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In the present study, we demonstrated that there is a direct relationship between scratching behaviors induced by itch and functional changes in the brain reward system. Using a conditional place preference test, the rewarding effect was clearly evoked by scratching under both acute and chronic itch stimuli. The induction of ΔFosB, a member of the Fos family of transcription factors, was observed in dopamine transporter (DAT)-positive dopamine neurons in the ventral tegmental area (VTA) of mice suffering from a chronic itch sensation. Based on a cellular analysis of scratching-activated neurons, these neurons highly expressed tyrosine hydroxylase (TH) and DAT genes in the VTA. Furthermore, in an in vivo microdialysis study, the levels of extracellular dopamine in the nucleus accumbens (NAcc) were significantly increased by transient scratching behaviors. To specifically suppress the mesolimbic dopaminergic pathway using pharmacogenetics, we used the TH-cre/hM4Di mice. Pharmacogenetic suppression of mesolimbic dopaminergic neurons significantly decreased scratching behaviors. Under the itch condition with scratching behaviors restricted by an Elizabethan collar, the induction of ΔFosB was found mostly in corticotropin-releasing hormone (CRH)-containing neurons of the hypothalamic paraventricular nucleus (PVN). These findings suggest that repetitive abnormal scratching behaviors under acute and chronic itch stimuli may activate mesolimbic dopamine neurons along with pleasant emotions, while the restriction of such scratching behaviors may initially induce the activation of PVN-CRH neurons associated with stress.

Near-infrared spectroscopy (NIRS) was used to monitor intraoperative regional oxygen saturation (rSONIRS sensors were applied to the forehead and flanks for cerebral rSOMean ages at surgery were N: 5.2 ± 8.2 days, MOp: 2.4 ± 2.9 years, and MMI: 3.8 ± 4.3 years. Despite significantly shorter operative times in N (169 ± 94 min; p 0.0001), PD was significantly worse; PD(C-rSO

Context: Yokukansan is a traditional Japanese herbal medicine that has an antiallodynic effect in patients with chronic pain. However, the mechanisms by which yokukansan inhibits neuropathic pain are unclear. Objective: This study aimed to investigate the molecular effects of yokukansan on neuroinflammation in U373 MG glioblastoma astrocytoma cells, which express a functional high-affinity neurokinin 1 receptor (substance P receptor), and produce interleukin (IL)-6 and IL-8 in response to stimulation by substance P (SP). Methods: We assessed the effect of yokukansan on the expression of ERK1/2, P38 MAPK, nuclear factor (NF)-κB, and cyclooxygenase-2 (COX-2) in U373 cells by western blot assay. Levels of IL-6 and IL-8 in conditioned medium obtained after stimulation of cells with SP for 24 h were measured by enzyme-linked immunosorbent assay. All experiments were conducted in triplicate. Results were analyzed by one-way ANOVA, and significance was accepted at p< 0.05. Results: Yokukansan suppressed SP-induced production of IL-6 and IL-8 by U373 MG cells, and downregulated SP-induced COX-2 expression. Yokukansan also inhibited phosphorylation of ERK1/2 and p38 MAPK, as well as nuclear translocation of NF-κB, induced by SP stimulation of U373 MG cells. Conclusion: Yokukansan exhibits anti-inflammatory activity by suppressing SP-induced production of IL-6 and IL-8 and downregulating COX-2 expression in U373 MG cells, possibly via inhibition of the activation of signaling molecules, such as ERK1/2, p38 MAPK, and NF-κB.

Both inhalational and intravenous anesthetics affect myocardial remodeling, but the precise effect of each anesthetic on molecular signaling in myocardial remodeling is unknown. Here, we performed in silico analysis to investigate signaling alterations in cardiomyocytes induced by inhalational [sevoflurane (Sevo)] and intravenous [propofol (Prop)] anesthetics. Bioinformatics analysis revealed that nuclear factor‐kappa B (NF‐kB) signaling was inhibited by Sevo and promoted by Prop. Moreover, nuclear accumulation of p65 and transcription of NF‐kB‐regulated genes were suppressed in Sevo‐administered mice, suggesting that Sevo inhibits the NF‐kB signaling pathway. Our data demonstrate that NF‐kB signaling is inhibited by Sevo and promoted by Prop. As NF‐kB signaling plays an important role in myocardial remodeling, our results suggest that anesthetics may affect myocardial remodeling through NF‐kB., The precise nature of the molecular alterations occurring after inhalation or intravenous anesthesia remains unclear. Here, in silico gene expression analysis of patient cardiomyocytes and a mouse animal model revealed that nuclear factor‐kappa B signaling is upregulated by sevoflurane and downregulated by propofol. Interestingly, this effect was observed only in the postanesthesia acute phase, not in the late phase.

