Dexmedetomidine attenuates surgery-induced cognitive deficit and hippocampal Mapt expression in aged mice

Background Postoperative cognitive dysfunction is a significant complication, but the mechanisms underlying this condition and its impact on the brain network are not fully elucidated. The goals of this study were to verify how the transcriptional network in the hippocampus of aged mice changes following sevoflurane/surgery-induced stress and to substantiate how dexmedetomidine influences the cognitive function and mRNA changes in the hippocampus.Materials and methods We first performed transcriptome analysis to confirm the changes of mRNA expression in the Naïve and Ope (surgery under sevoflurane) groups. Then, the mice were divided into four groups: Naïve, Sevo (sevoflurane exposure), Ope, and Dex (dexmedetomidine injection before surgery). We selected the Mapt gene, the upregulated expression of which has been observed in our transcriptome analysis and in neurodegenerative disorders, as the target gene and investigated whether the changes in its expression occurred in the hippocampus using quantitative rev transcription polymerase chain reaction (qRT-PCR). The cognitive function of mice was evaluated via the Barnes Maze test.Results In the qRT-PCR analysis, Mapt expression was significantly upregulated (2.60 ± 0.77 in mice from the Ope group vs. 1.00 ± 0.11 in mice from the Naïve group [mean ± SD for fold change]; p<0.01). Dexmedetomidine significantly attenuated the sevoflurane/surgery-induced upregulation of Mapt expression in the hippocampus (0.88 ± 0.32; p<0.01). Sevoflurane/surgery-induced stress also increased the time to identify the target box, and dexmedetomidine treatment inhibited the time extension 7, 14, and 28 days after the surgery.Conclusions Dexmedetomidine attenuates the sevoflurane/surgery-induced cognitive deficit and Mapt expression in the hippocampus of aged mice

Patients living with chronic non-cancer pain receiving opioid therapy in Japan: a grounded theory study

Through an examination of personal narratives, we sought to elucidate the experiences of people receiving chronic opioid therapy for chronic non-cancer pain. The participants were 34 adult volunteer outpatients treated in pain clinics. Data were collected using semi-structured interviews and analyzed using the grounded theory approach. The participants described their daily life experiences of chronic pain and opioid therapy. Informed consent and ethical approval were obtained. Six categories were extracted:“Barriers to living with chronic pain,”“Facing injustice or extreme chronic pain and catastrophizing,”“Making an attempt to improve one’s condition,”“Ambivalence about medical treatment,”“Finding a compromise while living with chronic pain,”and“Regaining a life.”These findings expand our understanding of Japanese patients with chronic non-cancer pain who receive opioid treatment and how they cope in their daily lives

Recombinant human soluble thrombomodulin is associated with attenuation of sepsisinduced renal impairment by inhibition of extracellular histone release

感染症によって重篤な臓器障害が引き起こされて敗血症に至る過程でDAMPs（damage － associated molecular patterns）の関与が注目されている．今回，ヒストンH3に着目し，ラット腹膜炎敗血症モデルを用いてリコンビナントトロンボモジュリン（rhTM）とその抗炎症作用をもつD1がヒストンH3濃度と腎障害に与える影響を検討した．rhTMとD1の投与は，ヒストンH3濃度上昇と血清クレアチニン値上昇を抑制し腎の組織障害が軽減し，生存率改善との関連が示唆された．これらの結果は臨床応用を見据えた場合，rhTMのD1領域が細胞外ヒストンH3蛋白を制御し，敗血症での治療戦略の一つとなる可能性が示唆された

The Efficacy and Safety of Dexmedetomidine for Sedation During Surgery Under Epidural or Spinal Anesthesia: A Randomized, Double-Blind, Placebo-Controlled Study

