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BACKGROUND: Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. METHODS: We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845-0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752-0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. CONCLUSIONS: The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.
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Environmental concerns, especially global warming, have prompted efforts to reduce greenhouse gas emissions. Healthcare systems, including anesthesia practices, contribute to these emissions. Inhalation anesthetics have a significant environmental impact, with desflurane being the most concerning because of its high global warming potential. This study aimed to educate anesthesiologists on the environmental impact of inhalation anesthetics and assess changes in awareness and practice patterns, specifically reducing desflurane use. This study included data from patients who underwent surgery under general anesthesia 1 month before and after education on the effects of inhalation anesthetics on global warming. The primary endpoint was a change in inhalational anesthetic use. Secondary endpoints included changes in carbon dioxide equivalent (CO2e) emissions, driving equivalent, and medical costs. After the education, desflurane use decreased by 50%, whereas sevoflurane use increased by 50%. This shift resulted in a reduction in the overall amount of inhalational anesthetics used. The total CO2e and driving-equivalent values decreased significantly. The cost per anesthesia case decreased, albeit to a lesser extent than expected. Education on the environmental impact of inhalation anesthetics has successfully altered anesthesiologists' practice patterns, leading to reduced desflurane usage. This change has resulted in decreased CO2e emissions and has had a positive effect on mitigating global warming. However, further research is required to assess the long-term impact of such education and the variability in practice patterns across different institutions.
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Anestésicos Inalatórios , Isoflurano , Humanos , Desflurano , Estudos Retrospectivos , Aquecimento Global/prevenção & controle , Pegada de Carbono , Salas CirúrgicasRESUMO
BACKGROUND This subgroup analysis of prospective observational research, involving 71 participants, compared the effects of anesthesia on microvascular reactivity in obese vs lean individuals using near-infrared spectroscopy and vascular occlusion tests. The correlation between the body mass index (BMI) and microvascular reactivity under general anesthesia was also investigated. MATERIAL AND METHODS This study enrolled adult patients classified as American Society of Anesthesiologists physical status I or II, undergoing elective surgery under general anesthesia. The microcirculatory variables measured before (Tpre) and 30 min following the induction of anesthesia (Tpost) were as follows: baseline tissue oxygen saturation (StO2), occlusion slope (∇occl), and recovery slope (∇recov). The patients were grouped according to their BMI (lean [BMI <25 kg/m²] vs obese [BMI ≥25 kg/m²]). Data are presented as medians and interquartile ranges. RESULTS There were 43 patients in the lean group and 28 in the obese group. At Tpre, baseline StO2, ∇occl, and ∇recov were not different between the 2 groups (P=0.860, 0.659, and 0.518, respectively). At Tpost, the baseline StO2 and ∇occl were not different between the 2 groups (P=0.343 and 0.791); however, the ∇recov was lower in the obese group than in the lean group (3.245 [2.737, 3.977] vs 4.131 [3.491, 4.843], P=0.003). At Tpost, BMI showed a moderate correlation with ∇recov (correlation coefficient: -0.319, P=0.007). CONCLUSIONS In obese patients, capillary recruitment capacity during general anesthesia is compromised compared to lean patients.
