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1.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919449

RESUMO

Inhalational anesthetics was previously reported to suppress glioma cell malignancy but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNAs upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

2.
Anesthesiology ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33930110
3.
J Magn Reson Imaging ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33728737

RESUMO

BACKGROUND: Metabolic syndrome increases the risk of chronic diseases such as cardiovascular disease and diabetes. Metabolic syndrome also has an impact on bone mineral density. However, the relationship between metabolic syndrome and bone marrow fat is unclear. PURPOSE: To determine factors associated with bone marrow fat concentration in subjects with and without metabolic syndrome. STUDY TYPE: Retrospective. POPULATION: One hundred and one women with metabolic syndrome (31.0 years ±5.1) and 96 female living liver transplant donors (32.0 years ±3.7). Our institutional review board approved the study. Each subject signed written informed consent. FIELD STRENGTH/SEQUENCE: 3.0 T MRI system and a commercially available chemical shift-encoded 3D sequence (Iterative Decomposition of water and fat with Echo asymmetry and Least Square Estimation). ASSESSMENT: Proton density fat fraction (PDFF) in liver, vertebral body, and paraspinal muscle (erector spinae) were measured from a single acquisition by a 15-year-experience orthopedic radiologist. The factors associated with PDFF were acquired. STATISTICAL TESTS: The analysis of covariance test, after adjustment for body mass index and age, was used to analyze the differences between metabolic syndrome and non-metabolic syndrome groups. A stepwise multiple regression analysis was used to determine which variables were independently associated with PDFF. RESULTS: Mean vertebral PDFF and alanine aminotransferase (ALT) were significantly lower in donors than subjects with metabolic syndrome (both P < 0.05). Serum vitamin D concentration, ferritin, and high-density lipoprotein (HDL) cholesterol were significantly higher in donors than subjects with metabolic syndrome (all P < 0.05). Multiple regression analysis revealed antidiabetic medicine, higher serum vitamin D concentration, lower waist circumference, lower ferritin, lower HDL, absence of metabolic syndrome, and lower ALT were significantly associated with lower vertebral PDFF (all P < 0.05). DATA CONCLUSION: Multiple factors affect bone marrow fat concentration in subjects with metabolic syndrome. Serum vitamin D concentration and antidiabetic medicine are associated with low bone marrow fat, whereas waist circumference, serum ferritin, metabolic syndrome, imbalanced lipid metabolism, and abnormal liver function are associated with high bone marrow fat. LEVEL OF EVIDENCE LEVEL: 3 TECHNICAL EFFICACY STAGE: 1.

5.
BMC Anesthesiol ; 21(1): 71, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750303

RESUMO

BACKGROUND: microRNAs (miRNAs) are single-stranded and noncoding RNA molecules that control post-transcriptional gene regulation. miRNAs can be tumor suppressors or oncogenes through various mechanism including cancer cell biology, cell-to-cell communication, and anti-cancer immunity. MAIN BODY: Anesthetics can affect cell biology through miRNA-mediated regulation of messenger RNA (mRNA). Indeed, sevoflurane was reported to upregulate miR-203 and suppresses breast cancer cell proliferation. Propofol reduces matrix metalloproteinase expression through its impact on miRNAs, leading to anti-cancer microenvironmental changes. Propofol also modifies miRNA expression profile in circulating extracellular vesicles with their subsequent anti-cancer effects via modulating cell-to-cell communication. CONCLUSION: Inhalational and intravenous anesthetics can alter cancer cell biology through various cellular signaling pathways induced by miRNAs' modification. However, this area of research is insufficient and further study is needed to figure out optimal anesthesia regimens for cancer patients.

