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1.
Pain Res Manag ; 2021: 5517150, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936350

RESUMO

Background: Pain aggravates the autonomic response to stress and raises neuroendocrine stress hormone levels. We compared the effects of propofol and sevoflurane on postoperative pain and neuroendocrine stress hormones. A prospective, randomized, and controlled trial was conducted with 60 patients. Methods: We randomly allocated patients to groups P (remifentanil/propofol, n = 30) and S (remifentanil/sevoflurane, n = 30). Preoperative blood samples were taken to measure serum adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), glucagon, cortisol, aldosterone, and prostaglandin E2 (PGE2) levels. Intraoperatively and postoperatively, clinical parameters were monitored at different time points. The hormone levels were again measured in the follicular fluid and blood postoperatively. Result: Demographic data were similar. The preoperative serum aldosterone levels were significantly higher in group P (p=0.001). Preoperative and postoperative serum ACTH, glucagon, cortisol, and PGE2 levels were significantly different in group P (p=0.009, p=0.004, p=0.029, and p=0.002); serum ACTH, glucagon, and PGE2 levels increased while serum cortisol levels decreased postoperatively. In group S, serum CRH and aldosterone levels, both increased in the postoperative period compared to the preoperative (p=0.001, p=0.006). Postoperatively, glucagon and PGE2 levels were both higher in group P than group S (p=0.019, p=0.015). In postoperative follicular fluid, glucagon and PGE2 levels were higher in group P, while cortisol levels were higher in group S (p=0.001, p=0.007, and p=0.001). Conclusion: The effects of anesthetic agents were different. In group P, in the preoperative and postoperative evaluation, ACTH, glucagon, and PGE2 increased postoperatively, while cortisol decreased. In group S, aldosterone and CRH increased postoperatively. Glucagon and PG E2 were higher in group P than S, postoperatively.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Sistemas Neurossecretores/fisiopatologia , Recuperação de Oócitos/métodos , Dor Pós-Operatória/tratamento farmacológico , Propofol/uso terapêutico , Sevoflurano/uso terapêutico , Adolescente , Adulto , Anestésicos Inalatórios/farmacologia , Feminino , Humanos , Masculino , Propofol/farmacologia , Estudos Prospectivos , Sevoflurano/farmacologia , Adulto Jovem
2.
J Pak Med Assoc ; 71(2(B)): 590-595, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33941941

RESUMO

Objectives: The Pain Rating index (PRi) is a new parameter for regulating analgesic depth of anaesthesia based on wavelet analysis. The aim of this study was to investigate the feasibility of PRi for depth regulation of sevoflurane anaesthesia. METHODS: We conducted a monocentric randomized controlled study from September 2017 to June 2018 in patients undergoing anterior cervical discectomy and fusion (ACDF) (n=44). Patients were randomly allocated into two groups and assigned 22 cases to each group: systolic blood pressure group (SBP group) and pain rating index group (PRi group). In SBP group, sevoflurane inhalation concentration (Cs) was adjusted to maintain SBP values at baseline values -20%~+20%; in PRi group, Cs was adjusted to maintain PRi values between 50 and 70. The primary endpoint was anaesthesia recovery time. Secondary endpoints included extubation time, sevoflurane consumption, number of intraoperative haemodynamic instability events /interventions, number of adverse events and postoperative visual analogue scale for pain. RESULTS: Patient demographic characteristics, surgical time and anaesthesia time did not differ between groups. Anaesthesia recovery time was shorter in PRi group than in SBP group (17.5±3.8min vs 21.5±2.8 min; P=0.001). Extubation time was also shorter in PRi group than in SBP group (21.9±1.7min vs 24.1±2.5min; P=0.001). Sevoflurane consumption was lower in PRi group than in SBP group (15.5±4.1ml vs 20.0±2.5ml; P=0.001). CONCLUSIONS: PRi was feasible to regulate depth of sevoflurane anaesthesia, which could shorten anaesthesia recovery time and extubation time, reduce sevoflurane consumption during general anaesthesia in patients undergoing cervical vertebra surgery.


