in two studies. A-δ fiber selective NEPs were recorded. Study 1: NEPs were recorded at control, under anesthetics administration: remifentanil at an effect-site concentration (Ce) of 1.0 ng/mL (n = 10), propofol at Ce of 0.5 µg/mL (n = 10), or sevoflurane at 0.2 minimum alveolar concentration (MAC) (n = 10), and recovery from the anesthetics. Study 2: NEPs were recorded at control and under administration of higher dose anesthetics: propofol at Ce of 0.5 and 1.0 µg/mL (n = 10) or sevoflurane at 0.2 and 0.5 MAC (n = 10). A P-value < 0.016 was considered statistically significant in multiple analyses. RESULTS: Study 1: Remifentanil at Ce of 1.0 ng/mL significantly suppressed the amplitude of NEPs (mean amplitude (standard deviation) of control vs. remifentanil administration: 16.8 µV (3.8) vs. 10.1 µV (2.5), P < 0.001). Propofol and sevoflurane did not suppress the amplitude significantly. Study 2: Propofol at Ce of 0.5 and 1.0 µg/mL and sevoflurane at 0.2 and 0.5 MAC did not suppress the amplitude significantly. CONCLUSION: The amplitude of A-δ fiber selective NEPs was suppressed by remifentanil but not propofol or sevoflurane. NEPs with intraepidermal electrical stimulation can assess the analgesic effect of anesthetics. CLINICAL TRIAL NUMBER: UMIN000038214 REGISTRY URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043328.

Effects of propofol and sevoflurane on social and anxiety-related behaviours in sleep-deprived rats.

BACKGROUND: Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats. METHODS: Twelve-week-old male Sprague-Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg-1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation. RESULTS: Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment. CONCLUSIONS: Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies.

Deciphering the antibiofilm potential of 2-Phenylethyl methyl ether (PEME), a bioactive compound of Kewda essential oil against Staphylococcus aureus.

Opportunistic pathogenic bacteria and their pathogenicity linked with biofilm infections become a severe issue as they resist the actions of multiple antimicrobial drugs. Naturally derived drugs having antibiofilm properties are more effective than chemically synthesized drugs. The plant derived essential oils are a rich source of phytoconstituents with widespread pharmacological values. In the present investigation, a major phytoconstituent, 2-Phenyl Ethyl Methyl Ether (PEME) of Kewda essential oil extracted from the flowers of Pandanus odorifer was explored for its prospective antimicrobial and anti-biofilm properties against ESKAPE pathogenic bacterial strains, Staphylococcus aureus and MTCC 740. The minimum inhibitory concentration (MIC) of PEME was found to be 50 mM against the tested bacterial strains. A gradual decrease in biofilm production was observed when PEME was treated with the sub-MIC concentration. The reduction in biofilm formation was noticeable from qualitative assay i.e., Congo Red Agar Assay (CRA) and further quantified by crystal violet staining assay. The decline in exopolysaccharides production was quantified, with the highest inhibition against MTCC 740 with a decrease of 71.76 ± 4.56% compared to untreated control. From the microscopic analysis (light and fluorescence microscopic method), PEME exhibited inhibitory effect on biofilm formation on the polystyrene surface. The in silico studies stated that PEME could invariably bind to biofilm associated target proteins. Further, transcriptomic data analysis suggested the role of PEME in the down-regulation of specific genes, agrA, sarA, norA and mepR, which are critically associated with bacterial virulence, biofilm dynamics and drug resistance patterns in S. aureus. Further, qRT-PCR analysis validated the role of PEME on biofilm inhibition by relative downregulation of agrA, sarA, norA and mepR genes. Further, advanced in silico methodologies could be employed in future investigations to validate its candidature as promising anti-biofilm agent.

Investigating the Protective Role of Biochaga Drug on Structural Changes of Bovine Serum Albumin in the Presence of Methyl tert-butyl Ether.