It has been considered that activation of peripheral μ-opioid receptors (MORs) induces side effects of opioids. In this study, we investigated the possible improvement of the immune system in tumour-bearing mice by systemic administration of the peripheral MOR antagonist naldemedine.The inhibitory effect of naldemedine on MOR-mediated signalling was tested by cAMP inhibition and β-arrestin recruitment assays using cultured cells. We assessed possible changes in tumour progression and the number of splenic lymphocytes in tumour-bearing mice under the repeated oral administration of naldemedine.Treatment with naldemedine produced a dose-dependent inhibition of both the decrease in the cAMP level and the increase in β-arrestin recruitment induced by the MOR agonists. Repeated treatment with naldemedine at a dose that reversed the morphine-induced inhibition of gastrointestinal transport, but not antinociception, significantly decreased tumour volume and prolonged survival in tumour-transplanted mice. Naldemedine administration significantly decreased the increased expression of immune checkpoint-related genes and recovered the decreased level of toll-like receptor 4 in splenic lymphocytes in tumour-bearing mice.The blockade of peripheral MOR may induce an anti-tumour effect through the recovery of T-cell exhaustion and promotion of the tumour-killing system.

Chronic postsurgical pain (CPSP) is a serious problem. We developed a mouse model of CPSP induced by electrocautery and examined the mechanism of CPSP. In this mouse model, while both incision and electrocautery each produced acute allodynia, persistent allodynia was only observed after electrocautery. Under these conditions, we found that the mRNA levels of Small proline rich protein 1A (Sprr1a) and Annexin A10 (Anxa10), which are the key modulators of neuropathic pain, in the spinal cord were more potently and persistently increased by electrocautery than by incision. Furthermore, these genes were overexpressed almost exclusively in chronic postsurgical pain-activated neurons. This event was associated with decreased levels of tri-methylated histone H3 at Lys27 and increased levels of acetylated histone H3 at Lys27 at their promoter regions. On the other hand, persistent allodynia and overexpression of Sprr1a and Anxa10 after electrocautery were dramatically suppressed by systemic administration of GSK-J4, which is a selective H3K27 demethylase inhibitor. These results suggest that the effects of electrocautery contribute to CPSP along with synaptic plasticity and epigenetic modification. Supplementary Information The online version contains supplementary material available at 10.1186/s13041-021-00854-y.

