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.

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.

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).

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.

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.

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.

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.

The effect of different anesthesia techniques on cerebral oxygenation in thoracic surgery.

OBJECTIVE: One-lung ventilation may cause negative changes in the oxygenation of cerebral tissue which results in post-operative cognitive dysfunction. We compared the potential effects of total intravenous anesthesia and inhalation general anesthesia techniques on cerebral tissue oxygenation. MATERIALS AND METHODS: In this prospective double-blind trial, patients whose standard anesthesia induction was done were randomly divided into two groups as group total intravenous anesthesia using propofol (Group T, n = 30) and group inhalation general anesthesia using sevoflurane (Group I, n = 30) based on anesthesia maintenance. The intraoperative cerebral oxygen saturation and pre-post-operative mini-mental status test scores of the patients were monitored and recorded. RESULTS: Baseline characteristics were similar between the two groups. The decrease of cerebral oxygen saturation more than 20% in total intravenous anesthesia group was significantly higher than inhalation group (p < 0.05). In both groups, the mini-mental status test values at the post-operative 3rd h were significantly lower than the pre-operative and post-operative 24th h values (p < 0.05). CONCLUSIONS: Inhalation general anesthesia provided better cerebral tissue oxygenation in thoracic surgery with one-lung ventilation compared to total intravenous anesthesia. However, there was no significant correlation between the presence of desaturation and post-operative cognitive dysfunction.

OBJETIVO: La ventilación unipulmonar puede provocar cambios negativos en la oxigenación del tejido cerebral que se traduce en una disfunción cognitiva postoperatoria. Comparamos los efectos potenciales de la anestesia total intravenosa y las técnicas de anestesia general por inhalación en relación con la oxigenación del tejido cerebral. MATERIAL Y MÉTODOS: En este ensayo prospectivo doble ciego, los pacientes en los que se realizó una inducción estándar de anestesia se dividieron aleatoriamente en dos grupos: grupo de anestesia intravenosa total con propofol (Grupo T, n = 30) y grupo de anestesia general por inhalación con sevoflurano (Grupo I, n = 30) basados en el mantenimiento de la anestesia. Se controlaron y registraron la saturación de oxígeno cerebral intraoperatoria y las valoraciones de la miniprueba de estado mental preoperatoria de los pacientes. RESULTADOS: Las características de base fueron similares entre los dos grupos. La disminución de la saturación de oxígeno cerebral de más del 20% en el grupo de anestesia intravenosa total fue significativamente mayor que en el grupo de inhalación (p < 0.05). En ambos grupos, los valores de la mini prueba del estado mental al cabo de la 3a. hora del período posoperatorio fueron significativamente más bajos que los valores preoperatorios y posoperatorios registrados al cabo de 24 horas (p < 0.05). CONCLUSIONES: La anestesia general por inhalación facilitó una mejor oxigenación del tejido cerebral en la cirugía torácica con ventilación unipulmonar en comparación con la anestesia intravenosa total. Sin embargo, no hubo una correlación significativa entre la presencia de desaturación y la disfunción cognitiva posoperatoria.

The effects of total intravenous and inhalation anesthesia maintenance on tissue oxygenation in coronary artery bypass graft surgery.

OBJECTIVE: The aim of this study is to evaluate the effect of total intravenous anesthesia (TIVA) and inhalational anesthesia techniques on tissue oxygenation in cardiac surgery. We compared the effects of midazolam-based TIVA and sevoflurane-based (SEVO) inhalation anesthesia maintenance on intraoperative central and regional tissue oxygenation parameters. PATIENTS AND METHODS: A total of 104 adult patients who were scheduled for elective isolated coronary bypass surgery were included in the study. All patients were divided into two groups: the TIVA group consisted of total intravenous anesthesia maintenance patients (n=52) and the SEVO group consisted of patients with inhalation anesthesia with sevoflurane maintenance (n=52). Tissue oxygenation values were observed with left-right cerebral and somatic left forearm Near-Infrared Spectroscopy (NIRS) sensors. The hemodynamic parameters, NIRS StO2, central (ScvO2) and peripheral venous oxygen saturations of the patients were recorded at six intraoperative time points. RESULTS: The effects of midazolam-based TIVA and sevoflurane-based inhalation anesthesia maintenance on intraoperative central and peripheral tissue oxygenation parameters were compared and it was found that in the left forearm NIRS StO2 and ScvO2 values were higher in the SEVO group than the TIVA group. Although not significantly different, forearm regional venous oxygen saturation was also higher in the SEVO group. CONCLUSIONS: The effects of anesthetic drugs on regional tissue oxygenation can become important in critical patients and challenging surgeries. Sevoflurane-based anesthesia provides better tissue oxygenation than TIVA in patients undergoing coronary bypass surgery.