Assuntos
Anestésicos Inalatórios , Éteres Metílicos , Período de Recuperação da Anestesia , Anestésicos Inalatórios/farmacologia , Pressão Sanguínea , Humanos , Éteres Metílicos/farmacologia , Dor , Sevoflurano/farmacologia
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(2): 235-246, 2021 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-33966704

RESUMO

Objective To explore the effect of dexmedetomidine(Dex)on sevoflurane-induced cognitive impairment in neonatal rats through Wnt signaling pathway. Methods Sixty 7-day-old SD rats were assigned into five groups:control group(without any intervention),Dex group(intraperitoneal injection of 25 µg/kg Dex),sevoflurane group(3% sevoflurane treatment for 4 hours),sevoflurane+Dex group(inhalation of 3% sevoflurane after injection of 25 µg/kg Dex for 4 hours),and sevoflurane+Dex+Wnt inhibitor group(Wnt inhibitor XAV393 and 25 µg/kg Dex were injected and 3% sevoflurane was inhaled for 4 hours).Three weeks later,Morris water maze was used to detect the cognitive function;TdT-mediated dUTP nick end labeling(TUNEL)staining was performed to detect the apoptosis of hippocampal neurons;neuronal nuclei (NeuN) staining was conducted to detect the survival of hippocampal neurons;Western blot was carried out to detect the expression of apoptosis-related proteins.The expression of the factors involved in Wnt/GSK-3ß/ß-catenin signaling pathway was detected by fluorescence quantitative polymerase chain reaction,and Western blot. Results Compared with the control group,there was no significant difference in the escape latency of Dex group(t=0.304,P=0.768);the escape latency in sevoflurane group(t=5.823,P=0.002),sevoflurane+Dex group(t=3.188,P=0.010),and sevoflurane+Dex+Wnt inhibitor group(t=5.784,P=0.002)was significantly prolonged.Compared with that in the sevoflurane group,the escape latency in sevoflurane+Dex group(t=3.646,P=0.005)was significantly shortened.Compared with that in sevoflurane+Dex group,the escape latency in sevoflurane+Dex+Wnt inhibitor group(t=3.296,P=0.008)was prolonged.Compared with that in the control group,the times of crossing platform in sevoflurane group(t=5.179, P=0.004),sevoflurane+Dex group(t=2.309,P=0.043),and sevoflurane+Dex+Wnt inhibitor group(t=3.871, P=0.003)decreased.Compared with that in sevoflurane group,the times of crossing platform in sevoflurane+Dex group(t=3.296,P=0.008)significantly increased.Compared with that in sevoflurane+Dex group,the times of crossing platform in sevoflurane+Dex+Wnt inhibitor group(t=2.361, P=0.041)reduced.Compared with the control group,there was no significant difference in the number of apoptotic cells in Dex group(t=1.920,P=0.127),and the number of apoptotic cells in sevoflurane group,sevoflurane+Dex group,and sevoflurane+Dex+Wnt inhibitor group increased by 16%(t=13.436,P=0.002),5%(t=7.752, P=0.001),and 11.5%(t=12.612,P=0.002),respectively.Compared with that in the sevoflurane group,the number of apoptotic cells in sevoflurane+Dex group and sevoflurane+Dex+Wnt inhibitor group decreased by 11%(t=8.521,P=0.002)and 5.5%(t=3.123,P=0.036),respectively.Compared with that in the sevoflurane+Dex group,the number of apoptotic cells in sevoflurane+Dex+Wnt inhibitor group increased by 6.5%(t=6.250,P=0.003).Compared with that in the control group,the number of positive cells in 0.15 mm2 area did not show significant difference in Dex group(t=0.898,P=0.136)and sevoflurane+Dex group(t=0.203,P=1.519),and that in sevoflurane group and sevoflurane+Dex+Wnt inhibitor group decreased by 31(t=4.702,P=0.009)and 26(t=3.948,P=0.014),respectively.Compared with that in sevoflurane group,the number of positive cells in sevoflurane+Dex group and sevoflurane+Dex+Wnt inhibitor group increased by 17(t=3.415,P=0.018)and 5(P=0.001),respectively.Compared with that in sevoflurane+Dex group,the