Hintergrund: Die Entwöhnung von einer längerfristigen maschinellen Beatmung bei tracheotomierten Patienten mit restriktiver Lungenfunktionsstörung ist extrem schwierig. Eine Sauerstoffgabe mit hoher Flussrate über das Tracheostoma liefert erwärmtes und befeuchtetes Sauerstoffgas mit >10 l/min. Jedoch liegen erst wenige Berichte zur Anwendung von Sauerstoff mit hoher Flussrate über Tracheostoma im Rahmen der Entwöhnung vom Beatmungsgerät bei Patienten mit restriktiver Lungenfunktionsstörung vor. Wir berichten über erfolgreiches Weaning vom Beatmungsgerät bei Patienten mit restriktiver Lungenfunktionsstörung mittels Sauerstoffgabe mit hoher Flussrate über Tracheostoma. Vorstellung der Fälle: Der erste Patient ist ein 78-jähriger Japaner mit schwerer Pneumokokken-Pneumonie, der nach Ösophagektomie wegen eines Ösophaguskarzinoms mehr als einen Monat lang beatmet wurde. Nach einer Tracheotomie wegen der längerfristigen maschinellen Beatmung entwickelte sich eine restriktive Lungenfunktionsstörung mit einem Atemzugvolumen von 230-240 ml und einer statischen Compliance von 14-15 ml/cm H2O mit 10 cm H2O Druckunterstützung. Das Weaning erfolgte unter inspiratorischer Unterstützung mit Sauerstoff mit hoher Flussrate über Tracheostoma über einen Zeitraum von 16 Tagen (Flussrate von 40 l/min und inspiratorische Sauerstofffraktion von 0,25). Der zweite Patient ist ein 69-jähriger Japaner, bei dem nach Ösophagektomie eine Aspirationspneumonie auftrat und der längerfristig über Tracheostoma beatmet wurde. Er entwickelte eine restriktive Lungenfunktionsstörung. Die Sauerstoffgabe mit hoher Flussrate über das Tracheostoma (Flussrate 40 l/min und inspiratorische Sauerstofffraktion von 0,25) erfolgte unter Messung des Atemwegsdrucks am Eingang des Tracheotomietubus. Folgende Werte wurden gemessen: 0,21-0,3 cm H2O, 0,21-0,56 cm H2O, 0,54-0,91 cm H2O, 0,76-2,01 cm H2O, 1,17-2,01 cm H2O und 1,76-2,01 cm H2O bei 10 l/min, 20 l/min, 30 l/min, 40 l/min, 50 l/min bzw. 60 l/min. Der Atemwegsdruck war kontinuierlich positiv und wurde auch während der Inspiration nicht negativ, was darauf hindeutet, dass die Sauerstoffgabe mit hoher Flussrate über Tracheostoma die Inspirationsanstrengung verringert. Das Weaning erfolgte unter inspiratorischer Unterstützung mit Sauerstoff mit hoher Flussrate über Tracheostoma über einen Zeitraum von 12 Tagen. Schlussfolgerungen: Die Sauerstoffgabe mit hoher Flussrate über Tracheostoma kann mit der Sauerstoffzufuhr die Inspirationsanstrengung verringern und das Atemzugvolumen vergrößern und so das Weaning nach Langzeitbeatmung bei Patienten mit restriktiver Lungenfunktionsstörung erleichtern.

Postherpetic itch (PHI), or herpes zoster itch, is an intractable and poorly understood disease. We targeted 94 herpes zoster patients to investigate their pain and itch intensities at three separate stages of the condition (acute, subacute, and chronic). We used painDETECT questionnaire (PDQ) scores to investigate the correlation between PHI and neuropathic pain. Seventy-six patients were able to complete follow-up surveys. The prevalence of PHI was 47/76 (62%), 28/76 (37%), and 34/76 (45%) at the acute, subacute, and chronic stages, respectively. PHI manifestation times and patterns varied. We investigated the relationship of PHI with neuropathic pain using the visual analog scale (VAS), which is a measure of pain intensity, and the PDQ, which is a questionnaire used to evaluate the elements of neuropathic pain. The VAS and PDQ scores did not differ significantly between PHI-positive and PHI-negative patients. A large neuropathic component was not found for herpes zoster itch, suggesting that neuropathic pain treatments may not able to adequately control the itch. Accordingly, we suggest that a more PHI-focused therapy is required to address this condition.

Background Weaning from prolonged mechanical ventilation is extremely difficult in tracheostomized patients with restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy supplies heated and humidified oxygen gas at > 10 L/minute. However, little has been reported on the use of high-flow oxygen via tracheostomy during weaning from ventilators in patients with restrictive pulmonary dysfunction. We report successful weaning from ventilators in patients with restrictive pulmonary dysfunction using high-flow oxygen via tracheostomy. Case presentation The first patient is a 78-year-old Japanese man with severe pneumococcal pneumonia who was mechanically ventilated for more than 1 month after esophagectomy for esophageal cancer. After he underwent tracheostomy because of prolonged mechanical ventilation, restrictive pulmonary dysfunction appeared: tidal volume 230–240 mL and static compliance 14–15 mL/cmH2O with 10 cmH2O pressure support ventilation. He was weaned from the ventilator under inspiratory support with high-flow oxygen via tracheostomy over a period of 16 days (flow at 40 L/minute and fraction of inspired oxygen of 0.25). The second patient is a 69-year-old Japanese man who developed aspiration pneumonia after esophagectomy and received prolonged mechanical ventilation via tracheostomy. He developed restrictive pulmonary dysfunction. High-flow oxygen via tracheostomy (flow at 40 L/minute with fraction of inspired oxygen of 0.25) was administered with measurement of the airway pressure and at the entrance of the tracheostomy tube. The measured values were as follows: 0.21–0.3 cmH2O, 0.21–0.56 cmH2O, 0.54–0.91 cmH2O, 0.76–2.01 cmH2O, 1.17–2.01 cmH2O, and 1.76–2.01 cmH2O at 10 L/minute, 20 L/minute, 30 L/minute, 40 L/minute, 50 L/minute, and 60 L/minute, respectively. The airway pressures were continuously positive and did not become negative even during inspiration, suggesting that high-flow oxygen via tracheostomy reduces inspiratory effort. He was weaned from the ventilator under inspiratory support with high-flow oxygen via tracheostomy over a period of 12 days. Conclusions High-flow oxygen via tracheostomy may reduce the inspiratory effort and enhance tidal volume by delivering high-flow oxygen and facilitate weaning from prolonged mechanical ventilation in patients with restrictive pulmonary dysfunction.

