Sepsis-associated neuroinflammation in the spinal cord

Septic patients commonly present with central nervous system (CNS) disorders including impaired consciousness and delirium. Today, the main mechanism regulating sepsis-induced cerebral disorders is believed to be neuroinflammation. However, it is unknown how another component of the CNS, the spinal cord, is influenced during sepsis. In the present study, we intraperitoneally injected mice with lipopolysaccharide (LPS) to investigate molecular and immunohistochemical changes in the spinal cord of a sepsis model. After LPS administration in the spinal cord, pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha mRNA were rapidly and drastically induced. Twenty-four-hour after the LPS injection, severe neuronal ischemic damage spread into gray matter, especially around the anterior horns, and the anterior column had global edematous changes. Immunostaining analyses showed that spinal microglia were significantly activated and increased, but astrocytes did not show significant change. The current results indicate that sepsis induces acute neuroinflammation, including microglial activation and pro-inflammatory cytokine upregulation in the spinal cord, causing drastic neuronal ischemia and white matter edema in the spinal cord

The inhibitory effects of Orengedokuto on inducible PGE2 production in BV-2 microglial cells

[Background and aim] Reactive microglia has been associated with neuroinflammation caused by the production of proinflammatory molecules such as cytokines, nitric oxide, and prostaglandins. The overexpression of these molecules may provoke neuronal damage that can cause neurodegenerative diseases. A traditional herbal medicine, Orengedokuto (OGT), has been widely used for treating inflammation-related diseases. However, how it influences neuroinflammation remains poorly understood. [Experimental procedure] This study investigated the effects of OGT on inflammatory molecule induction in BV-2 microglial cells using real-time RT-PCR and ELISA. An in vivo confirmation of these effects was then performed in mice. [Results and conclusion] OGT showed dose-dependent inhibition of prostaglandin E2 (PGE2) production in BV-2 cells stimulated with lipopolysaccharide (LPS). To elucidate the mechanism of PGE2 inhibition, we examined cyclooxygenases (COXs) and found that OGT did not suppress COX-1 expression or inhibit LPS-induced COX-2 upregulation at either the transcriptional or translational levels. In addition, OGT did not inhibit COX enzyme activities within the concentration that inhibited PGE2 production, suggesting that the effect of OGT is COX-independent. The inhibitory effects of OGT on PGE2 production in BV-2 cells were experimentally replicated in primary cultured astrocytes and mice brains. OGT can be useful in the treatment of neuroinflammatory diseases by modulating PGE2 expression

Association between intraoperative end-tidal carbon dioxide and postoperative nausea and vomiting in gynecologic laparoscopic surgery

Gynecologic laparoscopic surgery has a high incidence of postoperative nausea and vomiting (PONV). Studies suggest that low intraoperative end-tidal carbon dioxide (EtCO₂) is associated with an increased incidence of PONV, but the results have not been consistent among studies. This study investigated the association between intraoperative EtCO₂ and PONV in patients undergoing gynecologic laparoscopic surgeries under general anesthesia. This retrospective cohort study involved patients who underwent gynecologic laparoscopic surgeries under general anesthesia at Kyoto University Hospital. We defined low EtCO₂ as a mean EtCO₂ of < 35 mmHg. Multivariable modified Poisson regression analysis examined the association between low EtCO₂ and PONV during postoperative two days and the postoperative length of hospital stay (PLOS). Of the 739 patients, 120 (16%) had low EtCO₂, and 430 (58%) developed PONV during postoperative two days. There was no substantial association between low EtCO₂ and increased incidence of PONV (adjusted risk ratio: 0.96; 95% confidence interval [CI] 0.80–1.14; p = 0.658). Furthermore, there was no substantial association between low EtCO₂ and prolonged PLOS (adjusted difference in PLOS: 0.13; 95% CI − 1.00 to 1.28; p = 0.816). Intraoperative low EtCO₂, specifically a mean intraoperative EtCO₂ below 35 mmHg, was not substantially associated with either increased incidence of PONV or prolonged PLOS

Characteristics of Oxidative Storage Stability of Canola Fatty Acid Methyl Ester Stabilised with Antioxidants

The storage effects on the oxidation characteristics of fatty acid methyl ester of canola oil (CME) were investigated in this study.CME stabilised with two antioxidants, i.e.2,6-di-tert-bytyl-p-cresol (BHT) and 6,6-di-tert-butyl-2, 2'-methylendi-p-cresol (BPH), was stored at 20, 40 and 60°C.The oxidation stability data were measured by the Rancimat test method and it was found that both BHT and BPH addition increased the oxidation resistance of the CME. The results showed that when BPH or BHT was added at a concentration of 100 ppm, the oxidation induction period of the neat CME samples increased from 5.53 h to 6.93 hand 6.14 h, respectively. Comparing both antioxidants, BPH proved to be more effective in increasing the oxidation resistance when both antioxidants were added at the same concentration. Furthermore, the oxidation induction timedecreased linearly with the storage time. It was shown that the oxidation occurred rapidly in the first 8 weeks of storage. Later, a kinetic study was undertaken and first-order kinetics were applied to explain the oxidation characteristics of the CME added with antioxidants. This kinetic study focused on exploiting the activation energy values obtained from the Arrheniusequations. Also, the oxidation effects on other quality parameters, including acid value, peroxide value, kinematic viscosity, and water content, were examined