number of positive cells in sevoflurane+Dex+Wnt inhibitor group decreased by 12(t=3.010,P=0.039).Western blot was used to detect the gray values of caspase-3,Bax,and Bcl-2 in the hippocampus,which showed no significant difference between Dex group and control group(t=0.612,P=0.573; t=1.225,P=0.288;t=0.961,P=0.391).Compared with that in the control group,the expression of Bax(t=13.440,P=0.002;t=8.520,P=0.001; t=13.320,P=0.002)and caspase-3(t=9.860,P=0.001;t=6.120,P=0.004;t=11.620,P=0.003)were up-regulated and that of Bcl-2(t=7.671,P=0.002;t=2.880,P=0.045;t=6.280,P=0.003)was down-regulated in sevoflurane group,sevoflurane+DEX group,and sevoflurane+Dex+Wnt inhibitor group.Compared with that in sevoflurane group,the expression of Bax(t=8.130,P=0.001)and caspase-3(t=7.120,P=0.002)was down-regulated and that of Bcl-2(t=6.201,P=0.003)was up-regulated in sevoflurane+Dex group.Compared with that in sevoflurane+Dex group,the expression of Bax(t=7.310,P=0.002)and caspase-3(t=7.750,P=0.002)were up-regulated and that of Bcl-2(t=4.206,P=0.013)was down-regulated in sevoflurane+Dex+Wnt inhibitor group.The mRNA expression levels of Wnt3a,GSK-3ß,and ß-catenin in hippocampus were detected by fluorescence quantitative polymerase chain reaction.The mRNA expression levels of Wnt3a,GSK-3ß,and ß-catenin in the control group did not differ significantly from those in Dex group(t=1.230,P=0.290;t=0.901,P=0.418;t=1.837,P=0.140);the mRNA expression levels of Wnt3a and ß-catenin in the control group did not differ significantly from those in sevoflurane+Dex group(t=1.102,P=0.332;t=1.030,P=0.361).Compared with that in the control group,the protein expression of Wnt3a and ß-catenin in sevoflurane group(t=5.790,P=0.004;t=7.130,P=0.002)and sevoflurane+Dex+Wnt inhibitor group(t=7.130,P=0.002; t=5.500,P=0.005)was down-regulated,and the GSK-3ß expression was up-regulated in sevoflurane group(t=4.800,P=0.009),sevoflurane+Dex group(t=2.940,P=0.045),and sevoflurane+Dex+Wnt inhibitor group(t=3.100,P=0.042).Compared with that in sevoflurane group,the mRNA expression of Wnt3a(t=4.460,P=0.011)and ß-catenin(t=6.390,P=0.003)was up-regulated while that of GSK-3ß(t=4.160,P=0.004)was down-regulated in sevoflurane+Dex group.Compared with that in sevoflurane+Dex group,the mRNA expression of Wnt3a(t=5.730,P=0.005)and ß-catenin(t=4.640,P=0.010)was down-regulated while that of GSK-3ß(t=3.240,P=0.117)was up-regulated in sevoflurane+Dex+Wnt inhibitor group.Compared with that in the control group,the protein expression of Wnt3a and ß-catenin in Dex group(t=0.735,P=0.503;t=0.245,P=0.819)and sevoflurane+Dex group(t=1.623,P=0.180;t=1.159,P=0.311)did not differ significantly,while that in sevoflurane group(t=7.280,P=0.002; t=5.640,P=0.005)and sevoflurane+Dex+Wnt inhibitor group(t=7.240,P=0.002;t=4.970,P=0.008)was down-regulated. Compared with that in sevoflurane group,the protein levels of Wnt3a(t=6.410,P=0.003)and ß-catenin(t=4.640,P=0.015)were up-regulated in sevoflurane+Dex group.Compared with that in sevoflurane+Dex group,the protein expression of Wnt3a(t=6.360,P=0.003)and ß-catenin(t=4.640,P=0.016)was down-regulated in sevoflurane+Dex+Wnt inhibitor group.Compared with that in the control group,the expression(gray value)of P(ser9)-GSK-3ß/GSK-3ß in sevoflurane group(t=11.280,P=0.002),sevoflurane+Dex group(t=7.080,P=0.002),and sevoflurane+Dex+Wnt inhibitor group(t=9.970,P=0.001)were down-regulated.Compared with that in the sevoflurane group,the expression of P(ser9)-GSK-3ß/GSK-3ß were up-regulated in sevoflurane+Dex group(t=8.310,P <0.001).Compared with that in sevoflurane+Dex group,the expression of P(ser9)-GSK-3ß/GSK-3ß in sevoflurane+Dex+Wnt inhibitor group was down-regulated(t=5.510,P=0.005). Conclusion Dex can mediate Wnt/GSK-3ß/ß-catenin signaling pathway to inhibit sevoflurane-induced cognitive impairment in neonatal rats.