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Obesidade , Doenças Vasculares , Adulto , Humanos , Anestesia Geral , Índice de Massa Corporal , Capilares , Microcirculação , Estudos Observacionais como AssuntoRESUMO
OBJECTIVE: This study aimed to explore the effects of sedative doses of propofol and isoflurane on microcirculation in septic mice compared to controls. Isoflurane, known for its potential as a sedation drug in bedside applications, lacks clarity regarding its impact on the microcirculation system. The hypothesis was that propofol would exert a more pronounced influence on the microvascular flow index, particularly amplified in septic conditions. MATERIAL AND METHODS: Randomized study was conducted from December 2020 to October 2021 involved 60 BALB/c mice, with 52 mice analyzed. Dorsal skinfold chambers were implanted, followed by intraperitoneal injections of either sterile 0.9 % saline or lipopolysaccharide for the control and sepsis groups, respectively. Both groups received propofol or isoflurane treatment for 120 min. Microcirculatory parameters were obtained via incident dark-field microscopy videos, along with the mean blood pressure and heart rate at three time points: before sedation (T0), 30 min after sedation (T30), and 120 min after sedation (T120). Endothelial glycocalyx thickness and syndecan-1 concentration were also analyzed. RESULTS: In healthy controls, both anesthetics reduced blood pressure. However, propofol maintained microvascular flow, differing significantly from isoflurane at T120 (propofol, 2.8 ± 0.3 vs. isoflurane, 1.6 ± 0.9; P < 0.001). In the sepsis group, a similar pattern occurred at T120 without statistical significance (propofol, 1.8 ± 1.1 vs. isoflurane, 1.2 ± 0.7; P = 0.023). Syndecan-1 levels did not differ between agents, but glycocalyx thickness index was significantly lower in the isoflurane-sepsis group than propofol (P = 0.001). CONCLUSIONS: Propofol potentially offers protective action against microvascular flow deterioration compared to isoflurane, observed in control mice. Furthermore, a lower degree of sepsis-induced glycocalyx degradation was evident with propofol compared to isoflurane.
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Anestésicos Inalatórios , Isoflurano , Propofol , Sepse , Animais , Camundongos , Propofol/farmacologia , Isoflurano/farmacologia , Microcirculação , Sindecana-1 , Anestésicos Inalatórios/farmacologia , Sepse/tratamento farmacológico , Anestésicos Intravenosos/farmacologiaRESUMO
Though Honokiol was known to have anti-inflammatory, antioxidant, anticancer, antithrombotic, anti-viral, metabolic, antithrombotic, and neurotrophic activities, the underlying mechanisms of Honokiol on epithelial-mesenchymal transition (EMT) mediated liver fibrosis still remain elusive so far. Anti-EMT and antifibrotic effects of Honokiol were explored in murine AML-12 hepatocyte cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, wound healing assay, Western blotting and also in CCl4-induced liver injury mouse model by immunohistochemistry. Honokiol significantly suppressed transforming growth factor ß1 (TGF-ß1)-induced EMT and migration of AML-12 cells along with decreased EMT phenotypes such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in TGF-ß1-treated AML-12 cells. Consistently, Honokiol suppressed the expression of Snail and transmembrane protease serine 4 (TMPRSS4), but not p-Smad3, and activated E-cadherin in TGF-ß1-treated AML-12 cells. Additionally, Honokiol reduced the expression of ß-catenin, p-AKT, p-ERK, p-p38 and increased phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) and JNK in TGF-ß1-treated AML-12 cells via TGF-ß1/nonSmad pathway. Conversely, GSK3ß inhibitor SB216763 reversed the ability of Honokiol to reduce Snail, ß-catenin and migration and activate E-cadherin in TGF-ß1-treated AML-12 cells. Also, Honokiol suppressed hepatic steatosis and necrosis by reducing the expression of TGF-ß1 and α-SMA in liver tissues of CCl4 treated mice. These findings provide scientific evidence that Honokiol suppresses EMT and hepatic fibrosis via activation of E-cadherin/GSK3ß/JNK and inhibition of AKT/ERK/p38/ß-catenin/TMPRSS4 signaling axis.
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Leucemia Mieloide Aguda , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo , Proteínas Proto-Oncogênicas c-akt , Glicogênio Sintase Quinase 3 beta , Transição Epitelial-Mesenquimal , Cateninas/farmacologia , Fibrinolíticos/farmacologia , Caderinas , Cirrose HepáticaRESUMO
Sugammadex is a chemically modified γ-cyclodextrin that is used as a selective reversal agent for steroidal neuromuscular blockade. The use of sugammadex has greatly increased globally; however, little is known about its potential adverse effects in pregnant and lactating women or those using hormonal contraceptives. There are three important theoretical assumptions. Firstly, pregnancy-related physiological changes involve most organs and affect the pharmacokinetic profiles of medications. Considering the physiological changes in pregnant women and the pharmacokinetic properties of sugammadex, alterations in the dosage and safety profiles of sugammadex may occur during pregnancy. Secondly, very large and polarized sugammadex molecules are expected to have limited placental transfer to the fetus and excretion into breast milk. Finally, sugammadex can bind to steroidal neuromuscular blocking agents as well as other substances with similar structures, such as progesterone. As a result of using sugammadex, progesterone levels can be reduced, causing adverse effects such as early pregnancy cessation and failure of hormonal contraceptives. This narrative review aims to demonstrate the correlations between sugammadex and pregnancy, lactation, and reproductive potential based on previously published preclinical and clinical studies. This will bridge the gap between theoretical assumptions and currently unknown clinical facts. Moreover, this review highlights what anesthesia providers should be aware of and what actions to take while administering sugammadex to such patients.