Incidence, clinical characteristics and long-term prognosis of postoperative symptomatic venous thromboembolism: a retrospective cohort study

OBJECTIVES: The purpose of this study was to evaluate the incidence, clinical characteristics and prognosis of postoperative symptomatic venous thromboembolism (VTE) in Japan. DESIGN: Retrospective observational study. Two data sets, Contemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry and Japanese Society of Anesthesiologists (JSA) annual report, were used for current analyses. SETTING: Eighteen of 29 centres participated in the COMMAND VTE Registry. PARTICIPANTS: Acute symptomatic patients with VTE who had undergone surgery 2 months prior to the diagnosis at 18 centres from January 2010 to December 2013 were identified in the COMMAND VTE Registry. From each centre's JSA annual report, the overall population that had received anaesthetic management during this period was retrieved. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the incidences and clinical characteristics of postoperative symptomatic VTE. The secondary outcomes were recurrent VTE, major bleeding and all-cause death. RESULTS: We identified 137 patients with postoperative symptomatic VTE, including 57 patients with pulmonary embolism. The incidences of postoperative symptomatic VTE and pulmonary embolism were 0.067% and 0.028%, respectively, based on data from 2 03 943 patients who underwent surgery, managed by anaesthesiologists, during the study period. The incidences of postoperative symptomatic VTE varied widely, depending on surgical and anaesthetic characteristics. Postoperative symptomatic VTE occurred at a median of 8 days after surgery, with 58 patients (42%) diagnosed within 7 days. The cumulative incidence, 30 days after VTE, of recurrent VTE, major bleeding, and all-cause death was 3.0%, 5.2%, and 3.7%, respectively. CONCLUSION: This study, combining the large real-world VTE and anaesthesiology databases in Japan revealed the incidence, clinical features and prognosis of postoperative symptomatic VTE, providing useful insights for all healthcare providers involved in various surgeries. TRIAL REGISTRATION: Not applicable

母体への揮発性麻酔薬投与は胎児脳においてIL-6を誘導し神経発達に影響を及ぼす

京都大学0048新制・課程博士博士(医学)甲第22310号医博第4551号新制||医||1040(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 渡邉 大, 教授 万代 昌紀, 教授 影山 龍一郎学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Relationship between the Use of Fentanyl-Based Intravenous Patient-Controlled Analgesia and Clinically Significant Events in Laparoscopic Gynecological Surgery: A Single-Center Retrospective Cohort Study

Background: This study examined the relationship between the use of fentanyl-based intravenous patient-controlled analgesia (ivPCA) and the incidence of a clinically significant event (CSE), while considering both the analgesic effects and side effects in laparoscopic gynecological surgery. Methods: This study included 816 patients undergoing laparoscopic gynecological surgery under general anesthesia at Kyoto University Hospital between 2012 and 2018. The primary exposure was the use of fentanyl-based ivPCA. We defined an outcome measure&mdash;CSE&mdash;that integrates severe wound pain and vomiting assumed to negatively affect patient recovery. We performed multivariable logistic regression analysis to assess the independent relationship between ivPCA use and CSE. Results: Multivariable logistic regression analysis revealed that fentanyl-based ivPCA was independently associated with increased CSE (adjusted odds ratio (95% confidence interval): 1.80 (1.24&ndash;2.61), p = 0.002). Use of ivPCA was associated with a reduced incidence of postoperative severe wound pain (adjusted odds ratio (95% confidence interval): 0.50 (0.27&ndash;0.90), p = 0.022), but was also associated with an increased incidence of vomiting (adjusted odds ratio (95% confidence interval): 2.65 (1.79&ndash;3.92), p &lt; 0.001). Conclusion: The use of fentanyl-based ivPCA in laparoscopic gynecological surgery is associated with increased CSE

Characteristics of Oxidative Storage Stability of Canola Fatty Acid Methyl Ester Stabilised with Antioxidants

The storage effects on the oxidation characteristics of fatty acid methyl ester of canola oil (CME) were investigated in this study. CME stabilised with two antioxidants, i.e. 2,6-di-tert-bytyl-p-cresol (BHT) and 6,6-di-tert-butyl-2, 2’-methylendi-p-cresol (BPH), was stored at 20, 40 and 60°C. The oxidation stability data were measured by the Rancimat test method and it was found that both BHT and BPH addition increased the oxidation resistance of the CME. The results showed that when BPH or BHT was added at a concentration of 100 ppm, the oxidation induction period of the neat CME samples increased from 5.53 h to 6.93 h and 6.14 h, respectively. Comparing both antioxidants, BPH proved to be more effective in increasing the oxidation resistance when both antioxidants were added at the same concentration. Furthermore, the oxidation induction time decreased linearly with the storage time. It was shown that the oxidation occurred rapidly in the first 8 weeks of storage. Later, a kinetic study was undertaken and first-order kinetics were applied to explain the oxidation characteristics of the CME added with antioxidants. This kinetic study focused on exploiting the activation energy values obtained from the Arrhenius equations. Also, the oxidation effects on other quality parameters, including acid value, peroxide value, kinematic viscosity, and water content, were examined