Assuntos
Disfunção Cognitiva , Dexmedetomidina , Animais , Animais Recém-Nascidos , Disfunção Cognitiva/induzido quimicamente , Dexmedetomidina/farmacologia , Glicogênio Sintase Quinase 3 beta , Ratos , Ratos Sprague-Dawley , Sevoflurano/toxicidade , Via de Sinalização Wnt , beta Catenina/metabolismo
5.
Cell Prolif ; 54(6): e13042, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955094

RESUMO

OBJECTIVES: The effects of general anaesthetics on fetal brain development remain elusive. Radial glial progenitors (RGPs) generate the majority of neurons in developing brains. Here, we evaluated the acute alterations in RGPs after maternal sevoflurane exposure. METHODS: Pregnant mice were exposed to 2.5% sevoflurane for 6 hours on gestational day 14.5. Interkinetic nuclear migration (INM) of RGPs in the ventricular zone (VZ) of the fetal brain was evaluated by thymidine analogues labelling. Cell fate of RGP progeny was determined by immunostaining using various neural markers. The Morris water maze (MWM) was used to assess the neurocognitive behaviours of the offspring. RNA sequencing (RNA-Seq) was performed for the potential mechanism, and the potential mechanism validated by quantitative real-time PCR (qPCR), Western blot and rescue experiments. Furthermore, INM was examined in human embryonic stem cell (hESC)-derived 3D cerebral organoids. RESULTS: Maternal sevoflurane exposure induced temporary abnormities in INM, and disturbed the cell cycle progression of RGPs in both rodents and cerebral organoids without cell fate alternation. RNA-Seq analysis, qPCR and Western blot showed that the Notch signalling pathway was a potential downstream target. Reactivation of Notch by Jag1 and NICD overexpression rescued the defects in INM. Young adult offspring showed no obvious cognitive impairments in MWM. CONCLUSIONS: Maternal sevoflurane exposure during neurogenic period temporarily induced abnormal INM of RGPs by targeting the Notch signalling pathway without inducing long-term effects on RGP progeny cell fate or offspring cognitive behaviours. More importantly, the defects of INM in hESC-derived cerebral organoids provide a novel insight into the effects of general anaesthesia on human brain development.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Córtex Cerebral/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Receptores Notch/metabolismo , Sevoflurano/efeitos adversos , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Córtex Cerebral/patologia , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Feto/patologia , Humanos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Neurogênese/efeitos dos fármacos , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Transdução de Sinais/efeitos dos fármacos
6.
Oxid Med Cell Longev ; 2021: 6657529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986917

RESUMO

The cardioprotective effect of sevoflurane postconditioning (SPostC) is lost in diabetes that is associated with cardiac phosphatase and tensin homologue on chromosome 10 (PTEN) activation and phosphoinositide 3-kinase (PI3K)/Akt inactivation. T-LAK cell-originated protein kinase (TOPK), a mitogen-activated protein kinase- (MAPKK-) like serine/threonine kinase, has been shown to inactivate PTEN (phosphorylated status), which in turn activates the PI3K/Akt signaling (phosphorylated status). However, the functions of TOPK and molecular mechanism underlying SPostC cardioprotection in nondiabetes but not in diabetes remain unknown. We presumed that SPostC exerts cardioprotective effects by activating PTEN/PI3K/Akt through TOPK in nondiabetes and that impairment of TOPK/PTEN/Akt blocks diabetic heart sensitivity to SPostC. We found that in the nondiabetic C57BL/6 mice, SPostC significantly attenuated postischemic infarct size, oxidative stress, and myocardial apoptosis that was accompanied with enhanced p-TOPK, p-PTEN, and p-Akt. These beneficial effects of SPostC were abolished by either TOPK kinase inhibitor HI-TOPK-032 or PI3K/Akt inhibitor LY294002. Similarly, SPostC remarkably attenuated hypoxia/reoxygenation-induced cardiomyocyte damage and oxidative stress accompanied with increased p-TOPK, p-PTEN, and p-Akt in H9c2 cells exposed to normal glucose, which were canceled by either TOPK inhibition or Akt inhibition. However, either in streptozotocin-induced diabetic mice or in H9c2 cells exposed to high glucose, the cardioprotective effect of SPostC was canceled, accompanied by increased oxidative stress, decreased TOPK phosphorylation, and impaired PTEN/PI3K/Akt signaling. In addition, TOPK overexpression restored posthypoxic p-PTEN and p-Akt and decreased cell death and oxidative stress in H9c2 cells exposed to high glucose, which was blocked by PI3K/Akt inhibition. In summary, SPostC prevented myocardial ischemia/reperfusion injury possibly through TOPK-mediated PTEN/PI3K/Akt activation and impaired activation of this signaling pathway may be responsible for the loss of SPostC cardioprotection by SPostC in diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/enzimologia , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sevoflurano/farmacologia , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Coração/efeitos dos fármacos , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Inibidores da Agregação Plaquetária/farmacologia , Distribuição Aleatória , Ratos , Transdução de Sinais/efeitos dos fármacos
7.
Braz J Med Biol Res ; 54(7): e10213, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34008749

RESUMO

Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Canais de Potássio de Abertura Dependente da Tensão da Membrana , RNA Longo não Codificante , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proteínas Cromossômicas não Histona , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Sevoflurano/farmacologia
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 207-215, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829693

RESUMO

Objective: To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats. Methods: On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65). Results: In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency ( P=0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups ( P<0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group ( P=0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( P=0.048). Conclusion: The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.