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OBJECTIVES: To compare the analgesic efficacies of erector spinae plane (ESP) block and thoracic epidural analgesia (TEA) in video-assisted thoracic surgery (VATS). METHODS: Sixty patients undergoing VATS received patient-controlled TEA with a basal rate of 3 ml/hour (h), a bolus of 3 ml (Group E), or ESP block with programmed intermittent bolus infusions of 15 mL/3 h and a bolus of 5 ml (Group ES) for 2 postoperative days. The primary outcome was to compare pain scores at rest 24 h postoperatively between the 2 groups. Secondary outcomes included NRS score for 48 h, procedural time, dermatomal spread, use of rescue medication, adverse events, and patient satisfaction. RESULTS: Patients with continuous ESP block had a higher NRS score than those with TEA but no statistical difference at a specific time. The dermatomal spread was more extensive in the TEA group than in the ESP block group (p=0.016); cumulative morphine consumption was higher in the ESP block group (p=0.047). The incidence of overall adverse events in the TEA group was higher than in the ESP block group (p=0.045). CONCLUSION: Erector spinae plane block may be inferior to TEA for analgesia following VATS, but it could have tolerable analgesia and a better side effect profile than TEA. Therefore, it could be an alternative to TEA as a component of multimodal analgesia.
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Analgesia Epidural , Bloqueio Nervoso , Humanos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Anestésicos Locais/uso terapêutico , Estudos Prospectivos , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Ultrassonografia de IntervençãoRESUMO
BACKGROUND In elderly patients, spinal anesthesia-induced hypotension (SAH) can be frequently caused by reduced preload and stiff ventricles. The primary purpose of this study was to investigate the ability of ultrasonographic carotid artery flow measurements during the passive leg raise (PLR) test to predict SAH in elderly patients. The correlation between preoperative transthoracic echocardiography (TTE) measurements and SAH was also investigated. MATERIAL AND METHODS The patients aged over 65 years scheduled for elective surgery under spinal anesthesia were recruited. Preoperative TTE was performed in all patients. Corrected carotid flow time and carotid blood flow were measured in the supine, semirecumbent, and PLR positions. Ultrasonographic carotid artery flow and preoperative TTE measurements were compared between patients who developed SAH and those who did not. Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to test the association with SAH. RESULTS SAH occurred in 17 of 50 patients. Carotid blood flow in the semirecumbent position and preoperative mitral inflow E velocity could predict SAH, showing an area under the ROC curve of 0.754 (95% CI, 0.612-0.865) and 0.775 (95% CI, 0.634-0.881), respectively. However, according to the multivariate analysis, the independent risk factor for SAH was mitral inflow E velocity (OR 0.918, 95% CI 0.858-0.982, P=0.013). CONCLUSIONS In elderly patients, ultrasonographic carotid artery flow measurements failed to predict the occurrence of SAH. Only preoperative mitral inflow E velocity of TTE was selected as an independent risk factor for SAH.
