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Astaxanthin, a keto-carotenoid, is known to have potent antioxidant properties. This study aims to investigate the anti-inflammatory effect of astaxanthin and its mechanism in human neutrophils. The effects of astaxanthin on lipopolysaccharide (LPS)-stimulated human neutrophils were investigated in vitro. Neutrophils were isolated from healthy volunteers and stimulated with LPS in the presence and absence of astaxanthin. We assessed cytokine production, signaling pathway activation via mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB), and apoptosis. Astaxanthin's impact was evaluated at different concentrations, and both pretreatment and cotreatment protocols were tested. The results demonstrated that astaxanthin significantly reduced the production of pro-inflammatory cytokines TNF-α and IL-1ß in LPS-stimulated neutrophils. It effectively inhibited the phosphorylation of ERK1/2 MAPK, without notably affecting p38 MAPK or NF-κB pathways. Furthermore, astaxanthin promoted apoptosis in neutrophils, counteracting the apoptosis-delaying effects of LPS. These effects were more pronounced with pretreatment. In conclusion, astaxanthin has protective effects on inflammatory responses in neutrophils by reducing cytokine production and enhancing apoptosis while selectively modulating intracellular signaling pathways. Astaxanthin demonstrates significant potential as a therapeutic agent in the management of severe inflammatory conditions.
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BACKGROUND: Arytenoid dislocation is a rare laryngeal injury that may follow endotracheal intubation. We aimed to determine the incidence and risk factors for arytenoid dislocation after surgery under general anaesthesia. METHODS: We reviewed the medical records of patients who underwent operation under general anaesthesia with endotracheal intubation from January 2014 to December 2018. Patients were divided into the non-dislocation and dislocation groups depending on the presence or absence of arytenoid dislocation. Patient, anaesthetic, and surgical factors associated with arytenoid dislocation were determined using Poisson regression analysis. RESULTS: Among the 25,538 patients enrolled, 33 (0.13%) had arytenoid dislocation, with higher incidence after anterior neck and brain surgery. Patients in the dislocation group were younger (52.6 ± 14.4 vs 58.2 ± 14.2 yrs, P = 0.025), more likely to be female (78.8 vs 56.5%, P = 0.014), and more likely to be intubated by a first-year anaesthesia resident (33.3 vs 18.5%, P = 0.048) compared to those in the non-dislocation group. Patient positions during surgery were significantly different between the groups (P = 0.000). Multivariable Poisson regression identified head-neck positioning (incidence rate ratio [IRR], 3.10; 95% confidence interval [CI], 1.50-6.25, P = 0.002), endotracheal intubation by a first-year anaesthesia resident (IRR, 2.30; 95% CI, 1.07-4.64, P = 0.024), and female (IRR, 3.05; 95% CI, 1.38-7.73, P = 0.010) as risk factors for arytenoid dislocation. CONCLUSION: This study showed that the incidence of arytenoid dislocation was 0.13%, and that head-neck positioning during surgery, less anaesthetist experience, and female were significantly associated with arytenoid dislocation in patients who underwent surgeries under general anaesthesia with endotracheal intubation.
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Cartílago Aritenoides/lesiones , Intubación Intratraqueal/efectos adversos , Luxaciones Articulares/etiología , Posicionamiento del Paciente/efectos adversos , Adulto , Anciano , Anestesia General/métodos , Femenino , Movimientos de la Cabeza , Humanos , Incidencia , Luxaciones Articulares/epidemiología , Masculino , Persona de Mediana Edad , Cuello , Posicionamiento del Paciente/métodos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: In intubation using fiberoptic bronchoscope (FOB), partial or complete obstruction of upper airway makes the FOB insertion difficult. Thus, maneuvers to relieve such obstructions are recommended. There have been no studies to determine whether the sniffing or neutral position is superior for this purpose. Therefore, this study was performed to examine the effects of these two positions including vocal cord view. METHODS: Fifty-four patients scheduled to receive general anesthesia by orotracheal intubation were eligible for inclusion in the study with informed consent. After confirmation of proper head positioning depending on the group, the view of the vocal cord was acquired in each position. Images were reviewed using the percentage of glottic opening (POGO) score. RESULTS: A total of 106 images of vocal cords from 53 patients were obtained. The mean of difference of POGO score was 11.09, higher for the neutral position and standard deviation was 23.73 (p = 0.002). Neutral position increased POGO score in 31 patients and decreased POGO score in 13 patients compare to sniffing position (p = 0.017). There were no significant differences between the two head positions with regard to intubation time or degree of convenience during intubation. CONCLUSIONS: Neutral position improved the view of glottic opening than sniffing position during oral fiberoptic intubation. However, there was no difference in the difficulty of tube insertion between the two positions. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02931019 , registered on October 12, 2016.