Assuntos
Anestésicos Inalatórios , Transtorno do Deficit de Atenção com Hiperatividade , Anestésicos Inalatórios/toxicidade , Animais , Animais Recém-Nascidos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , Sevoflurano
9.
Int J Mol Sci ; 22(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800423

RESUMO

Ischemia reperfusion injury (IRI) is inevitable in kidney transplantation and negatively impacts graft and patient outcome. Reperfusion takes place in the recipient and most of the injury following ischemia and reperfusion occurs during this reperfusion phase; therefore, the intra-operative period seems an attractive window of opportunity to modulate IRI and improve short- and potentially long-term graft outcome. Commonly used volatile anesthetics such as sevoflurane and isoflurane have been shown to interfere with many of the pathophysiological processes involved in the injurious cascade of IRI. Therefore, volatile anesthetic (VA) agents might be the preferred anesthetics used during the transplantation procedure. This review highlights the molecular and cellular protective points of engagement of VA shown in in vitro studies and in vivo animal experiments, and the potential translation of these results to the clinical setting of kidney transplantation.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Isoflurano/uso terapêutico , Transplante de Rim , Rim/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Animais , Humanos
10.
J Int Med Res ; 49(4): 3000605211005936, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33906525

RESUMO

OBJECTIVE: Previous studies suggested that sevoflurane exerts anti-proliferative, anti-migratory, and anti-invasive effects on cancer cells. To determine the role of sevoflurane on gastric cancer (GC) progression, we evaluated its effects on the proliferation, migration, and invasion of SGC7901, AGS, and MGC803 GC cells. METHODS: GC cells were exposed to different concentrations of sevoflurane (1.7, 3.4, or 5.1% v/v). Cell viability, migration, and invasion were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assays. Immunohistochemical staining and immunoblotting were performed to analyze forkhead box protein 3 (FOXP3) protein expression in tissue specimens and cell lines, respectively. RESULTS: FOXP3 was downregulated in human GC specimens and cell lines. Functionally, FOXP3 overexpression significantly inhibited the proliferation, migration, and invasion of GC cells and accelerated their apoptosis. Moreover, sevoflurane significantly blocked GC cell migration and invasion compared with the findings in the control group. However, FOXP3 silencing neutralized sevoflurane-induced apoptosis and the inhibition of GC cell migration and invasion. Sevoflurane-induced apoptosis and the suppression of migration and invasion might be associated with FOXP3 overactivation in GC cells. CONCLUSIONS: Sevoflurane activated FOXP3 and prevented GC progression via inhibiting cell migration and invasion in vitro.


Assuntos
Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Sevoflurano/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
11.
BMC Pediatr ; 21(1): 177, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863305

RESUMO

BACKGROUND: Dental procedures under general anesthesia (DGA) was found to improve the oral health-related quality of children's life. However, some parents and pediatricians expressed concern about the neurotoxicity of general anesthesia. The purpose of this trial was to whether DGA in children has an adverse effect on neurocognition. METHODS: In this prospective, assessor-masked, controlled, equivalence trial, we recruited 340 children younger than 7 years who were undergoing caries treatment between Feb 1, 2019, and Aug 31, 2019, without factors affecting neurodevelopment. They received either sevoflurane-based general anesthesia or awake-local anesthesia. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition was used to evaluate the neurocognitive function of children at 6 months after surgery, and the Full-Scale IQ (FSIQ) was selected as the primary outcome. The predefined clinical equivalence margin was 5 (1/3 SD of FSIQ score). If the 95% CI of the difference between the average FSIQ score of the two groups is within - 5 to + 5, then the two groups are equivalent. RESULTS: The outcome data were obtained from 129 children in the general anesthesia group and 144 in the local anesthesia group. The median length of general anesthesia was 130 min (IQR 110-160). The mean FSIQ score in the general anesthesia group was 103·12 (SD 8.94), and the mean of the local anesthesia group was 103·58 (SD 8.40). There was equivalence in means of FSIQ score between the two groups (local minus general anesthesia 0.46, 95% CI - 2.35 to 1.61). There was no significant difference in FSIQ scores between different age groups and different anesthesia durations. Only the mother's education could affect the primary outcome. CONCLUSIONS: In this trial, prolonged DGA with a sevoflurane-only anesthetic in preschool children, does not adversely affect neurocognitive function at 6 months after surgery compared with awake-local anesthesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015216 . Registered Mar 15 2018.