BACKGROUND: The health benefits of natural products have a long history. Chaga (Inonotus obliques) is used in traditional medicine and is an essential antioxidant for protecting the body from oxidants. Reactive oxygen species (ROS) are produced routinely due to metabolic processes. However, environmental pollution factors such as methyl tert-butyl ether (MTBE) can increase oxidative stress in the human body. MTBE is widely used as a fuel oxygenator that can harm health. The widespread use of MTBE has posed significant threats to the environment by polluting environmental resources, including groundwater. This compound can accumulate in the bloodstream by inhaling polluted air, with a strong affinity for blood proteins. The primary mechanism of MTBE's harmful effects is ROS production. The use of antioxidants may help reduce MTBE oxidation conditions. The present study proposes that biochaga, as an antioxidant, can reduce MTBE damage in the bovine serum albumin (BSA) structure. METHODS AND RESULTS: This study investigated the role of different concentrations of biochaga in the structural change of BSA in the presence of MTBE by biophysical methods such as UV-Vis, fluorescence, FTIR spectroscopy, DPPH radical inhibition method, aggregation test, and molecular docking. Research at the molecular level is critical to investigate the structural change of proteins by MTBE and the protective effect of the ideal dose (2.5 µg/ml) of biochaga. CONCLUSION: the results of spectroscopic examinations showed that the concentration of 2.5 µg/ml of biochaga has the least destructive effect on the structure of BSA in the presence and absence of MTBE, and it can play as an antioxidant.

Brain DNA damaging effects of volatile anesthetics and 1 and 2 Gy gamma irradiation in vivo: Preliminary results.

Although both can cause DNA damage, the combined impact of volatile anesthetics halothane/sevoflurane/isoflurane and radiotherapeutic exposure on sensitive brain cells in vivo has not been previously analyzed. Healthy Swiss albino male mice (240 in total, 48 groups) were exposed to either halothane/sevoflurane/isoflurane therapeutic doses alone (2 h); 1 or 2 gray of gamma radiation alone; or combined exposure. Frontal lobe brain samples from five animals were taken immediately and 2, 6, and 24 h after exposure. DNA damage and cellular repair index were analyzed using the alkaline comet assay and the tail intensity parameter. Elevated tail intensity levels for sevoflurane/halothane were the highest at 6 h and returned to baseline within 24 h for sevoflurane, but not for halothane, while isoflurane treatment caused lower tail intensity than control values. Combined exposure demonstrated a slightly halothane/sevoflurane protective and isoflurane protective effect, which was stronger for 2 than for 1 gray. Cellular repair indices and tail intensity histograms indicated different modes of action in DNA damage creation. Isoflurane/sevoflurane/halothane preconditioning demonstrated protective effects in sensitive brain cells in vivo. Owing to the constant increases in the combined use of radiotherapy and volatile anesthetics, further studies should explore the mechanisms behind these effects, including longer and multiple exposure treatments and in vivo brain tumor models.

The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence.

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 µg g-1; ip injection) with or without 4 µg g-1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1ß (IL1ß), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.

Anesthetic Preferences for Cardiac Anesthesia: A Survey of the Society of Cardiovascular Anesthesiologists.

BACKGROUND: Volatile anesthetics have been historically preferred for cardiac anesthesia, but the evidence for their superiority to intravenous agents is mixed. We conducted a survey to better understand the current state of practice and the rationale behind provider preferences for anesthesia for cardiac surgery with cardiopulmonary bypass. We hypothesized that anesthetic preference would vary considerably among surveyed providers without a clear majority, as would the rationale behind those preferences. METHODS: Email invitations were sent to members of the Society of Cardiovascular Anesthesiologists, who were asked to identify the anesthetics or sedatives they typically prefer to administer during induction, prebypass, bypass, postbypass, and postoperative periods and why they prefer those agents. Members' beliefs regarding the importance of anesthetics on postoperative outcomes were also assessed. RESULTS: Invitations were sent on 2 separate dates to 3328 and 3274 members, of whom 689 (21%) responded. The median (interquartile range [IQR]) respondent age was 45 (37-56) years, 79% were men, and 75% were fellowship trained. The most frequently chosen drug for induction was propofol (80%). Isoflurane was the most frequently selected primary agent for the prebypass (57%), bypass (62%), and postbypass periods (50%). Sevoflurane was the second most frequently selected (30%; 17%, and 24%, respectively). Propofol was the third most frequently selected agent for the bypass (14%) and postbypass periods (17%). Ease of use was the most frequently selected reason for administering isoflurane and sevoflurane for each period. During bypass, the second most frequently selected rationale for using isoflurane and sevoflurane was institutional practice. A total of 76% responded that the perfusionist typically delivers the bypass anesthetic. Ischemic preconditioning, organ protection, and postoperative cognitive function were infrequently selected as rationales for preferring the volatile anesthetics. Most respondents (73%) think that anesthetics have organ-protective properties, especially isoflurane (74%) and sevoflurane (59%), and 72% believed that anesthetic choice contributes to patient outcome. The median (IQR) agreement (0 = strongly disagree to 100 = strongly agree) was 72 (63-85) for the statement that "inhaled anesthetics are an optimal maintenance anesthetic for cardiac surgery." CONCLUSIONS: In a survey of cardiac anesthesiologists, a majority of respondents indicated that they prefer volatile anesthetics for maintenance of anesthesia, that anesthetic selection impacts patient outcomes, and that volatile anesthetics have organ-protective properties. The members' rationales for preferring these agents possibly reflect that practical considerations, such as ease of use, effectiveness, and institutional practice, also influence anesthetic selection during cardiac surgery in addition to considerations such as organ protection.