6.
Int J Mol Sci ; 22(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673181

RESUMO

Inhalational anaesthetics were previously reported to promote ovarian cancer malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the role of sevoflurane- or desflurane-induced microRNA (miRNA) changes on ovarian cancer cell behaviour. The cultured SKOV3 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 h. Expression of miR-138, -210 and -335 was determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and Cell Counting Kit-8 (CCK8) assay with or without mimic miR-138/-210 transfections. The miRNA downstream effector, hypoxia inducible factor-1α (HIF-1α), was also analysed with immunofluorescent staining. Sevoflurane or desflurane exposure to cancer cells enhanced their proliferation and migration. miR-138 expression was suppressed by both sevoflurane and desflurane, while miR-210 expression was suppressed only by sevoflurane. miR-335 expression was not changed by either sevoflurane or desflurane exposure. The administration of mimic miR-138 or -210 reduced the promoting effects of sevoflurane and desflurane on cancer cell proliferation and migration, in line with the HIF-1α expression changes. These data indicated that inhalational agents sevoflurane and desflurane enhanced ovarian cancer cell malignancy via miRNA deactivation and HIF-1α. The translational value of this work needs further study.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desflurano/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/biossíntese , Neoplasias Ovarianas/metabolismo , RNA Neoplásico/biossíntese , Sevoflurano/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/patologia
7.
Korean J Anesthesiol ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596628

RESUMO

Cancer is responsible for almost 10 million deaths annually and, with an aging population, the incidence of cancer is expected to continue to rise. Surgery is an important treatment modality for patients with solid organ cancers. It has been postulated that, due to potentially overlapping processes underlying the development of malignancy and the therapeutic pathways of various anaesthetic agents, the choice of anaesthetic type and method of administration may affect post-operative outcomes in patients with cancer. This is a literature review of the most recent evidence extracted from various databases including PubMed, EMBASE, and the Cochrane, as well as journals and book reference lists. The review highlights the pathophysiological processes underpinning cancer development and the molecular actions of anaesthetic agents, pre-clinical and retrospective studies investigating cancer and anaesthetics, as well as ongoing clinical trials. Overall, there are conflicting results regarding the impact of regional vs. general anaesthesia on cancer recurrence, whilst the majority of data suggest a benefit of the use of intravenous propofol over inhalational volatile anaesthetics. The biological changes associated with the surgical inflammatory response offer a unique opportunity to intervene to counteract any potentially cancer-promoting effects.

8.
Br J Radiol ; 94(1119): 20200234, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417486

RESUMO

OBJECTIVES: To analyze vertebral fractures risk in patients with chest scans by evaluating vertebral hydroxyapatite concentration measured on spectral CT compared to trabecular attenuation value measured on conventional CT. METHODS: Our retrospective study reviewed CT of 216 patients. Analysis of vertebral (T11 - L1) hydroxyapatite concentration by spectral imaging and trabecular attenuation value by conventional CT imaging were performed in patients with chest CT examinations. Specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) were performed by using receiver operating characteristic (ROC) curves in patients with and without vertebral fractures. RESULTS: In male patients, vertebral hydroxyapatite concentration had high area under the ROC curve (0.916), by using the optimal threshold of 72.27 mg/cm3, specificity, sensitivity, NPV, and PPV were 91.7, 80.2, 36.7, and 98.7%, respectively. In female patients, vertebral hydroxyapatite concentration also had high area under the ROC curve (0.870), by using the optimal threshold of 74.79 mg/cm3, specificity, sensitivity, NPV, and PPV were 100.0, 77.8, 47.4, and 100.0%, respectively. Area under the ROC curve was significantly different between spectral CT-measured bone hydroxyapatite concentration and conventional CT-measured attenuation value in distinguishing vertebral fractures (p = 0.007 for males; p = 0.005 for females). CONCLUSIONS: Quantitative assessment with spectral CT may appear as higher accuracy than that of conventional CT imaging to analyze risk of vertebral fractures. Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures. ADVANCES IN KNOWLEDGE: Hydroxyapatite concentration measured with chest spectral CT may be used to evaluate risk of bone fractures.


Assuntos
Durapatita/metabolismo , Radiografia Torácica/métodos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/metabolismo , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Fraturas da Coluna Vertebral/metabolismo , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões
9.
J Affect Disord ; 281: 342-350, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33348177