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Raquianestesia , Hipotensão Controlada , Idoso , Humanos , Raquianestesia/efeitos adversos , Artérias Carótidas/diagnóstico por imagem , Artéria Carótida Primitiva , Estudos ProspectivosRESUMO
Background/purpose: Various studies have used stem cells in the field of bone tissue engineering to repair bone defects. Dental pulp stem cells (DPSCs) have multipotent properties and can be acquired in a noninvasive manner; therefore, they are frequently used in experiments in regenerative medicine. The objective of this study was to investigate the odontogenic/osteogenic differentiation of human DPSCs (hDPSCs) using propofol, a widely used intravenous anesthetic agent. Materials and methods: Alkaline phosphatase (ALP) staining was used to investigate the effects of various concentrations of propofol (5, 20, 50 and 100 µM) on the osteogenic differentiation of hDPSCs. Real-time qPCR and Western blot analysis were used to detect the effect of propofol on the expression of odontogenic/osteogenic genes, such as DMP1, RUNX2, OCN, and BMP2. Odontogenic/osteogenic differentiation of hDPSCs was estimated at days 7 and 14. Results: ALP staining of hDPSCs was significantly decreased by propofol treatment. The mRNA expression of DMP1, RUNX2, OCN, and BMP2 decreased after propofol treatment for 14 days. The protein expression of DMP1 and BMP2 was decreased by propofol at days 7 and 14, and that of RUNX2 was decreased by propofol at day 14 only. Conclusion: Propofol attenuated odontogenic/osteogenic differentiation of hDPSCs in vitro. This result suggests that propofol, which is widely used for dental sedation, may inhibit the odontogenic/osteogenic differentiation of hDPSCs.
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BACKGROUND: Microcirculatory disturbances are typically most severe during cardiopulmonary bypass (CPB), which occurs during cardiac surgeries. If microvascular reactivity compensates for microcirculatory disturbances during CPB, tissue hypoxemia can be minimized. The primary aim of this study was to assess whether microvascular reactivity during CPB could predict major adverse events (MAE) after cardiac surgery. METHODS: This prospective observational study included 115 patients who underwent elective on-pump cardiac surgeries. A vascular occlusion test (VOT) with near-infrared spectroscopy was performed five times for each patient: before the induction of general anesthesia, 30 min after the induction of general anesthesia, 30 min after applying CPB, 10 min after protamine injection, and post-sternal closure. The postoperative MAE was recorded. The area under the receiver operating characteristic (AUROC) curve analysis was performed for the prediction of MAE using the recovery slope. RESULTS: Of the 109 patients, MAE occurred in 32 (29.4%). The AUROC curve for the recovery slope during CPB was 0.701 (P < 0.001; 95% CI [0.606, 0.785]). If the recovery slope during CPB was < 1.08%/s, MAE were predicted with a sensitivity of 62.5% and specificity of 72.7%. CONCLUSIONS: Our study demonstrated that the recovery slope of the VOT during CPB could predict MAE after cardiac surgery. These results support the idea that disturbances in microcirculation induced by CPB can predict the development of poor clinical outcomes, thereby demonstrating the potential role of microvascular reactivity as an early predictor of MAE after cardiac surgery.
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Procedimentos Cirúrgicos Cardíacos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Humanos , Microcirculação , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
Though Morusin isolated from the root of Morus alba was known to have antioxidant, anti-inflammatory, antiangiogenic, antimigratory, and apoptotic effects, the underlying antitumor effect of Morusin is not fully understood on the glycolysis of liver cancers. Hence, in the current study, the antitumor mechanism of Morusin was explored in Hep3B and Huh7 hepatocellular carcninomas (HCC) in association with glycolysis and G1 arrest. Herein, Morusin significantly reduced the viability and the number of colonies in Hep3B and Huh7 cells. Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. Interestingly, Morusin significantly activated phosphorylation of the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but attenuated the expression of the p-mammalian target of protein kinase B (AKT), rapamycin (mTOR), c-Myc, hexokinase 2(HK2), pyruvate kinases type M2 (PKM2), and lactate dehydrogenase (LDH) in Hep3B and Huh7 cells. Consistently, Morusin suppressed lactate, glucose, and adenosine triphosphate (ATP) in Hep3B and Huh7 cells. Conversely, the AMPK inhibitor compound C reduced the ability of Morusin to activate AMPK and attenuate the expression of p-mTOR, HK2, PKM2, and LDH-A and suppressed G1 arrest induced by Morusin in Hep3B cells. Overall, these findings suggest that Morusin exerts an antitumor effect in HCCs via AMPK mediated G1 arrest and antiglycolysis as a potent dietary anticancer candidate.
