Neighborhood-level socioeconomic factors moderate the association between physical activity and relative age effect: a cross-sectional survey study with Japanese adolescents.

BACKGROUND: Relative age effect is defined as a phenomenon where children born early generally perform better than children born later in the same cohort. Physical activity is an important factor that might be influenced by the relative age effect. Socioeconomic factors (e.g., parent's income, education level) are also associated with the adolescent's physical activity. However, no existing study has examined whether socioeconomic factors moderate the relative age effect on the adolescent's physical activity. This study aims to clarify whether and how birth month and socioeconomic factors relate to organized sports and physical activity among adolescents in Japan. METHODS: We conducted a questionnaire survey targeting 21,491 adolescents who live in a widespread neighborhood. We included 8102 adolescents (4087 males and 4015 females: mean age 13.1 ± 1.4) in the analysis. Based on the participants' birth months, we divided them into four groups (April to June, July to September, October to December, January to March). We asked participants to report their organized sports participation. Using the International Physical Activity Questionnaire for Japanese Early Adolescents, we identified their moderate to vigorous physical activity (MVPA). Neighborhood-level socioeconomic factors (areal deprivation, average annual income, education level) were analyzed based on national surveys, such as the population census. We performed multilevel logistic and linear regression analysis for organized sports participation and MVPA, respectively. Moreover, a simple slope analysis was implemented if the interaction between birth month and socioeconomic factor was significant in the multilevel linear regression analysis. RESULTS: Among males, relatively younger adolescents (adolescents who were born later in the same grade) were less likely to participate in organized sports activites (OR=0.90, 95% CI 0.82-0.97, p<0.05), while both males and females engaged in less MVPA (b=-0.54, b=-0.25, p< 0.01, respectively). We observed an interaction between birth month and socioeconomic factors. Among males in low-income neighborhoods, and females in more deprived neighborhoods, relatively younger adolescents engaged in less MVPA. CONCLUSIONS: Socioeconomic factors moderate the relative age effect on adolescents' physical activity. The relative age effect on adolescents' physical activity might be more likely to appear among adolescents from socioeconomically disadvantaged neighborhoods.

Intraoperative Diagnosis of Bronchovenous Fistula During Lung Transplantation Using Transesophageal Echocardiography.

Bronchovenous fistula (BVF) is a rare complication and can cause arterial gas embolism in vital organs, including the heart and the brain, resulting in a high mortality rate. A 51-year-old man developed a BVF during pneumonectomy for lung transplantation, which quickly was diagnosed by transesophageal echocardiography (TEE). He required highairway-pressure ventilation due to his severely restrictive ventilatory impairment and had severe left pleural adhesion due to a history of pleurodesis. Intraoperatively, he had a coronary air embolism and required temporary treatment with central venoarterial extracorporeal membrane oxygenation (VA-ECMO), but showed no postoperative cardiac or neurologic complications. BVF may be formed during lung transplantation because lung transplantation recipients often receive high-airway-pressure ventilation and are vulnerable to bronchi and pulmonary vessel injuries during surgery. Intraoperative TEE can contribute to the early detection of air bubbles in the left heart circulation and is helpful for the prevention of arterial gas embolism.

Relationship between maternal healthy eating literacy and healthy meal provision in families in Japan.

This study examined the effects of maternal healthy eating literacy (HEL) on healthy meal provision in Japanese families. We conducted an online cross-sectional survey with 1899 mothers of pre-school children. Participants were divided into two groups based on their median score of eating out and consuming convenience foods, and demographic variables were compared between these groups. We assessed associations between HEL and healthy meal provision using Pearson's correlation coefficient (r) and multiple linear regression with healthy meal provision as the dependent variable and HEL as the independent variable, adjusting for age, education, work styles, household income, number of children and whether participants lived with a partner. Mothers exhibiting high scores on eating out/consuming convenience foods were more likely to be employed (p = 0.004), have only one child (p = 0.034), have lower education (p=0.011) and exhibit lower healthy meal provision (p < 0.001) and HEL scores (p < 0.001). In addition, HEL was associated with healthy meal provision (ß = 0.34, p < 0.001). Among mothers with higher scores on eating out/consuming convenience foods, HEL was associated with healthy meal provision (ß = 0.32, p < 0.001). This study suggests that maternal HEL is associated with healthy meal provision regardless of the degree of eating out/consuming convenience food. Thus, interventions to improve maternal HEL can help mothers to provide healthy meals when they eat out or consume convenience foods as family meals.

