AMPK reduces macrophage endotoxin tolerance through inhibition of TGF-ß1 production and its signaling pathway.

Adenosine monophosphate-activated protein kinase (AMPK) is involved in suppression of the development of endotoxin tolerance, which is a driver of the immunosuppression induced by sepsis. However, the mechanism by which AMPK inhibits the development of endotoxin tolerance has not been clearly elucidated. Therefore, the present study was performed to investigate the mechanism by which the AMPK activator, metformin, inhibits the development of endotoxin tolerance. Lipopolysaccharide (LPS) increased the production of transforming growth factor (TGF)-ß1 in macrophages, which was inhibited by metformin and resveratrol. Knockdown of AMPKα1 inhibited the suppressive effect of metformin on LPS-induced TGF-ß1 production. TGF-ß neutralizing antibody and TGF-ß type I receptor inhibitor increased the production of TNF-α and IL-6 via LPS restimulation in tolerized macrophages. LPS increased Smad2 phosphorylation, but this was inhibited in cells treated with TGF-ß neutralizing antibody or metformin. Smad2 knockdown inhibited the development of endotoxin tolerance, as evidenced by increased TNF-α production in response to LPS restimulation in tolerized macrophages. TGF-ß1 expression was increased, and the levels of TNF-α and IL-6 production induced by LPS stimulation were decreased, in splenocytes of cecal ligation and puncture (CLP) model mice compared to sham-operated controls. However, metformin treatment suppressed the production of TGF-ß1, and enhanced the production of TNF-α and IL-6 induced by LPS stimulation in splenocytes of CLP mice. These results indicated that AMPK activation inhibits LPS-induced TGF-ß1 production and its signaling pathway, thus suppressing the development of endotoxin tolerance in macrophages.

Comparison of the Nasal Cavity Guidance Methods' Effects during Nasotracheal Intubation Using a Preformed Nasotracheal Tube: A Prospective Randomized Controlled Trial.

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.

Comparison of Postoperative Recovery between Balanced and Total Intravenous Anesthesia in Patients Undergoing Off-Pump Coronary Artery Bypass (OPCAB) Surgery: A Prospective, Single-Blind Randomized Study.

Recovery after anesthesia has a significant impact on a patient's return to daily life. This study was performed to compare the postoperative quality of recovery according to the method of anesthesia administered among patients undergoing OPCAB using the Korean version of the Quality of Recovery-40 (QoR-40K) questionnaire. This single-blind, prospective study (trial number: KCT0004726) was performed using a population of 102 patients undergoing OPCAB under general anesthesia. The patients were randomly assigned to one of two groups using a computer-generated list: a total intravenous anesthesia group (Group T) and a balanced anesthesia group (Group B). The QoR-40K score was measured preoperatively and at 24 and 48 h after extubation. There was no significant difference in the QoR-40K scores between the groups at 24 and 48 h after extubation. In addition, there were no significant differences between groups with respect to any of the five dimensions of QoR-40K at 24 and 48 h after extubation. Finally, there were no differences in the postoperative opioid consumption, time to extubation, or length of hospital stay. In this study, there was no difference in the QoR-40K score at 24 h after extubation between Groups T and B. Therefore, both methods of anesthesia are suitable for use when performing OPCAB.

Ramped versus sniffing position in the videolaryngoscopy-guided tracheal intubation of morbidly obese patients: a prospective randomized study.

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.

A prospective randomized study of different height of operation table for tracheal intubation with videolaryngoscopy in ramped position.