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Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Flavonoides/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hexoquinase/metabolismo , Humanos , Lactato Desidrogenase 5/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana/metabolismo , Morus/química , Raízes de Plantas/química , Serina-Treonina Quinases TOR/metabolismo , Hormônios Tireóideos/metabolismo , Proteínas de Ligação a Hormônio da TireoideRESUMO
BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, are effective but still have limited efficacy. Therefore, combination therapy is preferable to using a single drug alone in high-risk patients. We performed a comparative study on the antiemetic effect of palonosetron, a 5-HT3 receptor antagonist, monotherapy vs palonosetron-midazolam combination therapy for the prevention of PONV. METHODS: A total of 104 female patients scheduled for breast cancer surgery were enrolled. They were randomly divided into 2 groups, a palonosetron monotherapy group (group P) and palonosetron-midazolam combination therapy group (group PM). Both groups received 0.075âmg palonosetron intravenously after induction of anesthesia. Patient-controlled analgesia (PCA) was applied according to the allocated group. Intravenous (IV)-PCA in group P consisted of fentanyl 20âµg/kg plus normal saline (total volume: 100âml); IV-PCA in group PM consisted of fentanyl 20âµg/kg plus midazolam 4âmg plus normal saline (total volume: 100âml). Efficacy parameters were collected during 0 to 1, 1 to 6, 6 to 24, and 24 to 48âhours postoperative time intervals. These measures included complete response (defined as no PONV and no rescue anti-emetic use) rate, incidence of PONV, sedation score, rescue antiemetic use, rescue analgesic use, and numerical rating scale (NRS) for pain. The complete response rate during the 0 to 24âhours interval was analyzed as the primary outcome. RESULTS: Although the complete response rate between 0 and 24âhours was higher in group PM (42.3% and 48.1% in group P and PM, respectively), there was no statistically significant difference (Pâ=â.55). The complete response rates in other time intervals were not different between the 2 groups as well. The sedation score and NRS score also showed no differences between the 2 groups. CONCLUSIONS: The combination therapy of palonosetron with midazolam did not lead to a greater reduction in the incidence of PONV than monotherapy in patients undergoing breast surgery and receiving IV-PCA containing fentanyl.
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Analgesia Controlada pelo Paciente/efeitos adversos , Neoplasias da Mama/cirurgia , Fentanila , Midazolam/administração & dosagem , Palonossetrom/administração & dosagem , Náusea e Vômito Pós-Operatórios , Anestésicos Intravenosos/administração & dosagem , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Mastectomia/efeitos adversos , Mastectomia/métodos , Midazolam/efeitos adversos , Pessoa de Meia-Idade , Palonossetrom/efeitos adversos , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Resultado do TratamentoRESUMO
PURPOSE: Anesthesia alters microcirculation and tissue oxygen saturation (StO2). We sought to examine changes in StO2 using near-infrared spectroscopy and a vascular occlusion test (VOT) during spinal anesthesia. METHODS: This prospective observational study was included 51 patients without comorbidities who underwent elective surgery under spinal anesthesia. We measured the StO2 in the lower extremity during VOT before and after intrathecal injection. RESULTS: The baseline, minimum, and maximum StO2 values during VOT significantly increased after intrathecal injection (baseline StO2 from 68.6 ± 7.3% to 77.1 ± 10.1%, minimum StO2 from 39.7 ± 14.9% to 48.8 ± 17.6%, and maximum StO2 from 74.2 ± 7.5% to 80.2 ± 10.0%, all P < 0.0001). The occlusion slope and ischemic stimulus did not significantly change after intrathecal injection. The reperfusion slope was 1.38 ± 0.69%/sec before intrathecal injection and significantly decreased to 1.15 ± 0.61%/sec after intrathecal injection (P = 0.0001). CONCLUSIONS: Our results showed that despite an increased perfusion, reperfusion rate was significantly decreased by spinal anesthesia. Further studies are required to confirm how these contradictory results (improving oxygenation while reducing microvascular reactivity) actually affect the clinical impact of spinal anesthesia on microvascular function.