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Broncoscopía/métodos , Tecnología de Fibra Óptica , Intubación Intratraqueal/métodos , Posicionamiento del Paciente/métodos , Adulto , Anciano , Anestesia General/métodos , Estudios Cruzados , Glotis , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Administration of arginine vasopressin (AVP) is associated with reducing jugular venous (SjvO2) and regional cerebral (rScO2) oxygen saturation under propofol-remifentanil (P/R) anaesthesia. We determined whether background anaesthetics modulate the effect of AVP on cerebral oxygenation and haemodynamics. METHODS: We randomly allocated 60 adult patients scheduled for shoulder surgery in the beach chair position (BCP) into 4 groups, to receive either an intravenous bolus of saline (groups PR-S and SN-S) or 0.05 U/kg AVP (groups PR-AVP and SN-AVP) under P/R or sevoflurane-nitrous oxide (S/N) anaesthesia (n = 15 each). Haemodynamic variables, SjvO2 and rScO2 were measured. RESULTS: AVP significantly increased mean arterial blood pressure (MAP) and decreased rScO2 in either anaesthetic group. AVP also decreased SjvO2 in the P/R groups but not in the S/N groups. The AVP-treated groups showed higher MAP and cerebral desaturation (>20% rScO2 decrease from baseline), along with lower HR and rScO2 in the BCP than those in the saline-treated groups. In contrast, AVP did not affect SjvO2 values or the incidence of SjvO 2 < 50%. Baseline SjvO2 was lower and the magnitude of its reduction in the BCP was greater in the PR-AVP group than in the SN-AVP group, and the lowest SjvO2 values were 37 ± 6 and 57 ± 8%, respectively (P < 0.001). CONCLUSIONS: The choice of anaesthetic regimen did not affect cerebral oxygenation or haemodynamics of AVP in the BCP. However, the negative effect of AVP on cerebral oxygenation should be considered, especially under P/R anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01687894 , registered on September 18, 2012.
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Arginina Vasopresina/administración & dosificación , Encéfalo/metabolismo , Oxígeno/metabolismo , Posicionamiento del Paciente , Vasoconstrictores/administración & dosificación , Anciano , Anestésicos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Circulación Cerebrovascular , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Éteres Metílicos/administración & dosificación , Persona de Mediana Edad , Óxido Nitroso/administración & dosificación , Oximetría , Piperidinas/administración & dosificación , Propofol/administración & dosificación , Estudios Prospectivos , Remifentanilo , Sevoflurano , Articulación del Hombro/cirugía , Método Simple Ciego , Espectroscopía Infrarroja CortaRESUMEN
BACKGROUND: Cervical necrotizing fasciitis (CNF) is a rare, aggressive form of deep neck space infection with significant morbidity and mortality rates. Serial surgical debridement acts as the cornerstone of CNF treatment; however, it often results in defects requiring complex reconstructions. CASE SUMMARY: We report two cases in which the keystone flap (KF) was used for CNF defect coverage: Case 1, an 85-year-old patient with CNF in the anterior neck, and Case 2, a 54-year-old patient with CNF in the posterior neck. Both patients received empirical intravenous antibiotic therapy and underwent serial debridement, enabling adequate wound preparation and stabilization. The final defect size measured 5.5 cm × 12 cm in Case 1 and 6 cm × 11 cm in Case 2. For defect coverage, we employed an 8 cm × 19 cm type II KF based on perforators from the superior thyroid artery in Case 1 and a 9 cm × 18 cm type II KF based on perforators from the transverse cervical artery in Case 2. Both flaps showed complete survival. No postoperative complications occurred in both cases, and favorable outcomes were observed at 7- and 6-month follow-ups in case 1 and 2, respectively. CONCLUSION: We effectively treated CNF-associated defects using the KF technique; KF is viable for covering CNF defects in carefully selected cases.