Does upper-body elevation affect sleepiness and memories of hypnagogic images after short daytime naps?

The present study aimed to examine the effects of a somatosensory stimulus on sleepiness and memories of hypnagogic imagery during short daytime naps. Participants experienced two daytime nap conditions: (1) a somatosensory stimulus was created by raising the upper part of the bed 20 min after turning off the light and (2) a somatosensory stimulus was not created; the angle of the upper part of the bed remained flat. Approximately 20 min and 30 s after turning off the light, participants were awakened and questioned regarding their subjective sleepiness and the presence or absence of hypnagogic imagery. Results showed that subjective sleepiness following the nap was reduced only in the raised condition, and hypnagogic imagery in the raised condition was lower than that in the flat condition. These findings may provide insight on developing new techniques for improving subjective conditions after awakening.

Rocuronium Has a Suppressive Effect on Platelet Function via the P2Y12 Receptor Pathway In Vitro That Is Not Reversed by Sugammadex.

Rocuronium is an aminosteroid nondepolarizing neuromuscular blocker that is widely used for anesthesia and intensive care. In this study, we investigated the effect of rocuronium on human platelet functions in vitro. The effects of rocuronium on platelet aggregation, P-selectin expression, and cyclic adenosine monophosphate (cAMP) levels in platelets were measured using an aggregometer, an enzyme immunoassay, and flow cytometry, respectively. Rocuronium inhibited ADP-induced platelet aggregation, P-selectin expression and suppression of cAMP production. These effects were not antagonized by equimolar sugammadex, a synthetic γ-cyclodextrin derivative that antagonizes rocuronium-induced muscle relaxation by encapsulating the rocuronium molecule. Morpholine, which constitutes a part of the rocuronium molecule but is not encapsulated by sugammadex, inhibited ADP-induced platelet aggregation. Vecuronium, which has a molecular structure similar to that of rocuronium but does not possess a morpholine ring, had no significant effect on ADP-induced platelet aggregation. These results indicate that rocuronium has a suppressive effect on platelet functions in vitro that is not reversed by sugammadex and suggest that this effect is mediated by blockade of the P2Y12 receptor signaling pathway via the morpholine ring of rocuronium.

Intraoperative Aortic Dissection during Lung Transplantation in a Patient with Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder affecting the lung, liver, and rarely skin. The most frequent features of AATD consist of chronic lung disorders related to protease-antiprotease imbalance in the respiratory system, to which lung transplantation is frequently indicated. We describe a case of aortic dissection in a 55-year-old male who underwent left single lung transplantation for respiratory failure due to AATD-related emphysema. Extracorporeal membrane oxygenation (ECMO) was indicated during the procedure, and an arterial cannula was placed into the descending aorta and a venous cannula was placed into the right femoral vein. Bronchial and vascular anastomoses were finished without any problems and ECMO was weaned off However, transesophageal echocardiography carried out at the end of the operation showed a dissected descending aorta. Alpha-1 antitrypsin (AAT) is the major serum inhibitor of seine proteinases, which enzymatically destroys collagen and elastin. Degeneration of connective tissues, in particular elastic tissues, is established in AATD, and decreased stiffness of the aorta due to degradation of elastic fibers has also been reported in AATD. In this patient, reduced AAT activity might have boosted the enzymatic destruction of his arterial walls, leading to enhanced vulnerability to aortic dissections.

Oral administration and younger age decrease plasma concentrations of voriconazole in pediatric patients.

Voriconazole is used for treating or preventing invasive aspergillosis and other invasive fungal infections. To minimize adverse reactions and to maximize treatment effects, therapeutic drug monitoring should be performed. However, it is challenging to optimize daily voriconazole dosing because limited data have been published so far on pediatric patients. We retrospectively analyzed voriconazole concentrations in patients aged 0-18 years. In addition, a literature review was conducted. In our study cohort, younger age and oral administration were significantly associated with lower plasma voriconazole concentrations (P < 0.01). An unfavorable outcome was associated with low concentrations of voriconazole (P = 0.01). Reports of voriconazole administration in pediatric patients show that higher doses are required in younger children and in patients receiving oral administration. Hence, the current data suggest that we should escalate both initial and maintenance doses of voriconazole in pediatric patients, particularly in patients of younger age receiving an oral administration of voriconazole.

Off-Pump Bilateral Cadaveric Lung Transplantation Is Associated With Profound Intraoperative Hypothermia.