Assuntos
Anestesia Geral , Saúde Bucal , Anestesia Geral/efeitos adversos , Pré-Escolar , Odontologia , Humanos , Estudos Prospectivos , Sevoflurano
12.
J Int Med Res ; 49(4): 300060520982104, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33843359

RESUMO

OBJECTIVE: Common inhalation anesthetics used for clinical anesthesia (such as sevoflurane) may induce nerve cell apoptosis during central nervous system development. Furthermore, anesthetics can produce cognitive impairments, such as learning and memory impairments, that continue into adulthood. However, the precise mechanism remains largely undefined. We aimed to determine the function of microRNA-1297 (miR-1297) in sevoflurane-induced neurotoxicity. METHODS: Reverse transcription-polymerase chain reaction assays were used to analyze miR-1297 expression in sevoflurane-exposed mice. MTT and lactate dehydrogenase (LDH) assays were used to measure cell growth, and neuronal apoptosis was analyzed using flow cytometry. Western blot analyses were used to measure PTEN, PI3K, Akt, and GSK3ß protein expression. RESULTS: In sevoflurane-exposed mice, miR-1297 expression was up-regulated compared with the control group. MiR-1297 up-regulation led to neuronal apoptosis, inhibition of cell proliferation, and increased LDH activity in the in vitro model of sevoflurane exposure. MiR-1297 up-regulation also suppressed the Akt/GSK3ß signaling pathway and induced PTEN protein expression in the in vitro model. PTEN inhibition (VO-Ohpic trihydrate) reduced PTEN protein expression and decreased the effects of miR-1297 down-regulation on neuronal apoptosis in the in vitro model. CONCLUSION: Collectively, the results indicated that miR-1297 stimulates sevoflurane-induced neurotoxicity via the Akt/GSK3ß signaling pathway by regulating PTEN expression.


Assuntos
MicroRNAs , Proteínas Proto-Oncogênicas c-akt , Sevoflurano/toxicidade , Animais , Apoptose , Proliferação de Células , Glicogênio Sintase Quinase 3 beta/genética , Camundongos , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
13.
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
14.
Medicine (Baltimore) ; 100(8): e24842, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663105

RESUMO

ABSTRACT: An association between animals and volatile anaesthetic requirements has been shown; however, evidence related to the postoperative outcome of human patients is lacking. Our aim was to investigate whether there is a difference in the requirement for sevoflurane among people undergoing gastrointestinal surgery.We observed 390 adult patients who underwent gastrointestinal surgery with an American Society of Anesthesiologists physical status of I or II with an expected surgery duration of > 2 hours. We used the bispectral index (BIS) to guide the regulation of end-tidal sevoflurane concentration (ETsevo). The mean ETsevo from 20 minutes after endotracheal intubation to 2 hours after the start of surgery was calculated for all patients. Differential sevoflurane requirements were identified according to ETsevo. The BIS, ETsevo, heart rate, mean arterial pressure, dose of sufentanil and cisatracurium, tracheal extubation time, incidence of intraoperative awareness, and incidence of postoperative nausea and vomiting were compared between patients with a low requirement for sevoflurane (group L) and patients with a high requirement for sevoflurane (group H).The mean ETsevo of the 390 patients was 1.55% ±â€Š0.26%. Based on our definition, patients with an ETsevo of < 1.29% were allocated to the low requirement group (group L; n = 69), while patients with an ETsevo of > 1.81% were allocated to the high requirement group (group H; n = 78). The ETsevo of group L was significantly lower than the ETsevo of group H (1.29% ±â€Š0.014% vs 1.82% ±â€Š0.017%, P < .001). There was no significant difference in the ETsevo, BIS, heart rate, mean arterial pressure, dose of sufentanil and cisatracurium, tracheal extubation time, incidence of intraoperative awareness, and incidence of postoperative nausea and vomiting. The tracheal extubation time in the L group was significantly shorter than that in the H group. No intraoperative awareness occurred.There was a significant difference in the requirement for sevoflurane in adult patients. The tracheal extubation time in group L was significantly shorter than that in group H.