Background Neutrophil gelatinase-associated lipocalin (NGAL) is a diagnostic marker for acute kidney injury (AKI). NGAL expression is highly induced not only in kidney injury but also in bacterial infection, inflammation, and cancer. The factors regulating NGAL expression are proinflammatory cytokines, and plasma NGAL levels have been increased in septic shock. However, there are no reports of urine neutrophil gelatinase-associated lipocalin (uNGAL) levels after open esophagectomy. Methods We prospectively enrolled critically ill patients, including patients with sepsis (n = 45) and patients who underwent open esophagectomy (n = 40). We compared vital signs, PaO2/FIO2, serum C-reactive protein (CRP) levels, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and uNGAL levels between the sepsis group and the esophagectomy group. Then, we investigated whether uNGAL is associated with the severity of illness and organ failure, and whether uNGAL is a reliable screening test for AKI. Results The median uNGAL levels, APACHE II score, SOFA score, and serum CRP levels were significantly (p p p Conclusions uNGAL levels were correlated with the severity of illness and organ failure in critically ill patients. The value of uNGAL increases under the surgical and inflammatory responses, thereby losing a significance of a screening test of AKI in critically ill patients.

Background Cardiac herniation is a serious postoperative complication of extrapleural pneumonectomy (EPP) and is reportedly preventable by reducing the suction pressure of the chest drain. Case presentation We describe a patient in whom respiratory failure, which was caused by impending tension pneumothorax after EPP, was successfully treated via normal suction pressure of the chest drain. A lower suction pressure (− 7 cmH2O) was chosen as an alternative to the setting typically used for postoperative drainage (− 15 cmH2O). As a result, the wound in the chest wall functioned as an antireflux check valve, leading to the development of impending tension pneumothorax. Conclusions Impending tension pneumothorax presents with an abnormal elevation of intrapleural pressure on the affected side. This phenomenon can be effectively treated by increasing the suction pressure in the chest drain.

Objectives To investigate an association between the preoperative plasma B-type natriuretic peptide (BNP) concentration and cerebral regional saturation (rSO2) measured using the INVOS oximeter (Medtronic, Minneapolis, MN). Design A retrospective data analysis. Setting Single university hospital. Participants Patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Interventions None. Measurements and Main Results Associations of variables obtained from preoperative blood laboratory tests and transthoracic echocardiography with baseline rSO2 before induction of general anesthesia were investigated using bivariate and multivariate regression analyses in 330 OPCAB patients. With bivariate analyses, age; body size–related variables such as weight and body surface area; hematologic function–related variables such as blood hemoglobin (Hb) concentration and arterial oxygen saturation; renal function–related variables including estimated glomerular filtration rate, creatinine, and blood urea nitrogen; hepatic function–related variables including cholinesterase, albumin, total bilirubin, and alanine aminotransferase; serum electrolytes including sodium, chloride, and phosphorus; BNP or log-transformed BNP; and 13 transthoracic echocardiography variables such as left ventricular ejection fraction highly significantly correlated with baseline rSO2 (p Conclusions Preoperative BNP and Hb concentrations were 2 major factors associated with INVOS rSO2 in patients undergoing OPCAB.