BACKGROUND: Previous studies have reported that the ramped position provides a better laryngoscopic view, reduces tracheal intubation time, and increases the success rate of endotracheal intubation. However, the patient's head height changes while in the ramped position, which in turn changes the relative positions of the patient and intubator. Thus, making these changes may affect the efficiency of tracheal intubation; however, few studies have addressed this problem. This study analyzed intubation time and conditions during tracheal intubation using videolaryngoscope in the ramped position. METHODS: This prospective study included 144 patients who were scheduled to receive general anesthesia for surgeries involving orotracheal intubation. The participants were randomly allocated to either the nipple or umbilical group according to the table height. Mask ventilation was assessed using the Warters grading scale. Tracheal intubation was performed using a McGrath MAC laryngoscope. The total intubation time, laryngoscopy time, tube insertion time, and difficulty of intubation (IDS score) were measured. RESULTS: The umbilical group had a significantly shorter laryngoscopy time (10 ± 3 vs. 16 ± 4 s), tube insertion time (18 ± 4 vs. 24 ± 6 s), and total intubation time (28 ± 5 vs. 40 ± 7 s) compared to the nipple group. No significant difference in the difficulty of mask ventilation was observed between the two groups. The IDS score was higher in the nipple than umbilical group. CONCLUSION: The lower (umbilical) table level reduced the intubation time and difficulty of videolaryngoscopy compared to the higher (nipple) table level. TRIAL REGISTRATION: This study was registered at KCT0005987, 11/03/2021, Retrospectively registered.

Head-neck movement may predispose to the development of arytenoid dislocation in the intubated patient: a 5-year retrospective single-center study.

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.

Sugammadex is associated with shorter hospital length of stay after open lobectomy for lung cancer: a retrospective observational study.

BACKGROUND: Sugammadex is associated with few postoperative complications. Postoperative pulmonary complications (PPC) are related to prolonged hospitalizations. Present study explored whether the use of sugammadex could reduce PPCs and thereby reduce hospital length of stay (LOS) after lung surgery. METHODS: We reviewed the medical records of patients who underwent elective open lobectomy for lung cancer from January 2010 to December 2015. Patients were divided into the sugammadex group and pyridostigmine group. The primary outcome was hospital LOS and secondary outcomes were postoperative complications and overall survival at 1 year. The cohort was subdivided into patients with and without prolonged LOS to explore the effects of sugammadex on outcomes in each group. Risk factors for LOS were determined via multivariate analyses. After propensity score matching, 127 patients were assigned to each group. RESULTS: Median hospital LOS was shorter (10.0 vs. 12.0 days) and the incidence of postoperative atelectasis was lower (18.1 vs. 29.9%) in the sugammadex group. However, no significant difference in overall survival between the groups was seen over 1 year (hazard ratio, 0.967; 95% confidence interval, 0.363 to 2.577). Sugammadex was a predictor related to LOS (exponential coefficient 0.88; 95% CI 0.82-0.95). CONCLUSIONS: Our data suggest that sugammadex is a preferable agent for neuromuscular blockade (NMB) reversal than cholinesterase inhibitors in this patient population. TRIAL REGISTRATION: This study registered in the Clinical Research Information Service of the Korea National Institute of Health (approval number: KCT0004735 , Date of registration: 21 January 2020, Retrospectively registered).

Resveratrol suppresses the reprogramming of macrophages into an endotoxin-tolerant state through the activation of AMP-activated protein kinase.

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.

Oral carbohydrate solution cause an inflammatory response when aspirated into the lungs in mice.

PURPOSE: Many studies have been published on the beneficial effects of oral carbohydrate solutions (OCS) administered prior to surgery. However, the risk of pulmonary aspiration cannot be excluded in all patients undergoing anesthesia. But, there are few studies on the safety of OCS at lung aspiration. METHODS: Experiments were conducted with mice (Nine- to ten-week-old male BALB/c mice weighted 23-26 g). Lung aspiration was performed by intratracheal administration of OCS and its major constituents, fructose and maltodextrin. Bronchoalveolar lavage fluid (BALF) was collected 3 and 24 h after lung aspiration. The level of Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and macrophage inflammatory protein-2 (MIP-2) were measured in BALF. The total white blood cell, neutrophil counts, wet to dry ratio and histological examination were performed in BALF and lung tissue, respectively, at 24 h after aspiration. RESULTS: The OCS increased the level of TNF-α, IL-6 and MIP-2 at 3 h and the neutrophil count at 24 h in BALFs, compared to a phosphate-buffered saline (PBS) group. The increase in IL-6 level induced by OCS was maintained for 24 h. The OCS also increased the number of white blood cells and the percentage of neutrophils in BALFs. Compared to fructose, maltodextrin significantly increased the production of MIP-2 in BALFs. OCS and maltodextrin also increased neutrophil recruitment in lung tissue. CONCLUSION: Aspiration of OCS may cause inflammation of the lungs. The preoperative use of OCS may require caution under specific clinical conditions, such as patients at risk of lung aspiration.