RESUMO

BACKGROUND: Depression is a common and serious complication in new mothers. We investigated the hypothesis that neuraxial labor analgesia is associated with a decreased risk of postpartum depression. METHODS: In this multicenter prospective cohort study with propensity score matching, 599 nulliparous women with single term cephalic pregnancy who planned vaginal delivery were enrolled and self-selected neuraxial analgesia or not. The primary outcome was 6-week postpartum depression assessed with the Chinese version Edinburgh Postnatal Depression Scale; a score of ≥10 was set as the threshold of postpartum depression. Logistic regression models were established to assess the association between neuraxial labor analgesia and postpartum depression. RESULTS: Of the 577 parturients who completed the study, 417 (72.3%) received neuraxial analgesia and 160 (27.7%) did not. After propensity score matching, 433 parturients were included in the analysis; of whom, 279 (64.4%) received neuraxial analgesia and 154 (35.6%) did not. The incidence of postpartum depression was lower in parturients with neuraxial analgesia than in those without (14.9% [62/417] vs. 23.8% [38/160], P=0.012 before matching; 13.3% [37/279] vs. 23.4% [36/154], P=0.007 after matching). After adjustment for confounding factors, neuraxial analgesia was associated with decreased odds of postpartum depression (odds ratio [OR] 0.50, 95% CI 0.28-0.88, P=0.015 before matching; OR 0.40, 95% CI 0.21-0.77, P=0.006 after matching). LIMITATIONS: As an observational study, unidentified confounders might influence the results. CONCLUSIONS: In nulliparae with single term cephalic pregnancy preparing to give vaginal delivery neuraxial analgesia during labor was associated with a decreased risk of 6-week postpartum depression.


Assuntos
Analgesia Epidural , Depressão Pós-Parto , Trabalho de Parto , Analgesia Epidural/efeitos adversos , Depressão Pós-Parto/epidemiologia , Feminino , Humanos , Gravidez , Pontuação de Propensão , Estudos Prospectivos
10.
Front Med (Lausanne) ; 7: 608259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262996

RESUMO

Background and Aim: The global pandemic of COVID-19 has posed an enormous threat to the economy and people's lives across various countries. Patients with COVID-19 most commonly present with respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. We aimed to study the relationship between GI symptoms and disease prognosis in patients with COVID-19. Methods: In a single-center and retrospective cohort study, the outcomes in COVID-19 patients with or without GI symptoms were compared. The propensity score is a conditional probability of having a particular exposure (COVID-19 patients with GI symptoms vs. without GI symptoms) given a set of baseline measured covariates. Survival was estimated using the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank-test. To explore the GI symptoms associated with ARDS, non-invasive ventilator treatment, tracheal intubation, tracheotomy, and CRRT, univariable and multivariable COX regression models were used. Results: Among 1,113 eligible patients, 359 patients with GI symptoms and 718 without GI symptoms had similar propensity scores and were included in the analyses. Patients with GI symptoms, as compared with those without GI symptoms, were associated with a similar risk of death, but with higher risks of ARDS, non-invasive mechanical ventilation in COVID-19 patients, respectively. Conclusions: The presence of GI symptoms was associated with a high risk of ARDS, non-invasive mechanical ventilation and tracheal intubation in patients with COVID-19 but not mortality.

11.
Cancer Med ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33280262

RESUMO

Lidocaine, one of the most commonly used local anesthetics during surgery, has been reported to suppress cancer cell growth via blocking voltage-gated sodium channels (VGSCs). VGSC 1.5 (NaV 1.5) is highly expressed in invasive cancers including ovarian cancer. This study aims to investigate whether lidocaine inhibits the malignancy of ovarian cancer through NaV 1.5 blockage. Human ovarian cancer, its metastatic cancer and normal ovarian tissues were probed with anti-NaV 1.5 antibody in situ. Human ovarian cancer A2780 and SKOV3 cells were cultured and their growth, epithelial-mesenchymal transition (EMT), migration, and invasion in the presence or absence of lidocaine together with underlying molecular mechanisms were assessed. Murine syngeneic ovarian cancer (ID8) model was also used to determine the chemotherapeutic efficiency of cisplatin in combination with lidocaine. The high level of NaV 1.5 expression was found in human ovarian cancer and even higher in its metastatic cancer but not in normal ovarian tissues. Lidocaine decreased the growth, EMT, migration, and invasion of human ovarian cancer A2780 and SKOV3 cells. Lidocaine enhanced the chemotherapeutic efficiency of cisplatin in both ovarian cancer cell cultures and a murine ovarian metastatic model. Furthermore, a downregulation of NaV 1.5 by siRNA transfection, or FAK inhibitor application, inhibited the malignant properties of SKOV3 cells through inactivating FAK/Paxillin signaling pathway. Our data may indicate that lidocaine suppresses the metastasis of ovarian cancer and sensitizes cisplatin through blocking NaV 1.5-mediated EMT and FAK/paxillin signaling pathway. The translational value of lidocaine local application as an ovarian cancer adjuvant treatment warrants further study.