Assuntos
Período de Recuperação da Anestesia , Anestesia Geral/métodos , Anestésicos Inalatórios/farmacocinética , Sevoflurano/farmacocinética , Extubação/efeitos adversos , Anestésicos Inalatórios/administração & dosagem , Estudos de Casos e Controles , Monitores de Consciência , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sevoflurano/administração & dosagem
15.
Life Sci ; 274: 119327, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711390

RESUMO

This study aimed to explore the potential target of the cardio-protective effect induced by sevoflurane anesthesia based on evidence from clinical samples and in vitro model. Forty patients undergoing mitral valve replacement were randomly allocated to receive sevoflurane or propofol-based anesthesia. Atrial muscle specimens were collected from all patients, of which 5 were used to perform transcriptomics analysis. The cTn-I concentration was tested before, at the end of, and 24 h after surgery. In in vitro study, the expression level of the identified target gene, i.e., THAP11, was studied in H9C2 cells treated with sevoflurane or propofol. Then, we studied cell viability using CCK-8 staining, apoptosis by using flow cytometry, and cell death by lactic acid dehydrogenase (LDH) detection in H9C2 cells exposed to oxygen glucose deprivation/reoxygenation (OGD/R) injury. THAP11 was the most significantly down-regulated gene in the transcriptomics analysis (P < 0.001), as confirmed in validation samples (P = 0.006). THAP11 mRNA levels in atrial muscle specimens were positively associated with cTn-I levels at 24-h postoperatively (determination coefficient = 0.564; P < 0.001). Sevoflurane treatment down-regulated THAP11 in H9C2 cell models, which promoted cell viability, inhibited cell apoptosis, and death in the OGD/R injury cell model. Up-regulation of THAP11 reduced the protective effect of sevoflurane treatment against OGD/R injury. Sevoflurane anesthesia down-regulates the expression of THAP11, which contributes to a cardio-protective effect. THAP11 down-regulation promotes cell viability, and inhibits cell apoptosis and death, thereby protecting again myocardial injury; it may therefore be a novel target for perioperative cardio-protection.


Assuntos
Cardiotônicos/farmacologia , Insuficiência da Valva Mitral/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Repressoras/antagonistas & inibidores , Sevoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Apoptose , Sobrevivência Celular , Regulação para Baixo , Feminino , Glucose/deficiência , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/patologia , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Oxigênio/metabolismo , Ratos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
16.
Life Sci ; 275: 119391, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33774026

RESUMO

Sevoflurane (Sev) has protective effects in acute lung injury (ALI), but the relevant mechanisms are still not fully understood. The present study aimed to determine whether Sev exerts a protective effect on lipopolysaccharide (LPS)-induced ALI by regulating ferroptosis. In this study, we found that Sev could protect mice from lung injury caused by LPS stimulation, including extenuating lung histological damage, pulmonary edema and pulmonary vascular permeability, and the content of inflammatory factors in Bronchoalveolar lavage fluid (BALF), as well as improving the survival rate of ALI mice, which was in line with the effects of ferroptosis inhibitor ferrostatin-1. Simultaneously, Sev could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced ALI to a certain extent. Additionally, the administration of Sev could inhibit ferroptosis caused by LPS, which was manifested by reducing the accumulation of MDA and Fe2+, and increasing the levels of GSH and GPX4 in the lung tissues of ALI mice. It was also observed in BEAS-2B cells that the increased MDA and Fe2+ levels and the decreased GSH and GPX4 levels caused by LPS could be rescued by ferrostatin-1 and Sev. LPS stimulation compensatory up-regulated heme oxygenase-1 (HO-1) expression in mouse lung tissues and BEAS-2B cells, which could be enhanced by Sev. Moreover, HO-1 depletion could offset the inhibitory effect of Sev on LPS-induced ferroptosis and inflammation in BEAS-2B cells. Taken together, Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Ferroptose/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Sevoflurano/farmacologia , Lesão Pulmonar Aguda/patologia , Animais , Western Blotting , Linhagem Celular , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia , Sevoflurano/uso terapêutico
18.
Int J Clin Pract ; 75(6): e14149, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33713396

RESUMO

AIM: The study aimed to investigate the effect of varying testosterone levels in the morning and evening on the depth of anaesthesia in patients who underwent a septoplasty. MATERIALS AND METHODS: Male patients who underwent septoplasty under general anaesthesia between September 2016 and September 2017 were included in the study. The patients were divided into two groups. The first group consisted of patients who were operated on in the morning hours (between 8.00 and 10.00) when the testosterone level was the highest and the second group consisted of patients who had the lowest testosterone level in the afternoon (between 14.00 and 16.00). Blood was taken from the brachial vein to measure the testosterone level of the patients and blood testosterone levels were measured by mass spectrometry before the induction of anaesthesia. RESULTS: Sixty patients were included in the study. The mean age of the patients was 33.77 ± 10.98 years. The rocuronium and propofol doses used in the morning group were significantly higher (P = .012 for propofol, P = .002 for rocuronium, P < .001 for rocuronium dose) (Table 2). Additionally, the time to reach saturation of sevoflurane doses in expirium and inspiration was later in the morning group (morning group at 15th minute, evening group at 10th minute). CONCLUSIONS: Sedation anaesthesia applied in patients who underwent septoplasty operation was associated with testosterone level and it was more difficult for patients to switch to sedation with increased testosterone level.