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This study analyzed the relationship between urine concentrations of phthalate metabolites (UCOM) and personal care products (PCPs) used in adults and examined the change in UCOM according to the usage frequency of PCPs based on raw data from the 3rd Korean National Environmental Health Survey conducted between 2015 and 2017. The relationship between PCP use frequency and UCOM was analyzed using multiple regression analysis, adjusting for baseline factors. The regression model consisted of a Crude Model with log-transformed UCOM before and after adjustment for urine creatinine concentrations. Model 1 was additionally adjusted for age, sex, and obesity, while Model 2 was additionally adjusted for smoking, alcohol consumption, pregnancy history, average monthly income of the household, and PCP exposure within the past 2 days. PCP usage frequency was significantly associated with the UCOM without adjustment for urine creatinine and correlated with demographic characteristics, urine creatinine concentration, and PCP exposure within the past 2 days. This study on exposure to urinary phthalates will play a crucial role in Korean public health by aligning with the fundamentals of research priorities and providing representative data on phthalate exposure for conducting population-level studies.
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Cosméticos , Contaminantes Ambientales , Ácidos Ftálicos , Femenino , Embarazo , Humanos , Exposición a Riesgos Ambientales/análisis , Creatinina/análisis , Ácidos Ftálicos/metabolismo , Cosméticos/análisis , Contaminantes Ambientales/metabolismoRESUMEN
Subciliary incision is a common approach for facial fracture surgery; however, it has a higher incidence of lower lid ectropion, which can be particularly challenging for beginning surgeons to manage. This study reports the usage of lateral tarsoplasty combined with a full-thickness skin graft (FTSG) to correct severe ectropion following the subciliary approach for infra-orbital rim fractures. We retrospectively reviewed all facial fracture cases involving infra-orbital rim fractures through a subciliary approach treated in our department between March 2021 and May 2023. Electronic medical records and clinical digital photographs of patients who met the inclusion criteria were reviewed. After reviewing 196 cases that used the subciliary approach, we found 6 patients (3.06%; 4 males and 2 females; mean age, 68.5 ± 4.89 years) with postoperative severe ectropion managed using lateral tarsoplasty and FTSG. The mean ectropion development and correction times after facial fracture surgery were 0.78 ± 0.24 and 0.91 ± 0.37 months, respectively. At the 12-month follow-up, all patients showed favorable outcomes, and the position of their lower eyelids was well maintained without ectropion recurrence. Based on these successful outcomes, lateral tarsoplasty combined with FTSG is proposed to be an effective and straightforward method for managing lower eyelid ectropion caused by facial fracture surgery.
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BACKGROUND: While awake, flexible bronchoscopic intubation has long been considered the gold standard for managing anticipated difficult airways, the videolaryngoscope has emerged as a viable alternative. In addition, the decision to perform awake intubation or to proceed with airway management after induction of general anesthesia should be grounded in a comprehensive assessment of risks and benefits. CASE PRESENTATION: A 41-year old female patient was scheduled for excision of bilateral, mobile, and pedunculated masses on both aryepiglottic folds, which covered almost the entire upper part of the glottis. We conducted a comprehensive evaluation of the patient's signs and symptoms, which included neither stridor nor dyspnea in any position, along with the otolaryngologist's opinion and the findings from the laryngeal fiberscopic examination. Given the potential challenges and risks associated with awake flexible bronchoscopic intubation for this patient, we decided to proceed with gentle tracheal intubation using a videolaryngoscope under general anesthesia. In case of failed mask ventilation and tracheal intubation, we had preplanned strategies, including awakening the patient or performing an emergent tracheostomy, along with preparations to support these strategies. Ensuring that mask ventilation was maintained with ease, the patient was sequentially administered intravenous propofol, remifentanil, and rocuronium. Under sufficient depth of anesthesia, intubation using a videolaryngoscope was successfully performed without any complications. CONCLUSIONS: Videolaryngoscopic intubation after induction of general anesthesia can be a feasible alternative for managing difficult airways in patients with supraglottic masses. This approachshould be based on a comprehensive preoperative evaluation, adequate preparation, and preplanned strategies to address potential challenges, such as inadequate oxygenation and unsuccessful tracheal intubation.