Background: Only a few studies have been reported on the use of dexmedetomidine for sedating surgical patients requiring epidural or spinal anesthesia. We conducted a randomized, double-blind, placebo-controlled, parallel-group study at 12 hospitals in Japan. Methods: Adult patients were randomly allocated to receive an intravenous administration of placebo or dexmedetomidine at 0.067, 0.25, 0.5 or 1.0 μg/kg over 10 min after epidural or spinal anesthesia. All dexmedetomidine groups received dexmedetomidine 0.2–0.7 μg/kg/h to maintain an Observer’s Assessment of Alertness/Sedation Scale (OAA/S) score of ≤ 4; however, propofol was administered to rescue patients who exceeded this score. Surgery was then started 15 min after study drug infusion in patients with OAA/S score of ≤ 4. The primary endpoint was the percentage of patients not requiring rescue propofol to achieve and maintain an OAA/S score of ≤ 4. Results: Of the 120 enrolled and randomized patients, 119 were treated the study: 22 received placebo and 97 received dexmedetomidine (23–25 patients per dose). Significantly more patients did not require propofol in the dexmedetomidine 0.5 and 1.0 μg/kg groups (68.0% and 80.0%, respectively) compared to the placebo group (22.7%) (P = 0.003 and P < 0.001, respectively). Common adverse events (AEs) were protocol-defined respiratory depression, bradycardia and hypotension. There was no significant difference in the incidence of AEs between the dexmedetomidine and the placebo groups. Conclusion: We concluded that loading doses of 0.5 and 1.0 μg/kg dexmedetomidine, followed by an infusion at a rate of 0.2–0.7 μg/kg/h, provide effective and well-tolerated sedation for surgical patients during epidural or spinal anesthesia. Clinical trials.gov identifier: NCT0143895

Duodenal ulcer accompanied by intractable right lateral chest pain (T6/T7 dermatomal segments)

Abstract A 48-year-old man who complained of a severe throbbing pain in his right lateral chest was referred to our department. His chest computed tomography (CT) and X-ray, abdominal CT and ultrasonography had revealed no abnormalities. Four days after admission to our ward the patient vomited and he requested upper gastrointestinal (GI) endoscopy: this showed duodenal ulcer. Treatment with omeprazole and sucralfate improved the duodenal ulcer; concurrently, the symptoms of chest pain were relieved

Efficacy and Practicality of Opioid Therapy in Japanese Chronic Noncancer Pain Patients

Background: Many Japanese adults suffer from chronic pain. However, 50% of these individuals discontinue treatment despite the persistence of pain. Both clinicians and patients in Japan tend to be concerned about the safety and efficacy of opioid therapy, and the use of opioids in chronic non-cancer pain remains less common in Japan than elsewhere. Aims: This study examined the effects of opioid therapy on the daily lives of patients with chronic noncancer pain in Japan, where use of opioids for this type of pain remains uncommon. Design: Prospective cross-sectional questionnaire study. Setting: Data were collected over two periods, between March and April 2014 at one hospital, and between February and April 2015 at the other hospital. Subjects were recruited at the respective clinics by the study interviewer between March 1, 2014 and April 15, 2014 and between February 1, 2015 and April 15, 2015. Participants/Subjects: This study included 34 outpatients with chronic non-cancer pain who were being treated with opioid analgesics at pain clinics in two hospitals in Sapporo. Methods: Thirty-four Japanese patients receiving opioid medications for chronic noncancer pain in outpatient pain clinics were enrolled. Participants underwent interviews and completed the Japanese versions of the Short Form 36 (SF-36v2) and the Coping Strategies Questionnaire (CSQ). Results: Sleep disruption, claiming compensation for work-related accidents, and current pain level were negatively correlated with opioid effectiveness (p < .05). Additionally, opioid effectiveness was negatively correlated with the catastrophizing subscale of the CSQ (r = -0.50, p < .01). The effects of opioid therapy had a low positive correlation with the emotional functioning role subscale of the SF-36v2 (r = 0.38, p < .05). Daily equivalent morphine dose was positively correlated with opioid therapy duration, interference with appetite, and current pain intensity. Morphine dose was also positively correlated with scores for the catastrophizing subscale of the CSQ(r = 0.36, p < .05) and negatively correlated with scores in all subdomains of the SF-36v2. Conclusions: It is important to focus on adaptive, cognitive, and emotional factors, such as emotional role functioning, to determine the efficacy of opioid treatment for chronic noncancer pain. Moreover, patients with catastrophizing significantly increased their morphine doses, resulting in an increased risk of overdose. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the American Society for Pain Management Nursing