Donepezil-related inadequate neuromuscular blockade during laparoscopic surgery: A case report.

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.

Avenanthramide C Prevents Neuronal Apoptosis via PI3K/Akt/GSK3ß Signaling Pathway Following Middle Cerebral Artery Occlusion.

Avenanthramides are a group of phenolic alkaloids that have been shown to have anti-inflammatory, anti-oxidant, anti-atherogenic, and vasodilation effects. The aim of the present study was to investigate the neuroprotective effect of avenanthramide-c (Avn-c) in focal brain ischemia and reperfusion injury using middle cerebral artery occlusion (MCAo) model with mice. Male C57BL/6 mice were divided into 4 groups: sham, control (MCAo), Avn-c, and Avn-c + LY294002 (phosphoinositide 3-kinase inhibitor) group. They were subjected to 60 min MCAo followed by reperfusion. Brain infarct volume and neurological deficit scores were measured after 24 h of reperfusion. We evaluated the blood brain barrier (BBB) integrity (ZO-1, VE-cadherin and occludin) and apoptosis (Bax, Bcl2, caspase3, Cytochrome C, and poly ADP ribose polymerase(PARP)-1). We also measured GSK3ß for evaluation of the downstream mechanism of Akt. We examined the effect of the Avn-c in the phosphoinositide 3-kinase pathway. Avn-c reduced neurological score and infarction size. Avn-c inhibited the MCAo-induced disruption of tight junction proteins. Avn-c decreased apoptotic protein expression (Bax, Cytochrome C, and cleaved PARP-1) and increased anti-apoptotic protein expression (Bcl2) after MCAo. Akt and GSK3ß were decreased in MCAo group and were restored in Avn-c group. This effect of Avn-c was abolished by PI3K inhibitor. In summary, Avn-c showed neuroprotective effects through PI3K-Akt-GSK3ß signaling pathway.

Antinociceptive role of neurotensin receptor 1 in rats with chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. METHODS: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. RESULTS: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. CONCLUSIONS: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

Incidental detection of a retained left atrial catheter via intraoperative transesophageal echocardiography in a patient undergoing tricuspid valve replacement: A case report.

RATIONALE: A cardiac foreign body can cause thrombosis or infection, but sometimes it may not cause any symptoms in a patient. The diagnosis is mainly performed using a radiological examination. Especially, ultrasound is useful not only for detecting the foreign body but also for hemodynamic findings. However, the disadvantage of ultrasound is that it cannot be used where shadows are generated because of poor permeability. The transesophageal echocardiography (TEE) is superior to transthoracic echocardiography (TTE) for identifying posterior cardiac structures because the probe is located in the esophagus behind the heart. Here, we report on the incidental finding of a foreign body in the left atrium through TEE during cardiac surgery. It did not cause any symptoms or signs for 20 years. PATIENT CONCERNS: A 75-year-old female patient with severe tricuspid regurgitation underwent tricuspid valve replacement (TVR) under general anesthesia. She had a history of mitral valve replacement (MVR) and tricuspid annuloplasty surgery 20 years ago. DIAGNOSIS: A hyper-echoic floating intracardiac foreign body was observed in the left atrium during TEE examination. It was not detected in the preoperative imaging studies such as X-ray, computed tomography, TTE. INTERVENTIONS: The cardiac foreign body found using TEE was visually confirmed through an incision in the left atrium. A long and thin foreign body was located in the right upper pulmonary vein to the left atrium, which was considered to be a left atrial catheter used during the MVR surgery performed 20 years ago. After removing the foreign body, the planned TVR operation proceeded. OUTCOMES: After removing the intracardiac foreign body and TVR, the patient was admitted into the intensive care unit followed by the general ward as planned, and discharged without any complications. LESSONS: TEE was very useful for diagnosing a foreign body in the posterior part of the heart. TEE performed during the perioperative period should be performed beyond the level of re-confirming the findings of TEE performed prior to surgery. If a retained catheter is detected, it may be appropriate to remove it considering the risk of complications.