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Raquianestesia , Bupivacaína/administração & dosagem , Extremidade Inferior/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Microvasos/efeitos dos fármacos , Adulto , Idoso , Raquianestesia/efeitos adversos , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Biomarcadores/sangue , Bupivacaína/efeitos adversos , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Saturação de Oxigênio , Estudos Prospectivos , Fluxo Sanguíneo Regional , Espectroscopia de Luz Próxima ao Infravermelho , Fatores de TempoRESUMO
Since the AKT/mammalian target of rapamycin (mTOR)/c-Myc signaling plays a pivotal role in the modulation of aerobic glycolysis and tumor growth, in the present study, the role of AKT/mTOR/c-Myc signaling in the apoptotic effect of Compound K (CK), an active ginseng saponin metabolite, was explored in HepG2 and Huh7 human hepatocellular carcinoma cells (HCCs). Here, CK exerted significant cytotoxicity, increased sub-G1, and attenuated the expression of pro-Poly (ADP-ribose) polymerase (pro-PARP) and Pro-cysteine aspartyl-specific protease (pro-caspase3) in HepG2 and Huh7 cells. Consistently, CK suppressed AKT/mTOR/c-Myc and their downstreams such as Hexokinase 2 (HK2) and pyruvate kinase isozymes M2 (PKM2) in HepG2 and Huh7 cells. Additionally, CK reduced c-Myc stability in the presence or absence of cycloheximide in HepG2 cells. Furthermore, AKT inhibitor LY294002 blocked the expression of p-AKT, c-Myc, HK2, PKM2, and pro-cas3 in HepG2 cells. Pyruvate blocked the ability of CK to inhibit p-AKT, p-mTOR, HK2, and pro-Cas3 in treated HepG2 cells. Overall, these findings provide evidence that CK induces apoptosis via inhibition of glycolysis and AKT/mTOR/c-Myc signaling in HCC cells as a potent anticancer candidate for liver cancer clinical translation.
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Carcinoma Hepatocelular , Ginsenosídeos/farmacologia , Neoplasias Hepáticas , Transdução de Sinais , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Glicólise , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Despite the importance of microcirculation in organ function, monitoring microcirculation is not a routine practice. With developments in microscopic technology, incident dark field (IDF) microscopy (Cytocam) has allowed visualization of the microcirculation. Dorsal skinfold chamber (DSC) mouse model has been used to investigate microcirculation physiology. By employing Cytocam-IDF imaging with DSC model to assess microcirculatory alteration in lipopolysaccharide (LPS)-induced endotoxemia, we attempted to validate availability of Cytocam-IDF imaging of microcirculation. METHODS: DSC was implanted in eight BALB/c mice for each group; control and sepsis. Both groups were given 72 hours to recover from surgery. The sepsis group had an additional 24-hour period of recovery post-LPS injection (4 mg/kg). Subsequently, a video of the microcirculation was recorded using Cytocam. Data on microcirculatory variables were obtained. Electron microscopy was implemented using lanthanum fixation to detect endothelial glycocalyx degradation. RESULTS: The microcirculatory flow index was significantly lower (control, 2.8±0.3; sepsis, 2.1±0.8; P=0.033) and heterogeneity index was considerably higher (control, 0.10±0.15; sepsis, 0.53±0.48; P=0.044) in the sepsis group than in the control group. Electron microscopy revealed glycocalyx demolishment in the sepsis group. CONCLUSIONS: Cytocam showed reliable ability for observing changes in the microcirculation under septic conditions in the DSC model. The convenience and good imaging quality and the automatic analysis software available for Cytocam-IDF imaging, along with the ability to perform real-time in vivo experiments in the DSC model, are expected to be helpful in future microcirculation investigations.