12.
Front Neurol ; 11: 556028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133006

RESUMO

Objective: This study aimed to investigate the brain functional alterations with resting-state functional magnetic resonance imaging (rs-fMRI) in older patients with knee osteoarthritis (KOA) before and after total knee arthroplasty (TKA) and to assess the causal relationship of the brain function and neuropsychological changes. Methods: We performed rs-fMRI to investigate brain function of 23 patients aged ≥65 with KOA and 23 healthy matched controls. Of the KOA patients, 15 completed postoperative rs-fMRI examinations. Analyzes of the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were used to estimate differences in brain functional parameters between KOA patients, postoperative patients, and the controls. The relationship between changes of pre- and post-surgical status in ALFF and neuropsychological test results was analyzed. Results: Compared with the controls, all patients with KOA exhibited decreased ALFF in the default mode network (bilateral angular gyrus, precuneus gyrus, medial superior frontal gyrus) and increased ALFF in the bilateral amygdala and cerebellum posterior lobe before surgery (P < 0.001). Altered ALFF persisted in the same brain regions 1 week postoperatively. The decreased ALFF in the left precuneus gyrus and middle temporal gyrus was found after surgery when compared with preoperative data (P < 0.01). Preoperatively, the KOA patients exhibited increased FC between the left precuneus gyrus and the right supplementary motor area compared to the controls (P < 0.001), but this connectivity became no significant difference after TKA. The left Cerebelum_9 was found to have decreased FC with the right precuneus gyrus postoperatively (P < 0.001) although this was not significantly different before surgery. The significantly altered ALFF values were not correlated with changes in cognitive assessment scores. Conclusion: In older patients with end-stage KOA, functional alterations in important brain regions were detected with the persistence and further changes observed at an early stage after knee replacement. Our data further our understanding of brain functional abnormalities and cognitive impairment in older patients following knee replacement, which may provide therapeutic targets for preventive/treatment strategy to be developed. Trial registration: Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, ChiCTR1800016437; Registered June 1, 2018.

13.
Neurobiol Dis ; 146: 105121, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33007389

RESUMO

The balance of excitatory and inhibitory neurons in the central nervous system is critical for maintaining brain function and sevoflurane, a general anesthetic and an GABA receptor modulator, may change the balance of excitatory and inhibitory neurons in the cortex during early brain development. Herein, we investigated whether prenatal sevoflurane exposure (PSE) disturbs cortical neuronal development and brain function. Pregnant rats at the gestational day 14.5 were subjected to sevoflurane exposure at 3.0% for 3 h and their offspring were studied thereafter. We found a significant increase of parvalbumin-positive neurons, vesicular GABA transporter (VGAT) and GAD67 expression, and GABA neurotransmitter, and a significant decrease of vesicular glutamate transporter 1 (VGLUT1) expression and glutamate in the medial prefrontal cortex (mPFC) of offspring. Pyramidal neurons showed atrophy with shorter dendrites, less branches and lower spine density visualized by Golgi stain and a decrease of excitability with the increased miniature inhibitory postsynaptic current (mIPSC) frequency and amplitude, the decreased miniature excitatory postsynaptic current (mEPSC) frequency and excitation/inhibition (E/I) ratio using whole-cell recording in offspring. There was a significant increase of inhibitory synapse in the mPFC detected by electron microscopy. Furthermore, PSE animals showed hypo-excitatory phenotype including depression-like behaviors and learning deficits. Thus, our studies provide novel evidence that PSE causes the persisted imbalance of excitatory and inhibitory neurons in the mPFC, and this is very likely the mechanisms of the sevoflurane-induced brain functional abnormalities.