OBJECTIVES: Changes in body temperature (BT) during lung transplantation never have been reported. The authors investigated the time-dependent changes in BT during lung transplantation and compared them between off-pump lung transplantation and lung transplantation using extracorporeal membrane oxygenation (ECMO). DESIGN: A retrospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent cadaveric lung transplantation (15 bilateral lung transplantation [BLT] and 31 single-lung transplantation [SLT]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients received multimodal therapy to prevent intraoperative hypothermia, including increased environmental temperature, intravenous fluid warming, and the use of forced-air and circulating water warmers. Data of BT during the surgery were collected, and the time course and the extent of BT decrease during the surgery were analyzed. ECMO support during the surgery was necessary for 66.7% of BLT patients and 35.5% of SLT patients; patient characteristics were comparable between off-pump and ECMO-supported lung transplantation. In patients undergoing off-pump BLT, BT decreased continuously to 32.9°C when reperfusion was completed and gradually recovered thereafter. The decrease in BT was significantly larger during off-pump BLT compared with ECMO-supported BLT (3.5°C±0.5°C compared with 0.6°C±0.5°C, p = 0.002) and was≥3°C in all patients. Patients undergoing off-pump SLT had a similar time trend for their BTs (continuous decrease until reperfusion and subsequent recovery), but the extent of BT decrease was much smaller than that in off-pump BLT patients (1.0°C±0.5°C). CONCLUSIONS: Patients undergoing off-pump BLT were at high risk of profound intraoperative hypothermia despite multimodal preventive therapy.

Comparison of general anesthesia and monitored anesthesia care in patients undergoing breast cancer surgery using a combination of ultrasound-guided thoracic paravertebral block and local infiltration anesthesia: a retrospective study.

PURPOSE: The aim of this study was to compare post-anesthesia recovery time and the incidence of hypotension episodes during anesthesia in breast cancer surgery between general anesthesia (GA) and monitored anesthesia care (MAC) retrospectively. Both techniques were combined with ultrasound-guided paravertebral block (US-PVB) and local infiltration anesthesia (LIA). METHODS: We reviewed the medical records of patients who received US-PVB for breast cancer surgery retrospectively and divided them into two groups based on the method of anesthetic management. In the GA group, anesthesia was induced using propofol and maintained by sevoflurane inhalation via a laryngeal mask airway after US-PVB was performed under sedation with midazolam. In the MAC group, US-PVB and surgery were carried out under sedation with propofol and remifentanil and supplemental oxygen through a facemask. All patients in both groups breathed spontaneously and received US-PVB and LIA with 0.5 % ropivacaine and diclofenac suppository for pain relief. RESULTS: Times from post-anesthesia care unit admission to fluid intake (mean ± SD; 79 ± 34 vs. 99 ± 33 min, P = 0.034) and gait (77 ± 45 vs. 109 ± 45 min, P = 0.013) were significantly shorter in the MAC group (n = 29) than in the GA group (n = 29). Average systolic blood pressure (SBP) was significantly lower (89 ± 11 vs. 99 ± 16 mmHg, P = 0.011) and the incidence of hypotension (SBP < 70 mmHg) was higher (52 vs. 21 %, P = 0.014) in the GA group than in the MAC group during anesthesia. CONCLUSION: MAC with US-PVB and LIA exhibited faster post-anesthesia recovery and a lower incidence of hypotension episodes during anesthesia than GA with US-PVB and LIA in breast cancer surgery.

[Prevention of Perioperative Aspiration Pneumonitis].

To prevent perioperative aspiration pneumonitis, it is necessary to reduce the volume and acidity of gastric content. The guideline for preoperative fasting published by Japanese Society of Anesthesiologists recommends fasting from intake of clear fluids, breast milk and nonhuman milk at least 2h, 4h and 6h, respectively, before elective procedures requiring general anesthesia, regional anesthesia or sedation/analgesia. Gastrointestinal stimulants, histamine-2 receptor antagonists, proton pump inhibitors, antacids, antiemetics, anticholinergics are effective for reduction of the volume or acidity of gastric content. However, the routine preoperative use of these drugs to reduce the risk of pulmonary aspiration in patients who have no apparent increased risk for pulmonary aspiration is not recommended.

[Difficult Ventilation Requiring Emergency Endotracheal Intubation during Awake Craniotomy Managed by Laryngeal Mask Airway].