Flavonoids from Rhododendron nivale Hook. f delay aging via modulation of gut microbiota and glutathione metabolism.

BACKGROUND: Rhododendron nivale Hook. f (R.n), one of the four Manna Stash used in Tibetan medicine to delay aging, possesses anti-aging pharmacological activity. However, which R.n ingredients contain anti-aging properties and the underlying mechanisms involved are unclear. HYPOTHESIS/PURPOSE: Based on interactions between gut microbiota and natural medicines and the important role of gut microbiota in anti-aging, the study investigated the hypothesis that R.n possesses anti-aging properties and the interaction of gut microbiota with R.n is responsible for its anti-aging effects. STUDY DESIGN: The primary active ingredients of R.n and their target function and pathway enrichment were explored. An aging mouse model was used to clarify the underlying anti-aging mechanisms of R.n. METHODS: Chromatography, spectroscopy, nuclear magnetic technology, and pharmacology were used to reveal the major active ingredients of ethanol extract residues of R.n (RNEA). The target function and pathway enrichment of these active ingredients were explored. Plasma metabolomics coupled with intestinal flora evaluation and bioinformatics analysis was used to clarify the underlying anti-aging mechanisms of RNEA. RESULTS: Myricetin-3-ß-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-ß-D-galactoside, and diplomorphanin B were separated and identified from RNEA. The network pharmacology study revealed that the active ingredients' target function and pathway enrichment focused mainly on the glutathione antioxidant system. In a D-galactose-induced mouse model of aging, RNEA was shown to possess suitable anti-aging pharmacological activity, as indicated by the amelioration of memory loss and weakened superoxide dismutase and glutathione peroxidase activities. Plasma metabolomics coupled with intestinal flora examination and bioinformatics analysis revealed that RNEA could regulate the expression of glutathione-related enzymes and ameliorate D-galactose-induced imbalances in methionine, glycine, and serine, and betaine and galactose metabolism. The results showed that RNEA reshaped the disordered intestinal flora and mitigated the D-galactose-mediated decline in glutathione oxidase expression, further confirming that the anti-aging effect of RNEA was closely related to regulation of the glutathione antioxidant system. CONCLUSION: RNEA, consisting of myricetin-3-ß-D-xylopyranoside, hyperin, goospetin-8-methyl ether 3-ß-D-galactoside, and diplomorphanin B, possesses anti-aging activity. The anti-aging effect of RNEA might be due to reshaping intestinal flora homeostasis, increasing the expression of glutathione peroxidase 4 in the intestines and liver, enhancing glutathione peroxidase activity, and reinforcing the glutathione antioxidant system.

Comparison of effects of sevoflurane versus propofol on left ventricular longitudinal global and regional strain in patients undergoing on-pump coronary artery bypass grafting.

Background: Assessment of myocardial deformation by quantifying peak systolic longitudinal strain (PSLS) is a sensitive and robust index to detect subclinical myocardial dysfunction. We hypothesize that sevoflurane by virtue of anesthetic preconditioning preserves myocardial function better than propofol. Aims: The authors have assessed the effects of sevoflurane and propofol on global longitudinal strain (GLS) as a primary outcome in patients undergoing on-pump coronary artery bypass grafting. Our secondary aim was to assess the pattern of regional distribution of segmental PSLS between the groups. Materials and Methods: Fifty patients with normal left ventricular function undergoing coronary artery bypass grafting were analyzed in this prospective observational study. Consecutive patients received either propofol (P) or sevoflurane (S) anesthesia. Measurements: Trans-esophageal echocardiographic images (mid-esophageal four-chamber, two-chamber, and three-chamber (long-axis)) were recorded during the precardiopulmonary bypass (CPB) and post-CPB period. Strain analysis (GLS/segmental PSLS) was done offline by investigators blinded to the study. The inotropic score, duration of inotropic support, and mechanical ventilation required were recorded. Results: Following cardiopulmonary bypass and coronary revascularization, GLS reduced significantly in both the groups (P < 0.05). In the S-group, significant reduction in segmental strain was observed only in apical segments including apex, whereas in P-group significant reduction in segmental strain was seen in mid- and apical segments. The postoperative VIS, duration of inotropes/vasopressor required, and mechanical ventilation were similar in both the groups. Conclusions: There are no significant differences in global left ventricular function as assessed by GLS between patients anesthetized with sevoflurane or propofol. However, regional PSLS was better preserved in the S-group compared to P-group.