Effect of transportation method on preoperative anxiety in children: a randomized controlled trial.

BACKGROUND: This study was performed to evaluate the effect of a wagon as a transport vehicle instead of the standard stretcher car to reduce children's anxiety of separation from parents. The secondary goal was to evaluate whether this anxiolytic effect was related to age. METHODS: We divided 80 children (age 2-7 years) into two groups. The stretcher group was transferred to the operating room on a conventional stretcher car, whereas the wagon group was transferred using a wagon. The level of anxiety was evaluated three times using the Modified Yale Preoperative Anxiety Scale (mYPAS): in the waiting area (T0), in the hallway to the operating room (T1), and before induction of anesthesia (T2). RESULTS: The mYPAS score was significantly lower in the wagon group (36.7 [31.7, 51.7]) than in the stretcher group (51.7 [36.7, 83.3]) at T1 (P = 0.007). However, there was no difference in the mYPAS score between the two groups at T2 (46.7 [32.5, 54.2] vs. 51.7 [36.7, 75.0], respectively, P = 0.057). The baseline anxiety tended to be lower with increasing age (r = -0.248, P = 0.031). During transportation to the operating room, the increase in the mYPAS score (T1-T0) was greater as the age of children decreased in the stretcher group (r = -0.340, P = 0.034). However, no correlation was observed in the wagon group (r = -0.053, P = 0.756). CONCLUSION: The wagon method decreased preoperative anxiety, suggesting that it may be a good alternative for reducing preoperative anxiety in children.

A retrospective study of the relationship between postoperative urine output and one year transplanted kidney function.

BACKGROUND: Kidney transplantation (KT) is the most obvious method of treating a patient with end-stage renal disease. In the early stages of KT, urine production is considered a marker of successful reperfusion of the kidney after anastomosis. However, there is no clear conclusion about the relationship between initial urine output after KT and 1-year renal function. Thus, we investigated the factors that affect 1-year kidney function after KT, including urine output. METHODS: This retrospective study investigated the relationship between urine output in the 3 days after KT and transplanted kidney prognosis after 1-year. In total, 291 patients (129 living-donor and 162 deceased-donor transplant recipients) were analyzed; 24-h urine volume per body weight (in kilograms) was measured for 3 days postoperatively. The estimated glomerular filtration rate (eGFR), determined by the Modification of Diet in Renal Disease algorithm, was used as an index of renal function. Patients were grouped according to eGFR at 1-year after KT: a good residual function group, eGFR ≥60, and a poor residual function group, eGFR < 60. RESULT: Recipients' factors affecting 1-year eGFR include height (P = 0.03), weight (P = 0.00), and body mass index (P = 0.00). Donor factors affecting 1-year eGFR include age (P = 0.00) and number of human leukocyte antigen (HLA) mismatches (P = 0.00). The urine output for 3 days after KT (postoperative day 1; 2 and 3) was associated with 1-year eGFR in deceased-donor (P = 0.00; P = 0.00 and P = 0.01). And, postoperative urine output was associated with the occurrence of delayed graft function (area under curve (AUC) = 0.913; AUC = 0.984 and AUC = 0.944). CONCLUSION: Although postoperative urine output alone is not enough to predict 1-year GFR, the incidence of delayed graft function can be predicted. Also, the appropriate urine output after KT may differ depending on the type of the transplanted kidney. TRIAL REGISTRATION: Clinical Research Information Service of the Korea National Institute of Health in the Republic of Korea (KCT0003571).