Background Maternal critical illness occurs in 1.2 to 4.7 of every 1000 live births in the United States and approximately 1 in 100 women who become critically ill will die. Patient characteristics and comorbid conditions are commonly summarized as an index or score for the purpose of predicting the likelihood of dying; however, most such indices have arisen from non-pregnant patient populations. We sought to systematically review comorbidity indices used in health administrative datasets of pregnant women, in order to critically appraise their measurement properties and recommend optimal tools for clinicians and maternal health researchers. Methods We conducted a systematic search of MEDLINE and EMBASE to identify studies published from 1946 and 1947, respectively, to May 2017 that describe predictive validity of comorbidity indices using health administrative datasets in the field of maternal health research. We applied a methodological PubMed search filter to identify all studies of measurement properties for each index. Results Our initial search retrieved 8944 citations. The full text of 61 articles were identified and assessed for final eligibility. Finally, two eligible articles, describing three comorbidity indices appropriate for health administrative data remained: The Maternal comorbidity index, the Charlson comorbidity index and the Elixhauser Comorbidity Index. These studies of identified indices had a low risk of bias. The lack of an established consensus-building methodology in generating each index resulted in marginal sensibility for all indices. Only the Maternal Comorbidity Index was derived and validated specifically from a cohort of pregnant and postpartum women, using an administrative dataset, and had an associated c-statistic of 0.675 (95% Confidence Interval 0.647–0.666) in predicting mortality. Conclusions Only the Maternal Comorbidity Index directly evaluated measurement properties relevant to pregnant women in health administrative datasets; however, it has only modest predictive ability for mortality among development and validation studies. Further research to investigate the feasibility of applying this index in clinical research, and its reliability across a variety of health administrative datasets would be incrementally helpful. Evolution of this and other tools for risk prediction and risk adjustment in pregnant and post-partum patients is an important area for ongoing study. Electronic supplementary material The online version of this article (10.1186/s12884-017-1558-3) contains supplementary material, which is available to authorized users.

Gabapentin (GBP) and pregabalin (PGB) exert antinociceptive effects on chronic nociceptive responses with neuropathic or inflammatory conditions. Furthermore, it is considered that GBP and PGB exhibit anti‑inflammatory effects by modulating the substance P (SP)‑mediated neurokinin‑1 receptor (NK1R; a SP receptor) response. Thus, in the present study, the effects of GBP and PGB on SP‑induced activation were investigated in the human glioblastoma astrocytoma U373 MG cell line, which expresses high levels of functional high‑affinity NK1R, and produces interleukin (IL)‑6 and IL‑8 in response to SP. The results indicated that GBP and PGB suppressed the SP‑induced production of IL‑6, and IL‑8 in U373 MG cells. Furthermore, GBP and PGB inhibited the SP‑induced phosphorylation of p38 mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB, and the nuclear translocation of NF‑κB in U373 MG cells. Together, these observations suggest that GBP and PGB likely prevent SP‑induced IL‑6 and IL‑8 production in U373 MG cells via the inhibition of signaling molecules, including p38 MAPK and NF‑κB, thereby exhibiting antineuroinflammatory effects.

Anesthesia for patient with large anterior mediastinal mass might induce life‐threatening complication. Maintaining the spontaneous breathing throughout the procedure and finding rescue position are the cornerstones of anesthetic management.

Thoracoscopic pulmonary lobectomy (TPL) techniques in infants and children are presented practically with concise descriptions and numerous illustrations. TPL is the treatment of choice for congenital pulmonary airway malformation and intralobar pulmonary sequestration, both now commonly diagnosed prenatally. Timing of surgery is somewhat controversial in asymptomatic cases with small isolated lesions. Incomplete fissures and history of chest infections are most problematic. Thorough understanding of anatomic relations preoperatively is vital for successful outcome and thin-slice computed tomography with 3D reconstruction of vessels is valuable. Judicious placement of trocars and switching instruments between trocars improves visualization and safety. Specific techniques for all commonly performed TPL are included.