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Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined. Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1. Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % â sec-1 at T0 and 3.59 [2.58-3.51] % â sec-1 at T1, P <0.001), but not in older group (2.61 [2.21-3.20] % â sec-1 at T0, 2.63 [1.90-3.60] % â sec-1 at T1, P = 0.949). Conclusions: General anesthesia could improve StO2 through increase of microvascular reactivity and decrease of tissue metabolism. However, microvascular reactivity to capillary recruitment under general anesthesia significantly improves in younger patients, not in older patients.
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Anestesia Geral/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Microcirculação/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Dor Processual/prevenção & controle , Adulto , Fatores Etários , Idoso , Envelhecimento/fisiologia , Anestesia Geral/métodos , Feminino , Humanos , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Oxigênio/análise , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia , Dor Processual/etiologia , Propofol/administração & dosagem , Propofol/efeitos adversos , Estudos Prospectivos , Remifentanil/administração & dosagem , Remifentanil/efeitos adversos , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
The purpose of this research was to identify metabolite change during barley (Hordeum vulgare) germination and reveal active principles for the anti-wrinkle activity. Barley was germinated with deionized water (DW) and mineral-rich water (MRW) for the comparison of the effect of mineral contents on the metabolites changes during germination. The effects of germinated barley extracts (GBEs) on collagen production and collagenase inhibition were evaluated in vitro using human dermal fibroblasts (HDFs). A pronounced anti-wrinkle activity was observed in the test group treated with the MRW-GBEs. In order to find out the active components related to the anti-wrinkle activity, an orthogonal projection to latent structure-discriminant analysis (OPLS-DA) was performed, using the data from secondary metabolites profiling conducted by UPLC-PDA-ESI-MS. The anti-wrinkle activity of MRW-GBEs was revealed to be associated with the increase of oligomeric compounds of procyanidin and prodelphinidin, indicating that it can be used as an active ingredient for anti-wrinkle agents.
Assuntos
Fibroblastos/efeitos dos fármacos , Germinação , Hordeum/metabolismo , Metaboloma , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Hordeum/crescimento & desenvolvimento , Humanos , Metaloproteinase 1 da Matriz/químicaRESUMO
Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-α and interlukin (IL)-1ß. Protein expressions of COX-2, PGE2, p38 and NF-κB were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1ß. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.
Assuntos
Âmnio/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Dexmedetomidina/farmacologia , Inflamação/tratamento farmacológico , Âmnio/citologia , Âmnio/imunologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Dexmedetomidina/uso terapêutico , Dinoprostona/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Objectives: The purpose of this study was to compare the effects of combined epidural-general anesthesia with those of general anesthesia alone on hemodynamic instability (intraoperative hypotension and hypertensive crisis) during pheochromocytoma and sympathetic paraganglioma surgery. Methods: A total of 119 patients' medical records were reviewed who were diagnosed as having pheochromocytoma and sympathetic paraganglioma on the basis of histological findings. Intraoperative hypotension was defined as a mean blood pressure < 60 mmHg or a decrease > 30% in baseline systolic blood pressure after adrenal vein ligation. Hypertensive crisis was defined as a systolic blood pressure > 200 mmHg or an increase > 30% in baseline systolic blood pressure during the operation. The predictor variables for intraoperative hypotension and hypertensive crisis were analyzed with logistic regression models. Data were presented as adjusted odds ratio with 95% confidence interval. Results: The independent predictors of intraoperative hypotension were an increased attenuation number on unenhanced computed tomography (1.112 [1.009-1.226], p = 0.033), a high baseline mean blood pressure (1.063 [1.012-1.117], p = 0.015), and the combined epidural-general anesthesia (5.439 [1.410-20.977], p = 0.014). In contrast, an increased attenuation number on unenhanced computed tomography was the only independent predictor of hypertensive crisis (1.087 [1.021-1.158], p = 0.009). Conclusions: The combined epidural-general anesthesia was not effective in attenuating hypertensive responses, but could have exacerbated intraoperative hypotension. These findings should be taken into account before selecting the anesthetic technique in pheochromocytoma and sympathetic paraganglioma surgery.