We report a case of difficult ventilation requiring emergency endotracheal intubation during awake craniotomy managed by laryngeal mask airway (LMA). A 45-year-old woman was scheduled to receive awake craniotomy for brain tumor in the frontal lobe. After anesthetic induction, airway was secured using ProSeal LMA and patient was mechanically ventilated in pressure-control mode. Patient's head was fixed with head-pins at anteflex position, and the operation started. About one hour after the start of the operation, tidal volume suddenly decreased. We immediately started manual ventilation, but the airway resistance was extremely high and we could not adequately ventilate the patient. We administered muscle relaxant for suspected laryngospasm, but ventilatory status did not improve; so we decided to conduct emergency endotracheal intubation. We tried to intubate using Airwayscope or LMA-Fastrach, but they were not effective in our case. Finally trachea was intubated using transnasal fiberoptic bronchoscopy. We discuss airway management during awake craniotomy, focusing on emergency endotracheal intubation during surgery.

Preoperative Hypercapnia as a Predictor of Hypotension During Anesthetic Induction in Lung Transplant Recipients.

OBJECTIVE: To determine the incidence and predisposing factors of hypotension during anesthetic induction in lung transplant recipients. DESIGN: Retrospective study. SETTING: University hospital. PARTICIPANTS: Patients who underwent lung transplantation between 2008 and 2013 (n = 68). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed the mean arterial pressure (MAP) from administration of anesthetic drugs to 10 minutes after endotracheal intubation (ie, the anesthetic induction) among participants who underwent lung transplantation. Patients were considered to have clinically significant hypotension (CSH) when the following criteria were fulfilled: An MAP decrease of>40% from baseline and MAP of<60 mmHg. Overall, 41.2% of patients experienced CSH during the induction of anesthesia. The preoperative partial pressure of carbon dioxide (PaCO2) was significantly higher in patients who experienced CSH during anesthetic induction than in those who did not (p = 0.005). Preoperative PaCO2 predicted the development of CSH during anesthetic induction (area under the curve = 0.702; p = 0.002), with an optimal cut-off point of 55 mmHg determined by maximizing the Youden index. The incidences of CSH during anesthetic induction for patients with (PaCO2 ≥ 55) and without (PaCO2<55) preoperative hypercapnia were 75.0% (95% confidence interval [CI] [53.8-89.2]) and 30.8% (95% CI 26.4-37.3), respectively. After adjustment for known predicting factors, the odds ratio for the relationship between preoperative hypercapnia and CSH during anesthetic induction was 12.54 (95% CI 3.10-66.66). CONCLUSIONS: Hypotension during anesthetic induction is common in lung transplant recipients, and is independently predicted by preoperative hypercapnia.

The clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation.

PURPOSE: We examined the clinical course of anesthetic induction in lung transplant recipients with pulmonary complications after hematopoietic stem cell transplantation (post-HSCT), focusing on ventilatory management. We aimed to determine the incidence of oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction in post-HSCT lung transplant recipients, and to explore factors associated with their development. METHODS: Nineteen consecutive patients who underwent lung transplantation post-HSCT at Kyoto University Hospital (Japan) were retrospectively studied. Data regarding patient characteristics, preoperative examination, and clinical course during anesthetic induction were analyzed. RESULTS: The incidence of oxygen desaturation (SpO2 < 90 %) during anesthetic induction and severe respiratory acidosis (pH < 7.2) after anesthetic induction were 21.1 and 26.3 %, respectively. Reduced dynamic compliance (Cdyn) during mechanical ventilation was significantly associated with oxygen desaturation during anesthetic induction (p = 0.01), as well as severe respiratory acidosis after anesthetic induction (p = 0.01). The preoperative partial pressure of carbon dioxide in arterial blood (PaCO2; r = -0.743, p = 0.002) and body mass index (BMI; r = 0.61, p = 0.021) significantly correlated with Cdyn, and multivariate analysis revealed that both PaCO2 and BMI were independently associated with Cdyn. CONCLUSIONS: Oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction frequently occur in post-HSCT lung transplant recipients. Low Cdyn may, at least partially, explain oxygen desaturation during anesthetic induction and severe respiratory acidosis after anesthetic induction. Moreover, preoperative hypercapnia and low BMI were predictive of low Cdyn.

[Persistent Bilateral Vocal Cord Paralysis after General Anesthesia in a Patient with Multiple System Atrophy: A Case Report].