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Herein, we present our experience using a single-stage peninsular-shaped lateral tongue flap (pLTF) to cover various intraoral defects and confirm the versatile utility and effective application of pLTF in intraoral defect reconstruction. This study included eight cases (six males and two females; average age 60.3 ± 16.9 years) of intraoral defect reconstruction performed by a single surgeon between August 2020 and May 2023 using the single-stage pLTF technique. Electronic medical records and photographs of the patients were collected and analyzed. The functional intraoral Glasgow scale (FIGS) was used to evaluate preoperative and postoperative tongue function. Defect sizes ranged from 3 cm × 3 cm to 4 cm × 6 cm. Notably, all defects were successfully covered with pLTFs, and the flap sizes ranged between 3 cm × 4.5 cm and 4.5 cm × 7.5 cm. The flaps completely survived without any postoperative complications. At follow-up (average, 9.87 ± 2.74 months), no patient had tumor recurrence or significant tongue functional deficits. The mean preoperative and postoperative FIGS were 14.75 ± 0.46 and 14.00 ± 0.92, respectively (p = 0.059). Thus, the single-stage pLTF technique is a good reconstructive modality for various small to moderate intraoral defect coverage in selected cases for personalized intraoral reconstruction.
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Nasotracheal intubation is mainly performed to provide a safe airway during maxillofacial surgeries. Several guiding devices are suggested to facilitate nasotracheal intubation and reduce complications. We attempted to compare intubation conditions during nasotracheal intubation using a nasogastric tube and a suction catheter, which are readily available in operating rooms. In this study, 114 patients undergoing maxillofacial surgery were randomly divided into the nasogastric tube guidance group (NG group) and the suction catheter guidance group (SC group). The primary outcome was the total intubation time. Moreover, the incidence and degree of epistaxis, the position of the tube in the nasal cavity after intubation, and the number of manipulations during intubation in the nasal cavity were investigated. The insertion time from the nostril to the oral cavity and the total intubation time were significantly shorter in the SC group than in the NG group (p < 0.001). The incidence of epistaxis was lower at 35.1% in the NG group and 43.9% in the SC group than the previously reported 60-80%, but there was no statistical difference between the two groups. The use of a suction catheter aid during nasotracheal intubation can be used effectively because it shortens the intubation time and does not increase complications.
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Cavidad Nasal , Cirugía Bucal , Humanos , Epistaxis/epidemiología , Epistaxis/etiología , Estudios Prospectivos , Intubación Intratraqueal/efectos adversosRESUMEN
BACKGROUND: Ramped positioning is recommended for intubating obese patients undergoing direct laryngoscopy. However, whether the use of the ramped position can provide any benefit in videolaryngoscopy-guided intubation remains unclear. This study assessed intubation time using videolaryngoscopy in morbidly obese patients in the ramped versus sniffing positions. METHODS: This is a prospective randomized study in patients with morbid obesity (n = 82; body mass index [BMI] ≥ 35 kg/m2). Patients were randomly allocated to either the ramped or the standard sniffing position groups. During the induction of general anesthesia, difficulty in mask ventilation was assessed using the Warters scale. Tracheal intubation was performed using a C-MAC® D-Blade videolaryngoscope, and intubation difficulty was assessed using the intubation difficulty scale (IDS). The primary endpoint was the total intubation time calculated as the sum of the laryngoscopy and tube insertion times. RESULTS: The percentage of difficult mask ventilation (Warters scale ≥ 4) was significantly lower in the ramped (n = 40) than in the sniffing group (n = 41) (2.5% vs. 34.1%, P < 0.001). The percentage of easy intubation (IDS = 0) was significantly higher in the ramped than in the sniffing group (70.0% vs. 7.3%, P < 0.001). The total intubation time was significantly shorter in the ramped than in the sniffing group (22.5 ± 6.2 vs. 40.9 ± 9.0, P < 0.001). CONCLUSIONS: Compared with the sniffing position, the ramped position reduced intubation time in morbidly obese patients and effectively facilitated both mask ventilation and tracheal intubation using videolaryngoscopy.