Renal function during sevoflurane or total intravenous propofol anaesthesia: a single-centre parallel randomised controlled study.

BACKGROUND: The choice of anaesthetic may influence regulation of renal perfusion and function. We investigated renal function in patients anaesthetised with propofol or sevoflurane before surgery and postoperatively. METHODS: Patients with ASA physical status 1-2 planned for spinal surgery were randomised to propofol or sevoflurane anaesthesia. Blood and urine were collected before anaesthesia, during anaesthesia (before surgery), during postoperative care, and the day after surgery. RESULTS: Twenty-seven patients completed the study protocol (average age, 51 yr; average BMI, 28 kg m-2) and 11 were women. Urine output and sodium excretion were lower during sevoflurane anaesthesia (n=14) than during propofol anaesthesia (n=13) (0.3 vs 1.1 ml kg-1 h-1 [P=0.01] and 2.6 vs 6.0 mmol h-1 [P=0.04], respectively). Urinary potassium excretion was lower during anaesthesia than after, without intergroup difference (2.3 vs 5.7 mmol h-1, P<0.001). Sevoflurane anaesthesia increased plasma renin compared with baseline (138 vs 23 mIU L-1, P<0.001) and propofol anaesthesia (138 vs 27 mIU L-1, P=0.008). Plasma arginine-vasopressin did not change significantly during anaesthesia, but was elevated postoperatively compared with baseline irrespective of anaesthetic (21 vs 12 ng L-1, P=0.02). Sevoflurane caused higher postoperative plasma creatinine than propofol (83 vs 66 mmol L-1, P=0.01). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not change significantly in either group. CONCLUSIONS: Sevoflurane anaesthesia reduced urine output and sodium excretion and increased plasma renin compared with propofol anaesthesia. The impact of this on acute kidney injury and fluid resuscitation during surgery warrants further investigation. CLINICAL TRIAL REGISTRATION: EudraCT: 2017-001646-10; Clinicaltrials.gov: NCT0333680.

Ethnopharmacological impact of Melaleuca rugulosa (Link) Craven leaves extract on liver inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed. AIM OF THE STUDY: The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. rugulosa leaves in relevance to their flavonoid content using an appropriate in vivo model. MATERIALS AND METHODS: The aqueous methanol extract of M. rugulosa leaves was administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for seven days prior to the initiation of liver-injury induced by paracetamol (3 g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum samples. The oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), were assessed in liver homogenate. The results were supported by histopathological and immuno-histochemical studies. The phytochemical investigation of the flavonoid-rich fraction of the aqueous methanol extract was accomplished using different chromatographic and spectroscopic techniques. RESULTS: The aqueous methanol extract of M. rugulosa leaves showed a powerful hepatoprotective activity evidenced by the significant reduction of MDA and NO levels, as well as increasing GSH and catalase activity. Moreover, the extract exhibited anti-inflammatory and antiapoptotic activities witnessed by decreasing TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract showed a significant decrease in liver weight/body weight (LW/BW) ratio, and total bilirubin induced by paracetamol. On the other hand, the chromatographic separation of the flavonoid-rich fraction afforded twenty known flavonoids namely; iso-orientin (1), orientin (2), isovitexin (3), vitexin (4), quercetin-3-O-ß-D-glucuronid methyl ether (5), quercetin-3-O-ß-D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), kaempferol-3-O-ß-D-mannuronopyranoside (9), kaempferol-7-O-methyl ether-3-O-ß-D-glucopyranoside (10), guaijaverin (11), avicularin (12), kaempferide-3-O-ß-D-glucopyranoside (13), astragalin (14), afzelin (15), luteolin (16), apigenin (17), quercetin (18), kaempferol (19), and catechin (20). CONCLUSION: The aqueous methanol extract of M. rugulosa leaves showed potential hepatoprotective, antioxidant, and anti-inflammatory activities against paracetamol-induced liver inflammation which is correlated at least in part to its considerable phenolic content.

Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting.

Pregnenolone methyl-ether (PME) is a synthetic derivative of the endogenous neuroactive steroid pregnenolone (PREG), which is an important modulator of several brain functions. In addition to being the precursor of steroids, PREG acts directly on various targets including microtubules (MTs), the functioning of which is fundamental for the development and homeostasis of nervous system. The coordination of MT dynamics is supported by a plethora of MT-associated proteins (MAPs) and by a specific MT code that is defined by the post-translational modifications of tubulin. Defects associated with MAPs or tubulin post-translational modifications are linked to different neurological pathologies including mood and neurodevelopmental disorders. In this review, we describe the beneficial effect of PME in major depressive disorders (MDDs) and in CDKL5 deficiency disorder (CDD), two pathologies that are joint by defective MT dynamics. Growing evidence indeed suggests that PME, as well as PREG, is able to positively affect the MT-binding of MAP2 and the plus-end tracking protein CLIP170 that are both found to be deregulated in the above mentioned pathologies. Furthermore, PME influences the state of MT acetylation, the deregulation of which is often associated with neurological abnormalities including MDDs. By contrast to PREG, PME is not metabolised into other downstream molecules with specific biological properties, an aspect that makes this compound more suitable for therapeutic strategies. Thus, through the analysis of MDDs and CDD, this work focuses attention on the possible use of PME for neuronal pathologies associated with MT defects.

Inhibitory Effects of Luteolin 7-Methyl Ether Isolated from Wikstroemia ganpi on Tnf-A/Ifn-Γ Mixture-Induced Inflammation in Human Keratinocyte.

Plants of the genus Wikstroemia are traditionally used in China to treat various inflammatory diseases. The purpose of this study was to isolate the components of Wikstroemia ganpi (Siebold & Zucc.) Maxim., to evaluate their anti-atopic activities and to identify candidates with anti-atopic therapeutics. A total of 24 compounds were isolated by bioassay-guided separation, including one novel compound, which was tilianin 5-methyl ether. The anti-atopic activities of the isolated compounds were determined using TNF-α-treated RBL-2H3 cells and HaCaT cells. The mRNA expressions of IL-4, IL-6, GM-CSF, G-CSF and TRPV1 were reduced by luteolin 7-methyl ether. The study shows that the luteolin 7-methyl ether isolated from W. ganpi is a potential therapeutic agent for the treatment of atopic dermatitis.

Genotoxic and mutagenic effects of methyl ether dillapiole on the development of Aedes aegypti (Diptera: Culicidae).

Dillapiole, extracted from Piper aduncum essential oil and its derivatives, has been shown to be a potential alternative to the control of Aedes aegypti, which has become resistant to synthetic insecticides. Methyl ether dillapiole (MED) and temephos (TM) were compared to complement the data on the genotoxicity and developmental changes of Ae. aegypti. Over four generations (G1 -G4 ), third stage larvae were treated with MED at 60, 80 and 100 µg/mL and TM at 0.002, 0.005 and 0.007 µg/mL for 4 h. Adult females were separated to estimate oviposition and hatching rates, and total egg length. Over the four generations, a significant reduction was recorded in oviposition and hatching rates, and in mean egg length (Tukey, P < 0.05), compared with the negative control (NC). Cytological slide preparations were done from adult oocytes and larval neuroblasts. The cumulative effects of genotoxic (bridges, budding and nuclear fragmentation) and mutagenic (micronucleus and chromosomal breakage) damage was observed in the neuroblasts and oocytes of exposed mosquitoes. Developmental changes and damage to the genome of MED-treated Ae. aegypti were greater than those caused by TM. Further studies should focus on understanding the effects of the MED molecule on Ae. aegypti.