Ginsenoside Rg3 promotes Fc gamma receptor-mediated phagocytosis of bacteria by macrophages via an extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent mechanism.

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.

Febrile convulsions during recovery after anesthesia in an infant with history of MMR vaccination: A case report.

RATIONALE: Seizures are rare during the perioperative period; in most cases, there is a previous history of epilepsy or surgery-associated seizures. Febrile convulsions may occur when the body temperature rises above 38°C; this is the most common cause of seizures in children. Febrile convulsions after general anesthesia in the postanesthetic care unit (PACU) without a past or family history are rare. Some reviews suggest that since anesthesia changes immunity, elective surgery should be postponed three weeks after live vaccination. PATIENT: A 12-month-old female with bilateral hearing loss underwent cochlear implantation under general anesthesia. She did not have any history of convulsions or developmental disorders. However, 1 week before surgery, measles-mumps-rubella (MMR) vaccination was given as a regular immunization. DIAGNOSES: Forty minutes after arrival at the PACU, sudden generalized tonic-clonic movement occurred during recovery and the patient's measured body temperature exceeded 38.0°C. INTERVENTIONS: Thiopental sodium was administered intravenously as an anticonvulsant, and the tonic-clonic movement stopped immediately. Endotracheal intubation was performed to secure the airway, and tepid massage and diclofenac ß-dimethylaminoethanol administration were performed to lower the patient's body temperature. OUTCOMES: There was no further fever and no seizures, and no other neurological deficits were observed until discharge. LESSONS: The anesthesiologist should check the recent vaccination history even if the patient has not developed particular symptoms after vaccination. It is important to know that febrile convulsions may occur in patients who have recently received MMR vaccination.

Comparison of the effect of sevoflurane or propofol anesthesia on the regional cerebral oxygen saturation in patients undergoing carotid endarterectomy: a prospective, randomized controlled study.

BACKGROUND: The monitoring of regional cerebral oxygen saturation (SrO2) using near-infrared spectroscopy is useful method to detect cerebral ischemia during. Sevoflurane and propofol decrease cerebral metabolic rate (CMRO2) in a similar manner, but the effects on the cerebral blood flow (CBF) are different. We hypothesized that the effects of sevoflurane and propofol on SrO2 were different in patients with deficits of CBF. This study compared the effect of sevoflurane and propofol on SrO2 of patients undergoing cerebral endarterectomy (CEA). METHOD: Patients undergoing CEA were randomly assigned to the sevoflurane or propofol group (n = 74). The experiment was preceded in 2 stages based on carotid artery clamping. The first stage was from induction of anaesthesia to immediately before clamping of the carotid artery, and the second stage was until the end of the operation after clamping of the carotid artery. Oxygen saturation (SrO2, SpO2), haemodynamic variables (blood pressure, heart rate), respiratory parameters (end-tidal carbon dioxide tension, inspired oxygen tension), concentration of anesthetics, and anesthesia depth (bispectral index score) were recorded. RESULTS: During stage 1 period (before carotid artery clamping), the mean value of the relative changes in SrO2 was higher (P = 0.033) and the maximal decrease in SrO2 was lower in the sevoflurane group compared with the propofol group (P = 0.019) in the contralateral (normal) site. However, there is no difference in ipsilateral site (affected site). SrO2 decreased after carotid artery clamping and increased after declamping, but the difference was not significant between two groups. Changes in mean arterial blood pressure was lower in sevoflurane group than propofol group after the carotid artery declamping (P = 0.048). CONCLUSION: Propofol-remifentanil anesthesia was comparable with sevoflurane-remifentanil anesthesia in an aspect of preserving the SrO2 in patients undergoing carotid endarterectomy. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02609087 , retrospectively registered on November 18, 2015.

Ginsenoside Rb1 increases macrophage phagocytosis through p38 mitogen-activated protein kinase/Akt pathway.

BACKGROUND: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. METHODS: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. RESULTS: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogen-activated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of p38α MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. CONCLUSION: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.