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Laringoscopios , Obesidad Mórbida , Humanos , Laringoscopía , Obesidad Mórbida/complicaciones , Estudios Prospectivos , Intubación IntratraquealRESUMEN
Resveratrol has been reported to have beneficial effects on sepsis by regulating the inflammatory response. However, it remains unclear if resveratrol plays a role in the development of endotoxin tolerance. Treatment with resveratrol in macrophages stimulated with primary lipopolysaccharide (LPS) resulted in the increased production of TNF-α and IL-6 induced by a 2nd dose of LPS (by 74.5 ± 12.9% and 63.4 ± 12%, respectively, compared to untreated cells, P < 0.05). This effect was inhibited by compound C, an AMPK inhibitor, and STO609, a calcium/calmodulin-dependent protein kinase-kinase (CaMKK) inhibitor. Resveratrol diminished the expression of interleukin-1 receptor-associated kinase M (IRAK-M) and Src homology 2 (SH2) domain-containing inositol-5-phosphatase 1 (SHIP1) by prolonging the exposure of cells to LPS (by 60.8 ± 16.3% and 70.3 ± 18.1%, respectively, compared to LPS only). The effect of resveratrol on the LPS-induced expression of IRAK-M and SHIP1 was inhibited by compound C or STO609. After a 2nd dose of LPS, resveratrol increased phosphorylation of ERK1/2, p38, and JNK in endotoxin tolerant macrophages. In vivo systemic administration of resveratrol prevented a significant increase in mortality rate by cecal ligation and puncture in LPS-induced endotoxin-tolerant mice. These results indicate that resveratrol induces AMPK activation through the Ca2+/CaMKKß pathway and suppresses the development of endotoxin tolerance by inhibiting LPS-induced expression of IRAK-M and SHIP1.
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Proteínas Quinasas Activadas por AMP/metabolismo , Endotoxemia/tratamiento farmacológico , Factores Inmunológicos/farmacología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Resveratrol/farmacología , Animales , Señalización del Calcio , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Endotoxemia/enzimología , Activación Enzimática , Mediadores de Inflamación/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos , Macrófagos/enzimología , Masculino , Ratones , Ratones Endogámicos BALB C , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
STUDY OBJECTIVE: To determine the effect of deep neuromuscular blockade (NMB) on surgical field conditions through multiple assessments during pneumoperitoneum and evaluate the effect of the depth of intraoperative NMB on the quality of postoperative recovery over multiple time periods. DESIGN: Prospective randomized study. SETTING: Operating room of a university hospital. PATIENTS: Eighty non-morbidly obese patients (ASA physical status 1-2) who were scheduled to undergo laparoscopic gastrectomy in the reverse Trendelenburg position. INTERVENTIONS: Patients were allocated to either the deep or moderate NMB group. The depth of NMB was maintained at a post-tetanic count of 1 for deep NMB with a continuous infusion of rocuronium and at a train-of-four count of 1 for moderate NMB with a small intermittent bolus of cisatracurium. MEASUREMENTS: Single-blinded scoring of the quality of the surgical field condition was performed by a surgeon using a five-point scale in a 15-min interval during pneumoperitoneum. The quality of postoperative recovery was assessed using the Postoperative Quality of Recovery Scale (PostopQRS) on the day before surgery (baseline) and 1 h, 1 day, and 6 days after surgery. MAIN RESULTS: Optimal surgical field condition was rated in 87.0% (449/516) and 72.3% (370/512) of all measurements during deep and moderate NMB, respectively (P < 0.001). The percentage of patients maintaining a good-to-optimal condition throughout pneumoperitoneum was higher in the deep NMB group than in the moderate NMB group. There were no significant differences in the percentage of recovered patients between the two groups for all domains and all timepoints. CONCLUSIONS: Multiple assessments of the surgical field condition demonstrated that deep NMB provided a more satisfactory surgical field condition than moderate NMB during laparoscopic gastrectomy. However, the quality of postoperative recovery, assessed using the PostopQRS, was not different between the two groups according to the depth of NMB.