Ca v 2.3 (R-type) voltage-activated Ca 2+ channels (VACCs), encoded by the calcium channel, voltage-dependent, R-type, α1E subunit ( CACNA1E ) gene, are responsible for transmission of somatic inflammatory pain, and activation of antinociception elicited by visceral inflammatory pain stimuli. Carriers of the minor G allele of the rs3845446 single-nucleotide polymorphism (SNP) of the CACNA1E gene reportedly exhibit a decrease in opioid requirements to control typical somatic inflammatory pain after orthognathic surgery (ie, a painful cosmetic surgery), suggesting the downregulation of Ca v 2.3 VACC function that is responsible for transmission of somatic inflammatory pain in these carriers. Gastrointestinal surgery involves somatic and visceral inflammatory pain, in which visceral inflammatory pain stimuli activate Ca v 2.3 VACC-mediated antinociception. Unknown is whether pain-related phenotypes after gastrointestinal surgery are affected in these carriers. The present study used a correlational design to examine the effect of the rs3845446 SNP on postoperative pain-related phenotypes in 2 groups of patients who underwent gastrointestinal surgery. Carriers of the minor G allele had greater opioid requirements after laparoscopic colectomy when intravenous patient-controlled analgesia was used, and reported higher pain scores after open gastrointestinal surgery when postoperative analgesia was managed with continuous epidural analgesia and rescue analgesics. These results suggest that pain-related phenotypes after gastrointestinal surgery are enhanced in carriers of the minor G allele of the rs3845446 SNP, possibly through impairment of Ca v 2.3 VACC function that is responsible for the activation of visceral inflammatory pain stimulus-elicited antinociception. Perspective Carriers of the minor allele of the rs3845446 SNP of the CACNA1E gene required more opioid or reported higher pain scores after gastrointestinal surgery, and required less opioid after orthognathic surgery. The difference may result from the presence of visceral inflammatory pain stimulus that activates Ca v 2.3 VACCs-mediated antinociception.

Thoracoscopic pulmonary lobectomy (TPL) is extremely challenging in cases where severe incomplete fissure causes densely fused pulmonary lobes (DFPL) since pulmonary arteries (PAs) are buried and completely concealed by DFPL. We describe TPL for DFPL including a technical tip to prevent pitfalls.Four congenital pulmonary airway malformation (CPAM) and DFPL (left-upper: 2, left-lower: 1, right-middle: 1) were treated. During TPL, DFPL prevent interlobar PAs from being identified and searching for them only promotes bleeding and air leakage, serious pitfalls that affect the safety and success of TPL. Our tip is to ligate and divide the pulmonary veins (PVs) at the pulmonary hilum and the hilar PA supplying the CPAM lobe to expose the bronchus of the lobe, which is then ligated and divided. The main PA supplying the lobe running underneath the DFPL is exposed and visible from the pulmonary hilum allowing the PA supplying the lobe to be ligated and divided safely. A line demarcating the fused fissure becomes apparent, and an endoscopic stapler or EnSealThere were no intra-/postoperative complications in any case. All patients performed well without respiratory tract-related symptoms after a mean follow-up of 4.6 years.TPL for DFPL in children with CPAM can be performed safely and successfully as a virtually bloodless procedure and without incidence of air leakage by ligating and dividing the PA after dividing the PVs and bronchus to the lobe.

Macrophages are key immune system cells involved in inflammatory processes. Classically activated (M1) macrophages are characterized by strong antimicrobicidal properties, whereas alternatively activated (M2) macrophages are involved in wound healing. Severe inflammation can induce postoperative complications during the perioperative period. Invasive surgical procedures induce polarization to M1 macrophages and associated complications. As perioperative management, it is an important strategy to regulate polarization and functions of macrophages during inflammatory processes. Although propofol has been found to exhibit anti-inflammatory activities in monocytes and macrophages, it is unclear whether propofol regulates the functions of M1 and M2 macrophages during inflammatory processes. This study therefore investigated the effects of propofol on human macrophage polarization. During M1 polarization, propofol suppressed the production of IL-6 and IL-1β but did not affect TNF-α production. In contrast, propofol did not affect the gene expression of M2 markers, such as IL-10, TGF-β, and CD206, during M2 polarization. Propofol was similar to the GABAA agonist muscimol in inducing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and inhibiting IL-6 and IL-1β, but not TNF-α, production. Knockdown of Nrf2 using siRNA significantly reduced the effect of propofol on IL-6 and IL-1β production. These results suggest that propofol prevents inflammatory responses during polarization of human M1 macrophages by suppressing the expression of IL-6 and IL-1β through the GABAA receptor and the Nrf2-mediated signal transduction pathway.

