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

Different effects of colloid and crystalloid solutions for fl uid resuscitation on hemodynamics and peripheral organ functions in acute hemorrhagic shock rats

Background: The impact of fl uid resuscitation on hemorrhagic shock may depend on the type of fl uids used. This study investigated the specifi c effects of fl uid resuscitation with colloids or crystalloids on the hemodynamics and peripheral organ functions, including mitochondrial activities, infl ammation, blood rheology, clotting and platelet functions.Methods: Hemorrhagic shock was induced in 48 anesthetized rats by blood withdrawal at 1 mL/kg/min. Withdrawal continued until mean arterial pressure (MAP) decreased to 30 mmHg and hypotension was maintained for 20 min. Rats received fl uid resuscitation with 6% hydroxyethyl starch 130/0.4 (HES, n = 12), 5% albumin (ALB, n = 12), normal saline (NS, n = 12) at 1 mL/kg/min or normal saline at 3 mL/kg/min (3-NS, n = 12). Changes investigated included hemodynamics, blood gas analysis, mitochondrial functions,cytokine concentrations, blood rheology, clotting and platelet functions after hemorrhage and fl uid resuscitation.Results: MAP in HES (55 ± 5 mmHg) and ALB (56 ± 12 mmHg) were signifi cantly higher than NS (23 ± 8 mmHg) and 3-NS (38± 5 mmHg) 45 min after resuscitation (P < 0.001). HES and ALB, but not NS signifi cantly attenuated mitochondrial dysfunction and infl ammatory responses. Colloids but not NS signifi cantly induced hemodilution and a consistent blood fl ow. Although there was no difference between HES and ALB, colloids interfered with clotting formation.Conclusion: Fluid resuscitation with colloids but not crystalloids preserved hemodynamics and peripheral organ function afterhemorrhagic shock. Although colloids modulated clotting formation via hemodilution, there was no difference between HES and ALB.departmental bulletin pape

Elevation and suppression of paraoxon-induced epileptic activity in the rat hippocampus

Background: Organophosphorus cholinesterase inhibitors and an elevated extracellular potassium concentration ([K+]e) elicit clinical epilepsy. We investigated (1) the epilepsy-inducing actions of paraoxon (POX) with elevated [K+]e and (2) the effects of atropine,pralidoxime, and selective muscarinic acetylcholine receptor (mAChR) antagonists on the actions of POX.Materials and Methods: Orthodromically elicited population spikes and fi eld excitatory postsynaptic potentials were simultaneously recorded from the CA1 region in rat hippocampal slices using a multi-electrode array system. Statistics were performed using ANOVA with Bonferroni testing (n = 6).Results: Epileptic activity was elicited in high (7.5, 9.0 mM) [K+]e with or without POX, but not in normal (4.5 mM) [K+]e. The incidence of epileptic activity with POX (83.3%) was signifi cantly higher (p < 0.05) than that without POX in 7.5 mM [K+]e (16.7%). The number of additional population spikes with POX (1.33 ± 1.03) was signifi cantly higher than that prior to and during treatment with atropine (0.16 ± 0.40 and 0.16 ± 0.40, respectively, p < 0.05) or prior to treatment with M1 and M3 mAChR antagonists (0 and 0.16 ± 0.40, respectively, p < 0.05), but not with pralidoxime, M2, or M4 mAChR antagonists in 7.5 mM [K+]e.Conclusion: POX-induced cholinesterase inhibition elicited epileptic activity in elevated [K+]e but not normal [K+]e. Treatment for hyperkalemia likely prevents development of epilepsy following organophosphate intoxication. Atropine, rather than pralidoxime, may be effective at inhibiting organophosphate-induced epileptic activity.departmental bulletin pape

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

Successful Anesthetic Management Using Dexmedetomidine Sequentially with Propofol in the Asleep-Awake-Asleep Technique for Elderly Patients Undergoing Awake Craniotomy

Anesthesiologists should supply proper sedation and high-quality awakening in awake craniotomy anesthesia. At our institution, we perform an asleep-awake-asleep technique for awake craniotomy anesthesia by using short-acting anesthetic drugs, such as propofol and remifentanil. However, elderly patients do not wake adequately in our normal protocol and hence are unable to complete the required neurological tasks. In this case series, we present the anesthetic management of three elderly patients with sequent use of propofol and dexmedetomidine as sedative agents for awake craniotomy. We hypothesized that this anesthetic protocol is advantageous in awake craniotomy management. For the awake phase, all patients were adequately awake and performed neurological tasks without adverse events and agitation. The use of dexmedetomidine sequentially with propofol in an asleep-awake-asleep technique for awake craniotomy in elderly patients might shorten the time to awakening and provide clear awakening