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Laparoscopía , Bloqueo Neuromuscular , Humanos , Neumoperitoneo Artificial/efectos adversos , Estudios Prospectivos , RocuronioRESUMEN
BACKGROUND: Donepezil is an acetylcholinesterase inhibitor used to improve cognition and delay disease progression in dementia patients by increasing acetylcholine levels. This drug may potentially interact with neuromuscular blocking agents (NMBAs) that act on muscular acetylcholine receptors during general anesthesia. Herein, we present a case of inadequate neuromuscular blockade with rocuronium, a nondepolarizing NMBA, in a dementia patient who had taken donepezil. CASE SUMMARY: A 71-year-old man was scheduled for laparoscopic gastrectomy. He had been taking donepezil 5 mg for dementia. General anesthesia was induced with propofol and remifentanil. The depth of neuromuscular blockade was monitored by train-of-four (TOF) stimulation. After the administration of rocuronium, the TOF ratio decreased at an unusually slow rate, and a TOF count of 0 was detected 7 min later. After intubation, a TOF count of 1 was detected within 1 min, and a TOF ratio of 12% was detected within 2 min. The TOF count remained at 4 even with an additional bolus and continuous infusion of rocuronium, suggesting resistance to this NMBA. Instead of propofol, an inhalation anesthetic was administered alongside another NMBA (cisatracurium). Then, the quality of neuromuscular blockade improved, and the TOF count remained at 0-1 for the next 70 min. No further problems were encountered with respect to surgery or anesthesia. CONCLUSION: Donepezil may be responsible for inadequate neuromuscular blockade during anesthesia, especially when total intravenous anesthesia is used.
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Stearoyl lysophosphatidylcholine (sLPC) has protective effects against several lethal sepsis models, even after induction of sepsis, which is associated with sLPC-mediated inhibition of high mobility group box 1 (HMGB1) release. This study investigated the mechanism by which sLPC inhibits lipopolysaccharide (LPS)-induced extracellular secretion of HMGB1 after the onset of sepsis. sLPC increased AMPK phosphorylation and the binding of AMPK to calcium/calmodulin-dependent protein kinase kinase ß (CaMKKß), one of the upstream signals of AMPK. Inhibition of CaMKKß activity decreased sLPC-mediated inhibition of HMGB1 release, and sLPC increased the concentration of intracellular calcium. Blocking of the macrophage G protein-coupled receptor G2A (G2A) suppressed AMPK phosphorylation, suppressed increases in the intracellular levels of calcium, and prevented the inhibition of HMGB1 release by sLPC. In particular, when macrophages were incubated with sLPC even after LPS treatment, sLPC increased the phosphorylation of AMPK and the binding of CaMKKß and AMPK, and suppressed the secretion of HMGB1. In addition, sLPC administered 1â¯h before or 4â¯h after establishment of sepsis significantly diminished circulating HMGB1 levels in mice. sLPC inhibited LPS-induced extracellular release of HMGB1 through the activation of the G2A/calcium/CaMKKß/AMPK pathway. These findings suggest that sLPC may be a potential anti-inflammatory agent for acute inflammatory conditions such as sepsis.
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Proteínas Quinasas Activadas por AMP/metabolismo , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo , Calcio/metabolismo , Espacio Extracelular/efectos de los fármacos , Proteína HMGB1/metabolismo , Lisofosfatidilcolinas/farmacología , Receptores CCR10/metabolismo , Animales , Espacio Extracelular/metabolismo , Lipopolisacáridos/farmacología , Lisofosfatidilcolinas/uso terapéutico , Macrófagos/citología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Células RAW 264.7 , Sepsis/tratamiento farmacológico , Sepsis/inmunología , Sepsis/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Overactivation of inflammatory cells, including macrophages and neutrophils, is associated with acute lung injury. BMS-470539 is a selective agonist of melanocortin 1 receptor, which triggers the inhibition of proinflammatory responses, suppressing neutrophil infiltration and protecting tissue. This study evaluated the effects of BMS-470539 on lipopolysaccharide-induced acute lung injury in a mouse model. METHODS: Mice received a subcutaneous injection of saline or BMS-470539 (18.47 mg/kg) 1 hour before an intratracheal injection of saline or lipopolysaccharide (20 µg). Mice were sacrificed to analyze the severity of pulmonary edema (lung wet-to-dry weight [W/D] ratio) and inflammatory responses (level of leukocytes, polymorphonuclear neutrophils [PMNs] and tumor necrosis factor alpha [TNF-α] in bronchoalveolar lavage fluid [BALF]), and neutrophil infiltration (myeloperoxidase activity). TNF-α activation was also measured in neutrophils from bone marrow. Survival was investigated in a second-hit sepsis mouse model. RESULTS: BMS-470539 improved sepsis-induced pulmonary edema, as demonstrated by a decreased W/D ratio (5.76%±0.83% to 3.81%±0.86%, P<0.05). The inflammatory response also improved, as shown by decreased levels of leukocytes (551±116 to 357±86×10²/mm³, P<0.05), PMNs (51.52%±16.23% to 18.41%±7.25%, P<0.01), and TNF-α (550±338 to 128±52 pg/ml, P<0.01) in the BALF. BMS-470539 also improved the inflammatory response, as shown by TNF-α levels (850±158 to 423±59 pg/ml, P<0.01) in neutrophils. BMS-470539 downregulated neutrophil infiltration in the lung (myeloperoxidase: 654±98 to 218±89 U/g, P<0.001). Lastly, BMS improved the survival rate (0% to 70%, P<0.01) in a mice multiple organ failure model. CONCLUSIONS: BMS-470539 improved lipopolysaccharide-induced acute lung injury and mortality in mice by affecting the inflammatory response.