14.
Anesth Analg ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33060490

RESUMO

BACKGROUND: Control of bleeding during laparoscopic liver resection (LLR) is important for patient safety. It remains unknown what the effects of mechanical ventilation with varying tidal volumes on bleeding during LLR. Thus, this study aims to investigate whether mechanical ventilation with low tidal volume (LTV) reduces surgical bleeding during LLR. METHODS: In this prospective, randomized, and controlled clinical study, 82 patients who underwent scheduled LLR were enrolled and randomly received either mechanical ventilation with LTV group (6-8 mL/kg) along with recruitment maneuver (once/30 min) without positive end-expiratory pressure (PEEP) or conventional tidal volume (CTV; 10-12 mL/kg) during parenchymal resection. The estimated volume of blood loss during parenchymal resection and the incidence of postoperative respiratory complications were compared between 2 groups. RESULT: The estimated volume of blood loss (median [interquartile range {IQR}]) was decreased in the LTV group compared to the CTV group (301 [148, 402] vs 394 [244, 672] mL, P = .009); blood loss per cm of transected surface of liver (5.5 [4.1, 7.7] vs 12.2 [9.8, 14.4] mL/cm, P < .001) and the risk of clinically significant estimated blood loss (>800 mL) were reduced in the LTV group compared to the CTV group (0/40 vs 8/40, P = .003). Blood transfusion was decreased in the LTV group compared to the CTV group (5% vs 20% of patients , P = .043). No patient in the LTV group but 2 patients in the CTV group were switched from LLR to open hepatectomy. Airway plateau pressure was lower in the LTV group compared to the CTV group (mean ± standard deviation [SD]) (12.7 ± 2.4 vs 17.5 ± 3.5 cm H2O, P = .002). CONCLUSIONS: Mechanical ventilation with LTV may reduce bleeding during laparoscopic liver surgery.

15.
Inflammation ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33029758

RESUMO

The widespread occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a pandemic of coronavirus disease 2019 (COVID-19). The S spike protein of SARS-CoV-2 binds with angiotensin-converting enzyme 2 (ACE2) as a functional "receptor" and then enters into host cells to replicate and damage host cells and organs. ACE2 plays a pivotal role in the inflammation, and its downregulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury and involving inflammatory responses. Severe patients of COVID-19 often develop acute respiratory distress syndrome and multiple organ dysfunction/failure with high mortality that may be closely related to the hyper-proinflammatory status called the "cytokine storm." Massive cytokines including interleukin-6, nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) released from SARS-CoV-2-infected macrophages and monocytes lead inflammation-derived injurious cascades causing multi-organ injury/failure. This review summarizes the current evidence and understanding of the underlying mechanisms of SARS-CoV-2, ACE2 and inflammation co-mediated multi-organ injury or failure in COVID-19 patients.

16.
Cell Death Dis ; 11(8): 681, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32826852

RESUMO

Certain miRNAs can attenuate hypoxia/re-oxygenation-induced autophagic cell death reported in our previous studies, but how these miRNAs regulate the autophagy-related cellular signaling pathway in preventing cell death is largely unknown. In the current study, the autophagy-related miRNAs of hsa-miR-20b were investigated in an in vitro model of hypoxia/re-oxygenation-induced endothelial autophagic cell death. Of these, miR-20b was found to be the most important miRNA which targeted on the key autophagy kinase ULK1 and inhibited hypoxia/re-oxygenation injury-induced autophagy by decreasing both autophagosomes and LC3I to II transition rate and P62 degradation. These processes were reversed by the transfection of an miR-20b inhibitor. Re-expression of ULK1 restores miR-20b-inhibited autophagy. Propofol, a commonly used anesthetic, promoted miR-20b and METTL3 expression and attenuated endothelial autophagic cell death. The inhibited endogenous expression of miR-20b or silenced METTL3 diminished the protective effect of propofol and accentuated autophagy. Additionally, METTL3 knockdown significantly inhibited miR-20b expression but up-regulated pri-miR-20b expression. Together, our data shows that propofol protects against endothelial autophagic cell death induced by hypoxia/re-oxygenation injury, associated with activation of METTL3/miR-20b/ULK1 cellular signaling.