We report a case of persistent bilateral vocal cord paralysis which developed after spine surgery under general anesthesia in a patient with multiple system atrophy. A 64-year-old woman was scheduled to receive spinal fusion surgery for kyphoscoliosis. She did not have apparent symptoms of vocal cord paralysis such as hoarseness before surgery. The surgery was performed smoothly under general anesthesia with endotracheal intubation. However, immediately after extubation, the patient developed severe upper airway obstruction and was re-intubated. Fiberoptic laryngoscopy revealed bilateral vocal cord abductor paralysis. Vocal cord paralysis did not improve and she received tracheotomy on the 12th day after surgery. She also showed symptoms of autonomic nervous system dysfunction and cerebellar ataxia, and was diagnosed as multiple system atrophy on postoperative day 64. We discuss differential diagnosis of persistent vocal cord paralysis after general anesthesia, and anesthetic management of a patient with multiple system atrophy.

[Postoperative Pain after Hybrid Video-assisted Thoracic Surgery].

BACKGROUND: Hybrid video-assisted thoracic surgery (hybrid VATS), combining television monitoring and direct visualization through mini-thoracotomy, has been established as a secure and minimally invasive operation for lung cancer. This study aimed to determine postoperative pain levels after hybrid VATS in which intraoperative internal intercostal nerve block is performed. We also examined whether additional use of postoperative continuous infusion of fentanyl improves postoperative pain control. METHODS: Data from 131 patients undergoing hybrid VATS were retrospectively analyzed. Thoracoscopic, internal intercostal nerve block was performed at the end of the procedure. Postoperative pain levels after hybrid VATS, and the impact of postoperative continuous infusion of fentanyl on postoperative pain levels and the incidence of postoperative nausea and vomiting (PONV) were examined. RESULTS: 46.6% of patients experienced severe postoperative pain (numerical rating scale 7-10) after hybrid VATS. Postoperative continuous infusion of fentanyl was not associated with reduction in postoperative pain score, but was independently associated with PONV [odds ratio 3.44 (1.52-8.20); P = 0.0027]. CONCLUSIONS: Intraoperative internal intercostal nerve block did not provide sufficient analgesia after hybrid VATS. Additional use of postoperative continuous infusion of fentanyl did not reduce pain score, but increased the incidence of PONV.

[Extracorporeal Membrane Oxygenation for Anesthesia Induction in a Patient with Severe Cardiorespiratory Impairment due to Mediastinal Angiosarcoma].

BACKGROUND: Mediastinal angiosarcoma is a rare intrathoracic tumor that can cause severe pleural and pericardial fibrosis. CASE REPORT: We report the anesthetic management for pericardiectomy and pleurolysis in a 33-year-old patient with a mediastinal angiosarcoma. He presented with severe restrictive ventilatory impairment and heart failure due to fibrosis of the pleura and pericardium. Spirometry indicated a forced vital capacity of 0.66 l, while arterial blood gas analysis under noninvasive positive pressure ventilation indicated hypercapnia (pH 7.44; Pa(CO2) 59.2 mmHg). His cardiac index was 1.36 l x min(-1) x m(-2). Anesthesia induction and positive pressure ventilation are associated with an extremely high cardiorespiratory risk; therefore, veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) with femoral cannulation was started prior to anesthesia induction. After achieving a stable circulation and adequate gas exchange, anesthesia was induced, and mechanical ventilation with intratracheal intubation was initiated. With ECMO and inotropic support stable hemodynamics was maintained throughout anesthesia induction and the operation was performed uneventfully under cardiopulmonary bypass. The patient was extubated on the first postoperative day and discharged one month after the operation. CONCLUSION: ECMO is a useful option to secure adequate gas exchange and circulation during anesthesia induction in patients with severe cardiopulmonary problems due to mediastinal tumors.

[Transient Femoral Nerve Palsy after Ilioinguinal-Iliohypogastric Nerve Block: Comparison of Ultrasound-guided and Landmark-based Techniques in Adult Inguinal Hernia Surgery].

BACKGROUND: Transient femoral nerve palsy (TFNP) is a well-known complication associated with ilioinguinal-iliohypogastric nerve block (IINB). We compared the incidence of TFNP after ultrasound-guided IINB and that after anatomical landmark-based IINB. METHODS: We reviewed medical records of adult patients (ASA-PS 1-3, Age 21-87) who had received inguinal hernia surgery under general anesthesia and LINB retrospectively. IINB was performed using 0.5% ropivacaine either by ultrasound-guidance (US group, n = 16) or by landmark-based technique (LM group, n =17). TFNP was defined as sensory loss in the anterior aspect of the thigh or weakness of quadriceps femoris muscle in the nerve-blocked side. RESULTS: The frequency of TFNP in US group (6%) was lower than that in LM group (41%) in the post-anesthesia care unit (P = 0.019). TFNP symptom was resolved completely on the morning after surgery. The incidence of severe-intermediate postoperative pain and analgesic requirement were not different between the two groups. CONCLUSIONS: This study revealed that ultrasound-guided technique is effective to lower the incidence of TFNP after IINB in adult inguinal hernia surgery.