Maternal sevoflurane exposure affects neural stem cell differentiation in offspring rats through NRF2 signaling.

Studies have shown that sevoflurane, a halogenated inhalational anesthetic, interferes with neurogenesis in the developing rodent brain. However, the mechanisms by which sevoflurane affects neural stem cells (NSCs) differentiation require further elucidation. Pregnant rats (gestational day 14) were anesthetized with 3.5% sevoflurane for 2 h, with or without ML385 pretreatment. ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor. NRF2 expression and the downstream Sonic Hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) signaling cascade were determined by western blotting in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure. Immunofluorescence and western blotting were performed to evaluate NSC neuronal and astrocytic differentiation in fetal brain tissues at 24 h and 72 h post-anesthesia as well as in the hippocampus on postnatal day (P) 28. Nissl staining was performed to measure the neuronal density on P28. Morris Water Maze tests were used to evaluate learning and memory function on P28-33. Neuronal and astrocytic differentiation of NSCs was markedly promoted in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure, accompanied by upregulated NRF2. However, neuronal reduction and astrocyte proliferation were observed in the rat hippocampus at P28. Pretreatment with ML385 reversed sevoflurane-induced premature differentiation of NSCs, accompanied by suppression of SHH/GLI1 signaling. Furthermore, ML385 rescued sevoflurane-induced decreased neuronal density and impaired learning and memory function in the offspring. Prenatal sevoflurane exposure promotes neuronal and astrocytic differentiation of NSCs in the fetal rat brain, leading to long-term neuron reduction but astrocyte proliferation in the postnatal rat hippocampus. Prenatal sevoflurane exposure modulates NSC differentiation through NRF2/SHH/GLI1.

Effects of propofol and sevoflurane on T-cell immune function and Th cell differentiation in children with SMPP undergoing fibreoptic bronchoscopy.

OBJECTIVES: The potentially different effects of commonly used anaesthetic agents propofol and sevoflurane on T-cell immune function and Th cell differentiation were investigated in patients with severe mycoplasmal pneumonia (SMPP) undergoing fibreoptic bronchoscopy. METHODS: Sixty children (2-12 years of age) with SMPP were randomized into the sevoflurane group and the propofol group. Patients in the sevoflurane group were anaesthetised with inhalational sevoflurane and intravenous remifentanil. Patients in the propofol group were anaesthetised with intravenous propofol and remifentanil. Patients in both groups underwent fibreoptic bronchoscopy and lavage therapy. We compared the clinical outcomes, cellular immunity function, and Th cell differentiation into Th1 and Th2 levels in both groups. RESULTS: There was no significant difference in clinical outcomes and hospital stay between the two groups (7.94 vs 7.36, p > .05). However, the CD3+ T cells, CD4+ T cells, and CD4+/CD8+ in the propofol group were significantly higher than those in the sevoflurane group (T1 51.96 vs 48.33, T2 58.08 vs 55.31, p < .05). The ratio of Th1/Th2 in the two groups was significantly increased postoperatively in both groups (Sevoflurane 8.53 vs 7.23, Propofol 9.35 vs 7.18), and the propofol group was significantly higher than the sevoflurane group (9.35 vs 8.53, p < .05). CONCLUSIONS: Propofol might have a less inhibitory effect on T lymphocytes in children with SMPP than sevoflurane. And propofol may have less impact on the differentiation of Th cells into Th1 cells and better preserving the Th1/Th2 ratio than sevoflurane. KEY MESSAGESThe pathogenesis of SMPP is still unclear, likely through alveolar infiltration with neutrophils and lymphocytes, lymphocyte/plasma cell infiltrates in the peri-bronchovascular area, and immune dysfunction.Recent experimental and clinical studies showed that sevoflurane might have immunosuppressive effects, and multiple studies confirmed that the immune function of children with SMPP had been reduced.This study found that propofol administered in children with SMPP had a less inhibitory effect on T lymphocytes than inhalational sevoflurane, had little inhibitory effect on the differentiation of Th cells into Th1 cells, and better preserve Th1/Th2 ratio and maintain the balanced immune function.