Assuntos
Propofol , Testosterona , Adulto , Eletroencefalografia , Humanos , Masculino , Sevoflurano , Adulto Jovem
19.
Medicine (Baltimore) ; 100(13): e25288, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787614

RESUMO

ABSTRACT: Target-controlled infusion of remifentanil is known to reduce cough effectively during emergence from general anesthesia. The effect of smoking on emergence cough remains controversial. Therefore, we aimed to investigate the effect-site concentration (Ce) of remifentanil in the male patients undergoing laparoscopic or robotic cholecystectomy for suppressing emergence cough in smokers and non-smokers.Twenty smokers and 24 non-smokers (sex, male; age range, 20-65 years) were enrolled in this study. Anesthesia was maintained using sevoflurane and remifentanil. The Ce of remifentanil in 50% (EC50) and 95% (EC95) of the patients required for suppressing emergence cough were determined for each group (smokers and non-smokers) using Dixon up-and-down method and isotonic regression method with a bootstrapping approach.Dixon up-and-down method revealed that the EC50 value was significantly higher in smokers (3.51 ±â€Š0.60 ng/mL) than in non-smokers (2.71 ±â€Š0.30 ng/mL) (P < 0.001). In smokers and non-smokers, isotonic regression revealed EC50 to be 4.40 (83% CI, 4.17-4.58) ng/mL and 2.58 (83% CI, 2.31-2.87) ng/mL, respectively, and EC95 to be 4.76 (95% CI, 4.73-4.78) ng/mL and 3.15 (95% CI, 3.04-3.18) ng/mL, respectively.The Ces of remifentanil required to prevent cough during emergence were significantly higher in smokers than in non-smokers. Therefore, clinicians should pay attention to the smoking history of a patient to prevent cough during emergence.


Assuntos
Anestesia Geral/efeitos adversos , Antitussígenos/administração & dosagem , Colecistectomia , Tosse/prevenção & controle , Remifentanil/administração & dosagem , Fumar/efeitos adversos , Adulto , Idoso , Período de Recuperação da Anestesia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Procedimentos Cirúrgicos Robóticos , Sevoflurano/administração & dosagem , Adulto Jovem
20.
Br J Anaesth ; 126(5): 1009-1021, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33722372

RESUMO

BACKGROUND: Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating therapy in a sevoflurane dose-sparing approach. METHODS: Neonatal rats were randomised to 6 h of sevoflurane 2.5%, sevoflurane 1% with or without three injections of dexmedetomidine every 2 h (resulting in 2.5, 5, 10, 25, 37.5, or 50 µg kg-1 h-1), or fasting in room air. Heart rate, oxygen saturation, level of hypnosis, and response to pain were measured during exposure. Neuronal cell death was quantified histologically after exposure. RESULTS: Sevoflurane at 2.5% was more injurious than at 1% in the hippocampal cornu ammonis (CA)1 and CA2/3 subfields; ventral posterior and lateral dorsal thalamic nuclei; prefrontal, retrosplenial, and somatosensory cortices; and subiculum. Although sevoflurane 1% did not provide complete anaesthesia, supplementation with dexmedetomidine dose dependently increased depth of anaesthesia and diminished responses to pain. The combination of sevoflurane 1% and dexmedetomidine did not reliably reduce neuronal apoptosis relative to an equianaesthetic dose of sevoflurane 2.5%. CONCLUSIONS: A sub-anaesthetic dose of sevoflurane combined with dexmedetomidine achieved a level of anaesthesia comparable with that of sevoflurane 2.5%. Similar levels of anaesthesia caused comparable programmed cell death in several developing brain regions. Depth of anaesthesia may be an important factor when comparing the neurotoxic effects of different anaesthetic regimens.


Assuntos
Anestésicos Inalatórios/toxicidade , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Sevoflurano/toxicidade , Anestésicos Inalatórios/administração & dosagem , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Morte Celular/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/prevenção & controle , Ratos , Ratos Wistar , Sevoflurano/administração & dosagem
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