Duloxetine, an antidepressant, is used for treatment of pain, but the factors related to its effectiveness are not well known, and therefore we have performed a retrospective study.Over a 22-month period from June 2012 patients with pain lasting for 3 months or more, with an NRS of 4 or higher, and given duloxetine within 3 months from their first diagnosis, were extracted from the medical records. These patients were compared and studied regarding their scores of the HADS (hos- pital anxiety and depression scale) at the time of first visit, duration of the disease, type of patient, and treat- ment effect after 1 month.The subjects were 61 patients, and they were categorized based on the presence of anxiety, the presence of dysphoria whether from organic or inor- ganic condition, and the duration of the disease, and no significant difference in the effectiveness of duloxetine was found.Duloxetine had an overall effectiveness of 50.8%, regardless of the presence of anxiety or depression, the duration of the disease and the type of diseases.

Indications for laparoscopic gynecologic surgery have been broadened. Although it is a rather noninvasive surgical procedure, it requires meticulous anesthetic management. Intraoperatively, hemodynamic and respiratory changes occur due to carbon dioxide insuf- flation, increased intraperitoneal pressure, and head- down position. Ventilator setting should be changed to cope with decreased chest-lung compliance and increased load of carbon dioxide during pneumoperitoneum in the head-down position. Mild hypercarbia may be per- mitted during this period to avoid ventilator-induced lung injury. Because the incidence of postoperative nausea and vomiting is high, it is recommended to use total intravenous anesthesia and prophylactic use of multiple antiemetics such as droperidol and dexameth- asone.

Surgical patients often take medications for preex- isting diseases. It is recommended to continue antihy- pertensive agents on the day of surgery in hyperten- sive patients. Two exceptions are angiotensin II recep- tor antagonist (ARB) and angiotensin converting enzyme inhibitors (ACEi) because of increased risk of hypotension during anesthesia. It is important to re- sume antihypertensive agents within a day or a few days postoperatively. Antipsychotic agents and antiepi- leptic drugs often cause arrhythmias and hypotension. The risk of neuroleptic malignant syndrome and sero- tonin syndrome should be noted. The patients on chronic opioids should require meticulous perioperative pain manageient Decisions about continuing or with- holding medications should be made on a case-by-case basis.

A multiplex analysis for profiling the expression of candidate microRNAs (miRNAs), which are small noncoding RNAs that function as key post-transcriptional regulators, may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we performed a miRNA array analysis using tissues of the dorsal root ganglion (DRG), a primary site for pain processing, obtained from mice with partial sciatic nerve ligation. Among 1135 total miRNAs, 26 miRNAs showed up-regulation (more than 2-fold change) and only 4 miRNAs showed down-regulation (less than 0.5-fold change) in the DRG of nerve-ligated mice. In a RT-qPCR assay, the levels of miR-21, miR-431, and miR-511-3p were significantly increased on the ipsilateral side of the DRG from 3 to 7 days after sciatic nerve ligation. These elevations were almost absent in IL-6 knockout mice. Furthermore, the expression level of miR-21, but not those of miR-431 or miR511-3p, was significantly increased in exosomes extracted from blood of nerve-ligated mice. These findings suggest that the increased expression of IL-6-regulated miR-21, miR-431, and miR-511-3p in the DRG and increased exosomal miR-21 extracted from blood after sciatic nerve ligation may play at least a partial role in neuropathic pain. Synapse 70:317-324, 2016. © 2016 Wiley Periodicals, Inc.

Obstetric anesthesiologists are supposed to understand the uterotonics and tocolytics used in the perinatal period to provide a better clinical practice. This review describes current consensus of uterotonics and tocolytics used in the perinatal period that an obstetric anesthesiologist should know.Rational use of uterotonics for cesarean section has been well studied in the past decades. Oxytocin remained as a first line uterotonics for cesarean section. For continuous infusion, it is reported that ED90 is higher for laboring parturients than for nonlaboring parturients (6.2 vs. 44.2 IU/h) implying that protocol for oxytocin infusion should be different between laboring patients with prior exposure to oxytocin and nonlaboring patients. For bolus administration, 'rule of three' has been proposed and its efficacy has been reported. When oxytocin fails to achieve sufficient uterine contraction, second-line agents must be administered, and it has been reported that methylergonovine is a superior second-line uterotonic to carboprost. On the other hand, the role of tocolytic agents in obstetric anesthesia has not been well studied.Anesthesiologists involved in obstetric anesthesia should be able to determine the appropriate uterotonic for cesarean section and know the indication of tocolytics in perinatal period.