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Ginsenoside Rg3 is a steroidal saponin abundant in Korean red ginseng that has high anti-inflammatory activity. Rg3 exerts an immunomodulatory effect in acute inflammatory conditions such as bacterial infections. In this study, we determined the effect of Rg3 on bacterial uptake by macrophages and the related intracellular signaling pathways. Rg3 increased macrophage phagocytosis of IgG-opsonized Escherichia coli and IgG-opsonized beads (IgGbeads), but not of non-opsonized beads. Rg3 also enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinase (p38 MAPK), but not that of Akt. The inclusion of IgGbeads in macrophage cultures also increased the phosphorylation of ERK1/2 and p38, but co-culture of macrophages with non-opsonized beads did not affect the phosphorylation of ERK1/2 and p38. The Rg3-induced promotion of phagocytosis was inhibited by PD98059, an ERK1/2 inhibitor, and SB203580, a p38 inhibitor. PD98059 inhibited Rg3-induced p38 MAPK phosphorylation, but SB203580 did not suppress ERK1/2 phosphorylation. Culture of macrophages with Rg3 increased actin polymerization, and this effect was inhibited by SB203580 and PD98059. The Rg3-induced increase in phagocytosis was also inhibited by NSC23766, a Rac1 inhibitor and CASIN, a Cdc42 inhibitor. Intraperitoneal injection of Rg3 increased the phosphorylation of ERK1/2 and p38 as well as the phagocytosis of bacteria by lung cells. These results demonstrate that ginsenoside Rg3 enhances macrophage phagocytosis of bacteria by activating the ERK1/2 and p38 MAPK pathways.
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Bacterias/patogenicidad , Ginsenósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Receptores de IgG/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Células Cultivadas , Imidazoles/farmacología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Piridinas/farmacología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: The aims of this study were to compare the efficacy of sevoflurane inhalation alone, intravenous remifentanil alone, and the combination of sevoflurane inhalation and remifentanil as pretreatment for the prevention of rocuronium-induced withdrawal movement in pediatric patients. METHODS: In this prospective, randomized study, 90 American Society of Anesthesiologists physical status I or II pediatric patients aged 3 to 10 years were randomly allocated to one of three treatment groups: The Group S comprising the patients receiving sevoflurane inhalation, the Group R comprising those doing intravenous remifentanil 0.5 µg/kg and the Group C comprising those doing sevoflurane inhalation+intravenous remifentanil 0.5 µg/kg. The response of the patients was graded based on a 4-point scale. RESULTS: The overall incidence of withdrawal movement on rocuronium injection was 54% (16/30) in the Group S, 57% (17/30) in the Group R and 17% (5/30) in the Group C. There was no significant difference in the incidence of withdrawal movements on rocuronium injection between the Group S and Group R. In addition, the incidence of withdrawal movements and generalized movement on rocuronium injection was significantly lower in the Group C as compared with the Group S and R (P < 0.05). CONCLUSIONS: Our results indicate not only that there was no significant difference in the degree of the effect in lowering the incidence of withdrawal movements on rocuronium injection between sevoflurane inhalation and intravenous remifentanil but also that it was significantly higher when combined with intravenous remifentanil as compared with the single use of sevoflurane inhalation or intravenous remifentanil.