[Evaluation of postoperative pain intensity after ear, nose, and throat surgery--the effect of intraoperative fentanyl use].

BACKGROUND: This study was designed to determine postoperative pain levels after ear, nose, and throat (ENT) surgery, and also to examine whether intraoperative fentanyl use during ENT surgery enhances the quality of postoperative pain control. METHODS: The distribution of pain scores and rescue analgesic requirements among 198 patients undergoing ENT surgery were examined. Multivariate logistic regression analysis was performed to identify independent factors associated with moderate to severe postoperative pain (maximal pain score ≥ 5 on the numerical rating scale) and postoperative nausea and vomiting (PONV). RESULTS: 27.8% of patients experienced moderate to severe postoperative pain after ENT surgery. The distribution of postoperative pain levels was similar among procedures performed on different anatomical regions. Intraoperative fentanyl use was not associated with moderate to severe postoperative pain (adjusted odds ratio (95% confidence interval) :1.03 (0.51-2.13))]. On the other hand, intraoperative fentanyl use was independently associated with PONV [3.10 (1.25-8.92); P = 0.0138]. CONCLUSIONS: Prevalence of moderate to severe postoperative pain after ENT surgery was approximately 28%. Intraoperative fentanyl use was not associated with a decreased incidence of moderate to severe postoperative pain, but was significantly associated with PONV.

Dual roles of PGE2-EP4 signaling in mouse experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). Although prostaglandin (PG) concentrations are increased in cerebrospinal fluid of MS patients, the role of PGs in MS is unknown. We examined this issue by subjecting mice deficient in each PG receptor type or subtype to EAE induction and using agonists or antagonists selective for each of the four PGE receptor (EP) subtypes. Among PG receptor-deficient mice, only EP4(-/-) mice manifested significant suppression of EAE, which was mimicked in wild-type mice and to a greater extent, in EP2(-/-) mice by administration of the EP4 antagonist ONO-AE3-208 during the immunization phase. EP4 antagonism during immunization also suppressed the generation of antigen-specific T helper (Th) 1 and Th17 cells in wild-type mice and to a greater extent, in EP2(-/-) mice. ONO-AE3-208 administration at EAE onset had little effect on disease severity, and its administration throughout the experimental period did not cause significant reduction of the peak of disease, suggesting that, in addition to its facilitative action during the immunization phase, EP4 exerts a preventive action in the elicitation phase. Administration of the EP4 agonist ONO-AE1-329 at EAE onset delayed and suppressed disease progression as well as inhibited the associated increase in permeability of the blood-brain barrier. Thus, PGE(2) exerts dual functions in EAE, facilitating Th1 and Th17 cell generation redundantly through EP4 and EP2 during immunization and attenuating invasion of these cells into the brain by protecting the blood-brain barrier through EP4.

Dual modulation of the T-cell receptor-activated signal transduction pathway by morphine in human T lymphocytes.

PURPOSE: In this study, we aimed to investigate the effect of morphine on the activation of extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB), both of which play crucial roles in T-cell activation. METHODS: Human CD3+ T cells and Jurkat T cells were stimulated by anti-CD3 antibody or phorbol 12-myristate 13-acetate plus ionomycin with or without 24-h pretreatment with morphine. Activation of ERK was assessed by immunoblot analysis of phosphorylated ERK. Activation of the NF-κB signaling pathway was examined by analyzing nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation using immunoblotting, and interleukin-2 (IL-2) gene expression using quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: Morphine pretreatment enhanced ERK phosphorylation, but inhibited IκBα phosphorylation and IL-2 gene expression in activated T cells. The effects of morphine on ERK phosphorylation and IL-2 gene expression were not antagonized by naloxone. We detected κ-opioid receptor transcript in T cells, but U50,488, a κ-receptor-selective agonist, did not enhance ERK phosphorylation. CONCLUSION: Morphine enhances ERK signaling, whereas it inhibits NF-κB signaling in activated human T cells. These effects of morphine are unlikely to be mediated by known opioid receptors.