17.
Br J Anaesth ; 125(4): 548-559, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32807382

RESUMO

BACKGROUND: Circadian differences in the induction, maintenance, or emergence from volatile anaesthesia have not been well studied. METHODS: The minimal alveolar concentration (MAC) for preventing movement in response to a painful stimulus, MAC for loss of righting reflex (MACLORR), and MAC for recovery of righting reflex (MACRORR) in C57BL/6J male mice with isoflurane or sevoflurane exposure were measured during either the light or dark phase. Time to onset of loss of righting reflex (TimeLORR) and recovery of righting reflex (TimeRORR) upon exposure to 1 MAC of isoflurane or sevoflurane were determined. EEG was also monitored in the light and dark phase under isoflurane or sevoflurane exposure. The noradrenergic toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was used to deplete noradrenergic neurones in the locus coeruleus to explore the impact of norepinephrine on these measurements. RESULTS: MACLORR, TimeLORR, and MAC did not show light- or dark-phase-dependent variations for either isoflurane or sevoflurane exposure. However, MACRORR was higher and TimeRORR was shorter in the dark phase than in the light phase for both isoflurane and sevoflurane exposure. The EEG delta wave power was higher but theta wave power was lower in the light phase than that in the dark phase during the rest state and emergence of anaesthesia. These light- and dark-phase-dependent changes in emergence were abolished in DSP-4-treated mice. CONCLUSION: Our data show that circadian differences exist during emergence but not during induction or maintenance of sevoflurane or isoflurane anaesthesia. The locus coeruleus noradrenergic system may contribute to these differences.


Assuntos
Anestésicos Inalatórios/farmacologia , Ritmo Circadiano/fisiologia , Locus Cerúleo/fisiologia , Norepinefrina/fisiologia , Anestésicos Inalatórios/farmacocinética , Animais , Benzilaminas/farmacologia , Temperatura Corporal/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reflexo de Endireitamento/efeitos dos fármacos
18.
Br J Anaesth ; 125(4): 492-504, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32798069

RESUMO

Postoperative delirium is a relatively common and serious complication. It increases hospital stay by 2-3 days and is associated with a 30-day mortality of 7-10%. It is most prevalent in older patients, those with existing neurocognitive disorders, and those undergoing complex or emergency procedures. Preclinical and clinical research in recent years has uncovered more about the pathophysiology of postoperative delirium and may yield more potential therapeutic options. Using the enhanced recovery pathway framework of risk stratification, risk reduction, and rescue treatment, we have reviewed the current clinical evidence on the validity of delirium prediction scores for the surgical population, the effectiveness of perioperative delirium risk reduction interventions, and management options for established delirium. Effective perioperative interventions include depth of anaesthesia monitoring, intraoperative dexmedetomidine infusion, and multimodal analgesia. Choice of general anaesthetic agent may not be associated with significant difference in delirium risk. Several other factors, such as preoperative fasting, temperature control, and blood pressure management have some association with the risk of postoperative delirium; these will require further studies. Because of the limited treatment options available for established delirium, we propose that risk assessment and perioperative risk reduction may be the most effective approaches in managing postoperative delirium.


Assuntos
Delírio/terapia , Complicações Pós-Operatórias/terapia , Comportamento de Redução do Risco , Transfusão de Sangue , Delírio/prevenção & controle , Hidratação , Humanos , Manejo da Dor , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Medição de Risco
19.
20.
Inflammation ; 43(6): 2021-2032, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32830308

RESUMO

NETosis is a type of regulated cell death dependent on the formation of neutrophil extracellular traps (NET), where net-like structures of decondensed chromatin and proteases are produced by polymorphonuclear (PMN) granulocytes. These structures immobilise pathogens and restrict them with antimicrobial molecules, thus preventing their spread. Whilst NETs possess a fundamental anti-microbial function within the innate immune system under physiological circumstances, increasing evidence also indicates that NETosis occurs in the pathogenic process of other disease type, including but not limited to atherosclerosis, airway inflammation, Alzheimer's and stroke. Here, we reviewed the role of NETosis in the development of organ injury, including injury to the brain, lung, heart, kidney, musculoskeletal system, gut and reproductive system, whilst therapeutic agents in blocking injuries induced by NETosis in its primitive stages were also discussed. This review provides novel insights into the involvement of NETosis in different organ injuries, and whilst potential therapeutic measures targeting NETosis remain a largely unexplored area, these warrant further investigation.

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